Hepatitis C: 25 Years Old, and Fading

Digestive Disease Week (DDW) 2015

William F. Balistreri, MD


June 15, 2015

In This Article

The Natural History of Chronic Hepatitis C

Rates of HCV-Related Liver Transplantation Continue to Rise

The implementation of HCV screening among high-risk groups and birth cohorts was postulated to lead to earlier detection and treatment of HCV, thereby preventing progression to cirrhosis-related complications and the need for liver transplantation. However, it is not clear whether HCV screening programs have in fact effectively reduced HCV-related liver transplantation.

Using data from the United Network for Organ Sharing registry and the National Health and Nutrition Examination Survey, Aguilar and colleagues[4] compared the trends in HCV prevalence with wait-list registrations for HCV-related new liver transplantation and HCV-related liver transplantation surgeries performed in the United States. HCV trends were calculated from 2001 to 2012 using 2-year groupings and were further stratified to determine sex- and race-specific variations.

The overall prevalence of HCV in the United States decreased by 17%, with a 26% decrease in men but a 6% increase in women. During this same period, HCV prevalence decreased by 12% in non-Hispanic white persons, 5% in black persons, and 13% in Hispanic persons. However, new wait-list registrations among patients with chronic HCV increased by 32% overall, with a 39% increase among men and 18% increase among women. When stratified by race, wait-list registrations increased by 24% in non-Hispanic white persons, 109% in black persons, and 30% in Hispanic persons.

Overall, liver transplantation surgeries performed for HCV-related liver disease also increased by 32% (36% in men and 23% in women). When stratified by race, HCV-related liver transplantation surgeries increased by 19% in non-Hispanic white persons, 138% in black persons, and 39% in Hispanic persons.

Thus, despite the overall decreasing prevalence of HCV in the United States, the number of patients with progressive HCV leading to liver transplantation wait-list registration and needing liver transplantation surgery continues to rise. Although non-Hispanic white men accounted for the majority of liver transplantations, black patients demonstrated the largest increase, more than doubling during the study period.

Identifying Patients at High Risk for Disease Progression

Konerman and colleagues[5] suggested that existing predictive models of the risk for disease progression in patients with chronic hepatitis C have limited accuracy in risk-stratifying patients because they are restricted to data at baseline combined with a single follow-up. Thus, they applied novel statistical methods integrating longitudinal data from the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) trial, in an attempt to improve the accuracy of predicting clinical outcomes.

This trial included 533 patients with HCV who had Ishak fibrosis scores > 3 and were nonresponsive to prior therapy; 134 patients had a liver-related clinical outcome during a median follow up of 6.5 years. Longitudinal models were shown to outperform baseline models for such outcomes as fibrosis progression and liver-related clinical outcomes (ie, HCC, liver transplantation, hepatic decompensation, liver-related death).

The most important independent predictors of these outcomes were serum albumin, ALT, and total bilirubin levels and platelet counts. The negative predictive value was 81%-85% for baseline models and 90% for the longitudinal model.

The authors concluded that prediction models that incorporate longitudinal data can capture nonlinear disease progression and thus outperform baseline models. Longitudinal models increase true-positive rates by 30%, allowing accurate identification of a larger percentage of patients with the greatest need for initiation of treatment. The observed high negative predictive value also suggests that these models may be useful in the management of HCV infection at both the patient and population level.

Cirrhosis and the Incidence of Decompensation

The projected public health burden of HCV is based on old natural history studies. One presentation[6] suggested a need to reexamine the natural history of HCV because the current patient cohort is older and confounded by a higher prevalence of obesity, and other comorbid conditions that may affect the outcome of the disease. Therefore, investigators conducted a retrospective cohort study at Kaiser Permanente Southern California.

From 2002-2013, 60,338 adults had an HCV diagnosis code or a positive HCV RNA lab test. Of these, 33,124 HCV cases met inclusion criteria and were matched with 164,221 controls. Mean age of the HCV cases and non-HCV controls was 54 years. Among case-patients, 41% were white and 27% were Hispanic; among controls, the respective proportions were 46% and 28%.

Prevalent cirrhosis was found in 19% of the HCV-infected cohort and 1.4% of the non-HCV controls. The incident decompensation rate among previously compensated HCV patients with cirrhosis was 47%, which was almost twice the incident decompensation rate among non-HCV cirrhotic controls. Of note, 23% of HCV cases were diagnosed with cirrhosis after a median follow-up of 2 years, which indicates that the rates of development of HCV-related cirrhosis and decompensation are higher than previously reported. The authors attributed this to aging of the HCV cohort and associated comorbidities, such as obesity. Multivariable analyses to explore the relationship between baseline comorbid conditions and the incidence of cirrhosis and decompensation are ongoing.


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