Having antibodies against the core implies natural contact, and that it is IgG, which is not acute. The absence of e antigen rules out active replication. And the persistence of surface antigen (HBsAg) and virus DNA indicates that it is still present. Together, these indicate an asymptomatic carrier. Carriers of the pre-core mutant usually have recurrent symptomatic periods and increased liver inflammation. There would be insufficient data to rule it out completely, but it is not among the answers and indicates a completely normal physical examination.

Having antibodies against the core implies natural contact, and that it is IgG, which is not acute. The absence of e antigen rules out active replication. And the persistence of surface antigen (HBsAg) and virus DNA indicates that it is still present. Together, these indicate an asymptomatic carrier. Carriers of the pre-core mutant usually have recurrent symptomatic periods and increased liver inflammation. There would be insufficient data to rule it out completely, but [HIDDEN] and indicates a completely normal physical examination.

Indicate the clinical situation in relation to hepatitis B virus infection in a 5-year-old patient from Nigeria, with normal physical examination and the following serology for hepatitis B: HBsAg + / ANTI-HBs - / HbeAg - / ANTI-HBe + / ANTI-HBc IgM - / ANTI-HBc IgG + / DNA HBV +:

Frequency and persistence of serologic markers following three different manifestations of hepatitis B virus infection.

30 asymptomatic chronic carriers of hepatitis B surface antigen (HBsAg), 6 asymptomatic blood donors transiently infected with hepatitis B virus, and 38 patients with acute hepatitis B were tested for HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc. Comparison of these results revealed significant variation in the frequency of HBeAg which was present in 1 (3.3%) carrier, 2 (33.3%) of the transiently positive donors, and in 24 (63.2%) of the patients with acute hepatitis. Anti-HBe was found in 28 (93.3%) of the carriers, 4 (66.6%) of the transiently positive donors, and in 8 (21%) of the patients. Variation was also seen in the strength of anti-HBc, with only the chronic carriers having titres which were consistently high (above 1,000). Retesting the two groups of donors after a period of approximately 2 years showed no change in the serologic status of the chronic carriers, while amongst the transient HBsAg positives the 2 HBeAg reactives had seroconverted, 1 of the anti-HBe positives had become non-reactive, and 2 of the 6 had developed anti-HBs. 6 of the patients with acute hepatitis B were serologically reexamined during convalescence and showed results similar to those seen in the transiently HBsAg-positive donors, with clearance of HBsAg in all, seroconversion from HBeAg to anti-HBe in 4, and the production of anti-HBs in 4.

[Atypical serological profiles in hepatitis B infections: investigation of S gene mutations in cases with concurrently positive for HBsAg and anti-HBs].

Hepatitis B virus (HBV) causes different clinical manifestations, ranging from asymptomatic carriage to fulminant or chronic hepatitis. Serological tests are widely used for the diagnosis of HBV infections to detect viral markers. However, facing with atypical serological profiles in some patients leads to problems in interpreting of the results and management of the patients. The aims of this study were to investigate the atypical serologic profiles seen in patients screened for HBV infection and the S gene mutations in patients with concurrent positivity of HBsAg and anti-HBs. A total of 592 sera from patients (332 male, 260 female; age range: 13-84 years, mean age: 43.9 years) prediagnosed as HBV infection between January to September 2013, and screened for HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc-IgM, anti-HBc-total and HBV-DNA) were included in the study. Of those samples 364 were screened only for HBsAg and anti-HBs markers. S gene mutations were investigated by direct sequencing method in sera which were concurrent positive for HBsAg and anti-HBs. In our study, 5.2% (31/592) of the sera yielded atypical serologic profiles. Of these 13 cases were concurrently positive for HBsAg and anti-HBs; nine were HBeAg positive, anti-HBe and HBV-DNA negative; eight were HBeAg, anti-HBe and HBV-DNA positive; and one was HBsAg and anti-HBs negative, anti-HBe and HBV-DNA positive. The rate of concurrent positivity of HBsAg and anti-HBs was 3.6% (13/364), while 76.9% (10/13) of those cases were also positive for HBV-DNA. DNA sequencing was performed for seven out of 10 samples which were positive for HBsAg, anti-HBs and HBV-DNA, however three samples were not used because of the low amounts. Sequence analysis of seven samples showed S gene mutations in two samples, one was sS143L with sS193L, a HBV vaccine escape mutation, and the other was sP120R, a HBV immune escape mutation. Of the patients 2.7% (10/364) was negative for both HBsAg and anti-HBs; in which nine were HBV-DNA negative and anti-HBe positive, while one was positive for both HBV-DNA and anti-HBe. The rate of concurrent positivity of HBeAg and anti-HBe was found as 1.4% (8/592), and all of these samples were HBV-DNA positive. No single positivity for HBsAg, anti-HBc, anti-HBs or HBV-DNA was not detected in any of the patients. In conclusion, HBsAg and anti-HBs concurrent positivity was the most frequently detected atypical profile in our study (3.6%), and in some (2/7) of these patients S gene mutations were determined.

Seroconversion

On a serological assay, the presence of hepatitis B surface antigen (HBsAg) indicates an individual with a currently active hepatitis B infection, whether acute or chronic. The presence of core antibody (anti-HBc) indicates an individual with an infection in general, whether current or previously resolved. The presence of surface antibody (anti-HBs) indicates an individual with immunity to hepatitis B, whether due to previously resolved infection or due to hepatitis B vaccination. For example, an individual who has never had any exposure to HBV, either by vaccine or by infection, would test negative for the entire serology panel. An individual who has been vaccinated and never had an infection will test seropositive for anti-HBs due to vaccination and negative for markers of infection. An individual with an acute HBV infection would test positive for HBsAg and anti-HBc (total and IgM) while negative for anti-HBs. An individual with a chronic infection would test positive for HBsAg and

The etiology of acute hepatitis superimposed upon previously unrecognized asymptomatic HBsAg carriers.

To study the etiology of acute hepatitis superimposed upon previously unrecognized asymptomatic HBsAg carriers, paired sera were collected in acute and convalescence phases for measurement of HBeAg, anti-HBe, hepatitis B virus DNA and anti-delta from 76 adult patients with acute hepatitis who were HBsAg positive but IgM anti-HBc negative or positive only at low titer. None of them were IgM anti-hepatitis A virus positive on admission. Of the 34 patients who were HBeAg positive initially, two (5.9%) were diagnosed as having delta superinfection, and another two (5.9%) were suspected to have non-A, non-B virus superinfection because of a transient decrease of serum hepatitis B virus DNA. The remaining 30 (88.2%) cases were hepatitis B virus DNA negative with or without anti-HBe seroconversion on follow-up. The episodes of acute hepatitis in these cases may represent "immune clearance of HBeAg" or "immune clearance of hepatitis B virus with delayed anti-HBe seroconversion," respectively, in the natural course of chronic hepatitis B virus infection. Of the patients who were anti-HBe positive initially, 23 (54.8%) were diagnosed as having delta superinfection, including eight with de novo seroconversion of anti-delta and 15 with a rising titer of anti-delta; 10 (23.8%) were positive for hepatitis B virus DNA and were considered as reactivation of hepatitis B virus, and the other nine (21.4%) were suspected as having non-A, non-B virus superinfection.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatitis B -- Evaluation -- Interpretation of Serologic Markers

Following serologic markers are often tested: Hepatitis B surface antigen (HBsAg), antibody to Hepatitis B surface antigen (anti-HBs), Hepatitis B core Ab (Anti-HBc) IgM, Hepatitis B core Ab (Anti-HBc) IgG, Hepatitis B e antigen (HBeAg), and Hepatitis B e antibody (anti-HBe). [10] HBsAg: Acute infection (less than 6 months) or chronic infection (more than 6 months). Anti-HBs: Recovery from acute infection or immunity from vaccination. HBeAg: Mostly associated with high viral load. Anti-HBe: Low replicative phase. Anti-HBc IgM: Acute infection, an only marker present in the window period, can be present during exacerbation of chronic infection. Anti-HBc IgG: Exposure to infection, chronic infection (if present along with HBsAg), recovery from acute infection (if present with anti-HBs), if isolated presence, may represent occult infection.

Hepatitis B

Shortly after the appearance of the HBsAg, another antigen called e antigen (HBeAg) will appear. Traditionally, the presence of HBeAg in a host's serum is associated with much higher rates of viral replication and enhanced infectivity; however, variants of the virus do not produce the 'e' antigen, so this rule does not always hold true. During the natural course of an infection, the HBeAg may be cleared, and antibodies to the 'e' antigen (anti-HBe) will arise immediately afterwards. This conversion is usually associated with a dramatic decline in viral replication. If the host is able to clear the infection, eventually the HBsAg will become undetectable and will be followed by IgG antibodies to the surface antigen and core antigen (anti-HBs and anti HBc IgG). The time between the removal of the HBsAg and the appearance of anti-HBs is called the window period. A person negative for HBsAg but positive for anti-HBs either has cleared an infection or has been vaccinated previously.

Window period

Hepatitis B Two periods may be referred to as window period in hepatitis B infection: (1) the period that elapses during HBsAg to HBsAb seroconversion, i.e. between the disappearance of surface antigen (HBsAg) from serum and the appearance of HBsAb (anti-HBs), and (2) the period between infection and appearance of HBsAg. During the window of HBsAg to HBsAb seroconversion, IgM anti-core (HBc-IgM) is the only detectable antibody. HBV DNA may be positive as well. This window period does not occur in persons who develop chronic hepatitis B, i.e. who continue to have detectable HBV DNA for greater than 6 months (HbsAg remains positive), or in people who develop isolated HBcAb positivity, i.e. who lose HBsAg, but do not develop HBsAb (HBV DNA may or may not remain positive). See also Incubation period, the time between infection and the appearance of symptoms References HIV/AIDS Serology

Seroconversion

individual with an acute HBV infection would test positive for HBsAg and anti-HBc (total and IgM) while negative for anti-HBs. An individual with a chronic infection would test positive for HBsAg and total anti-HBc (IgM and IgG), but negative for IgM anti-HBc and anti-HBs. An individual who has successfully resolved their HBV infection will test negative for HBsAg, positive for anti-HBc, and may test negative or positive for anti-HBs, although most will test positive.

Seroconversion

In the typical disease course for hepatitis B, the individual will first seroconvert for hepatitis B surface antigen (HBsAg). While some can convert within one week, most individuals take about four weeks after initial infection to convert. Anti-core antibodies (anti-HBc) are the first antibodies produced by the body, first in short-term IgM (anti-HBc IgM), and subsequently in long-term IgG; while levels of IgM anti-HBc will peak around sixteen weeks after exposure and fall within about seven to eight months, IgG anti-HBc will remain detectable in the serum as a sign of chronic infection for years. IgM anti-HBc concentration will fall regardless of whether or not the individual clears the infection. The window period for HBsAg/anti-HBs testing occurs as concentration of HBsAg falls and before the body develops anti-HBs antibodies, lasting approximately six to eight weeks in most individuals. During this time, serology assays can test for total anti-HBc. Levels of anti-surface antibody

Vaccine-induced seropositivity

Hepatitis B When a person gets a hepatitis B vaccine then the most common test for hepatitis B will show them to be positive. The usual course of action, in this case, is to give the person a panel of tests for HBsAg, anti-HBc, and anti-HBs (hepatitis B surface antigen, anti-hepatitis B core, and anti-hepatitis B surface). A person who has never been exposed to hepatitis B but has gotten the vaccine will be positive for anti-HBs but negative for the other two tests in the panel. Other combinations of positive and negative in this test can mean other things, such as acute, chronic, or past infection.

Hepatitis

Viral hepatitis Viral hepatitis is primarily diagnosed through blood tests for levels of viral antigens (such as the hepatitis B surface or core antigen), anti-viral antibodies (such as the anti-hepatitis B surface antibody or anti-hepatitis A antibody), or viral DNA/RNA. In early infection (i.e. within 1 week), IgM antibodies are found in the blood. In late infection and after recovery, IgG antibodies are present and remain in the body for up to years. Therefore, when a patient is positive for IgG antibody but negative for IgM antibody, he is considered immune from the virus via either prior infection and recovery or prior vaccination. In the case of hepatitis B, blood tests exist for multiple virus antigens (which are different components of the virion particle) and antibodies. The combination of antigen and antibody positivity can provide information about the stage of infection (acute or chronic), the degree of viral replication, and the infectivity of the virus.

Occult hepatitis B virus infection with positive hepatitis B e antigen.

Hepatitis B e antigen (HBeAg) is a marker to indicate active replication of hepatitis B virus (HBV). Occult HBV infection (OBI), referred to persistence of HBV DNA in serum and/or liver without detectable serum hepatitis B surface (HBsAg), usually has low HBV DNA levels. The presence of HBeAg in OBI is unusual. We report 2 patients who presented negative for HBsAg but positive for HBeAg and HBV DNA. HBV markers were quantified in the longitudinal sera in a period of 1-2years. The HBV DNA sequences were analyzed in 2 patients' sera and 1 patient's liver. Both patients were also positive for total anti-HBs and anti-HBc but negative for anti-HBe and anti-HBc IgM. HBV DNA levels were 234-567IU/ml in case 1 and 42-1130IU/ml in case 2. The alignment analysis of the S gene showed that HBV in both patients was genotype C, serotype adr. Cloning analysis of the a determinant of HBsAg showed that the immune escape mutants were predominant in both patients over the follow-up period. The HBV had double mutations (A1762T and G1764A) in the basal core promoter but had no mutation in the pre C/C gene in both patients. The patients with negative HBsAg but positive HBeAg may represent a unique type of OBI. Test for HBeAg would be critical to identifying such type of OBI.

Obstentrics_Williams

Figure 55-2 details the sequence of the various HBV antigens and antibodies in acute infection. The first serological marker to be detected is the hepatitis B surface antigen (HBsAg) , often preceding the increase in transaminase levels. As HBsAg disappears, antibodies to the surface antigen develop (anti-HBs), marking complete resolution of disease. Hepatitis B core antigen is an intracellular antigen and not detectable in serum. However, anti -HBc is detectable wi thin weeks of HBsAg appearance. The hepatitis Be antigen (HBeAg) is present during times of high viral replication and often correlates with detectable HBV DNA. After acute hepatitis, approximately 90 percent of adults recover completely. The 10 percent who remain chronically infected are considered to have chronic hepatitis B. Chronic HBV infection is oten asymptomatic but may be clinically suggested by persistent anorexia, weight loss, fatigue, and

Hepatitis B

The surface antigen (HBsAg) is most frequently used to screen for the presence of this infection. It is the first detectable viral antigen to appear during infection. However, early in an infection, this antigen may not be present and it may be undetectable later in the infection as it is being cleared by the host. The infectious virion contains an inner "core particle" enclosing viral genome. The icosahedral core particle is made of 180 or 240 copies of the core protein, alternatively known as core antigen, or HBcAg. During this 'window' in which the host remains infected but is successfully clearing the virus, IgM antibodies specific to the core antigen (anti-HBc IgM) may be the only serological evidence of disease. Therefore, most diagnostic panels contain HBsAg and total anti-HBc (both IgM and IgG).

The significance of the Australia antigen (HBsAg) persistent healthy carrier "status": a long-term follow-up study of 34 cases.

Thirty-four persistent healthy carriers of HBsAg (serum HBsAg detectable for longer than 3 months with normal liver function tests and normal liver histology or slight aspecific abnormalities) were discovered by routine testing of household relatives of B virus hepatitis patients. The carriers were followed-up for 11 to 37 months by clinical control, liver function tests and liver needle biopsy. None carrier had previous jaundice. During the follow-up period, in 17 of the 34 subjects, was there no evidence of deterioration in either clinical state, liver function of pathological findings. In 5 of the 34 carriers, HBsAg disappeared from serum after a period ranging from 6 to 12 months. The remaining 12 cases developed clinical and histological picture of acute viral hepatitis after 6 to 29 months (mean 12 months). Of these 12 patients, 6 recovered and become HBsAg; 2 remained HBsAg healthy carriers despite normalization of biochemical and histological abnormalities; 3 progressed from the acute stage to antigen positive CAH. The remaining one case could not be followed-up after the acute hepatitis. Our data indicate that the outcome of the HBsAg carrier state is unpredictable and stress the need of long-term follow-up surveillance.

[Asymptomatic carriers of HBsAg: is a follow-up necessary?].

We evaluated the clinical and epidemiological data of 142 HBsAg carriers. This prospective trial is part of a program of study and follow-up in HVB patients. The median age was 34.58 years old, males 56.3%. The average follow-up was 32.4 months. Complete clinical history, routine analysis, liver function tests, alfa-fetoprotein, serology for HVB, HCV and HDV and abdominal ecography were done in all patients. DNA-HVB was done only in special cases. Patients with less than 6 months of follow-up were excluded. The 118 remaining carriers were classified into two groups, depending on ALT values. Group 1 (normal ALT): included 98 carriers, 3 of them developed an active chronic hepatitis that was treated with interferon. A small CHC was diagnosed in another patient and it was resected. Group 2 (elevated ALT): included 20 carriers, only 9 of them agreed to biopsy and we found severe hepatic lesions in 4 of them. No group presented coinfection with HCV or HDV. No patient died. We conclude that the study and follow-up of asymptomatic HBsAg carriers permits an early diagnosis and treatment of the complications of this pathology (chronic hepatitis, CHC, etc); in our study, three patients developed chronic hepatitis, successfully treated with interferon, and one small size CHC was diagnosed in another patient. The study of relatives permits also detect subclinic liver disease and facilitates vaccination to prevention transmission of this infection.

The significance of HB antigenemy in apparently healthy persons in the clinic for liver diseases.

The study tries to clarify the affliction of liver as a consequence of the permanent HB antigenemy in apparently healthy persons. The study proves beyond doubt that in the majority of the HB antigen carriers such histological changes of the liver can be found that can be attributed only to an infection by the hepatitis virus. The majority of the HB antigen carriers are suffering either from the chronic focal (58%) or from the diffuse (21%) persistent hepatitis. A smaller percentage is suffering from more dangerous hepatopathies (acute viral hepatitis 4,2%, hepatitis chron. aggressiva 4.2%, cirrhosis 1,4%). The kind of the illness can be determined with the histological examination only because of the absence of the clinical symptomatology and because of the liver function tests are in such cases frequently normal. Our investigations indicate that the diffuse and focal forms of persistent hepatitis can remain unchanged overlong periods and the same histological findings over a number of years. The chronic persistent hepatitis, however, may develop through clinically imperceptible changes into a chronic aggressive hepatitis, and the inapparent acute hepatitis can even pass over directly into cirrhosis. The identification of various forms of hepatitis, from light instances to the most severe cases, among the HB antigen carriers proves that the acute viral hepatitis of the type B may have in all the phases of its development a clinically asymptomatic course; it may even asymptomatically pass over into hepatopathies of the most severe kinds. The state of health of persons with HB antigenemy must be systematically followed up. For these reasons the histological examinations of the bioptic liver material that are made from time to time during the follow up of the illness have a decisive role.

Hepatitis -- Evaluation -- Chronic Infection

Evaluation of hepatitis B virus infection can be complicated, and some uncommon but possible scenarios should be kept in mind while investigating. Patients can test negative for HBsAg and anti-HBs but can have the presence of anti-HBc. This situation is possible when the result is false positive but can also happen in patients who are in the time window where they have cleared HBsAg from the blood, but anti-HBs has not yet appeared. Some patients who have cleared hepatitis B virus infection but have lost the anti-HBs over the years can test negative both for HBsAg and anti-HBs but positive for anti-HBc.  Also, patients infected with the hepatitis B virus many years ago can sometimes develop a core mutant variant of the hepatitis B virus where they can test negative for HBeAg and positive for anti-HBe even though the virus may still be active and is replicating. When lab findings like these are detected, the hepatitis B virus DNA PCR assay to check for viral replication is recommended.

[Basic and clinical aspects of hepatitis virus carriers].

Among the six species of hepatitis viruses, HBV (hepatitis B virus) and HCV (hepatitis C virus) can induce persistent infection. HBV and HCV are transmitted parenterally, of which maternal transmission and transfusion-associated infection is a major route respectively. We opened the special clinic for carriers detected through blood donation, and followed them at regular intervals for their health care. The prevalence rate of HBV carriers decreased from 3.0% to 1.2% in these 10 years, and that of HCV decreased from 0.9 to 0.4% in these 4 years. Prevalence rate of HBV peaks at 50s and that of HCV peaks at 60s. Due to nearly complete screening of donated blood, post-transfusion hepatitis almost disappeared. HBV vaccine for neonates born from infected mothers reduced the new incidence of HBV carriers. In HBV carriers seroconversion of HBeAg to HBeAb occurs at teens with transient hepatitis and appearance of mutant virus. Ninety percent of the carriers remains healthy for the lifetime but some of them aggravate into chronic hepatitis leading to HCC (hepatocellular carcinoma). In HCV acute infection at adult age succeeds to chronic infection and eventually to liver cirrhosis with sporadic appearance of HCC. On the other hand, less than 50% of HCV carriers seem to be asymptomatic and do not lead to grave disease. In HBV carriers tendency to reject the virus occurs and eventually HBV is cleared in some percentage of the population. In contrast HCV does not tend to be cleared. HBsAb is a defensive antibody. In contrast HCVAb is not a defensive antibody but an infective antibody like HBcAb. DNA polymerase is a good marker of disease state in HBV, and HCV RNA is a good marker of HCV proliferation. Treatment with IFN is sometimes effective for seroconversion in HBV, and for eradication of virus in HCV.

[Polyclonal activation due to Epstein-Barr virus superinfection in a case with chronic hepatitis B].

Primary infection with Epstein-Barr virus (EBV) often occurs subclinically during childhood, resulting in a latent infection of B lymphocytes. In this report, a chronic hepatitis B case who presented with a serologic profile mimicking acute hepatitis B virus (HBV) infection and exhibiting transient autoantibody positivities because of the polyclonal activation of B cells due to EBV reactivation has been presented. The test results of 56 years old male patient who suffered from fatigue and pain on the right upper quadrant, revealed high levels of liver enzymes (AST: 187 U/L, ALT: 569 U/L), positivity of HBsAg, anti-HBc IgG and anti-HBe, and negativity of anti-HBc IgM, HBeAg and anti-HBs. Since HBV-DNA level was found 405,974 copies/mL by quantitative real time polymerase chain reaction (PCR), the patient was taken into follow-up. At the 6th month AST and ALT levels further elevated (352 U/L and 609 U/L, respectively), and anti-HBc IgM and anti-HBs became positive in addition to the previous positive markers of HBV. With the suspicion of superinfection, further laboratory investigations yielded negative results in CMV-IgM and Paul Bunnel test, while positive results in EBV anti-VCA IgM and IgG, anti-EBNA IgM and IgG, anti-p22 IgM and IgG and anti-EA IgM. In the follow-up period high levels of autoantibody positivities [rheumatoid factor (42.200 U/ml), anti-nuclear antibody (1/100) and anti-Ro-52] together with increased levels of total IgG, IgM and IgA were detected. In the following months, the levels of transaminases, total immunoglobulins and HBV-DNA have distinctively decreased, and in the 20th month the previous HBV profile regained (HBsAg, anti-HBc IgG and anti-HBe positive, anti-HBc IgM and anti-HBs negative, HBV-DNA: 6984 copies/ml) and the other pathological test results returned to normal. As a result, ALT increases seen during the course of chronic hepatitis B should not always be considered as HBV manifestations and the unusual serologic patterns should be evaluated as a consequence of superinfection with various viral agents.

[Hepatitis B with a fatal outcome in a 3-month-old infant of a healthy chronic carrier mother].

A 81 day old male infant developed an acute hepatitic failure and died shortly thereafter. Determinations of HBs antigen and antibody (AB) and HBeAg and AB were performed in the parents and sibling of the infected child. The mother and a sister were an asymptomatic carrier of HBsAg, the first HBeAg positive and the second HBeAB positive. An elder sibling was HBsAg and HBeAg positive in this serum. The father was anti-HBs positive. In the family of the sister, the man and two childs were HBsAg and anti-HBsAB negative. A new baby in the family of the propositus born and a combination of HB vaccine and HBIg (hepatite B immuno-globulin) was started at birth. Unfortunately the child died of S.D.I.S. (Sudden Death Infant Syndrome). The HB vaccine was immuno-genetic in this infant and the anti-HBs in the immuno-globulin M (IgM) was positive as in several adults controls. This case allow us to discuss vertical transmission of hepatitis B, the clinical aspect of neonatal hepatitis and the preventing HB infection by combinaison of HB vaccine and HBIg.

Hepatitis B virus infection in Ethiopian immigrants to Israel.

Two groups of immigrants from Ethiopia, one of 86 and the other of 165 individuals, aged 0-40, were examined for hepatitis B virus (HBV) infection in 1987-88, 3-7 years after their arrival in Israel. The results were compared with those obtained in the same age-group among Ethiopians who immigrated to Israel in 1980-82. The immigrants were found to be in good physical condition, their liver function tests were normal and no clinical evidence of chronic liver disease was found. Of the 22 children aged 0-4, 16 had anti-HBs as a result of vaccination at birth against HBV and they were excluded from the comparative study. In the age-groups 5-40 there was no significant change in the percentage of individuals positive for HBsAg, anti-HBs or anti-HBc only, compared with the group examined in 1980-82. There were two significant findings in this study: a) In 1987-88 [corrected], 8-9% of HBsAg-positive individuals had HBeAg and 64-81% had anti-HBe, while in 1980-82, 36% of those positive for HBsAg had HBeAg and only 25% had anti-HBe. b) At the time of arrival recent infection by HBV was indicated by the presence of IgM anti-HBc in 57% of those positive for HBsAg and 21% in whom anti-HBc was the sole serological HBV marker. In 1987-88 no IgM anti-HBc was found in HBsAg-positive persons or in those with anti-HBc only. These results indicate that most HBV infections in this population had occurred before their arrival in Israel. There is a profound change in the epidemiology of HBV infection in this Ethiopian population following immigration, which is probably due to environmental changes as well as to vaccination against HBV of all young children aged less than or equal to 3 years.

[Natural history of the state of asymptomatic carrier of HBsAg: 7-year follow-up].

Ninety-six chronic asymptomatic HBsAg carriers underwent liver biopsy. Liver histology was normal in 5 cases, showed nonspecific changes in 67, chronic persistent hepatitis in 18, and chronic-active hepatitis in 6. Seventy-four patients were followed for up to 105 months (mean 80 months) in order to evaluate the occurrence of clinical, biochemical, serological or histological changes. Only two patients cleared the HBsAg, respectively 10 and 96 months after undergoing liver biopsy; the latter patient became anti-HBs positive 6 months after he cleared HBsAg. All 10 patients who initially were negative for both HBeAg and anti-HBe became anti-HBe positive during follow-up. All 4 patients who were HBeAg positive at the time of liver biopsy cleared HBeAg 6 to 39 months thereafter. Two of them became anti-HBe positive. None of the patients initially HBeAg negative became positive for this antigen during follow-up. Significant increases of serum transaminases were observed in 5 patients; in one superinfection by delta agent was documented, the other 4 being constantly anti-delta negative. Three of the latter patients underwent repeat liver biopsy, which showed progression from minimal changes to chronic persistent hepatitis in one, and from minimal changes to chronic active hepatitis in another. In the third patient, repeat biopsy showed persistence of chronic persistent hepatitis. chronic hepatitis occurs in about 25% of chronic asymptomatic HBsAg carriers; clearance of HBsAg is a rare event among these patients; the HBe system has little diagnostic or prognostic value; delta superinfection is rare; however, deterioration of liver histology may occur even in the absence of delta superinfection.

InternalMed_Harrison

Another important serologic marker in patients with hepatitis B is HBeAg. Its principal clinical usefulness is as an indicator of relative infectivity. Because HBeAg is invariably present during early acute hepatitis B, HBeAg testing is indicated primarily in chronic infection. In patients with hepatitis B surface antigenemia of unknown duration (e.g., blood donors found to be HBsAg-positive) testing for IgM anti-HBc may be useful to distinguish between acute or recent infection (IgM anti-HBc-positive) and chronic HBV infection (IgM antiHBc-negative, IgG anti-HBc-positive). A false-positive test for IgM anti-HBc may be encountered in patients with high-titer rheumatoid factor. Also, IgM anti-HBc may be reexpressed during acute reactivation of chronic hepatitis B.

Occult Hepatitis B Virus Infection and Associated Genotypes among HBsAg-negative Subjects in Burkina Faso.

The presence of HBV DNA in the liver (with detectable or undetectable HBV DNA in the serum) of individuals tested HBsAg negative by currently available assays is defined occult B Infection (OBI). It remains a potential transmission threat and risk to HBV chronic infection. The purpose of this study was to determine the OBI prevalence among HBsAg negative subjects and to characterize associated genotypes. Blood samples of 219 HBsAg-negative subjects tested by ELISA were collected. HBV DNA was investigated in all samples. Viral loads were determined using quantitative real-time PCR. All samples were screened for HBV markers (anti-HBc, anti-HBe, HBsAg). The Pre-S/S region of the HBV genome was sequenced. The database was analyzed using the SPSS and Epi info software. Phylogenetic analysis was performed using the BioEdit and MEGA software. Of the 219 samples, 20.1% were anti-HBc positive, 1.8% HBeAg and 22.8% were anti-HBe positive. Fifty-six (56) (25.6%) of the samples had a detectable HBV DNA and viral loads ranging from 4 IU/mL to 13.6 10<sup6</sup IU/mL. Sixteen of them (16/56) had a viral load < 200 IU/mL, resulting in an OBI prevalence of 7.3% (16/219) in our study. The remaining 40 subjects had viral loads > 200 IU/mL, resulting in a "false OBI" prevalence of 18.3% (40/219). HBV genotype E was predominant followed by the quasi-sub-genotype A3. A single "false OBI" strain had the characteristic mutation G145R. Other mutations were observed and all located in the major hydrophilic region (MHR) of the S gene. The study reported a prevalence of 7.3% of occult hepatitis B infection. It confirms the predominance of genotype E and the existence of a subgroup of quasi-sub-genotype A3 of HBV in Burkina Faso. It further provides information on the presence of "false OBI." This study has found mutations in the major hydrophilic region (MHR) of the pre-S/S gene of HBV.

[The follow-up of serum aminotransferase levels and investigation of hepatitis B virus load in inactive HBsAg carriers].

The aim of this study was to follow-up the serum alanine aminotransferase (ALT) levels in inactive HBsAg carriers during one year period and investigate the association between hepatitis B virus (HBV) DNA levels detected at the end of the year. At May 2005, 61 patients with HBeAg negative/anti-HBe positive chronic HBV infection, followed in our viral hepatitis clinic were included to the study. The patients' ultrasonographic examination of the liver were normal, they had no history of taking alcohol or routine medication, were anti-HCV seronegative and had normal ALT levels during the last 6 months and at the beginning of the study. Serum ALT levels of patients were followed in the 3rd, 6th and 12th months of the study, and blood HBV-DNA levels were analysed quantitatively in 12th month. During the one year period 89% (54/61) of the patients yielded continously normal ALT levels, while 11% (7/61) showed at least one ALT value above the normal levels (ALT > 1.2x). Total HBV-DNA positivity rate was found as 59% (36/61). In inactive HBsAg carrier group,--namely HBeAg negative and serum ALT levels constantly normal--57.4% (31/54) of patients were HBV-DNA positive and 23 (42.6%) were negative. Amongst the HBV-DNA positive patients the viral load were detected as 10(4)-10(5) copies/ml in six (19.4%), and <10(4) copies/ml in 25 (80.6%) patients. In patients who had at least one ALT value above normal limits, 71.4% (5/7) of them were found HBV-DNA positive; two with HBV-DNA values of >10(5) copies/ml and three with values between 10(4)-10(5) copies/ml. In conclusion, although ALT levels may be normal, it should always be taken into consideration that more than half of inactive HBsAg carriers exhibited low level viral replication, thus HBV-DNA and liver enzyme levels should be monitored routinely in order not to miss the acute manifestations.

InternalMed_Harrison

well as those with chronic HBV infection, anti-HBc is predominantly of the IgG class. Infrequently, in ≤1–5% of patients with acute HBV infection, levels of HBsAg are too low to be detected; in such cases, the presence of IgM anti-HBc establishes the diagnosis of acute hepatitis B. When isolated anti-HBc occurs in the rare patient with chronic hepatitis B whose HBsAg level is below the sensitivity threshold of contemporary immunoassays (a low-level carrier), anti-HBc is of the IgG class. Generally, in persons who have recovered from hepatitis B, anti-HBs and anti-HBc persist indefinitely.

Patients who have chronic hepatitis B infection can have positive HBsAg for life.  These patients can be inactive carriers of the hepatitis B virus or may have active chronic hepatitis. All patients with chronic hepatitis B virus infection have the presence of anti-HBc. If HBeAg may or may not be present, but if it present in patients with active chronic hepatitis, it can indicate viral replication. Similarly, hepatitis B virus DNA may or may not be present, but high levels indicate active chronic hepatitis. Patients with chronic infection of hepatitis B usually have an absence of anti-HBs, but the presence of anti-HBs with positive HBsAg in patients with chronic infection with the hepatitis B virus means that the antibody was unsuccessful in inducing the viral clearance.

[Asymptomatic HBs antigenemia in pregnant women].

The authors have dispensarized for more than ten years HBsAg carriers at the Second Medical Clinic of the Olomouc Faculty Hospital when antigenaemia was detected during blood donorship. Since 1990 the authors dispensarize also women where HBs antigenaemia was revealed during pregnancy. In the presented paper the authors analyze this group of women. In 1990-1991 the authors examined blood samples for HBsAg from 12,042 symptom-free pregnant women. HBsAg positivity was proved in 34 women (0.28%). Eleven women (32.3%) are regularly followed up since delivery. The authors know nothing about the fate of 10 women (29.4%), as they did not respond to repeated invitations to the surgery. It must be however mentioned that 6 of them are Vietnamese and probably left Czechoslovakia. Four women (11.7%) did not attend the clinic for examination but the authors know that they were delivered of their babies elsewhere. In the remainder, i.e. 8 women the delivery was normal, usually in term. The neonates were passively as well as actively immunized at the appropriate dates. Their umbilical blood (if collected) was HBsAg positive, while the venous blood was in all instances negative. All 20 women who attended examination were throughly examined (ultrasound, HBeAg, HBeAb etc.) and the clinical picture is that of a "healthy" HBsAg carrier (not verified by histological examination).

Pathology_Robbins

Anti-HBs antibody appears after the acute disease is over and usually is not detected until a few weeks to several months after HBsAg disappears. Anti-HBs may persist for life and confers protection, which is the rationale for current vaccines containing HBsAg. HBeAg and HBV DNA appear in serum soon after HBsAg and signify ongoing viral replication. Persistence of HBeAg is an indicator of progression to chronic hepatitis. The appearance of anti-HBe antibodies implies that an acute infection has peaked and is on the wane. IgM anti-HBc becomes detectable in serum shortly before the onset of symptoms, concurrent with the onset of elevated serum aminotransferase levels (indicative of hepatocyte destruction). Over a period of months, the IgM anti-HBc antibody is replaced by IgG anti-HBc. As in the case of anti-HAV, there is no direct assay for IgG anti-HBc; its presence is inferred from decline of IgM anti-HBc in the face of rising total anti-HBc.

Jade Ribbon Campaign

Reasons for lack of diagnosis The danger of hepatitis B lies in its silent transmission and progression. Many chronic hepatitis B carriers are asymptomatic (have no symptoms) and feel perfectly healthy. Chronically infected individuals may exhibit normal blood tests for liver function and be granted a clean bill of health. The diagnosis cannot be made without a specific blood test for the presence of the hepatitis B surface antigen (HBsAg), a marker for chronic infection. Since the detection of hepatitis B is so easily missed, even by doctors, it is also up to the patient to specifically request the HBsAg test. Early detection not only benefits the person tested, but prevents infection from being passed silently from one child to another, and from one generation to another.

[Seven-year follow-up studies on asymptomatic HBs Ag carriers].

This report covers 7-year follow-up studies on 35 HBs Ag carriers whose anti-HBc titer levels were 10 (log 2) or more and who had normal liver functions at the start of the studies, when 9 of them (25.7%) were HBe Ag positive, 24 (68.6%) anti-HBe positive and 2 (5.7%) negative to both. 1. There was no significant difference in the incidence of abnormal SGPT levels as a whole between HBe Ag positives and anti-HBe positives. But abnormally high SGPT levels of 100 KU or more were observed at a higher percentage among HBe Ag positives (4/9. 44.4%) than among anti-HBe positives (1/24. 4.2%. p less than 0.02). 2. Based on the results of the 7-year studies, all cases were classified into six clinical stages. HBe Ag positives were divided into three groups by the stage with different SGPT levels: 5 cases (15.2%) whose SGPT leves never rose above 50 KU were classified as Stage 1; 3 cases with chronic active hepatitis (9.6%) whose highest SGPT levels were over 200 KU (2 new cases and 1 case with a relapse of chronic inactive hepatitis) as Stage 2 and 1 case (3.0%) seroconverted to anti-HBe positive following an acute relapse of chronic inactive hepatitis as Stage 3. Anti-HBe positives were divided into another three groups similarly according to their mean HBs Ag titer levels: 6 cases (18.2%) whose mean HBs Ag titer levels ranged from 10 to 13 (log 2) were classified as Stage 4; 13 cases (39.4%) whose mean HBs Ag titer levels ranged from 6 to 9 as Stage 5 and 5 cases (15.2%), including 2 cases turned negative to HBs Ag, whose mean HBs Ag titer levels were below 5 as Stage 6. The average age of each group increased wth its clinical stage, namely, 32.6 in Stage 1, 34.3 in Stage 2, 33.0 in Stage 3, 34.5 in Stage 4 and 37.0 in Stage 5, but the average age in Stage 6 was 29.0. 3. All HBe Ag positives showed fluctuations in HBs Ag titer levels. The fluctuations were particularly noteworthy among cases with chronic active hepatitis in Stage 2 during an acute relapse. The HBs Ag titers rose just before the acute relapses in a case of chronic active hepatitis when SGPT levels went over 200 KU. This suggested a proliferation of the virus. On the other hand, in anti-HBe positives, a decrement of the virus was suggested by the fact that an increasing proportion of cases showed their HBs Ag titer levels to fluctuate or to become lower with the progress of stages (p less than 0.05) and two cases turned negative to HBs Ag as plotted in Stage 6. And the proportion of cases with abnormal SGPT levels decreased with the progress of stages (p less than 0.05). One case whose SGPT level was 125 KU, highest among anti-HBe positives, followed the clinical course of chronic inactive hepatitis and lowered in HBs Ag titer. 4. Between HBe Ag and anti-HBe cases, there were considerable differences in the occurrence of liver disturbances and their clinical courses...


Refeeding syndrome occurs in patients with previous malnutrition exposed to either oral, enteral or parenteral nutritional therapy. All responses are causes of malnutrition except 3.

Refeeding syndrome occurs in patients with previous malnutrition exposed to either oral, enteral or parenteral nutritional therapy. All responses are causes of malnutrition except [HIDDEN].

A patient on enteral nutritional support presents 72 hours after starting enteral nutrition with a CBC showing hypophosphoremia and hypokalemia, with clinical signs of heart failure. The patient is diagnosed with refeeding syndrome. Indicate which of the following is NOT considered a risk factor for a patient presenting with this condition:

Refeeding syndrome in patients with gastrointestinal fistula.

Although refeeding syndrome has been well documented in starved patients, obese patients, those with anorexia nervosa, malnourished elderly individuals, and certain postoperative patients, little is known about the presence and the importance of refeeding syndrome in patients with gastrointestinal fistula and insufficient nutrition support over the long term. The objective of this study was to estimate the morbidity of this syndrome in these patients, to assess the safety and efficacy of our graduated refeeding regimen, and to emphasize the importance of this syndrome. One hundred fifty-eight patients with gastrointestinal fistula during the past 2 y were reviewed. Fifteen of these patients were diagnosed as having refeeding syndrome. They were started on the refeeding procedure according to our regimen, and changes in their serum levels of electrolytes were recorded. The symptoms and signs they presented were noted. All patients were successfully advanced to full nutrition support. During the refeeding procedure, patients presented with weakness, paralysis of limbs, slight dyspnea, paresthesia, tachycardia, edema, and diarrhea. Serum phosphorus concentration decreased in all patients within 24 h of refeeding, reaching a mean nadir after 3.3 +/- 1.5 d and another 6.1 +/- 2.1 d to return to above 0.70 mM/L upon phosphorus supplementation. Three patients treated with growth hormone presented more severe hypophosphatemia (<0.20 mM/L) than the others. 1) Refeeding syndrome occurs commonly in patients with malnutrition secondary to gastrointestinal fistula. 2) Alterations in phosphate metabolism are central to the refeeding syndrome. 3) Supplementation with electrolytes (including especially phosphate) and vitamins is the focal point of the treatment of this syndrome. 4) Growth hormone treatment may aggravate hypophosphatemia.

[Malnutrition and total parenteral nutrition: a cohort study to determine the incidence of refeeding syndrome].

The Refeeding Syndrome is conformed by a series of clinical manifestations related to electrolytic alterations associated with the restarting of the nutritive contribution both enteral and parenteral. To detect the Refeeding Syndrome incidence in malnourished patients who required nutritional, enteral or endovenous support and its relationship with mortality. A cohort study was performed in the service of Nutritional Support of the IMSS (Social Security Mexican Institute) Specialties Hospital CMN León, from June 1995 to May 1996. All patients with mild and severe malnutrition were included, they received endovenous or enteral nutritious support for more than 7 days, without presenting previous electrolytic unbalance. Serum potassium, phosphorous, and magnesium levels were determined before starting the nutritious support and also on the 3rd, 7th, and 10th days. Descriptive statistics, Student's t and Z test were used, with a 5% significance level. 148 patients with total nutritional support, 23 (16%) of them with restrained malnutrition and 65 (44%) with severe deficit. 54 men and 34 women with an average age of 51.6 +/- 19.4 years. Nineteen patients were eliminated due to a nutrition period of less than 7 days, and other 19 were also eliminated for presenting electrolytic alterations before the nutritive support started. An incidence of 48% of electrolytic alterations compatible with the refeeding syndrome was the result in the remaining 50 patients. The alterations were: hypomagnesemia 13/24, hypokalemia 12/24 and hypophosphatemia 4/24; in 55% of the cases the syndrome appeared at the third day of administration. Hospital sojourn of patients with the syndrome was 26.7 +/- 18 days vs 15.3 +/- 7 (p < 0.05) of those who did not present it. 15 patients died, 5 of them had electrolytic alterations before nutrition, 7 (29%) with refeeding syndrome and 3 (12%) did not presented it (p = 0.059). Refeeding Syndrome is a frequent entity in malnourished patients submitted to enteral or parenteral nutrition; at least in this study it was of 48%; its presence was followed by a longer hospital stay and a higher mortality rate.

Occurrence of refeeding syndrome in adults started on artificial nutrition support: prospective cohort study.

Refeeding syndrome is a potentially life-threatening condition characterised by severe intracellular electrolyte shifts, acute circulatory fluid overload and organ failure. The initial symptoms are non-specific but early clinical features are severely low-serum electrolyte concentrations of potassium, phosphate or magnesium. Risk factors for the syndrome include starvation, chronic alcoholism, anorexia nervosa and surgical interventions that require lengthy periods of fasting. The causes of the refeeding syndrome are excess or unbalanced enteral, parenteral or oral nutritional intake. Prevention of the syndrome includes identification of individuals at risk, controlled hypocaloric nutritional intake and supplementary electrolyte replacement. To determine the occurrence of refeeding syndrome in adults commenced on artificial nutrition support. Prospective cohort study. Large, single site university teaching hospital. Recruitment period 2007-2009. 243 adults started on artificial nutrition support for the first time during that admission recruited from wards and intensive care.  occurrence of the refeeding syndrome. Secondary outcome: analysis of the risk factors which predict the refeeding syndrome. Tertiary outcome: mortality due to refeeding syndrome and all-cause mortality. 133 participants had one or more of the following risk factors: body mass index <16-18.5≥(kg/m(2)), unintentional weight loss >15% in the preceding 3-6 months, very little or no nutritional intake >10 days, history of alcohol or drug abuse and low baseline levels of serum potassium, phosphate or magnesium prior to recruitment. Poor nutritional intake for more than 10 days, weight loss >15% prior to recruitment and low-serum magnesium level at baseline predicted the refeeding syndrome with a sensitivity of 66.7%: specificity was >80% apart from weight loss of >15% which was 59.1%. Baseline low-serum magnesium was an independent predictor of the refeeding syndrome (p=0.021). Three participants (2% 3/243) developed severe electrolyte shifts, acute circulatory fluid overload and disturbance to organ function following artificial nutrition support and were diagnosed with refeeding syndrome. There were no deaths attributable to the refeeding syndrome, but (5.3% 13/243) participants died during the feeding period and (28% 68/243) died during hospital admission. Death of these participants was due to cerebrovascular accident, traumatic injury, respiratory failure, organ failure or end-of-life causes. Refeeding syndrome was a rare, survivable phenomenon that occurred during hypocaloric nutrition support in participants identified at risk. Independent predictors for refeeding syndrome were starvation and baseline low-serum magnesium concentration. Intravenous carbohydrate infusion prior to artificial nutrition support may have precipitated the onset of the syndrome.

Delayed appearance of refeeding syndrome in a patient with anorexia nervosa: A case report.

Refeeding syndrome (RFS) can be a severe and life-threatening complication of anorexia nervosa (AN) associated with electrolyte abnormalities and organ damage, and occurs with the transition from a prolonged catabolic to anabolic state, particularly with an overzealous nutrient supply. There is no unequivocal definition of RFS, although hypophosphatemia is recognized as a crucial factor in its pathogenesis. RFS can be responsible for cardiovascular complications, such as heart failure, left ventricular damage, and arrhythmias, because of different potential mechanisms: electrolyte imbalances, increased retention of sodium and liquids secondary to insulin secretion, and excessive fat emulsion supplementation. We report on the case of a 13-y-old male patient with severe AN in whom a delayed and reversible myocardial dysfunction was documented during cautious nutritional replenishment, even in the absence of serum electrolyte imbalances. Seven days after the inception of integrative enteral nutrition, heart failure was unexpectedly documented as follows: reduction in fraction ejection, presence of mild bilateral perimalleolar edema, and increased n-terminal prohormone of brain natriuretic peptide. A more pronounced water restriction protocol and delayed achievement of goal feeding rate, resulting also in lower sodium intake, were implemented to reduce cardiac overload with a full resolution of the complication in approximately 2 mo. Refeeding patients with AN could be complicated by heart failure despite cautious nutritional replenishment and regardless of electrolyte imbalance, even in a later phase of recovery. Therefore, strict adherence to recommendations for nutritional replenishment and close monitoring of cardiac function should always be considered when refeeding patients with AN.

Refeeding syndrome

Clinical situations The syndrome can occur at the beginning of treatment for anorexia nervosa when patients have an increase in calorie intake and can be fatal. It can also occur after the onset of a severe illness or major surgery. The shifting of electrolytes and fluid balance increases cardiac workload and heart rate. This can lead to acute heart failure. Oxygen consumption is increased which strains the respiratory system and can make weaning from ventilation more difficult. Diagnosis Refeeding syndrome can be fatal if not recognized and treated properly. An awareness of the condition and a high index of suspicion are required in order to make the diagnosis. The electrolyte disturbances of the refeeding syndrome can occur within the first few days of refeeding. Close monitoring of blood biochemistry is therefore necessary in the early refeeding period.

Metabolic and nutritional needs to normalize body mass index by doubling the admission body weight in severe anorexia nervosa.

Anorexia nervosa exhibits one of the highest death rates among psychiatric patients and a relevant fraction of it is derived from undernutrition. Nutritional and medical treatment of extreme undernutrition present two very complex and conflicting tasks: (1) to avoid "refeeding syndrome" caused by a too fast correction of malnutrition; and (2) to avoid "underfeeding" caused by a too cautious refeeding. To obtain optimal treatment results, the caloric intake should be planned starting with indirect calorimetry measurements and electrolyte abnormalities accurately controlled and treated. This article reports the case of an anorexia nervosa young female affected by extreme undernutrition (BMI 9.6 kg/m(2)) who doubled her admission body weight (from 22.5 kg to 44 kg) in a reasonable time with the use of enteral tube feeding for gradual correction of undernutrition. Refeeding syndrome was avoided through a specialized and flexible program according to clinical, laboratory, and physiological findings.

Death resulting from overzealous total parenteral nutrition: the refeeding syndrome revisited.

Commentary is provided on the pivotal paper by Weinsier and Krumdieck from 1981 describing 2 patients who developed profound and fatal refeeding syndrome following initiation of aggressive total parenteral nutrition. This classic description was among the first to describe the overwhelming cardiovascular and pulmonary manifestations that can accompany parenteral refeeding with carbohydrate in chronically malnourished patients. The syndrome has also been described with oral and enteral nutrition. One of the hallmarks of the syndrome is hypophosphatemia. Since 1981, dosing schemes for addressing hypophosphatemia have been refined. Other manifestations of the syndrome include other electrolyte abnormalities such as hypokalemia and hypomagnesemia, hyperglycemia, fluid and sodium retention, and neurologic and hematologic complications. Case reports of refeeding syndrome continue to be published, particularly in the anorexia nervosa population. Stressed, critically ill patients may be at risk of refeeding following short periods of fasting; hypophosphatemia is commonly encountered in this situation. It behooves the current nutrition support practitioner to keep in mind the types of patients at risk of refeeding syndrome and to approach refeeding of such patients with caution and careful monitoring.

Enteral nutrition for feeding severely underfed patients with anorexia nervosa.

Severe undernutrition nearly always leads to marked changes in body spaces (e.g., alterations of intra-extracellular water) and in body masses and composition (e.g., overall and compartmental stores of phosphate, potassium, and magnesium). In patients with severe undernutrition it is almost always necessary to use oral nutrition support and/or artificial nutrition, besides ordinary food; enteral nutrition should be a preferred route of feeding if there is a functional accessible gastrointestinal tract. Refeeding of severely malnourished patients represents two very complex and conflicting tasks: (1) to avoid "refeeding syndrome" caused by a too fast correction of malnutrition; (2) to avoid "underfeeding" caused by a too cautious rate of refeeding. The aim of this paper is to discuss the modality of refeeding severely underfed patients and to present our experience with the use of enteral tube feeding for gradual correction of very severe undernutrition whilst avoiding refeeding syndrome, in 10 patients aged 22 ± 11.4 years and with mean initial body mass index (BMI) of 11.2 ± 0.7 kg/m(2). The mean BMI increased from 11.2 ± 0.7 kg/m(2) to 17.3 ± 1.6 kg/m(2) and the mean body weight from 27.9 ± 3.3 to 43.0 ± 5.7 kg after 90 days of intensive in-patient treatment (p < 0.0001). Caloric intake levels were established after measuring resting energy expenditure by indirect calorimetry, and nutritional support was performed with enteral feeding. Vitamins, phosphate, and potassium supplements were administered during refeeding. All patients achieved a significant modification of BMI; none developed refeeding syndrome. In conclusion, our findings show that, even in cases of extreme undernutrition, enteral feeding may be a well-tolerated way of feeding.

Extremely severe anorexia nervosa: Hospital course of 354 adult patients in a clinical nutrition-eating disorders-unit.

The clinical nutrition-eating disorders-unit in Raymond Poincaré Hospital is a reference center for the management of severe malnutrition and its complications in patients with anorexia nervosa (AN). The purpose of this study is to specify socio-demographic, anamnesic and clinical characteristics of AN patients hospitalized for extreme malnutrition, to identify types and prevalence of medical complications presented during their hospitalization for refeeding and the evolution of patients nutritional status. Demographic, clinical and paraclinical data of 354 severely malnourished AN patients were collected, during their first hospitalization in the unit, between November 1997 and January 2014, through medical records. The prevalence of medical complications was compared between the 2 AN subtypes (restricting and binging-purging). 339 patients were female and mean age was 28.7 ± 10.7 years old. Duration of AN was 9.5 ± 9 years, 173 (48.9%) patients had a restricting AN subtype. BMI at admission was 12.2 ± 1.6 kg/m<sup2</sup, 280 (79.3%) patients had already been hospitalized for AN in other hospitals before. Psychiatric comorbidities were present in 168 (47.5%) patients. Associated somatic comorbidities concerned 70 (19.8%) patients. Outcomes during hospitalization were marked by 4.1 ± 3.9 kg weight gain on 36.9 ± 30.5 days. Enteral nutrition was provided in 304 (85.9%) patients. Main medical complications during hospitalization were: anemia (79%), neutropenia (53.9%), hypertransaminasemia (53.7%), osteoporosis (46.3%), hypokalemia (39.5%), hypophosphatemia (26%), hypoglycemia (13.8%), infectious complications (24.3%), cardiac dysfunction (7.1%), and proven gelatinous bone marrow transformation (6.5%). Hypokalemia was more frequent in binging-purging subtype. Lympho-neutropenia and hypertransaminasemia were more frequent in restricting subtype. During their hospitalization, 35 (10%) patients were referred to medical intensive care unit and 5 patients died. AN patients hospitalized for severe malnutrition in a specialized clinical nutrition unit have severe and frequent medical complications. Psychiatric comorbidities are also frequent and could complicate medical care. A specialized and multidisciplinary management of these patients is therefore essential.

Safe refeeding management of anorexia nervosa inpatients: an evidence-based protocol.

Anorexia nervosa is associated with several serious medical complications related to malnutrition, severe weight loss, and low levels of micronutrients. The refeeding phase of these high-risk patients bears a further threat to health and potentially fatal complications. The objective of this study was to examine complications due to refeeding of patients with anorexia nervosa, as well as their mortality rate after the implementation of guidelines from the European Society of Clinical Nutrition and Metabolism. We analyzed retrospective, observational data of a consecutive, unselected anorexia nervosa cohort during a 5-y period. The sample consisted of 65 inpatients, 14 were admitted more than once within the study period, resulting in 86 analyzed cases. Minor complications associated with refeeding during the first 10 d (replenishing phase) were recorded in nine cases (10.5%), four with transient pretibial edemas and three with organ dysfunction. In two cases, a severe hypokalemia occurred. During the observational phase of 30 d, 16 minor complications occurred in 14 cases (16.3%). Six infectious and 10 non-infectious complications occurred. None of the patients with anorexia nervosa died within a follow-up period of 3 mo. Our data demonstrate that the seriousness and rate of complications during the replenishment phase in this high-risk population can be kept to a minimum. The findings indicate that evidence-based refeeding regimens, such as our guidelines are able to reduce complications and prevent mortality. Despite anorexia nervosa, our sample were affected by serious comorbidities, no case met the full diagnostic criteria for refeeding syndrome.

Refeeding syndrome

Treatment In critically ill patients admitted to an intensive care unit, if phosphate drops to below 0.65 mmol/L (2.0 mg/dL) from a previously normal level within three days of starting enteral or parenteral nutrition, caloric intake should be reduced to 480 kcals per day for at least two days while electrolytes are replaced. Daily doses of thiamine, vitamin B complex (strong) and a multivitamin and mineral preparation are strongly recommended. Blood biochemistry should be monitored regularly until it is stable. Although clinical trials are lacking in patients other than those admitted to intensive care, it is commonly recommended that energy intake should remain lower than that normally required for the first 3–5 days of treatment of refeeding syndrome for all patients.

Hypokalemia during the early phase of refeeding in patients with cancer.

Refeeding syndrome occurs in patients with severe malnutrition when refeeding begins after a long period of starvation. This syndrome increases the risk of clinical complications and mortality. Hypophosphatemia is considered the primary characteristic of the syndrome. The aim of our study was to investigate the presence of other electrolyte alterations in patients with cancer during the early stage of refeeding. In this observational study, we enrolled 34 patients with cancer of the upper aerodigestive tract receiving upfront radiotherapy who were also enrolled in a nutrition program. A caloric intake assessment, anthropometric measurements and biochemical laboratory tests were performed. Significant weight loss (∼20%) was found in these patients. In the patients receiving artificial nutrition, we found lower levels of potassium and total protein compared with those who were fed orally (p = 0.03 for potassium and 0.02 for protein, respectively). Patients on enteral tube feeding had a higher caloric intake compared with those who were fed orally (25±5 kcal/kg/day vs. 10±2 kcal/kg/day). Hypokalemia, like hypophosphatemia, could be a complication associated with refeeding in patients with cancer. Hypokalemia was present in the early stages of high-calorie refeeding.

Refeeding syndrome: a potentially fatal condition but remains underdiagnosed and undertreated.

To describe two cases of successfully prevented refeeding syndrome in a high-risk group of patients. Case 1 was a 70-y-old woman who presented with a 4-mo history of poor dietary intake and ill health due to a connective tissue disease leading to myositis and dysphagia and complicated by respiratory failure needing mechanical ventilation. Twelve hours after starting nasogastric tube feeding, she developed a cardiac arrest from which she was successfully resuscitated. Repeated attempts to wean her from the ventilator failed. Case 2 was a 15-y-old girl who was readmitted after a total colectomy for severe ulcerative colitis with diarrhea and vomiting leading to significant weight loss. Her body mass index was 11.4 kg/m(2). In case 1, after consultation by the clinical nutrition team, the diagnosis of refeeding syndrome was made and the patient was duly started on a high-protein, high-fat, low-carbohydrate diet, multivitamin and trace-element supplements, and electrolyte infusion. Subsequently she was successfully weaned from the ventilator. In case 2, further investigation by the clinical nutrition team revealed low baseline electrolyte concentrations including potassium, magnesium, calcium, and phosphate and low serum albumin. Her low body mass index and baseline electrolyte concentrations put her at high risk of developing refeeding syndrome. She was initially started on low-calorie feeding, multivitamin and minerals, and her electrolytes were carefully monitored. She made a good recovery. Refeeding syndrome is a life-threatening, underdiagnosed, treatable condition but there is a need for a wider awareness of the condition among health professionals.

Refeeding syndrome: clinical and nutritional relevance.

Feedback syndrome is characterized clinically by neurological alterations, respiratory symptoms, arrhythmias and heart failure few days after refeeding. It happens due to severe electrolyte changes, such as hypophosphatemia, hypomagnesemia and hypokalemia associated with metabolic abnormalities that may occur as a result of nutritional support (oral, enteral or parenteral) in severely malnourished patients. To evaluate its causes and the preventive dietary measures aiming to reduce the morbimortality. Was conducted literature review in SciELO, LILACS, Medline / PUBMED, Cochrane Library and government websites in Portuguese, English and Spanish. The survey was about the last 15 years, selecting the headings: refeeding syndrome, malnutrition, hypophosphatemia, hypokalemia, hypomagnesemia. The monitoring of metabolic parameters and electrolyte levels before starting nutritional support and periodically during feeding should be based on protocols and the duration of therapy. Patients at high risk and other metabolic complications should be followed closely, and depletion of minerals and electrolytes should be replaced before starting the diet. A multidisciplinary team of nutrition therapy can guide and educate other health professionals in prevention, diagnosis and treatment of the syndrome.

[The incidence of the refeeding syndrome in cancer patients who receive artificial nutritional treatment].

We determine the incidence of the malnutrition syndrome and its relation with probable risk factors, in 106 patients, with a mean age of 53.3 +/- 15.4 years, with a diagnosis of cancer confirmed histologically, and who received artificial nutrition either enterally or endovenously, during an average of 16.8 +/- 2 days, which included a supply of 60 to 100 mmol/day of phosphorus. We considered there to be a renutrition syndrome when there as hypophosphatemia; < 2.5 mmol/l, which took place during the nutritional treatment phase, and previous to which, the patients had normal serum levels of phosphorus. The serum electrolyte concentrations were measured prior to the start of the treatment, and daily during the first week, and later every 3 days until the end. The study variables were: age, sex, type of cancer, degree of malnutrition, degree of hypophosphatemia, day on which in occurred, and clinical manifestations associated to this. The relative risk was calculated for the variables of age, sex, malnutrition and cancer. The incidence of the renutrition syndrome was 24.5%; it was more frequent in the enteral group than in the endovenous group (37.5% vs. 18.9%, p < 0.005); and it took place 72 hours after starting the nutritional support, in 61.5% of the cases, with a mean phosphorus concentrations of 1.9 mmol/l; the most frequent clinical manifestations were the neuromuscular ones (30%), and the most frequent type of cancer was lymphoma (15.4%). The risk factors were age greater than 60 years (RR = 1.7), and moderate or severe malnutrition 8RR = 2.0). We conclude that the prevalence of the renutrition syndrome is high in the cancer patients, despite an intense preventive treatment with phosphorus.

Life-threatening refeeding syndrome in a severely malnourished anorexia nervosa patient.

Overzealous refeeding in chronically malnourished anorexia nervosa patients may cause life-threatening complications. We describe a 14-year-old girl with anorexia nervosa who had a decrease in body weight from 45 kg to 25.5 kg over an 18-month period. She received 40 kcal.kg-1.d-1 carbohydrate-rich nutrition via enteral and parenteral routes. Her serum phosphate concentration dropped from a baseline of 1.39 mmol/L (4.3 mg/dL) to 0.19 mmol/L (0.6 mg/dL) on Day 4 of refeeding. Concurrent with the development of hypophosphatemia, she became drowsy and developed generalized muscle weakness, impaired myocardial contractility, thrombocytopenia, and gastrointestinal bleeding. Fluid overload with pulmonary edema complicated her recovery from these adverse events. After intravenous phosphate supplementation and fluid restriction, the symptoms of refeeding syndrome gradually resolved within 2 weeks. In chronically malnourished anorexia nervosa patients, nutritional support should be instituted gradually to avoid rapid electrolyte shifts and fluid overload. Serum phosphate concentrations, fluid status, and blood cell counts should be closely monitored.

Anorexia (symptom)

Sudden cardiac death Anorexia is a relatively common condition that can lead patients to have dangerous electrolyte imbalances, leading to acquired long QT syndrome which can result in sudden cardiac death. This can develop over a prolonged period of time, and the risk is further heightened when feeding resumes after a period of abstaining from consumption. Refeeding syndrome Care must be taken when a patient begins to eat after prolonged starvation to avoid the potentially fatal complications of refeeding syndrome. The initial signs of refeeding syndrome are minimal, but can rapidly progress to death. Thus, the reinitiation of food or oral intake is usually started slowly and requires close observation under supervision by trained healthcare professionals. This is usually done in a hospital or nutritional rehabilitation center. Management Anorexia can be treated with the help of orexigenic drugs.

A standard enteral formula versus an iso-caloric lower carbohydrate/high fat enteral formula in the hospital management of adolescent and young adults admitted with anorexia nervosa: a randomised controlled trial.

The nutritional rehabilitation of malnourished patients hospitalised with anorexia nervosa is essential. The provision of adequate nutrition must occur, while simultaneously, minimising the risk of refeeding complications, such as electrolyte, metabolic, and organ dysfunction. The aim of this study was to compare the efficacy and safety of an iso-caloric lower carbohydrate/high fat enteral formula (28% carbohydrate, 56% fat) against a standard enteral formula (54% carbohydrate, 29% fat). Patients (aged 15-25 years) hospitalised with anorexia nervosa were recruited into this double blinded randomised controlled trial. An interim analysis was completed at midpoint, when 24 participants, mean age 17.5 years (± 1.1), had been randomly allocated to lower carbohydrate/high fat (n = 14) or standard (n = 10) feeds. At baseline, there was no significant difference in degree of malnutrition, medical instability, history of purging or serum phosphate levels between the two treatment arms. A significantly lower rate of hypophosphatemia developed in patients who received the lower carbohydrate/high fat formula compared to standard formula (5/14 vs 9/10, p = 0.013). The serum phosphate level decreased in both feeds, however it decreased to a larger extent in the standard feed compared to the lower carbohydrate/high fat feed (standard feed 1.11 ± 0.13 mmol/L at baseline vs 0.88 ± 0.12 mmol/L at week 1; lower carbohydrate/high fat feed 1.18 ± 0.19 mmol/L at baseline vs 1.06 ± 0.15 mmol/L at week 1). Overall, serum phosphate levels were significantly higher in the lower carbohydrate/high fat feed compared with standard feed treatment arm at Week 1 (1.06 ± 0.15 mmol/L vs 0.88 ± 0.12 mmol/L, p < 0.001). There was no significant difference in weight gain, number of days to reach medical stability, incidence of hypoglycaemia, or hospital length of stay. The results of this study indicate that enteral nutrition provided to hospitalised malnourished young people with anorexia nervosa using a lower carbohydrate/high fat formula (28% carbohydrate, 56% fat) seems to provide protection from hypophosphatemia in the first week compared to when using a standard enteral formula. Further research may be required to confirm this finding in other malnourished populations. ANZCTR, ACTRN12617000342314. Registered 3 March 2017, http://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12617000342314.

Specialized refeeding treatment for anorexia nervosa patients suffering from extreme undernutrition.

Refeeding severely malnourished patients with Anorexia nervosa requires specialized in-patient treatment to reduce medical risks, to avoid refeeding syndrome and other life-threatening situations. The authors present a retrospective cohort nutritional rehabilitation study of 33 very severe Anorexia nervosa in-patients, aged 22.8 ± 7.6 years (mean ± SD) and with an initial body mass index ≤ 12 kg/m(2), treated in a specialized Eating Disorders Unit. Thirty-three female patients were included and treated. Mean BMI increased from 11.3 ± 0.7 Kg/m(2), to 13.5 ± 1 Kg/m(2), and mean body weight from 29.1 ± 3.2 Kg to 34.5 ± 3.3 Kg, after 60 days of intensive in-patient treatments (p < 0.0001). Feeding was carefully instituted; caloric intake levels were established after measuring REE by indirect calorimetry. Nutritional support was initiated with temporary nasogastric feeding in 30 patients, and with oral supplementation in 3 patients. Vitamins, potassium and phosphate supplements were administered during refeeding. All patients achieved a significant increase in body weight, none developed refeeding syndrome as far as laboratory and clinical investigations were concerned. Our findings show that, even in cases of extreme undernutrition, if feeding is performed cautiously and in a specialized unit, it is possible to avoid the refeeding syndrome.

Heart risk associated with weight loss in anorexia nervosa and eating disorders: electrocardiographic changes during the early phase of refeeding.

Refeeding syndromes with electrolyte aberrations, heart failure and arrhythmias may complicate the nutritional rehabilitation of emaciated patients with eating disorders. Therefore, electrocardiographic (ECG) changes and changes in serum electrolyte concentrations following refeeding were studied in 37 admissions of 32 teenage girls with eating disorders. On admission they were all on a weight-losing course and weighed 37.0+/-8.0 kg (mean +/- SD) following a weight loss of 14.2+/-7.2 kg. On ECG recordings there was a prolongation of the QT interval and an increased QT dispersion. Serum concentrations of sodium, potassium and magnesium were with few exceptions normal. Serum concentrations of creatinine were high in relation to the low body weight, indicating protein catabolism. The first 2 wk of refeeding resulted in a weight gain of 1.7+/-0.2 kg without signs of refeeding syndromes or electrolyte aberrations. QT prolongation and dispersion normalized within the 3 d of refeeding. It is concluded that oral refeeding of patients with eating disorders and weight loss can be performed efficiently and without causing refeeding syndromes. QT pathology, a consequence of acute starvation and a risk factor for cardiac arrhythmias, normalizes within days. In view of the need to balance adequate refeeding and reduction of QT pathology against the risks of refeeding syndromes the start of refeeding of severely emaciated patients is best performed in a hospital setting where monitoring of ECG and serum electrolytes is possible.

Anorexia nervosa

Refeeding syndrome The rate of refeeding can be difficult to establish, because the fear of refeeding syndrome (RFS) can lead to underfeeding. It is thought that RFS, with falling phosphate and potassium levels, is more likely to occur when BMI is very low, and when medical comorbidities such as infection or cardiac failure, are present. In those circumstances, it is recommended to start refeeding slowly but to build up rapidly as long as RFS does not occur. Recommendations on energy requirements vary, from 5–10 kcal/kg/day in the most medically compromised patients, who appear to have the highest risk of RFS, to 1900 kcal/day. Prognosis

Nutritional management of celiac crisis in an elderly adult: A case report of the rare presentation of celiac disease in a 75-y-old woman.

In adults, a very uncommon presentation of celiac disease (CD) is a celiac crisis, a life-threatening and severe form of the disease having a dramatic onset with diarrhea and metabolic acidosis with electrolyte and fluid imbalance. Treatment of celiac crisis requires a gluten-free diet; however, the risk for refeeding syndrome (RFS) should be considered in patients showing marked malabsorption symptoms and important unintentional weight loss. Therefore, to avoid metabolic and potentially fatal complications of re-nutrition, nutritional management is crucial for a safe recovery after a celiac crisis. This review reports the rare onset of celiac crisis in a 75-y-old woman presenting with severe malnutrition resulting in >40% weight loss in 3 mo, after a period of severe diarrhea and vomiting. She arrived at the hospital showing electrolyte imbalance, hypoalbuminemia, lower limb edema, multiple bowel movements (>10/d) with steatorrhea, sarcopenia with profound asthenia, hyporexia due to intolerance to any food, and vomiting after meals. After being diagnosed with CD, the first approach was a gluten-free diet, which demonstrated only small and slow improvements of gastrointestinal symptoms. Therefore, a second approach was parenteral nutrition (PN) support that dramatically helped the patient's recovery. Here we describe the nutritional management during the inpatient stay for clinical stabilization and the following outpatient visits during and after the support with PN, until the patient's complete recovery to a regular follow-up.

Failure to thrive

failure to thrive then treatment is directed towards the underlying condition. Special care should be taken to avoid refeeding syndrome when initiating feeds in a malnourished patient. Refeeding syndrome is caused by a shift in fluid and electrolytes in a malnourished person as they receive artificial refeeding. It is potentially fatal, and can occur whether receiving enteral or parenteral nutrition. The most serious and common electrolyte abnormality is hypophosphatemia, although sodium abnormalities are common as well. It can also cause changes in glucose, protein, and fat metabolism. Incidence of refeeding syndrome is high, with one prospective cohort study showing 34% of ICU experienced hypophosphatemia soon after feeding was restarted.

[Hypophosphatemia and refeeding syndrome: a severe and underdiagnosed adverse effect].

A 68-year-old woman was hospitalised because of generalised weakness and development of confusional state, related to severe hyponatremia, probably due to an eating disorder with malnutrition. During the first days of hospitalisation the patient eats surprising large amounts of food. The worsening of the confusional state in spite of normalisation of natremia, and the progressive development of anemia and thrombocytopenia, leads to the discovery of a new onset severe hypophosphatemia. The rapid fall in plasma levels of phosphorus, magnesium and potassium are the main futures of the refeeding syndrome. Its clinical manifestations are neurological, muscular, haematological and renal. The development of this syndrome is associated with a high mortality. The refeeding syndrome is seen when carbohydrates are introduced after a period of malnutrition. Identification of patients at risk for the refeeding syndrome (anorexia nervosa, chronic alcoholism, chronic malnutrition, elderly patients, oncology patients), the introduction of cautious progressive nutrition and the careful monitoring of vital signs, electrolytes levels and fluid balance, allows to prevent morbidity and mortality of this syndrome.

Severe hypophosphatemia in a patient with anorexia nervosa during enteral refeeding.

Hypophosphatemia is a seldom but potentially fatal complication of the nutritional recovery or refeeding syndrome in patients with protein-calorie malnutrition or starvation. We report here the case of a 35-year-old anorexic patient who presented a severe but uncomplicated hypophosphatemia during enteral refeeding, despite phosphorus supplementation. Serum phosphorus monitoring is recommended in severely malnourished anorexic patients, particularly during the first week of refeeding, be it parenteral or enteral.

Refeeding syndrome: relevance for the critically ill patient.

To provide an overview of recent findings concerning refeeding syndrome (RFS) among critically ill patients and recommendations for daily practice. Recent literature shows that RFS is common among critically ill ventilated patients. Usual risk factors for non-ICU patients addressed on ICU admission do not identify patients developing RFS. A marked drop of phosphate levels (>0.16 mmol/l) from normal levels within 72 h of commencement of feeding, selects patients that benefit from hypocaloric or restricted caloric intake for at least 48 h resulting in lower long-term mortality. RFS is a potentially life-threatening condition induced by initiation of feeding after a period of starvation. Although a uniform definition is lacking, most definitions comprise a complex constellation of laboratory markers (i.e. hypophosphatemia, hypokalemia, hypomagnesemia) or clinical symptoms, including cardiac and pulmonary failure. Recent studies show that low caloric intake results in lower mortality rates in critically ill RFS patients compared with RFS patients on full nutritional support. Therefore, standard monitoring of RFS-markers (especially serum phosphate) and caloric restriction when RFS is diagnosed should be considered. Furthermore, standard therapy with thiamin and electrolyte supplementation is essential.

VIPoma

Symptoms and signs The major clinical features are prolonged watery diarrhea (fasting stool volume > 750 to 1000 mL/day) and symptoms of hypokalemia and dehydration. Half of the patients have relatively constant diarrhea while the rest have alternating periods of severe and moderate diarrhea. One third have diarrhea < 1yr before diagnosis, but in 25%, diarrhea is present for 5 yr or more before diagnosis. Lethargy, muscle weakness, nausea, vomiting and crampy abdominal pain are frequent symptoms. Hypokalemia and impaired glucose tolerance occur in < 50% of patients. Achlorhydria is also a feature. During attacks of diarrhea, flushing similar to the carcinoid syndrome occur rarely. Diagnosis Besides the clinical picture, fasting VIP plasma level may confirm the diagnosis, and CT scan and somatostatin receptor scintigraphy are used to localise the tumor, which is usually metastatic at presentation.

Cardiac arrest and delirium: presentations of the refeeding syndrome in severely malnourished adolescents with anorexia nervosa.

To describe the clinical presentation of the refeeding syndrome and highlight the dangers of performing nutritional rehabilitation too rapidly in a severely malnourished patient. Retrospective case review of adolescents admitted with anorexia nervosa who developed the refeeding syndrome. Between July 1993 and July 1994, 3 of 48 adolescent females developed the refeeding syndrome. While the cardiac complications occurred in the first week of refeeding, the delirium characteristic of this syndrome occurred later and was more variably related to hypophosphatemia. Refeeding malnourished patients with anorexia nervosa can be associated with hypophosphatemia, cardiac arrhythmia and delirium. Refeeding patients with anorexia nervosa who are < 70% of ideal body weight should proceed with caution, and the caloric prescription should be increased gradually. Supplemental phosphorus should be commenced early and serum levels maintained above 3.0 mg/dL. Cardiac and neurologic events associated with refeeding are most likely to occur within the first weeks, justifying close monitoring of electrolyte and cardiac status.

Rapid renutrition improves health status in severely malnourished inpatients with AN - score-based evaluation of a high caloric refeeding protocol in severely malnourished inpatients with anorexia nervosa in an intermediate care unit.

Refeeding syndrome is a feared complication of refeeding patients with anorexia nervosa. There are now a number of controlled studies showing that refeeding with an initial high calorie count is more beneficial than cautious refeeding and is safe under continuous monitoring. However, there have yet not been studies in severe anorexia nervosa. We present an observational study in two different samples. The first sample consists of those 1075 out of a total of 3230 patients with anorexia nervosa treated in our hospital within 4 years for whom a complete admission laboratory was available and who had an age of at least 18 years at admission. A risk score was calculated from the number of pathological laboratory values out of 12 parameters indicating either refeeding syndrome or health hazards related to malnutrition. The second sample was obtained from a special ward for patients with eating disorders medically at-risk. During the period in question, 410 patients with anorexia nervosa were treated there. 142 patients had a BMI of 13 or less and at the same time a complete data set with the mentioned 12 laboratory parameters at admission and weekly in the following 4 weeks after admission. The risk represented by the laboratory parameters is significantly and negatively correlated to BMI and much higher for the group of patients with a BMI below 13 than for those with a higher BMI (χ<sup2</sup sig < 0.000). The 142 patients in the special care unit gain an average of more than 4.1 kg within 4 weeks on the high-calorie diet. With this rapid weight gain, the risk score decreases highly significantly. Neither hypophosphatemia nor rhabdomyolysis is found under phosphate substitution. Hyperhydration occurred often, which manifests itself in the drop in haematocrit by the second week. Under thorough medical surveillance, supplementation of phosphate and thiamine, and substitution of electrolytes whenever necessary rapid renutrition appeared to be save even in extremely malnourished inpatients with anorexia nervosa. As measured by the laboratory values, the health status of the severely malnourished patients improves significantly on a high-calorie diet. Except for hyperhydration, there was no evidence of a refeeding syndrome.

Refeeding syndrome as treatment complication of anorexia nervosa.

Refeeding syndrome (RS) is one of the serious complications during treatment of anorexia nervosa. It includes hormonal and metabolic changes that occur during the process of refeeding in chronically malnourished patient when nutrition is introduced in an excessive and improper amount. RS manifests in water-electrolyte imbalances, including hypophosphatemia (the mostimportant diagnosticmarker), hypokalemia, hyponatremia, hypomagnesaemia, fluid retention, vitamin deficiency and metabolic acidosis. It applies to either oral and parenteral supplementation. In the treatment of malnourished patients with anorexia nervosa, it is essential to establish an initial caloric amount that will stimulate weight gain from the beginning of treatment, increase its effectiveness while minimizing the risk of RS. Recent research suggests that the current recommendations may be too stringent in this respect and require further updating. Awareness of the risks associated with RS, including significant mortality, appears to be currently insufficient also among physicians. There is a need for far more specialized multidisciplinary centers for patients with anorexia nervosa and also appropriate algorithms and standards of care for that population. The aim of this paper is to systematize the current knowledge about RS and RS prevention, to increase awareness of its occurrence and present the results of the latest research on safe resupplementation of patients suffering from anorexia nervosa.

Enteral refeeding syndrome after long-term total parenteral nutrition.

Early enteral feeding (EF) may result in fever, elevated white blood cell count, increased serum levels of liver enzymes, and diarrhea. We name the complications "enteral refeeding syndrome", as a subtype of refeeding syndrome, because they are likely to result from long-term lack of lumen nutrition. The aim of this study was to investigate the characteristics of enteral refeeding syndrome after long-term total parenteral nutrition (TPN), and the solution for the disease. We collected the clinical data of 100 patients with gastrointestinal fistula, who were cured from Apirl 2001 to July 2002. Their fasting time, daily stool frequency, body temperature, heart rate, respiratory rate, levels of transaminases, alkaline phosphatase (AKP), and gamma-glutamylcyclotransferase (gamma-GT), white blood cell count, and systemic inflammatory reaction syndrome (SIRS) score were recorded before and 1, 3, 5, 10, and 15 days after EF. Student's t test and analysis of variance were used to analyze the data. Of the 100 patients, 56 were cured after selective resection of intestinal fistula, 15 were cured by emergency operation, and 29 recovered spontaneously. The levels of AKP and gamma-GT increased significantly on the 3rd day after EF [On the 3rd day after EF, (243.0 +/- 121.6) U/L and (177.2 +/- 109.9) U/L vs. before EF (181.5 +/- 127.5) U/L and (118.4 +/- 94.2) U/L, P < 0.05], and decreased gradually afterwards. The SIRS scores on the 1st day (1.05 +/- 1.08) and 3rd day (0.96 +/- 1.11) after EF were significantly higher than that before EF (0.72 +/- 0.84), then decreased to 0.83 +/- 0.91, 0.49 +/- 0.73 and 0.32 +/- 0.60 on the 5th, 10th and 15th days after EF. The number of patients with diarrhea at 1, 3, 5, 10 and 15 days post-EF were 31, 26, 12, 13, and 7, respectively. The longer the TPN lasts, the more severe the enteral refeeding syndrome becomes. Continuous EF is effective for the syndrome. Early enteral nutrition is useful in preventing it.

Refeeding procedures after 43 days of total fasting.

Refeeding syndrome encompasses fluid and electrolyte imbalances and metabolic, intestinal, and cardiorespiratory derangements associated with appreciable morbidity and mortality. Although refeeding syndrome has been well documented in concentration-camp subjects, and more recently during parenteral therapy of critically ill patients, little is known about the importance of refeeding syndrome during recovery from a hunger strike. Thus, we studied the response to a four-step dietary replenishment routine in eight hunger strikers who refused food for 43 d. In this retrospective, observational study, we assessed the safety and efficacy of the refeeding procedure and analyzed the clinical and nutritional course of the cohort during both starvation and refeeding, mainly on the basis of clinical as well as a few biochemical determinations. During starvation, average weight loss was about 18% and, with the exception of occasional oral vitamins and electrolytes, the subjects consumed only water. Available body-composition and biochemical profiles showed no clinically significant changes during starvation, but one-half of the group displayed spontaneous diarrhea at some time before refeeding. Stepwise nutritional replenishment lasted for 9 d, after which all patients tolerated a full, unrestricted diet. Only one episode of diarrhea occurred during this phase, and both clinical and biochemical indexes confirmed a favorable clinical course, without any manifestation of refeeding syndrome. In conclusion, we observed the following: 1) Hypophosphatemia and other micronutrient imbalances did not occur, nor was macronutrient intolerance detected. 2) Despite some episodes of diarrhea, nutritional replenishment was not associated with significant enteral dysfunction. 3) There was some fluid retention, but this was mild. 4) Acute-phase markers were abnormally elevated during the refeeding phase, without associated sepsis or inflammation.