Hepatitis C Watch

Rate of HCC Varies with Age and Gender

For years, researchers have theorized that coinfection with hepatitis B virus (HBV) and HCV increased the risk of developing hepatocellular carcinoma (HCC) more than either infection alone. Now, due to a study published in the Journal of Clinical Oncology on August 22, 2011, this relationship seems to be more complex than previously thought.

Researchers from Harvard University enrolled subjects from Taiwan between the ages of 30 and 65 years from 1991 to 1992. Serum samples were collected and tested for seromarkers and viral load of HBV and HCV. Newly diagnosed HCC was also detected. Of the 23,820 subjects, 477 developed HCC. The incidence of HCC was 38.35% for men with both viruses and 27.40% for women with both viruses. Men and women who were seropositive only for hepatitis B surface antigen (HBsAg) had cumulative lifetime HCC rates of 27.38% and 7.99%, respectively. The researchers also observed that the hazard ratio (HR) of HCC was 22.38 in men with both viruses who were older than 65 years and 27.29 in women with both viruses who were older than 65 years.

The researchers also demonstrated another layer of complexity when evaluating the HCC correlation between serum markers and gender: “Multivariate adjusted hazard ratio of developing HCC decreased with age in HBsAg-seropositive men but increased with age in anti-HCV-seropositive women.” Understanding the impact of age and gender on risk of developing HCC may guide clinicians in setting surveillance and treatment goals.

Metformin Shown to Decrease Carcinoma in HCV Cirrhosis Patients

Type 2 diabetes and hyperinsulinemia are common in patients with HCV cirrhosis, and they are associated with a higher incidence of HCC. For this reason, scientists have been interested in examining if improving insulin resistance in patients with HCV cirrhosis may decrease the rates of HCC. In a recent study published in the August 2011 issue of the Journal of Clinical Endocrinology and Metabolism, researchers observed a cohort of 100 patients with diabetes with ongoing HCV cirrhosis in a screening program for HCC and analyzed whether the use of metformin would decrease the rate of HCC.

The patients received routine diabetic care: 29 were treated with dietary modifications alone, 26 were treated with metformin with or without other antidiabetic agents, 17 with insulin secretagogues alone, and 28 with insulin treatment alone. After 5 years of follow-up, the researchers found that although the occurrence of HCC was 9.5% in metformin-treated patients, the occurrence was 31.2% in those not treated with metformin, a significant difference (P = .001). Multivariate Cox regression analysis identified male gender, metformin treatment, and serum gamma glutamyl transpeptidase and alpha-fetoprotein levels as independently associated with HCC occurrence.

If insulin plays a role in development of HCC, then why do other treatment modalities for type 2 diabetes not have such a profound effect as metformin? The researchers of the study believe that the effect of metformin may be direct or indirect. Indirect effects of metformin include enhanced insulin sensitivity as well as activation of adenosine monophosphate-activated protein kinase (AMPK) in the liver. AMPK has been shown to play a role in tumor suppression and signaling pathways responsible for regulating cell growth and metabolism. Another drug class that acts similarly to metformin is the thiazolidinediones, which were not included in this study and warrant further investigation.

The Oral Drugs Are Here: AASLD Updates HCV Treatment Guidelines

With the advent of new oral therapies that are more specific to the hepatitis C virus (HCV), the American Association for the Study of Liver Diseases (AASLD) published its updated guidelines for the treatment of HCV in the October 2011 issue of Hepatology. The guidelines are endorsed by numerous medical associations, including the Infectious Diseases Society of America, the American College of Gastroenterology, and the National Viral Hepatitis Roundtable.

The new guidelines suggest a departure from interferon monotherapy or interferon in combination with ribavirin alone, and instead advocate the inclusion of newer oral agents from the drug class called protease inhibitors. Although these agents are very effective according to clinical studies, they should not be used alone and should always be combined with interferon with or without ribavirin. The guidelines also advise how to adjust doses of drugs that interact with the newer agents, and provide recommendations on handling viral resistance and when to test for genetic polymorphisms.

Although the new oral medications hold promise, the guidelines do provide some caveats to their widespread use. The new oral medications are only approved for patients with HCV genotype 1 and not for other genotypes, patients with post-transplant recurrent HCV, patients coinfected with HIV, or pediatric patients. For all these patients, traditional treatment modalities are required.