Fibrosis and disease progression in hepatitis C

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. (HEPATOLOGY 2002;36:S47-S56.)

Natural History of Hepatitis C

“…However, in paired liver biopsies, elevated ALT levels were associated with progression of fibrosis. 11–13,14 Serum ALT was not predictive of development of clinical outcomes, however the AST/ALT ratio was predictive. 76 Patients with elevated serum ALT levels are also found to have increased risk for hepatocellular carcinoma.…”

Use of Wisteria Floribunda Agglutinin-Positive Human Mac-2 Binding Protein in Assessing Risk of Hepatocellular Carcinoma Due to Hepatitis B Virus

“…36 On the contrary, HCV, primary biliary cirrhosis, and autoimmune hepatitis are more insidious in nature, resulting in slowly progressive fibrosis. 37,38 Probably due to this unsatisfactory accuracy of M2BP, the combination of WFA + -M2BP and LS could not enhance the overall accuracy in predicting all fibrosis stages in comparison to LS (all P  > .05). Apart from cross-sectional analysis, which appeared unsatisfactory, we similarly explored the prognostic value of WFA + -M2BP from a longitudinal aspect.…”

Liver Stiffness Measurement among Patients with Chronic Hepatitis B and C: Results from a 5-Year Prospective Study

“…A study of hemophiliacs showed that 32% exhibited more than 2 kPa of regression during 3.7 years of follow-up [21]. Among hepatitis B patients, Castera et al [24] reported that 81% (9/11) with an initial LSM value of >7.2 kPa regressed to normal values during 22 months of follow-up, and Kim et al [25] reported that 30% (34/114) of patients with F3+ in biopsy regressed more than 30% during 13 months. For comparison, studies using repeated biopsy have reported that up to 24% exhibited decreasing fibrosis during 3–4 years of untreated follow-up [24]–[26].…”