Regression of hepatic steatosis in morbidly obese persons after gastric bypass. Nonalcoholic fatty liver disease treated by gastroplasty. Surgically-induced weight loss significantly improves nonalcoholic fatty liver disease and the metabolic syndrome. Roux-en-Y gastric bypass improves the nonalcoholic steatohepatitis (NASH) of morbid obesity. Gastric bypass surgery improves metabolic and hepatic abnormalities associated with nonalcoholic fatty liver disease. Weight loss and non-alcoholic fatty liver disease: falls in gamma-glutamyl transferase concentrations are associated with histologic improvement. Non-alcoholic steatohepatitis: effect of Roux-en-Y gastric bypass surgery. Regression of liver steatosis following gastroplasty or gastric bypass for morbid obesity. Changes in liver histology accompanying massive weight loss after gastroplasty for morbid obesity. Nonalcoholic fatty liver disease: Improvement in liver histological analysis with weight loss. Histological behavior of hepatic steatosis in morbidly obese patients after weight loss induced by bariatric surgery. Hepatic outcomes after jejunoileal bypass: is there a publication bias? Roux-en-Y gastric bypass improves liver histology in patients with non-alcoholic fatty liver disease. Duodenal switch has no detrimental effects on hepatic function and improves hepatic steatohepatitis after 6 months. Resolution of nonalcoholic steatohepatits after gastric bypass surgery. Prospective study of the long-term effects of bariatric surgery on liver injury in patients without advanced disease. Histological findings in the liver before and after gastric bypass. Liver abnormalities in severely obese subjects: effect of drastic weight loss after gastroplasty. The evolution of severe steatosis after bariatric surgery is related to insulin resistance. Effects of bariatric surgery on nonalcoholic fatty liver disease: preliminary findings after 2 years. Effects of surgical treatment of the metabolic syndrome on liver fibrosis and cirrhosis.
Morbid obesity has been associated with hepatic steatosis and occasional cirrhosis. Despite producing weight loss, intestinal bypass procedures formerly performed to correct morbid obesity, often worsened steatosis and fibrosis, and occasionally resulted in hepatic failure. Current surgical procedures of choice for morbid obesity involve gastric bypass with gastrojejunostomy. Ninety-one liver biopsies taken at the time of gastric bypass for morbid obesity (mean body weight 125.8 kg), and 106 biopsies taken from the same patients from 2 to 61 months later (mean body weight 89.4 kg) were studied. Steatosis and perisinusoidal fibrosis were assessed in histologic sections. Serum albumin, alkaline phosphatase, aspartate aminotransferase (AST), and total bilirubin levels were measured before most biopsies were taken. Both pre- and post-gastric bypass hepatic steatosis varied directly with body weight (r = .5231, P < .001). Steatosis varied inversely with length of time after gastric bypass (r = .4590, P < .001). Of the original biopsies, 37% had lipid vacuoles in at least 26% of hepatocytes. After gastric bypass, 65 patients had reduced steatosis, 18 patients with no steatosis, and 5 patients with minimal steatosis had no change, and 3 patients had increased steatosis. Pre-gastric bypass biopsies from 13 patients had perisinusoidal fibrosis (PSF) that was marked with bridging in three patients, was moderate in one patient, and slight in nine patients. Following gastric bypass, PSF was eliminated in 10 patients, reduced in one patient, and the same in two patients. One patient developed PSF after gastric bypass. Of the three patients who had undergone previous intestinal bypass procedures, two had slight PSF in the biopsies taken at the time of gastric bypass, and one of these had slight PSF in the follow-up biopsy. Serum biochemical abnormalities tended to be slight. Before gastric bypass, serum albumin was low in 11% of cases, alkaline phosphatase was high in 14% of cases, AST was high in 11% of cases, and total bilirubin was high in 1% of cases. After gastric bypass, there was a small reduction in mean serum albumin from 43 g/L before to 41 g/L afterward (P < .05), and a slight rise in mean total bilirubin from 7.0 mumol/L before to 9.6 mu mol/L afterward (P < .01). Most hepatic fatty change and probably some PSF occurring in morbidly obese persons is reduced or eliminated with weight loss following gastric bypass surgery. Nonalcoholic steatohepatitis (NASH), which is the most severe histologic form of nonalcoholic fatty liver disease (NAFLD), is emerging as the most common clinically important form of liver disease in obese patients. The prevalence of NASH may increase with the rise in the rate of obesity and metabolic syndrome in affluent communities. The aim of this work is to describe clinical and histopathologic findings and correlate liver tissue damage to the length of duration of the obesity in the group of patients who underwent surgery as obesity treatment. Eighty-seven severely or morbidly obese patients underwent gastroplasty. Each patient was evaluated with complete clinical and laboratory medical assessment together with wedge liver biopsy taken from 59 unselected patients during the surgery. Patients were followed up for 41 months. Repeat liver biopsy was taken from 10 patients. Pathologic analysis recorded the presence and degree of steatosis, portal and lobular inflammation and fibrosis. Age, body mass index (BMI), and laboratory assessment correlated with pathologic data. Male patients showed more pronounced metabolic syndrome and fatty liver damage. Patients who become obese in childhood or as teenagers showed no differences in metabolic syndrome and NAFLD in mature age. There was statistically significant association between BMA, elevated transaminases, NAFLD, and fibrosis. Significant weight reduction was observed within first year after surgery, was slower in the second year, and stabilized within third year. Remarkable improvement followed in biological markers of metabolic syndrome. Ninety-six percent of initial liver biopsies had steatosis; 16% developed steatohepatitis and mild perivenular fibrosis. Significant improvement of the degenerative and inflammatory hepatic lesions in repeated biopsies and liver function readings was noted within 8 months after surgery. Obesity is a major and independent risk factor for the metabolic syndrome, NAFLD, NASH, and fibrosis. Surgical treatment improves metabolic abnormalities and hepatic lesions in long-term observations. To evaluate the effects of surgical weight loss on fatty liver disease in severely obese patients.
                Nonalcoholic fatty liver disease (NAFLD), a spectrum that extends to liver fibrosis and cirrhosis, is rising at an alarming rate. This increase is occurring in conjunction with the rise of severe obesity and is probably mediated in part by metabolic syndrome (MS). Surgical weight loss operations, probably by reversing MS, have been shown to result in improvement in liver histology.
                Patients who underwent laparoscopic surgical weight loss operations from March 1999 through August 2004, and who agreed to have an intraoperative liver biopsy followed by at least one postoperative liver biopsy, were included.
                There were 70 patients who were eligible. All patients underwent laparoscopic operations, the majority being laparoscopic Roux-en-Y gastric bypass. The mean excess body weight loss at time of second biopsy was 59% +/- 22% and the time interval between biopsies was 15 +/- 9 months. There was a reduction in prevalence of metabolic syndrome, from 70% to 14% (P < 0.001), and a marked improvement in liver steatosis (from 88% to 8%), inflammation (from 23% to 2%), and fibrosis (from 31% to 13%; all P < 0.001). Inflammation and fibrosis resolved in 37% and 20% of patients, respectively, corresponding to improvement of 82% (P < 0.001) in grade and 39% (P < 0.001) in stage of liver disease.
                Surgical weight loss results in significant improvement of liver morphology in severely obese patients. These beneficial changes may be associated with a significant reduction in the prevalence of the metabolic syndrome. Hepatic steatosis and nonalcoholic steatohepatitis (NASH) have been increasingly implicated in the genesis of hepatic fibrosis and cirrhosis. However, no consensus exists about whether weight reduction may reverse this process.
                To assess the effect of Roux-en-Y gastric bypass (RYGBP) on the histological evolution of NASH diagnosed in 64 patients by routine liver biopsy ("first" biopsy) performed during surgery, we performed a "second" biopsy after 23.5 +/- 8.4 months in 16 patients (14 female, 2 male).
                From the first to the second biopsy, BMI decreased from 53.4 +/- 8.8 kg/m2 to 31.1 +/- 4.7 kg/m2, arterial hypertension decreased from 75% to 43.8%, and type 2 diabetes decreased from 43.8% to zero. On the first biopsy, nonalcoholic fatty liver disease (NAFLD) type 3 was observed in 12 patients (75%) and type 4 in 4 (25%). The second biopsy revealed complete regression of NAFLD in 15 patients (93.7%) and only 1 (6.3%) had NAFLD type 1 (mild steatosis without inflammation). Complete regression of necroinflammatory activity was observed in all patients. Among the 4 patients presenting fibrosis in the first biopsy, complete remission was observed in 1 and improvement in 1. Two continued to show the same degree of fibrosis without evidence of disease activity. No worsening of steatosis, necroinflammatory activity or fibrosis was observed in any of the patients, and none progressed to cirrhosis.
                RYGBP improves steatosis, necroinflammatory activity and hepatic fibrosis in patients with morbid obesity and NASH. Most patients with extreme obesity have nonalcoholic fatty liver disease (NAFLD). Although gastric bypass (GBP) surgery is the most common bariatric operation performed in obese patients in the United States, the effect of GBP surgery-induced weight loss on the metabolic and hepatic abnormalities associated with NAFLD are not clear.
                Whole-body glucose, fatty acid and lipoprotein kinetics, liver histology, and hepatic cellular factors involved in inflammation and fibrogenesis were evaluated in 7 extremely obese subjects (body mass index, 58 +/- 4 kg/m(2)) before and 1 year after GBP surgery.
                At 1 year after surgery, subjects lost 29% +/- 5% of initial body weight (P < .01); palmitate rate of appearance in plasma, an index of adipose tissue lipolysis, decreased by 47% +/- 4% (P < .01); endogenous glucose production rate decreased by 27% +/- 7% (P < .01); and very-low-density lipoprotein-triglyceride secretion rate decreased by 44% +/- 9% (P < .05). In addition, GBP surgery-induced weight loss decreased hepatic steatosis but did not change standard histologic assessments of inflammation and fibrosis. However, there was a marked decrease in hepatic factors involved in regulating fibrogenesis (collagen-alpha1(I), transforming growth factor-beta1, alpha-smooth muscle actin, and tissue inhibitor of metalloproteinase 1 expression and alpha-smooth muscle actin content) and inflammation (macrophage chemoattractant protein 1 and interleukin 8 expression) (P < .05, compared with values before weight loss).
                These data demonstrate that weight loss induced by GBP surgery normalizes the metabolic abnormalities involved in the pathogenesis and pathophysiology of NAFLD and decreases the hepatic expression of factors involved in the progression of liver inflammation and fibrosis. The ability for aminotransferase levels to track histological features of non-alcoholic fatty liver disease (NAFLD) with weight loss has not been examined.
                We examined the effect of weight loss following laparoscopic adjustable gastric banding surgery on the histological features of NAFLD and plasma aminotransferase concentrations (AST, ALT and GGT) in 60 (12M, 48F) selected severely obese patients. All 120 paired biopsies were de-identified and scored for lobular steatosis, fibrosis, inflammation, Mallory bodies and NASH.
                30 patients (50%) had baseline histological features of non-alcoholic steatohepatitis (NASH). Repeat biopsies were taken at 29.5+/-10 months after baseline. Mean weight loss was 31.5+/-18 kg. There were improvements in AST, ALT, GGT, lobular steatosis, inflammation and fibrosis between baseline and follow-up (P<0.001 for all). Only 6 (10%) of repeat biopsies showed NASH. No change in aminotransferase concentrations predicted the change in steatosis, but changes in AST and GGT predicted improved scores for inflammation, fibrosis, Mallory bodies and NASH. The lowering of GGT best predicted the improvements in inflammation, fibrosis and NASH.
                With weight loss, falls in GGT and, to a lesser extent, in AST, are predictive of improved lobular inflammation and fibrosis, key prognostic features of NAFLD. Non-alcoholic steatohepatitis (NASH) is an increasingly prevalent problem. Treatment options are still under investigation. The primary aim of the study was to determine whether weight loss, achieved through Roux-en-Y gastric bypass (RYGBP), improved histopathology in obese patients with biopsy proven NASH.
                One hundred and forty-nine patients were identified from a surgical database as having RYGBP for obesity and concomitant intra-operative liver biopsies from October 2001 to September 2003. Thirty-five patients were found to have evidence of NASH at the time of surgery. Nineteen patients were contacted and underwent repeat percutaneous liver biopsies. Biopsies were evaluated and compared in blinded fashion by an experienced hepatopathologist. Fasting lipid panel, insulin and glucose, hemoglobin A1c (HgbA1c), and liver enzymes were obtained.
                Significant differences were noted in the following variables pre- and post-bypass surgery: body mass index 46.8-28.8 kg/m2 (p < 0.001); body weight in kilograms 132.1-79.7 (p < 0.001); glucose 102.9-94.1 mg/dL (p = 0.015); Hgb A1c 5.79-5.15% (p = 0.026); high density lipoprotein 45.7-64.4 mg/dL (p < 0.001); low density lipoprotein 112-88.6 mg/dL (p = 0.003); triglycerides 132.1-97 mg/dL (p = 0.013). Significant improvements in steatosis, lobular inflammation, portal, and lobular fibrosis were noted. Histopathologic criteria for NASH were no longer found in 17/19 patients (89%).
                Weight loss after gastric bypass surgery in obese patients with NASH results in significant improvement in glucose, HgbA1c. and lipid profiles. Furthermore, RYGBP results in significant improvement in the histological features of NASH with resolution of disease in a majority of these patients. 15 consecutive persons aged under 50 with an overweight exceeding 75% were examined clinically, biochemically and with liver biopsy after gastric bypass (7 patients) or gastroplasty (8 patients). After 1 year the occurrence of steatosis had fallen from 73 to 40% which, together with a marked decrease in individual gradings of fatty changes, represented a significant regression of the steatosis. Likewise, discrete inflammatory and granulomatous changes largely disappeared. In no case was fibrosis present. Serum alkaline phosphatases preoperatively increased above normal range in 20% but their mean level was significantly reduced after 12 months of weight loss. Other liver function tests remained normal and stable. In contrast to published experience with jejunoileal bypass operations liver steatosis associated with morbid obesity seems to be morphologically and biochemically reversed together with the weight reduction obtained by gastroplasty or gastric bypass. Nonalcoholic steatohepatitis (NASH) is common in morbid obesity. Our goal was to evaluate the alterations in liver histology and biochemistry before and after weight loss in 51 morbidly obese patients following Mason's vertical banded gastroplasty.
                Two biopsies were performed (on entry and after an average of 18 months), while 16 of these subjects had a third biopsy 17 months after the second.
                On entry, steatosis and steatohepatitis (mostly grade 3) were present in 98.0% and fibrosis (mostly stage 2) in 94.1% of the subjects. After an excess weight loss of 66%, steatosis and steatohepatitis improved significantly (P<0.001). Although a significant overall decrease in fibrosis occurred (P=0.002), 21 patients (41.1%) did not change and only 6 patients (11.7%) increased in fibrosis. None developed cirrhosis. The decrease in steatohepatitis was significantly correlated (P=0.011) with the reduction of BMI. Fasting serum glucose, lipids, lipoproteins, transaminases, gamma-glutamyl transpeptidase, alkaline phosphatase and fibrinogen were also significantly improved at the time of the second biopsy. The third biopsy performed in 16 of the subjects showed further significant improvement in liver histology.
                NASH improved significantly with massive weight loss in non-diabetic, non-alcoholic, morbidly obese subjects, while fibrosis improved in nearly half of the patients. The effect of significant weight loss on nonalcoholic fatty liver disease remains unclear. In this case series of 36 selected obese patients, we examined the effect of weight loss on nonalcoholic fatty liver disease, including nonalcoholic steatohepatitis (NASH) and hepatic fibrosis. These 36 patients (11 males, 25 females) had paired liver biopsies, the first at the time of laparoscopic adjustable gastric band placement and the second after weight loss. Second biopsies were obtained from two groups: those requiring a subsequent laparoscopic procedure (n = 19) and those with index biopsy score of 2 or greater for zone 3-centric hepatic fibrosis (n = 17). All biopsies were scored, blinded to the patient's identity and clinical condition, for individual histological features and for NASH stage and grade. Initial biopsies demonstrated NASH in 23 patients and steatosis in 12 patients. Repeat biopsies were taken at 25.6 +/- 10 months (range, 9-51 months) after band placement. Mean weight loss was 34.0 +/- 17 kg, and percentage of excess weight loss was 52 +/- 17%. There were major improvements in lobular steatosis, necroinflammatory changes, and fibrosis at the second biopsy (P <.001 for all). Portal abnormalities remained unchanged. Only four of the repeat biopsies fulfilled the criteria for NASH. There were 18 patients with an initial fibrosis score of 2 or more compared with 3 patients at follow-up (P <.001). Those with the metabolic syndrome (n = 23) had more extensive changes before surgery and greater improvement with weight loss. In conclusion, weight loss after surgery provides major improvement or resolution of obesity and metabolic syndrome-associated abnormal liver histological features in severely obese subjects. Hepatic steatosis has a high prevalence among morbidly obese patients. Its relation to steatohepatitis and cirrhosis has been extensively studied among these patients. The aim of this study was to evaluate the behavior of hepatic steatosis with weight loss 1 year after bariatric surgery.
                This study is a historical cohort that compared liver biopsies obtained from morbidly obese patients during the bariatric operation, with percutaneous biopsies taken from the same patient 1 year after surgery. The results were compared with weight loss, patients' profile (gender, age, body mass index (BMI) and waist/hip ratio), and with the presence of co-morbidities such as diabetes, hypertension, and dyslipidemia.
                90 patients who had liver biopsies taken at the operation and postoperative period for bariatric surgery were included. The prevalence of hepatic steatosis was 87.6%. The average percent of excess weight loss was 81.4%. On the second biopsy, 16 patients (17.8%) of the total had the same degree of steatosis, 25 (27.8%) improved their steatosis pattern and 49 (54.4%) had normal hepatic tissue. There was no statistical difference regarding age, BMI, waist/hip ratio, and co-morbidities (P>0.05), but there was a difference in gender (P=0.044).
                Significant improvement in the hepatic histology of steatosis was observed after weight loss induced by bariatric surgery in most patients. There was no patient with a worsening in the histology. One of the reasons why jejunoileal bypass (JIB) was abandoned were reports of liver failure. The aim of this study was to describe histological findings in the intraoperative and follow-up liver biopsies of a cohort of super-obese patients who had undergone JIB.
                50 consecutive patients underwent JIB. Samples of liver biopsies performed intraoperatively (41 patients) and in the follow-up (31 patients) were evaluated. Brunt's scale was used.
                Mean age at operation was 37.9 +/- 7.6 years, and 15 patients (30.6%) had diabetes type 2, 20 (40.8%) had dyslipidemia, 29 (59.2%) had high blood pressure, and one (0.5%) had hepatitis C. Mean BMI preoperatively was 52.8 +/- 7.5 kg/m(2). Mean follow-up time was 67.0 +/- 42.8 months. At the time of the latest liver biopsy, the mean BMI was 35.7 +/- 7.5 kg/m(2). The % excess weight loss (%EWL) was 62.4 +/- 20.0%. 8 deaths (16%) have occurred, none from liver-related complications. At liver biopsy during the JIB operation, NAFLD was confirmed in 36 patients (86.7%) and NASH in 13 (31.7%). In 25 patients with mean follow-up of 4.8 +/- 4.0 years, there was no statistically significant change in the liver histology regarding the extent of steatosis (P=0.20), steatohepatitis (P=0.74) and fibrosis (P=0.71).
                There was a significant metabolic improvement, maintenance of the %EWL, and no worsening of liver histology. There has possibly been a publication bias concerning liver outcomes, where the type of JIB and the concomitance of hepatitis C were not taken into account. Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in the United States and is prevalent in morbidly obese patients. While weight loss and treatment of risk factors are recommended, the reported effects of bariatric surgery on NAFLD are mixed.
                We examined liver histology at the time of Roux-en-Y gastric bypass surgery and at elective incisional hernia repair after weight loss for 16 patients at one center. Slides were read by one pathologist, blinded to clinical data, using the Brunt criteria. Clinical and laboratory data were extracted from chart review. Alcohol use was ascertained by two interviews.
                At baseline, the mean age was 44 years, 50% were women, 88% were white, and the mean BMI was 51 kg/m2. None had significant alcohol use. On initial biopsy, all patients showed steatosis, 94% had inflammation, 88% had ballooning degeneration, 88% had perisinusoidal fibrosis, and 81% had portal fibrosis. The mean time between the two biopsies was 305 +/- 131 (SD) days. The mean weight loss was 118 +/- 29 lb. Steatosis improved in 15 of 16 patients, with resolution in 13. Twelve of 15 patients with inflammation at baseline showed improvement, and 12 of 14 showed less ballooning. Six of 14 patients with perisinusoidal fibrosis and 6 of 13 with portal fibrosis showed improvement. No patient had worsening of steatosis, inflammation, ballooning, or fibrosis.
                Our study shows improvement in all of the histological features of NAFLD after Roux-en-Y gastric bypass surgery-induced weight loss, despite significant histopathology at baseline and substantial weight loss. Nonalcoholic steatohepatitis (NASH) is a common histological finding on liver biopsy in morbidly obese patients. The condition, although benign, can progress to cirrhosis and liver failure. We investigated the effect of the duodenal switch (DS) operation on hepatic function and architecture, specifically hepatic steatosis and NASH.
                Between November 1999 and June 2004, 697 DS operations were performed for the treatment of morbid obesity. A Tru-Cut needle liver biopsy was routinely performed during the DS operation. Liver function tests were drawn preoperatively for AST and ALT, and again postoperatively at 6, 12 and 18 months and yearly thereafter. Repeat Tru-Cut liver biopsy was performed on all patients (n = 78) who underwent a second intra-abdominal operation for any indication > or = 6 months postoperatively. The pathologist evaluated the 2 sets of liver biopsies in a blinded fashion. The hepatic adipose tissue content and the degree of hepatitis were compared in these patients.
                A transient worsening of the AST (13% of the baseline value, P<.02) and ALT ( 130-160% of the baseline value, P<.0001) levels was found at 6 months after the DS operation. Normal levels were achieved by 12 months postoperatively. A progressive improvement of about 3 grades in severity of NASH and a 60% improvement in hepatic steatosis, were seen by 3 years after the DS operation.
                DS improves both hepatic steatosis and its resulting inflammation. No detrimental effects on hepatic function were noted after 6 months. Nonalcoholic fatty liver disease (NAFLD) has been increasingly recognized as a common chronic liver condition. Previous studies have been variable regarding the histological outcomes after rapid weight loss. The aim of this study was to characterize the histopathologic changes in NASH following laparoscopic Roux-en-Y Gastric Bypass surgery (LRYGBP).
                We retrospectively analyzed paired needle liver biopsies taken during and following LRYGBP in 39 patients according to the recent NIH-based NAFLD criteria.
                The cohort included 33 females and 6 males (range 24-57 years). 23 patients (58.9%) had steatohepatitis, 12 with fatty liver (30.7%), and 4 were normal (10.2%). Follow-up needle liver biopsies were performed at a mean interval of 18 months (range 6-41 months). No significant differences in length or number of portal tracts between the paired biopsies were noted. The mean decrease in weight and BMI was 50.2 kg and 18.2 kg/m2, respectively. The initial prevalence of hepatic pathology: steatosis (89.7%), hepatocellular ballooning (58.9%), and centrilobular/perisinusoidal fibrosis (50%) improved significantly after LRYGBP: steatosis (2.9%), ballooning (0%), and centrilobular fibrosis (25%). Mitigation in the lobular inflammation score (2.23+/-0.63 vs 1.95+/-0.56, P=0.01) and stage of fibrosis (1.14+/-1.05 to 0.72+/-0.97, P=0.002) were also noted. However, no improvements were detected in portal tract inflammation and fibrosis.
                Over a mean period of 18 months, histological improvements and resolution of NASH occurs after LRYGBP. Long-term studies are warranted to assess for potential changes in the portal regions or relapse of NASH that could result with weight regain or malnutrition. Severe obesity is implicated in development of nonalcoholic fatty liver disease (NAFLD). Bariatric surgery induces weight loss and increases survival time of obese patients, but little is known about its effects on liver damage. We performed a 5-year prospective study to evaluate fibrosis and nonalcoholic steatosis (NASH) in severely obese patients after bariatric surgery.
                Bariatric surgery was performed on 381 patients. Clinical and biological data, along with liver biopsies, were collected before and at 1 and 5 years after surgery.
                Five years after surgery, levels of fibrosis increased significantly, but 95.7% of patients maintained a fibrosis score <or= F1. The percentage of patients with steatosis decreased from 37.4% before surgery to 16%, the NAFLD score from 1.97 to 1, ballooning from 0.2 to 0.1. Inflammation remained unchanged. The percentage of patients with probable or definite NASH decreased significantly over 5 years, from 27.4% to 14.2%. The kinetics of insulin resistance (IR) paralleled that of steatosis and ballooning; the greatest improvements occurred within the first year and were sustained 5 years later. Steatosis and ballooning occurred more frequently in patients with a refractory IR profile. In multivariate analysis, the refractory IR profile independently predicted the persistence of steatosis and ballooning 5 years later.
                Five years after bariatric surgery for severe obesity, almost all patients had low levels of NAFLD, whereas fibrosis slightly increased. Steatosis and ballooning were closely linked to IR; long-term effects could be predicted by early improvement in IR. Bariatric surgery results in massive loss of excess weight, changes in co-morbidities and improvement in quality of life. In these patients, liver histology taken before or during surgery reveals several histological abnormalities. In a prospective study of patients previously submitted to gastric bypass, we determined the changes in liver histology late after the surgery.
                In 16 out of a total of 557 patients who were submitted to open gastric bypass, a second liver biopsy was taken during the repair of an incisional hernia, performed at a mean of 17 months after the gastric bypass.
                All patients had lost weight, now having a mean BMI of 28.6 kg/m(2) (which had been 44.3 kg/m(2) before gastric bypass). One patient with normal pre-operative liver histology remained normal at the second study. 11 out of 15 who had had liver abnormalities returned to a normal condition or had only minimal change (73.3%). 2 patients (13.3%) showed improvement, while 1 patient presented a slight worsening of liver condition. One patient who had had liver cirrhosis showed no change.
                Gastric bypass for morbid obesity is followed by a dramatic improvement or normalization of liver histological abnormalities in the great majority of the patients. Liver cirrhosis in the one patient remained unchanged. To examine the factors associated with liver steatosis in severely obese subjects and to test the potential reversibility of fatty liver after weight loss.
                Retrospective clinical study.
                528 obese patients before bariatric surgery and 69 obese subjects of the initial cohort evaluated before and 27+/-15 months after gastroplasty.
                Fatty deposition (scored as mild, moderate or severe) and inflammatory changes were evaluated in liver biopsies; clinical (body mass index (BMI), age, gender, duration of obesity) and biological (glucose, triglycerides, liver enzymes) parameters were related to histological findings.
                74% of the 528 biopsies showed fatty change, estimated as mild in 41% of cases, moderate in 32% and severe in 27%. The prevalence of steatosis was significantly higher in men than in women (91% vs 70%, P = 0.001) and in patients with impaired glucose tolerance or type 2 diabetes compared with nondiabetics (89% vs 69% P = 0.001). The severity of the steatosis was associated with BMI (P = 0.002) but not with the duration of obesity or the age of the patient. When compared with patients without fatty change, those with liver steatosis had significantly higher fasting plasma glucose (5.5 mmol/l vs 5.1 mmol/l, P = 0.007) and triglycerides (1.8 mmol/l vs 1.3 mmol/l, P = 0.002). Mean serum liver enzyme activities (alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl-transpeptidase (gammaGT) were significantly (P < 0.001) increased in patients with fatty change but remained within laboratory reference values. In the 69 patients who have been evaluated after a marked weight reduction (-32+/-19kg), 45% of the biopsies were considered as normal (vs 13% before, P < 0.001) while pure fatty change was still observed in 38% of the patients (vs 83% before, P = 0.001). However, the severity of the steatosis was significantly (P < 0.001) reduced (mild: 62% vs 21%; moderate: 23% vs 37%; severe: 15% vs 42%). In addition, a significant increase of hepatitis was observed in 26% of the biopsies (vs 14% before, P < 0.05).
                Liver steatosis in obese subjects is associated with men, diabetic status, BMI, higher fasting glucose and hypertriglyceridaemia. Postgastroplasty weight loss reduces liver steatosis, but seems to increase the incidence of inflammatory lobular hepatitis. In severely obese patients, factors implicated in the evolution of severe steatosis after bariatric surgery remain unresolved. Our aim was to determine whether insulin resistance (IR) influences the histologic effects induced by bariatric surgery.
                We prospectively included 185 severely obese patients (body mass index >/=35 kg/m(2)) referred for bariatric surgery. The evolution of IR (IR index = 1/quantitative insulin sensitivity check index) and liver injury with consecutive biopsy was concomitantly assessed before and 1 year after surgery.
                At preoperative biopsy, 27% of severely obese patients disclosed severe steatosis (>/=60%). The alanine aminotransferase (P = .01) and IR indexes (P = .04) were independent predictive factors of severe steatosis at baseline. One year after surgery, surgical treatment induced a decrease in body mass index (9.5 kg/m(2); P < .0001), steatosis score (8.5%; P < .0001), and IR index (0.29; P < .0001). The preoperative IR index (P = .01) and preoperative steatosis (P = .006) were independent predictive factors in the persistence of severe steatosis after surgery. Moderate or severe steatosis was more frequently observed in patients who had conserved a higher IR index after surgery than in patients who had improved their IR index (44% vs 20.2%; P = .04).
                IR was independently associated with severe steatosis and predicted its persistence after surgery. The amelioration of IR after surgery is associated with a decrease in the amount of fat. Taken together, the results of this prospective study in severely obese patients demonstrate that severe steatosis and its evolution after surgery are intimately connected with IR. Although nonalcoholic fatty liver disease (NAFLD) is very common among morbidly obese patients, the effect of weight loss after bariatric surgery on inflammation and fibrosis related to NAFLD is still a matter of debate. The aim of this study was to evaluate the impact of Roux-en-Y gastric bypass (RYGB) surgery on NAFLD with a follow up of 2 years.
                Eighteen consecutive NAFLD patients with body mass index >40 kg/m(2) undergoing gastroplasty with RYGB were enrolled, and wedge liver biopsy was obtained at the operation. After 2 years, these patients underwent percutaneous liver biopsy.
                At baseline, 67% of patients had nonalcoholic steatohepatitis (NASH) and 33% had steatosis, according to the NASH Clinical Research Network Scoring System (NAS) for biopsy. Cirrhosis was present in 5.5% of the patients with NASH. After a mean excess weight loss of 60%, steatosis disappeared in 84% and fibrosis disappeared in 75% of the patients. Hepatocellular ballooning disappeared in 50%. A slight lobular inflammatory infiltrate remained in 81%, apparently unrelated to fatty degeneration. As liver biochemical variables had been found within normal limits in 92.3% of patients at initial biopsy, no difference was found 2 years later. Lipid profile and blood sugar plasma concentration were closer to normal in all patients after 2 years (P < 0.05).
                Aspects of NAFLD including steatohepatitis improved significantly with massive weight loss at 2 years after RYGB surgery. No patient in this series had progression of hepatic fibrosis. Both weight loss and gastrointestinal surgery for obesity can cause liver disease, making their role in the treatment of obesity-related liver disease controversial.
                Six hundred eighty-nine severely obese women (n=551) and men (n=138), BMI=47+/-9 kg.m(-2) (mean+/-SD), without known liver disease, underwent biliopancreatic diversion (BPD) with liver biopsy. Fourteen patients (2%) had cryptogenic cirrhosis, 11 of whom underwent multiple repeat biopsies. After 38+/-18 kg weight loss, 104 of the 689 patients underwent routine second biopsies during reoperations 41+/-25 months after BPD. All biopsy specimens were graded for steatosis, fibrosis, and inflammation by a blinded hepatopathologist.
                All 689 patients lost weight accompanied by improvements in the metabolic syndrome. Among the 104 patients who underwent reoperation, severe fibrosis (grade 3-5) decreased in 28 whereas mild fibrosis (grade 1-2) appeared in 42. Increased fibrosis was related to low-normal serum albumin, uncontrolled diarrhea, low intake of alcohol, and menopausal status. Fibrosis and inflammation decreased over time (P<.01). The 11 patients with cirrhosis exhibited decreased fibrosis from a mean grade 5 to grade 3, as well as reduced inflammation, Mallory bodies, and glycogenated nuclei. Seven patients had disappearance and 2 regression of nodules and fibrous bridging.
                The metabolic syndrome of obesity is a determinant of liver fibrosis and cirrhosis, treatable by substantial weight loss after malabsorptive surgery.
The lack of randomised clinical trials and quasi-randomised clinical studies precludes us to assess the benefits and harms of bariatric surgery as a therapeutic approach for patients with NASH. Limitations of all other studies with inferior design did not allow us to draw any unbiased conclusion on bariatric surgery for treatment of NASH.