As Incidence of HCV Infection Increases, a New Mouse Model to Study

The incidence of hepatitis C virus (HCV) infection and its complications—hepatocellular carcinoma (HCC) and cirrhosis—are increasing, according to Fasiha Kanwal et al. Fortunately, a new mouse model has been created to study disease progression and treatment, as described by Michael Washburn et al. These findings were reported in separate articles in the April issue of Gastroenterology.

HCV infection is very difficult to study in patients—little is known about how the virus evades host immunity and establishes chronic infection in the liver. In fact, little is even known about its prevalence or that of its associated liver disorders.

Kanwal et al. calculated the annual prevalence of cirrhosis, decompensated cirrhosis and HCC in a national sample of veterans in the United States who were diagnosed with HCV. They found that the number of individuals with HCV increased from 17,261 in 1996 to 106,242 in 2006. Importantly, the prevalence of cirrhosis and HCC among HCV-infected patients increased significantly (see below figure). Kanwal et al. also found an increase in the proportion of patients with cirrhosis who died each year, with annual mortality rates reaching 7% in 2006.

Prevalence of cirrhosis, decompensated cirrhosis and HCC, 1996–2006, among veterans with HCV infection.

These data are the first to provide direct and contemporary estimates of time trends for the burden of cirrhosis, from the largest assembled group of patients with HCV anywhere in the world. However, Kanwal et al. state that the quality of health care given to patients with HCV infection falls far short of that recommended by practice guidelines.

In a search for tools to better understand how HCV infection progresses and to test new therapies, Washburn et al. developed mice with a human immune system and liver tissue. They did so by transplanting human hematopoietic stem cells and hepatocyte progenitors into mice, which could then be infected with HCV. These mice, called AFC8-hu HSC/Hep, developed liver inflammation, hepatitis and fibrosis, just like in humans.

Although other human–mouse chimeric liver models have been developed, they allowed analyses of only limited aspects of HCV infection and pathogenesis. The AFC8-hu HSC/Hep mice should provide more information about how HCV infection progresses. Washburn et al. found that stellate cells and expression of human fibrogenic genes were activated, and the mice generated a human immune T-cell response against the virus.

A better understanding of how HCV infection leads to fibrosis and cancer are needed, as Kanwal et al. concluded that there are deficits in care of patients with HCV infection and cirrhosis. The authors state that because of the significant increase in the number of patients with cirrhosis, along with data indicating gaps in the quality of care, the US health care system should focus more attention on treating patients with HCV infection, particularly those with cirrhosis.

More Information on HCV Infection:

Read the articles online:
Kanwal F, Hoang T, Kramer JR, et al.  Increasing prevalence of hcc and cirrhosis in patients with chronic hepatitis c virus infection. Gastroenterology 2011;140:1182-1188.e1.

Washburn ML, Bility MT, Zhang L, et al. A humanized mouse model to study hepatitis c virus infection, immune response, and liver disease. Gastroenterology 2011;140:1334-1344.

About Kristine Novak, PhD, Science Editor

Dr. Kristine Novak is the science editor for Gastroenterology and Clinical Gastroenterology and Hepatology, both published by the American Gastroenterological Association. She has worked as an editor at biomedical research journals and as a science writer for more than 12 years, covering advances in gastroenterology, hepatology, cancer, immunology, biotechnology, molecular genetics, and clinical trials. She has a PhD in cell biology and an interest in all areas of medical research.
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