the incidence of acute hepatitis b ( hbv ) is largely reduced during the last 20 years as a result of the use of vaccination and routine blood donor screening 1 and , nowadays , in western countries , the risk of hbv infection is limited to sexual intercourses , intravenous drug users and , in a few cases , in patients undergoing dental therapy , acupuncture , piercing and tattooing 2 - 4 .
most symptomatic patients recover and treatment is not necessary ; when there are signs of severe liver failure , treatment is recommended in order to reduce the risk of progression to fulminant or subfulminant hepatitis and the need of emergency liver transplantation 5 .
a randomised controlled trial on standard interferon versus placebo shows greater hbs seroconversion in patients treated with 10 mu / tiw 6 . with regard to lamivudine , studies with a limited number of patients and case reports are encouraging 7 - 9 while the only randomised controlled study available does not show a significant clinical and biochemical improvement compared to placebo at a dose of 100 mg / daily 10 .
we report our experience on treatment with high dose lamivudine , in a series of 5 patients with severe acute hbv infection .
from november 2006 to march 2007 , 5 patients with acute hbv related hepatitis were admitted to our department : 4 patients were hbeag positive and 1 anti hbe positive .
the diagnosis was based on consistent clinical and virological findings ( medical history , jaundice , hypertransaminasemia , hbsag positivity , igm anti - hbc > 1.20 mu / ml and presence of serum hbv - dna by pcr ) and exclusion of other known causes of liver damage .
all patients underwent ultrasonography guided liver biopsy to confirm the diagnosis . the decision to treat
was based on the prolongation of inr together with increasing values of bilirubin and alt .
four patients received lamivudine 200 mg / daily until clearance of serum hbv - dna was reached and then 100 mg / daily until resolution ( clearance of hbsag and appearance of anti - hbs antibodies ) .
one patient received 100 mg / daily because of renal impairment ( creatinine clearance 32 ml / min ) .
patients were followed up for at least six months ( range : 6 - 11 months ) after the end of treatment .
the decision to treat was based on the prolongation of inr together with increasing values of bilirubin and alt .
four patients received lamivudine 200 mg / daily until clearance of serum hbv - dna was reached and then 100 mg / daily until resolution ( clearance of hbsag and appearance of anti - hbs antibodies ) .
one patient received 100 mg / daily because of renal impairment ( creatinine clearance 32 ml / min ) .
patients were followed up for at least six months ( range : 6 - 11 months ) after the end of treatment .
the median period of hospitalization was 13 days ( 12 - 15 ) and no patient had complications , both related to underlying disease or to therapy .
we observed a prompt decrease of alt ( -1399 iu / l in a week , -2120 iu / l in two weeks ) and serum bilirubin ( -15 mg in a week , -23.9 mg in two weeks ) .
the complete normalization of transaminases and bilirubinemia occurred on average after 5.5 weeks and 3 weeks , respectively .
all hbeag+ patients lost e - antigen and seroconverted to anti hbe ; they lost hbsag within six months from the start of treatment and 4/5 developed anti - hbs at a protective titre ( > 10 mu / ml ) .
we observed an average drop of hbv - dna of 1.58 logarithms in a week and 3.38 logarithms in two weeks .
all patients cleared hbv - dna ( evaluated by pcr ) in two months on average .
differently from previous studies , we have chosen to treat acute hepatitis b with a higher dose of lamivudine ( 200 mg / day instead of 100mg / day ) achieving a rapid viral clearance and clinical improvement .
all patients were discharged by the hospital , in spite of disease severity at presentation , within 13 days from the start of oral antiviral treatment . from our data , treatment with nucleoside analogues for severe and fulminant hepatitis b ( acute or exacerbation of a chronic infection ) is certainly indicated .
in fact , early antiviral treatment shortens and improves the symptomatic phase of infection and allows a ready clinical and biochemical improvement . on the other hand ,
when patients with end stage liver disease are treated with nucleoside analogues , the dramatic improvement of hepatic function often leads to withdrawal from the liver transplantation list . in our experience ,
, the development of a chronic infection , since all patients displayed undetectable hbv - dna and cleared hbsag
. severe or fulminant acute hepatitis b generally do not evolve to a chronic disease , since the immune response that causes liver damage also leads to the viral clearance . in this setting , with the use of nucleoside analogues we obtained a prompt hepatic biochemical and functional improvement and a strong suppression of viral replication , which probably enforced the ongoing process of recovery .
furthermore , we reduced the risk of fatal outcome which can occur in some of these patients . with the use of a double dose of lamivudine ( 200 mg / day ) we obtained a decrease of viral load even faster than observed in previous studies : in fact we observed an average decrease of serum hbv - dna of 3.38 log
iu / ml in the first two weeks of treatment , respect to 1 log decrease in one month reported by other authors 11 . to the best of our knowledge , only the studies of tillman et al . and by kumar et al .
from those studies two major results emerge : the number of responders ( hbv - dna negative ) is higher in the treated group compared to controls ( 91.6% against 71.6% ) .
even though not statistically significant , this figure outlines a trend and should not be underestimated .
furthermore , the number of adverse events ( death and transplantation ) was significantly lower in both studies in the treated groups ( 5.2% against 21.6% in controls ) .
the lack of a control group is certainly a limitation but according to recent guidelines treatment is indicated for patients with fulminant hepatitis b and those with protracted , severe acute hepatitis b ; therefore , a control group in this setting would likely not be judged ethical .
however , in light of our results and from data previously published , the only ethical choice in patients with severe and fulminant acute hepatitis b seems to be the treatment with oral antiviral drugs . on the basis of our results
we suggest that , with regard to lamivudine , a higher dose provides an effective and fast healing of severe acute hepatitis . despite the low genetic barrier of lamivudine , we chose it because at that time it was the drug with the fastest antiviral activity among those available .
it is conceivable that new available drugs for the treatment of hepatitis b ( i.e. entecavir and telbivudine ) might be even better in reaching a rapid decrease in viral load and a faster recovery in patients with fulminant or severe acute hepatitis .
 treatment for acute hepatitis b is recommended in order to reduce the risk of progression to fulminant hepatitis and the need of olt . 
 we report our experience on treatment with high dose lamivudine , in patients with severe acute hbv infection . 
 the diagnosis was based on clinical and virological findings and exclusion of other known causes of liver damage . the decision to treat 
 was based on the prolongation of inr together with increasing values of bilirubin and alt . 
 four patients received lamivudine 200 mg / daily until clearance of serum hbv - dna and then 100 mg / daily until clearance of hbsag and appearance of anti - hbs antibodies . 
 one patient received 100 mg / daily because of chronic renal impairment . 
 the median period of hospitalization was 13 days , and none of the patients had complications , related either to underlying disease or to therapy . 
 the complete normalization of serum transaminases and bilirubin occurred on average after 5.5 weeks and 3 weeks respectively . 
 all patients cleared serum hbv - dna within three months , lost hbeag and hbsag and seroconverted to anti - hbe ; four patients developed anti - hbs at a protective titre . 
 early antiviral treatment attenuates the clinical and biochemical impairment leading to fast healing and promoting complete recovery . 
Introduction
Patients and Methods
Treatment
Results
Discussion