Outcome of liver transplantation in hepatitis C virus-infected patients who received hepatitis C virus-infected grafts.

BACKGROUND & AIMS: The present organ shortage has brought into question the suitability of hepatitis C virus (HCV)-positive grafts. This study reviewed the outcome of such transplantations in our institution. METHODS: Twenty-three HCV-positive patients who underwent orthotopic liver transplantation (OLT) for end-stage liver disease with HCV-positive grafts in 1992-1995 were studied. Only patients who survived more than 30 days were included in the analysis. Control group included 169 patients who underwent transplantation for HCV-related cirrhosis and received HCV-negative organs. RESULTS: Patients who received HCV-infected organs had a cumulative survival rate of 89% and 72% at 1 and 5 years, respectively, vs. 88% and 73% for the control group (NS). There was no difference in graft survival, incidence of cirrhosis, mean hepatitis activity index score, fibrosis, or mean activity of serum transaminases. There was a trend toward lower incidence of recurrent hepatitis C in the study group compared with control (21% vs. 23% at 1 year and 47% vs. 64% at 5 years; NS). Patients in whom the donor strain became predominant after transplantation had significantly longer disease-free survival than patients who retained their own HCV strain (P < 0.003). CONCLUSIONS: HCV-infected livers transplanted into HCV-infected recipients do not appear to convey a worse outcome in the initial years after OLT than HCV-negative grafts.     

Use of direct-acting antiviral agents in hepatitis C virus-infected liver transplant candidates

Since the advent of direct acting antiviral(DAA) agents, chronic hepatitis C virus(HCV) treatment has evolved at a rapid pace. In contrast to prior regimen involving ribavirin and pegylated interferon, these newer agents are highly effective, well-tolerated, have shorter course of therapy and safer essentially in all HCV patients including those with advanced liver disease and following liver transplantation. Clinicians caring for HCV-infected patients on the liver transplant(LT) waitlist are often faced with a dilemma whether to treat HCV infection before or after liver transplantation. Sustained virological response(SVR) rates following HCV treatment may improve hepatic function sufficiently enough to negate the need for LT in certain patients. On the other hand, the decrease in MELD without improvement in quality of life in certain patients may lead to delay or dropout from potentially curative LT surgery list. In this context, our review focuses on the approach to and optimal timing of DAA-based treatment of HCV infection in LT candidates in the peri-transplant period.     

Comparison of clinical features and liver histology in hepatitis C-positive dialysis patients and renal transplant recipients

Objective: Liver biopsies in hepatitis C virus (HCV)-positive end stage renal disease (ESRD) patients before or after renal transplantation were compared to study the effect of transplant-related immunosuppression. Methods: In this prospective study all patients on the active transplant list and all patients with functioning renal transplants at our hospital were tested for HCV antibody (ELISA-2) over a 30-month period. HCV infection was confirmed by polymerase chain reaction in most patients. All HCV-positive patients were asked to undergo liver biopsy without regard to serum transaminase levels. Patients were interviewed, examined, and had detailed chart review. By protocol, liver histology was evaluated according to stage and inflammatory activity in a blinded fashion. Results: There were 129 HCV-antibody–positive patients, of 795 tested. Sixty-seven agreed to liver biopsy. Of these, 22 patients had never been transplanted and 45 had received transplants. Mean transplant duration before biopsy was 41.2 months (range, 1–204 months). Transplant patients had significantly longer duration of ESRD and estimated duration of HCV infection than patients not transplanted. Dialysis patients had significantly more portal inflammatory activity and lymphoid follicles on biopsy whereas transplant patients had more piecemeal necrosis and steatosis. However, the total histological activity score and stage were similar between groups. Multivariate analysis confirmed the association between transplant and steatosis. But independent variables including transplant duration, HCV infection duration, and ESRD duration were not correlated with histological findings. Conclusion: Renal transplantation may not be associated with an increased risk of progressive liver disease in HCV-positive patients, compared with ESRD patients receiving chronic dialysis. Long-term studies with serial liver biopsies are needed to resolve this issue.     

B-cell clonality in the liver of hepatitis C virus-infected patients

AIM： The association of hepatitis C virus （HCV） infection with type Ⅱ mixed cryoglobulinemia is well established, but the role of HCV in B-cell lymphoma remains controversial. In patients with HCV infection, B-cell clonal expansions have been detected in peripheral blood and bone marrow, and a high prevalence of B-cell non-Hodgkin＇s lymphomas has been documented. Liver biopsies in chronic HCV infection frequently show portal lymphoid infiltrates with features of B follicles, whose clonality has not yet been investigated. The object of this study was to determine the frequency of liver-infiltrating monoclonal B-cells in 40 patients with HCV infection.
METHODS： Eight hundred and forty-eight patients were studied prospectively, including 40 HCV-positive patients and 808 patients with chronic hepatitis B virus （HBV） infection. Immunohistochemical study for B- and T-cell markers was performed on the paraffin-embedded liver tissue sections. The clonality of lymphoid B-cells was tested using a polymerase chain reaction （PCR） approach designed to identify immunoglobulin heavy chain gene （IgH） rearrangements.
RESULTS： Liver-infiltrating monoclonal B-cells were detected in the liver for 4 （10%） of 40 HCV-positive patients but were present in only 3 （0.37%） of 808 liver biopsy specimens with chronic HBV infection. Chisquare testing showed that the monoclonal B-cells infiltration in the liver was more frequent in the HCV-infected patients （P = 0.000）. A clonal IgH rearrangement was detected in 5 （71.4%） of 7 liver biopsy specimens with monoclonal B-cells infiltration. In 2 of 5 patients with both a clonal B-cell expansion and monoclonal B-cells infiltration in the liver, a definite B-cell malignancy was finally diagnosed.
CONCLUSION： Liver-infiltrating monoclonal B-cells are detected in the liver of patients with chronic HCV and HBV infection. A high percentage of patients with monoclonal B-cells infiltration and B-cell clonality in the liver were finally diagnosed as having a definite B-cell malignancy.     

Impact of hepatitis C virus infection in renal transplant recipients.

OBJECTIVES: The impact of hepatitis C virus (HCV) infection on the success of renal transplant is controversial. We assessed the effect of HCV infection on graft and patient survival in renal allograft recipients. METHODS : We retrospectively analyzed medical records of renal allograft recipients who were transplanted between June 1990 and March 2004. Patients were divided into those positive and negative for anti-HCV antibody. Graft and patient survival were compared between the groups. RESULTS : Of 126 patients studied (median age 34.5 years, range, 16-60; 111 men), 35 were positive for anti-HCV antibody. In seven patients, the antibodies were detected for the first time after renal transplant. Mean patient and graft survival duration in the anti-HCV negative group was longer (55 [SD 2] months [95% CI, 51-58]) than in the anti-HCV positive group (50 [SD 4] months [95% CI, 43-58]) (p< 0.05). Twenty-two patients died - 8 (22.8%) in the anti-HCV positive group and 14 (15.3%) in the negative group. In the anti-HCV positive group, infections were the cause of death in 5 patients and 3 patients died of liver cell failure. In the anti-HCV negative group, corresponding figures were 13 and one. CONCLUSION: HCV infection is a bad prognostic indicator for patient and graft survival duration in renal transplant recipients. Infections are the commonest cause of death in renal transplant recipients.     

Vitamin D3 modulates T lymphocyte responses in hepatitis C virus-infected liver transplant recipients

Background

Aim of the present study was to investigate whether 1,25(OH)(2)D(3) (Vitamin D3) modulates T lymphocyte functions in patients transplanted for hepatitis C virus-related cirrhosis.

Methods

Sixteen patients and ten healthy subjects were investigated. T lymphocytes were activated in vitro in the presence or absence of Vitamin D3 and then the proliferative response and IFN-γ and TNF-α production were assessed.

Results

Vitamin D3 potently reduced T-lymphocyte proliferation in a dose-related fashion. Similarly, FACS analysis and ELISA testing demonstrated that Vitamin D3 significantly decreased the response frequency and the response intensity of IFN-γ and TNF-α production in the whole CD3-positive T lymphocyte population as well as in “naive” CD4+ CD45RA+ and “memory” CD4+ CD45RO+ T lymphocyte subsets. The inhibitory effect of Vitamin D3 on T-cell proliferation and cytokine production was not different between patients and controls. No toxic effects were exerted by Vitamin D3 even at the higher concentration used (10 nM). Finally, no statistically significant correlation was found between 25(OH)D serum levels and the proliferative response or cytokine production of T lymphocytes from transplanted patients.

Conclusions

This study demonstrates that in patients transplanted for hepatitis C virus-related cirrhosis Vitamin D3 modulates T lymphocyte activation, and provides a rationale for the evaluation of this compound as an immunosuppressive agent in liver-transplanted patients.     

慢性丙型肝炎患者肝组织内的淋巴瘤样病变及其意义

HCV感染是导致慢性肝炎、肝硬化和肝细胞肝癌的主要原因之一.据估计全球约1.7亿人感染HCV,约70%转为慢性,其中又有约20%～30%在10～30年发展为肝硬化,进而可导致肝细胞肝癌的发生.     

抗病毒治疗对慢性乙型肝炎患者肝脏组织学的影响

目的分析慢性乙型肝炎患者的不同抗病毒治疗方式与疗程对肝组织学的影响,探讨临床用药的最佳方案。方法回顾性总结142例慢性乙型肝炎患者,分析其用药方式、疗程、肝脏生化学、病毒学、血清学、肝组织学等相关指标。结果病毒学完全应答:干扰素组58.93%(33/56),核苷(酸)类似物组90.20%(46/51),未抗病毒组0;HBeAg转阴率:干扰素组39.29%(22/56),核苷(酸)类似物组15.68%(7/51),未抗病毒组6%(2/35);HBsAg转阴率:干扰素组21.43%(12/56),核苷(酸)类似物组1.96%(1/51),未抗病毒组0;组织学应答:炎症改善方面,疗程≤1年者为干扰素组核苷(酸)类似物组未抗病毒组,疗程1年者为核苷(酸)类似物组干扰素组未抗病毒组,而肝组织纤维化改善方面,不论疗程长短均为核苷(酸)类似物组干扰素组未抗病毒组。结论抗病毒治疗获得病毒学应答者肝脏组织学均能得到不同程度的改善;核苷(酸)类似物抗病毒治疗2年以上者肝组织学改善程度优于干扰素。     

Efficacy of telaprevir-based therapy in stable liver transplant patients with chronic genotype 1 hepatitis C

Background and rationale. The REPLACE study (NCT01571583) investigated telaprevir-based triple therapy in patients who have recurrent genotype 1 hepatitis C virus (HCV) infection following liver transplantation and are on a stable immunosuppressant regimen of tacrolimus or cyclosporin A. Patients received telaprevir 750 mg 8-hourly with pegylated interferon 180 μg weekly and ribavirin 600 mg daily, followed by a further 36 weeks of pegylated interferon and ribavirin alone and 24 weeks of follow-up. Efficacy (sustained virological response [SVR] 12 weeks after last planned study dose), safety and tolerability of telaprevir throughout the study were assessed. Pharmacokinetics of telaprevir, tacrolimus and cyclosporin A were also examined.Results. In total, 74 patients were recruited. Overall, 72% (53/74; 95% CI: 59.9 to 81.5) of patients achieved SVR at 12 weeks following completion of treatment. Anticipated increases in plasma concentrations of tacrolimus and cyclosporin A occurred during telaprevir treatment and were successfully managed through immunosuppressant dose reduction and, for tacrolimus, reduced dosing frequency. Safety and tolerability of telaprevir-based triple therapy were generally comparable with previous data in non-transplant patients, although rates of reported anemia (55% [41/74]) were higher. Elevated plasma creatinine (46% [34/74]) was observed during REPLACE - consistent with the post-liver transplant population and the co-administered immunosuppressants.Conclusion. Telaprevir-based triple therapy in patients with recurrent genotype 1 HCV infection following liver transplantation produced high rates of SVR. Therapeutic concentrations of immunosuppressants were maintained successfully through dose modification during telaprevir treatment.     

Limitations of current liver transplant immunosuppressive regimens: renal considerations

BACKGROUND:The use of calcineurin inhibitor (CNI)-based immunosuppressive regimens following liver transplantation (LTx) has improved the outcomes of the recipients.However,CNI has nephrotoxicity and causes short-and long-term renal complications.The progressive structural changes can be irreversible in the long-term,leading to chronic kidney dysfunction.The present review was to evaluate the different strategies of CNI application to renal function in liver recipients.DATA SOURCES:PubMed database was searched for relevant articles in English on the issue of immunosuppressive regimen and kidney injury that related to early minimization of CNI after LTx.RESULTS:Total avoidance of CNI from post-LTx immunosuppressive regimens has been associated with unacceptable high rates of acute,steroid resistant rejections;late conversion from CNI to non-nephrotoxic immunosuppressant failed to recover renal function.Early CNI minimization and conversion to non-nephrotoxic immunosuppressant,although had no effect on patient survival rates,improved glomerular filtration rate.The combination of everolimus (a mammalian target of rapamycin inhibitor) and tacrolimus not only maintains immunosuppressive efficacy but also minimizes kidney injury.CONCLUSIONS:Up to now,protocols entirely avoiding CNI have not passed the primary safety endpoint of patient and graft survival,as well as the FDA mandated endpoint of biopsy proven acute rejection.Thus,early CNI minimization after LTx is the most rational approach preserving post-transplant renal function.     

Recurrent hepatitis C after liver transplant

End stage liver disease from hepatitis C is the most common indication for liver transplantation in many parts of the world accounting for up to 40% of liver transplants. Antiviral therapy either before or after liver transplantation is challenging due to side effects and lower efficacy in patients with cirrhosis and liver transplant recipients, as well as from drug interactions with immunosuppressants. Factors that may affect recurrent hepatitis C include donor age, immunosuppression, IL28B genotype, cytomegalovirus infection, and metabolic syndrome. Older donor age has persistently been shown to have the greatest impact on recurrent hepatitis C. After liver transplantation, distinguishing recurrent hepatitis C from acute cellular rejection may be difficult, although the development of molecular markers may help in making the correct diagnosis. The advent of interferon free regimens with direct acting antiviral agents that include NS3/4A protease inhibitors, NS5B polymerase inhibitors and NS5A inhibitors holds great promise in improving outcomes for liver transplant candidates and recipients.     

The impact of diabetes and obesity on liver histology in patients with hepatitis C

Aim:   An association between diabetes mellitus and HCV has been recognized previously. No study has examined whether there is an independent association between the degree of hepatic fibrosis and the incidence of diabetes in HCV patients when controlling for other risk factors.
Methods:   We reviewed the charts of 264 consecutive patients with chronic HCV infection at a referral liver centre from January 1991 to December 1999. Demographic background, medical history, laboratory and liver biopsy results were retrieved.
Results:   The prevalence of diabetes was 16.3%. Gender, intravenous drug use, steatosis scores, aminotransferase levels and iron studies were similarly distributed in patients with and without diabetes (all p > 0.05). In contrast, mean age was greater in the diabetic group (49.8 vs. 44.3, p = 0.003). The prevalence of diabetes was substantially higher in African-Americans (p = 0.001) and those with BMI > 30 (p = 0.015). Although the fibrosis score was higher in diabetics ( ρ  = 0.14, p = 0.03), that association did not remain significant when controlling for diabetes risk factors (p > 0.3). The degree of steatosis and fibrosis both tended to increase with increasing BMI ( ρ  = 0.47, p < 0.001 and ρ  = 0.13, p = 0.03, respectively). Even after controlling for diabetes, age, gender, race, and current alcohol use, those associations remained (both p < 0.001).
Conclusions:   The prevalence of diabetes in our group of HCV patients was high, consistent with other studies. Diabetes is not an independent predictor of degree of fibrosis. Body mass index is an independent predictor of both fibrosis and steatosis in HCV patients.     

Serum alpha-fetoprotein levels and liver histology in patients with chronic hepatitis C

Objective: The clinical and morphological significance of a raised alpha-fetoprotein (AFP) level in patients with chronic hepatitis C is undefined. We sought to determine the relation between serum AFP level and liver histology in this population.
Methods: We reviewed the clinical and histological records of 200 consecutively evaluated patients with chronic hepatitis C whose serum AFP levels were recorded. Two groups were studied: group I = 125/200 (62%) patients with normal AFP, < 10 ng/ml; and group II = 75/200 (38%) patients with raised AFP, > 10 ng/ml. The groups were compared according to age, gender, duration of disease, histology, and history of alcohol abuse.
Results: There was no significant difference in serum AFP based on age, gender, alcohol consumption, or disease duration. Significant histological differences were observed: cirrhosis was present in 57 (45%) patients in group I versus 51 (68%) in group II (   p < 0.001  ). Hepatocellular carcinoma was more frequent in group II (14/75 [19%]) than in group I (1/125 [1%]) (   p < 0.001  ). Ten of 77 (13%) noncirrhotic patients and 51/108 (47%) cirrhotic patients had a raised AFP (   p < 0.002  ; relative risk, 3.262; confidence interval [C.I.], 1.912–5.564). A derived AFP level of 17.8 ng/ml maximized specificity for predicting histological outcome: one of 76 (1.3%), 29/108 (26.8%), and 14/15 (93.3%) patients were noncirrhotic, cirrhotic, or had HCC, respectively. This derived AFP value is 35% sensitive and 98.6% specific for cirrhosis, with a positive predictive value of 97.7%.
Conclusions: A serum AFP level >17.8 ng/ml strongly suggests the diagnosis of cirrhosis in a population of patients with chronic hepatitis C.     

合并肾功能衰竭的肝移植患者接受肾脏替代治疗的价值

目的 回顾性分析合并急性肾功能衰竭的肝移植受体移植术前的危险因素,并探讨肾脏替代治疗(RRT)作为其移植前过渡治疗措施的价值. 方法收集2001年1月-2008年1月在卫生部移植医学工程技术研究中心由于急性肾功能衰竭而接受RRT的肝移植受体患者,依据不同预后对肝移植受体的临床特征进行分组对比分析;按接受不同RRT种类对肝移植受体的临床特征进行分组对比分析.用逻辑回归法分析能预测合并肾功能衰竭肝移植受体病死率的指标.对数据进行f检验、χ2检验、Logistic回归分析.结果 在接受RRT的患者中,有31.25%的患者因为肝移植而生存或者出院,68.75%的患者在等待移植期间死亡.死亡组患者与移植组相比,有更高的多器官功能障碍评分(4.98±2.32与4.45±2.02,P=0.008)、更低的平均动脉压[(56.5±7.1)mm Hg与(65.4±12.9)mm HgP=0.040;1 mm Hg=0.133 kPa].RRT的平均治疗天数在连续性肾脏替代治疗组和间歇血液透析组之间的差异没有统计学意义.与间歇血液透析组相比,连续性肾脏替代治疗组有更高的多器官功能障碍评分(4.82±2.12与3.45±1.91,P=0.040)、更低的平均动脉压[(56.0±14.2)mm Hg与(68.5±15.3)mm Hg,P=0.002]、更低的血清肌酐浓度[(320.12±185.15)μmol/L与(420.55±158.32)μmol/L,JP=0.008].肾功能衰竭受体术前平均动脉压越低,则死亡风险越高. 结论对患有急性肾功能衰竭的肝移植受体应用RRT是可取的.尽管病死率仍高,但可使部分患者得以肝移植而生存.     

Chronic hepatitis C infection in patients with end stage renal disease: characterization of liver histology and viral load in patients awaiting renal transplantation

OBJECTIVES: Hepatitis C virus (HCV) is common in patients with end stage renal disease (ESRD) awaiting renal transplantation (RT). However, few data are available on the liver histology and viral titer in these patients relative to patients with HCV and normal renal function. The aims of this study were to assess liver histology, quantitative HCV-RNA titer, and alanine aminotransferase (ALT) levels in patients with ESRD awaiting RT, and to identify clinical predictors of histological progression to advanced bridging fibrosis and/or cirrhosis. METHODS: A total of 50 consecutive patients (mean age 42 yr, 62% male) with ESRD and HCV, who were awaiting RT, underwent liver biopsy. Two HCV populations, one with persistently normal ALT and another with elevated ALT, both with normal renal function, served as controls. HCV-RNA titer was assessed by quantitative PCR. RESULTS: Of the patients with ESRD, 94% had normal ALT. Log HCV RNA titer was significantly higher in patients with ESRD (5.8+/-0.3) than in either normal ALT (5.4+/-0.1) or elevated ALT (5.3+/-0.1) controls (p < 0.05). Knodell Histological Activity Index (HAI) in patients with ESRD was similar to that observed in control patients with normal ALT (4.8+/-0.4 vs 4.9+/-0.4) but significantly less (p < 0.05) than that observed in control patients with elevated ALT (8.4+/-0.5). The percentage of patients with bridging fibrosis or cirrhosis was similar in patients with ESRD and controls with persistently normal ALT (22% vs 13%) but significantly less (p < 0.001) than that observed in control patients with elevated ALT (48%). No significant differences in ALT, HCV-RNA titer, duration on hemodialysis, or time from first possible exposure was observed between ESRD patients with advance fibrosis (n = 11) and those with mild disease (n = 39). CONCLUSIONS: Our data suggest that liver biopsy is necessary to exclude significant liver pathology in patients with HCV and ESRD, and to help define those patients in whom interferon treatment might be helpful.     

Clinical progression of hepatitis C virus-related chronic liver disease in human immunodeficiency virus-infected patients undergoing highly active antiretroviral therapy

Little is known about the natural history of liver disease in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected subjects under highly active antiretroviral therapy (HAART). The objectives of this study were to obtain information about the mortality, the incidence of hepatic decompensations, and the predictors thereof in this population. In a multicenter cohort study, the time to the first hepatic decompensation and the survival of 1,011 antiretroviral na?ve, HIV/HCV-coinfected patients who started HAART and who were followed prospectively were analyzed. After a median (Q1-Q3) follow-up of 5.3 (2.9-7.1) years, 59(5.83%) patients developed a hepatic decompensation and 69 (6.82%) died, 30 (43%) of them because of liver disease. The factors independently associated [HR (95% CI)] with the occurrence of hepatic decompensations were age older than 33 years [2.11 (1.18-3.78)], female sex [2.11 (1.07-4.15)], Centers for Disease Control stage C [2.14 (1.24-3.70)], a diagnosis of cirrhosis at baseline [10.86 (6.02-19.6)], CD4 cell gain lower than 100/mm3 [4.10 (2.18-7.69)] and less than 60% of the follow-up with undetectable HIV viral load [5.23 (2.5-10.93)]. Older age [2.97 (1.18-7.50)], lack of HCV therapy [11.32 (1.44-89.05)], hepatitis D virus coinfection [16.15 (2.45-106.48)], a diagnosis of cirrhosis at recruitment [13.69 (5.55-34.48)], hepatic encephalopathy [62.5 (21.27-200)] and lower CD4 cell gain [3.63 (1.45-9.09)] were associated with mortality due to liver failure. CONCLUSION: End-stage liver disease is the primary cause of death in HIV/HCV-coinfected patients under HAART. Higher increase of CD4 cell counts, lack of markers of serious liver disease and therapy against HCV are factors associated with better hepatic outcome.     

Characteristics of hepatitis C in renal transplant candidates

GOALS: To characterize hepatitis C in renal transplant candidates and to compare hepatitis C-related liver disease between patients with end-stage renal disease (ESRD) and well-matched control subjects without renal disease. BACKGROUND: Hepatitis C is common in dialysis patients and can cause morbidity and mortality in renal transplant recipients. Patients with advanced hepatitis C often are excluded from renal transplantation. STUDY: Forty-six renal transplant candidates and 46 control subjects matched for age, sex, and race without renal disease were included. Demographic, laboratory, and histologic data were compared between patients with ESRD and control subjects. RESULTS: Alanine aminotransferase levels were significantly lower in patients with ESRD (p < 0.001). Hepatitis C virus RNA levels were similar between groups. Patients with ESRD had less inflammatory activity (p < 0.001) and a lower proportion of bridging fibrosis or cirrhosis (13%) than control subjects (30%, p = 0.043). Clinical and laboratory features did not predict histologic grade or stage of hepatitis C in patients with ESRD. Two complications of percutaneous liver biopsy occurred per three diagnoses of cirrhosis in patients with ESRD. No complications occurred with transjugular liver biopsy in this group. CONCLUSIONS: Patients with ESRD had less severe hepatitis C than did control subjects. Clinical measurements did not predict histologic findings in renal transplant candidates. Transjugular liver biopsy should be considered to stage hepatitis C in renal transplant candidates due to the risk of percutaneous biopsy in uremic patients.     

Effect of weight reduction on liver histology and biochemistry in patients with chronic hepatitis C

BACKGROUND: Steatosis occurs in more than 50% of patients with chronic hepatitis C and is associated with increased hepatic fibrosis. In many of these patients the pathogenesis of steatosis appears to be the same as for patients with non-alcoholic fatty liver disease-that is, related to visceral adiposity and obesity. METHODS: The effect of a three month weight reduction programme on liver biochemistry and metabolic parameters was examined in 19 subjects with steatosis and chronic hepatitis C. Paired liver biopsies were performed in 10 subjects, prior to and 3-6 months following the intervention, to determine the effect of weight loss on liver histology. RESULTS: There was a mean weight loss of 5.9 (3.2) kg and a mean reduction in waist circumference of 9.0 (5.0) cm. In 16 of the 19 patients, serum alanine aminotransferase levels fell progressively with weight loss. Mean fasting insulin fell from 16 (7) to 11 (4) mmol/l (p<0.002). Nine of 10 patients with paired liver biopsies had a reduction in steatosis irrespective of viral genotype. In these subjects the median modified Knodell fibrosis score decreased from 3 to 1 (p=0.04) and activated stellate cells significantly decreased (p<0.004). CONCLUSIONS: Weight loss in patients with chronic hepatitis C may be associated with a reduction in steatosis and abnormal liver enzymes and an improvement in fibrosis, despite the persistence of the virus. Weight reduction may provide an important adjunct treatment strategy for patients with chronic hepatitis C.