Hepatitis: Asselah T

Marcellin P, Asselah T, Lada O. · No affiliation provided · Gastroenterol Clin Biol. · Pubmed #18662604 No free full text.

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Moucari R, Asselah T. · No affiliation provided · Rev Med Interne. · Pubmed #18556093 No free full text.

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Marcellin P, Asselah T. · No affiliation provided · J Hepatol. · Pubmed #16246449 No free full text.

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Asselah T, Ripault MP, Marcellin P. · No affiliation provided · Gastroenterol Clin Biol. · Pubmed #14770105 No free full text.

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Asselah T, Benhamou Y, Marcellin P. · INSERM, U773, Centre de Recherche Bichat-Beaujon CRB3, Service d'hépatologie, Hôpital Beaujon, Clichy, France. · Liver Int. · Pubmed #19207967 No free full text.

Abstract: Chronic hepatitis C is among the leading causes of chronic liver disease worldwide, with approximately 170 million people infected. The severity of disease varies from asymptomatic chronic infection to cirrhosis and hepatocellular carcinoma. Recently,advances have been made, with the combination of pegylated interferon (PEG-IFN) and ribavirin leading to a sustained virological response (SVR) in approximately 55% of cases. In genotypes 2 or 3, SVR rates reach 80%; in genotype 1 SVR rates is 50%. Furthermore, SVR appears to be long lasting, associated probably with a reduction in the risk of cirrhosis and hepatocellular carcinoma. Despite this progress, treatment failure still occurs in about half of the patients. Furthermore, therapy results in several side effects and high costs. These limitations have led to important development of novel compounds under the name of specifically targeted antiviral therapy for HCV (STAT-C). Also, considering side effects and treatment cost, prediction of virological non-response is mandatory. The management of chronic hepatitis C must include better knowledge of viral cycle and mechanisms of non response. The development of new molecules such as HCV enzyme inhibitors is ongoing. The aim of this review is to summarize results obtained with STATC: protease and polymerase inhibitors.

Asselah T, Bièche I, Sabbagh A, Bedossa P, Moreau R, Valla D, Vidaud M, Marcellin P. · INSERM, U773, Centre de Recherche Bichat-Beaujon CRB3, Paris, France. · Gut. · Pubmed #19074178 links to  free full text

Abstract: Hepatitis C virus (HCV) is a major cause of chronic liver disease, with about 170 million people infected worldwide. Up to 70% of patients will have persistent infection after inoculation, making this disease a significant cause of morbidity and mortality. The severity of disease varies widely, from asymptomatic chronic infection to cirrhosis and hepatocellular carcinoma. Since the discovery of HCV, the treatment of hepatitis C has considerably improved. Recently, combination of pegylated interferons with ribavirin gives a response rate of about 55%. Treatment is indicated in patients with moderate or severe fibrosis. The tolerability of combination treatment is relatively poor, with a frequent flu-like syndrome and an impaired quality of life. In addition to viral and environmental behavioural factors, host genetic diversity is believed to contribute to the spectrum of clinical outcomes in HCV infection. The sequencing of the human genome, together with the development of high-throughput technologies that measure the function of the genome, have afforded unique opportunities to develop profiles that can distinguish, identify and classify discrete subsets of disease, predict the disease outcome or predict the response to treatment. This paper reviews the published literature on gene expression associated with HCV infection (HCV infection, fibrosis progression), and also according to response to treatment.

Asselah T, Lada O, Moucari R, Marcellin P. · Université Paris 7-Denis-Diderot, Hôpital Beaujon, Pôle des Maladies de l'Appareil Digestif, Service d'Hépatologie, Centre de Recherche Biomédicale Bichat Beaujon CRB3, INSERM U773. · Expert Opin Investig Drugs. · Pubmed #19012511 No free full text.

Abstract: Chronic hepatitis B virus (HBV) infection, affecting approximately 350 million people worldwide, is associated with significant morbidity and mortality. In the past 10 years, hepatitis B therapy research has led to a multitude of available antiviral therapies: IFN-alpha, pegylated IFN-alpha(2a), lamivudine, adefovir, entecavir, telbivudine and tenofovir. To further improve reductions in viral load and resistance profiles, development of new HBV therapeutic strategies has been an important focus. One such therapy is clevudine, an analogue of the beta-L configuration. Clevudine is already licensed in Korea for anti-HBV therapy (Bukwang Pharmaceuticals, Seoul, Korea). Unique to clevudine is its ability to maintain antiviral activity following discontinuation of therapy. Typically, hepatitis B treatment requires continuous therapy to prevent reactivation. Sustained response is uncommon except in hepatitis B antigen (HBeAg)-positive patients who developed HBeAg seroconversion. This article reviews chronic HBV and its therapy options. Specifically, it describes clevudine's potent and sustained antiviral activity as observed in vitro and in vivo.

Peffault de Latour R, Ribaud P, Robin M, Valla D, Marcellin P, Socié G, Asselah T. · Service d'Hématologie-Greffe, Hôpital Saint Louis, 75475 Paris, France. · J Hepatol. · Pubmed #18433917 No free full text.

Abstract: Hepatitis C virus (HCV) is a major cause of liver disease worldwide. After allogeneic Hematopoietic Cell Transplant (HCT), HCV is known to be associated with transient hepatitis in the immediate post-transplant period, and a potential risk factor of veno-occlusive disease (SOS). Very recently, HCV-infected HCT recipients have been shown to be at higher risk of earlier cirrhosis, leading to greater morbidity and mortality. Long-term survivors after HCT are thus at a high risk for HCV-related complications and, as a consequence, the treatment of HCV infection becomes critical. We describe here the potential clinical complications in HCV-infected recipients, in the short, but also the long-term follow-up after HCT. The pathophysiology of liver fibrosis is discussed as well as the present recommended therapy in this particular population.

Asselah T, Lada O, Moucari R, Martinot M, Boyer N, Marcellin P. · Service d'Hépatologie, INSERM U773, CRB3, University of Paris VII, Hôpital Beaujon, 92110 Clichy, France. · Clin Liver Dis. · Pubmed #17981231 No free full text.

Abstract: This article summarizes the results obtained with interferon alfa and pegylated interferon alfa, as monotherapy and in combination with lamivudine, in the treatment of chronic hepatitis B.

Moucari R, Marcellin P, Asselah T. · Pôle des maladies de l'appareil digestif, Service d'hépatologie et INSERM U773 CRB3, Université Paris VII, Hôpital Beaujon, Clichy. · Gastroenterol Clin Biol. · Pubmed #17925761 No free full text.

Abstract: Liver steatosis is frequent in patients with chronic hepatitis C. Two main types are described: (1) "viral steatosis" induced by the virus, especially genotype 3, which probably inhibits the "Microsomal Triglyceride Transfer Protein", thus decreasing "Very Low Density Lipoprotein" secretion and leading to triglyceride accumulation within hepatocytes; (2) "metabolic steatosis" which is a feature of the metabolic syndrome and insulin resistance, a systemic disorder associated with a high risk of cardiovascular disease and diabetes mellitus. Insulin resistance induces intrahepatic triglyceride accumulation due to excess free fatty acid flux from increased adipose tissue lipolysis as well as increased intrahepatic lipogenesis through activation of the "Sterol Response Element Binding Protein". Hepatitis C Virus itself can also be responsible for insulin resistance, possibly through impairment of the insulin signalling pathway because of increased"Tumor Necrosis Factor Alpha" levels and/or upregulated "Cytokine Signalling Suppressor" expression. Insulin resistance and steatosis, appear to be associated with fibrosis progression and impairment of sustained response to antiviral treatment.

Asselah T, Boyer N, Ripault MP, Martinot M, Marcellin P. · Service d'Hépathologie and INSERM U 773, University of Paris VII, Beaujon Hospital, Clichy, France. · Minerva Gastroenterol Dietol. · Pubmed #17415342 No free full text.

Abstract: Chronic hepatitis C is a major cause of cirrhosis and primary liver cancer (hepatocellular carcinoma). Decompensated cirrhosis or hepatocellular carcinoma secondary to hepatitis C is the first cause of liver transplantation in Europe and in the United States. The prognosis of chronic hepatitis C depends on the progression of fibrosis which determines the risk of developing cirrhosis and its complications. Knowledge of the natural history and the factors associated with the progression of fibrosis is essential for the patient's management. The risk of the progression of fibrosis is difficult to predict in one particular patient. Liver biopsy remains the best test to evaluate the severity of fibrosis, determine its prognosis and discuss the therapeutic options. At present, in a patient with hepatitis C, combined therapy associating pegylated alpha interferon and ribavirin results in a sustained response in approximately 55% of cases. Based on existing results, the sustained virological response with this treatment option appears to be long lasting, to be associated with a histological benefit and is also probably associated with a reduction in the risk of cirrhosis and hepatocellular carcinoma. The management of hepatitis C virus infections must include better knowledge of the natural history of the disease and existing available antiviral treatments (pegylated interferon and ribavirin) as well as in depth knowledge of the aims of treatment, the results obtained, the predictive factors of response and side effects. With close follow-up, doses can be rapidly modified and erythropoietin more frequently administered; new molecules may also be developed in this context. This paper will discuss the natural history, the factors associated with the progression of fibrosis, the predictive factors of response to treatment, and existing and future treatments for hepatitis C.

Asselah T, Bièche I, Paradis V, Bedossa P, Vidaud M, Marcellin P. · Service d'Hépatologie and INSERM U773, CRB3, University of Paris VII, AP-HP Hôpital Beaujon, Clichy, France. · Semin Liver Dis. · Pubmed #17295174 No free full text.

Abstract: Hepatitis C virus (HCV) is a major cause of chronic liver disease worldwide. The severity of disease varies widely from mild illness to cirrhosis and hepatocellular carcinoma. The progression of liver fibrosis in HCV patients determines the prognosis and, thus, the need for and urgency of therapy. In addition to viral and environmental behavioral factors, host genetic diversity is believed to contribute to the spectrum of clinical outcomes of patients chronically infected with HCV. The sequencing of the human genome together with the development of high-throughput technologies has provided opportunities to distinguish discrete subsets of HCV disease and predict the disease outcome or the response to therapy. This article reviews genetic, genomic, and proteomic aspects associated with the natural history of HCV infection (i.e., viral clearance, fibrosis progression) and the response to therapy.

Asselah T, Boudjema H, Francoz C, Sobesky R, Valla D, Belghiti J, Marcellin P, Durand F. · Service d'Hépatologie et Unité INSERM CRB3, Université Paris VII. · Gastroenterol Clin Biol. · Pubmed #17185970 No free full text.

Abstract: Hepatitis C virus-related end-stage liver disease, alone or in combination with alcohol, has become the leading indication for liver transplantation in most transplant programs accounting for approximately half of transplants performed in European centers. Hepatitis C virus infection recurs virtually in every post-transplant patient. The natural history of hepatitis C after liver transplantation is variable. Progression of chronic hepatitis C virus is more aggressive after liver transplantation with a cumulative probability of developing graft cirrhosis estimated to reach 30% at 5 years. Approximately 10% of the patients with recurrent disease will die or require re-transplantation within 5 years post-transplantation. Several factors, including those related to the virus, the host, the environment and the donor, are probably implicated in the outcome. The immune status represents the main significant variable in influencing disease severity in hepatitis C virus-infected patients; with higher HCV viral load and the significant association described between the degree of immunosuppression and disease severity. Interventions to prevent, improve, or halt the recurrence of hepatitis C virus infection have been evaluated by multiple small studies worldwide with similar overall rates of virological clearance of approximately 9-30%. Current consensus recommends combination therapy with pegylated interferon and ribavirin for those patients with histological recurrence of hepatitis C virus infection and fibrosis. Therapy is adjusted to tolerance and rescued with granulocyte colony-stimulating factor and erythropoietin for bone marrow suppression. In this article we present a comprehensive review of post-transplant hepatitis C virus infection; in particular fibrosis progression and the major challenges according to treatment.

Marcellin P, Boyer N, Asselah T. · Division of Hepatology and INSERM CRB3, University of Paris VII, Beaujon Hospital, Clichy, France. · Minerva Gastroenterol Dietol. · Pubmed #16554704 No free full text.

Abstract: Five agents are currently approved for the treatment of chronic hepatitis B: standard interferon-alpha (IFN-alpha), pegylated interferon-alpha 2a (PEG-IFN-alpha 2a), lamivudine, adefovir and entecavir. Each agent has inherent limitations. IFN and PEG-IFN-alpha 2a are effective in a minority of patients and have frequent side effects that limit their tolerability. The efficacy of lamivudine is limited by the emergence of drug-resistant hepatitis B virus (HBV) mutants, restricting its utility as a long-term therapy. Adefovir is well tolerated and associated with a low incidence of resistance but its antiviral effect is not optimal. Entecavir, which has been recently registered, has a more potent anti-viral effect but its long term efficacy and resistance profile is still not known. These antivirals induce a sustained response after withdrawal of therapy in only a minority of patients and therefore the treatment needs to be indefinitely administered in the majority of patients. After a brief summary of the natural history of chronic hepatitis B in order to understand the indications and the objectives of therapy, this review focuses on treatment of HBeAg-negative chronic hepatitis B with IFN and PEG-IFN-alpha 2a.

Asselah T, Castelnau C, Marcellin P. · Service d'hépatologie, Inserm CRB3, Université Paris VII, Hôpital Beaujon, Clichy (92). · Presse Med. · Pubmed #16493337 No free full text.

Abstract: Chronic hepatitis B develops in 3 phases: immune tolerance, where viral replication is strong and there is little or no fibrosis; immune activity phase with low viral replication and rapidly developing fibrosis as well as an elevated risk of cirrhosis; low viral replication and remission, with a risk, nonetheless, of reactivation. Antiviral treatment is indicated in patients with moderate or severe levels of either fibrosis or activity (necrotic and inflammatory lesions). Standard interferon treatment produces a prolonged response rate on the order to 20-40%; side effects are frequent but generally mild and reversible when treatment stops. Pegylated interferon (standard interferon conjugated with polyethylene glycol) has substantially better efficacy and comparable tolerance. Lamivudine (a nucleoside analog) has several advantages over interferon: oral administration, excellent tolerance, and rapid antiviral effect. Its principal disadvantage is the frequency of resistant mutations. Adefovir and entecavir have oral administration, are well tolerated and associated with a low incidence of resistance. They induce a sustained response after withdrawal of therapy in only a minority of patients and therefore the treatment needs to be indefinitely administered in the majority of patients.

Condat B, Asselah T, Zanditenas D, Estampes B, Cohen A, O'Toole D, Bonnet J, Ngo Y, Marcellin P, Blazquez M. · Service d'hépato-gastroentérologie, Hôpital Saint-Camille, Bry sur Marne, France. · Eur J Gastroenterol Hepatol. · Pubmed #16462543 No free full text.

Abstract: We report the case of a 45-year-old man with HCV treated with pegylated interferon-alpha/ribavirin, in whom fatal cardiomyopathy occurred. Cardiomyopathy is a rare complication of high dose of standard interferon but has never been reported with pegylated interferon. The relationship between pegylated interferon-alpha/ribavirin and the development of cardiomyopathy is highly probable for the following reasons: (1) a cardiologist consultation with specific investigations had been performed before treatment excluding a pre-existing cardiomyopathy; (2) symptoms of advanced dilated cardiomyopathy appeared immediately after the end of treatment; (3) other causes of cardiomyopathy have been ruled out. In all except one of the 21 reported cases with standard interferon, cardiomyopathy was reversible. In our patient, fatal cardiomyopathy occurred with a usual dose of pegylated interferon-alpha. Clinicians should be aware of this potential complication when evaluating the ratio benefit/risk of treatment in patients with chronic hepatitis C infection.

Asselah T, Ripault MP, Castelnau C, Giuily N, Boyer N, Marcellin P. · Seroice d'Hépatologie and INSERM CRB3, Unioersity Paris 7, Hôpital Beaujon, AP-HP, Clichy, France. · J Clin Virol. · Pubmed #16461210 No free full text.

Abstract: In recent years, marked progress has been made in the treatment of chronic viral hepatitis. Recent studies suggest that pegylated interferons (PEG IFNs) are more effective than standard IFNs in the treatment of chronic hepatitis B. So far, the combination of PEG IFN with lamivudine, used simultaneously, is disappointing in terms of short-term efficacy. However, long-term efficacy needs to be addressed and different schedules of combination, for example sequential, need to be evaluated. A number of nucleoside analogues, with favourable toxicity profiles and a promise of increased effectiveness against HBV, are in various stages of clinical development. Entecavir has recently been approved in the USA. The future of chronic hepatitis B therapy seems to be in the combination of different drugs. Ideally, the optimal drugs to combine would meet the following criteria: they should have a potent antiviral effect, an excellent safety profile and the duration of therapy should be limited. Indeed, the concept of combination therapy has been recently developed in order to increase efficacy and to decrease the occurrence of viral resistance. However, so far there are few data available and no combination therapy demonstrated a clear benefit as compared with monotherapy. More potent drugs and new combinations together with the understanding of the mechanisms of resistance to therapy are challenges to improve the efficacy of treatment and decrease in the future the global burden related to chronic hepatitis B.

Asselah T, Rubbia-Brandt L, Marcellin P, Negro F. · Service d'Hépatologie and INSERM CRB3, Hôpital Beaujon, Clichy 92110, France. · Gut. · Pubmed #16344578 links to  free full text

Abstract: Hepatic steatosis is a common histological feature of chronic hepatitis C. Various factors are associated with hepatic steatosis, including obesity, high alcohol consumption, diabetes type II, and hyperlipidaemia. These factors may contribute to steatosis in patients with chronic hepatitis C. In humans, hepatitis C virus (HCV) genotype 3 is more commonly associated with steatosis. In vitro studies and the transgenic mouse model have suggested that the HCV core protein (genotype 1) can induce lipid accumulation within hepatocytes. However, what is the relevance of steatosis in chronic hepatitis C? It seems that in certain populations, steatosis may be associated with fibrosis progression and this may be genotype specific. The mechanisms underlying this association are unknown; neither is it clear whether this holds true for all patients or only a subgroup. Indeed, after antiviral treatment, virus related steatosis disappears whereas the host associated steatosis remains unaffected. This review describes and discusses the basic and clinical aspects of the relationship between steatosis and progression of fibrosis, and response to treatment in patients with chronic hepatitis C.

Marcellin P, Asselah T, Boyer N. · Service d'Hépatologie, INSERM U-481 and Centre de Recherche Claude Bernard sur les Hépatites Virales, Hôpital Beaujon, Clichy, France. · J Viral Hepat. · Pubmed #15985003 No free full text.

Abstract: In the last years, marked progress has been made in the treatment of chronic hepatitis B. The efficacy of lamivudine, the first nucleoside analogue available, is limited by the high incidence of resistance. Adefovir, which was recently approved has a comparable efficacy with a very low frequency of resistance. However, adefovir needs to be indefinitely administered as withdrawal of therapy is generally associated with reactivation and sustained response is uncommon. Recent large randomized controlled trials showed that PEG IFNs induce relatively high sustained response rates both in HBeAg positive and HBeAg negative chronic hepatitis B. So far, the combination of PEG IFN with lamivudine, used simultaneously, is disappointing in terms of short-term efficacy. However, long-term efficacy needs to be assessed and different schedules of combination (for example sequential) need to be evaluated. A number of nucleoside analogues, with favourable toxicity profiles and a promise of increased effectiveness against HBV, are at various stages of clinical development. Results of phase III trials of entecavir and emtricitabine confirmed their efficacy. However, while entecavir is associated with a low incidences of resistance, emtricitabine is associated with a relatively high incidence of resistance which limits its use as a monotherapy. The efficacy and safety of new and more potent drugs like telbivudine and clevudine need to be confirmed. The future of chronic hepatitis B therapy seems to be in the combination of different drugs. Ideally, the optimal drugs to combine would meet the following criteria: they should have different sites of action on HBV DNA replication, a potent antiviral effect, an excellent safety profile and they should induce a sustained response with a limited duration of therapy. Indeed, the concept of combination therapy has been recently developed in order to increase efficacy and to decrease the occurrence of viral resistance. However, so far few combinations have been evaluated. No combination therapy demonstrated a benefit as compared with monotherapy. More potent drugs and new combinations together with the understanding of the mechanisms of resistance to therapy are important challenges to improve the efficacy of treatment and decrease in the future the global burden related to chronic hepatitis B.

Marcellin P, Asselah T, Boyer N. · Service d'hépatologie et Inserm U481, hôpital Beaujon, 92110 Clichy. · Rev Prat. · Pubmed #15913114 No free full text.

Abstract: Three drugs are currently available for the treatment of chronichepatitis B: interferon-alpha, lamivudine and adefovir dipivoxil. Standard interferon-alpha induces a sustained response in only a minority of patients (10-30 %) and is associated with a poor tolerability which limits duration of therapy. The nucleoside (lamivudine) and nucleotide (adefovir dipivoxil) analogs have the advantages of oral administration and excellent tolerance. Lamivudine, administered for 12 months, induces a sustained response in approximately 20 % of the HbeAg positive and in 5 % of the HBeAg-negative patients. Long-term therapy increases the rate of sustained response but is impaired by a high rate of resistance (50 % at 3 years). Adefovir dipivoxil, administered for 12 months, induces a sustained response in 12 % of HBeAg-positive patients. Adefovir has a similar antiviral efficacy in HBeAg-negative patients. The incidence of resistance to adefovir is low (6 % at 3 years). Thus, the currently available drugs have a limited effectiveness and new more powerful drugs or new therapeutic strategies are necessary. Recent studies showed that the efficacy of pegylated interferon was higher than the standard interferon. Evaluated therapeutic combinations, pegylated interferon and lamivudine on the one hand and to adefovir and lamivudine on the other hand, did not show superiority as compared to the monotherapy by pegylated interferon and to adefovir, respectively. A number of nucleoside analogs, with favorable toxicity profiles and a promise of increased effectiveness against HBV, are at various stages of clinical development. Results of phase III trials of entecavir confirmed its efficacy and safety leading to registration in the next future. Emtricitabine does not seem more effective than lamivudine. The results of phase II studies of telbivudine and clevudine are promising. However, one may expect that their use in monotherapy could not induce a high rate of sustained response and that long-term therapy or combination should be needed to improve efficacy and/or reduce resistance.

Asselah T, Ripault MP, Marcellin P. · Hépatologie, INSERM U481, Hôpital Beaujon, Clichy, France. · Gastroenterol Clin Biol. · Pubmed #15864198 No free full text.

This publication has no abstract.

Marcellin P, Asselah T, Ripault MP, Boyer N. · Unit of Hepatology, Claude Bernard Research Center on Viral Hepatitis, INSERM U-481, Hospital Beaujon, Clichy, France. · Minerva Gastroenterol Dietol. · Pubmed #15719004 No free full text.

Abstract: Since the discovering of the hepatitis C virus in 1989, the treatment of hepatitis C has considerably improved. Initially, with interferon alpha used as a single drug, the sustained virological response rate was below 20%. Then, with the use of combination therapy of interferon a with ribavirin, the response rate increased to 41%. More recently, combination of pegylated interferons with ribavirin give a response rate of about 54-63%. The long-term follow-up studies showed that sustained virological response is generally associated with clinical and histological improvement. The indication of therapy is mainly based on the results of the liver biopsy which is the best way to assess the prognosis of the liver disease. Therefore, treatment is indicated in patients with moderate or severe necroinflammation or fibrosis. The tolerability of combination therapy is relatively poor with a frequent flu-like syndrome and an impaired quality of life. Factors associated with a poor response to treatment are essentially genotype 1 and high viral load. To further improve the efficacy of therapy, different new drugs are under investigation (amantadine, cytokines). These drugs may be candidates for new combinations. In addition, intensive research is currently done for the development of inhibitors of viral enzymes (helicase, protease or polymerase) and anti-sense oligonucleotides, ribozymes and therapeutic vaccine.

Asselah T, Castelnau C, Boyer N, Ripault MP, Marcellin P. · Service d'Hépatologie, INSERM U481, Hôpital Beaujon, 92110 Clichy. · Gastroenterol Clin Biol. · Pubmed #15671931 No free full text.

This publication has no abstract.

Asselah T, Martinot M, Boyer N, Marcellin P. · Service d'Hépatologie, INSERM U 481 et Centre de Recherche Claude-Bernard sur les Hépatites Virales, Hôpital Beaujon, Clichy. · Gastroenterol Clin Biol. · Pubmed #12687958 No free full text.

This publication has no abstract.

Marcellin P, Asselah T, Boyer N. · Service d'Hépatologie and INSERM U 481, Hôpital Beaujon, Clichy, France. · Hepatology. · Pubmed #12407576 No free full text.

Abstract: The progression of fibrosis in chronic hepatitis C determines the ultimate prognosis and thus the need and urgency of therapy. Fibrogenesis is a complex dynamic process, which is mediated by necroinflammation and activation of stellate cells. The liver biopsy remains the gold standard to assess fibrosis. Scoring systems allow a semiquantitative assessment and are useful for cross-sectional and cohort studies and in treatment trials. The rate at which fibrosis progresses varies markedly between patients. The major factors known to be associated with fibrosis progression are older age at infection, male gender, and excessive alcohol consumption. Viral load and genotype do not seem to influence significantly the progression rate. Progression of fibrosis is more rapid in immunocompromised patients. Hepatic steatosis, obesity, and diabetes may also contribute to more rapid progression of fibrosis. There are no tests that reliably predict the rate of progression of fibrosis in an individual patient. High serum alanine aminotransferase (ALT) levels are associated with a higher risk of fibrosis progression, and worsening of fibrosis is uncommon in patients with persistently normal serum aminotransferase levels. Serum markers for fibrosis are not reliable and need to be improved and validated. Liver biopsy provides the most accurate information on the stage of fibrosis and grade of necroinflammation, both of which have prognostic significance. Repeating the liver biopsy, 3 to 5 years after an initial biopsy is the most accurate means of assessing the progression of fibrosis.