Interferon-based therapy reduced liver fibrosis progression over 5 years in hepatitis C patients who achieved sustained virological response, and most of those with advanced liver damage prior to treatment experienced fibrosis regression, according to findings presented at the 2009 Digestive Disease Week meeting (DDW 2009) last month in Chicago.

Research on the long-term effects of interferon-based therapy for chronic hepatitis C virus (HCV) infection have produced conflicting results. Several studies have shown that fibrosis progression may be slowed, halted, or even reversed in individuals who achieve sustained virological response (SVR). Outcomes in non-responders are less clear.

Mitchell Shiffman and colleagues from Virginia Commonwealth University Medical Center reported follow-up findings from a prospective cohort study (initiated in 1998) looking at long-term histological outcomes in chronic hepatitis C patients treated with conventional or pegylated interferon, with or without ribavirin.

A total of 755 patients underwent a baseline liver biopsy and received a single course of interferon-based therapy or no treatment. Of this initial group, 230 were followed without additional treatment for 5 years before undergoing a repeat biopsy. This group included 41 patients who declined therapy and 189 who received treatment but did not achieve SVR (continued undetectable HCV viral load 24 weeks after completion of therapy). Participants with no evidence of fibrosis at baseline who achieved SVR did not receive a repeat biopsy.

At baseline, untreated patients, treated patients without SVR, and treated patients who achieved SVR were not significantly different with respect to age (average 46 years), sex (55% male), and baseline HCV RNA (5.7 IU/ml).

However, inflammation, fibrosis, and serum ALT were lower in the untreated group (i.e., these patients were least likely to be deemed to require therapy). The SVR group had fewer African-Americans and people with HCV genotype 1 (i.e., these individuals were less likely to achieve sustained response). The analysis did not include patients with other causes of liver disease besides HCV, HIV-HCV coinfection, chronic kidney failure, or prior organ transplants.

Results

Patients who achieved SVR continued to have undetectable HCV RNA throughout the 5 year follow-up period.

After 5 years, inflammation and fibrosis scores increased significantly in the untreated group (by 2.1 and 1.1, respectively) and the treated group without SVR (by 1.6 and 0.5, respectively).

More patients with no fibrosis at baseline and no treatment experienced liver disease progression (28% vs 11%).

Liver histology improved significantly in treated patients who achieved SVR.

After 5 years, all treated SVR patients with portal fibrosis and 80% with bridging fibrosis at baseline had no fibrosis.

20% of sustained responders experienced resolution of cirrhosis.

"Interferon treatment reduces the rate of histologic progression over 5 years compared to [no treatment], even in HCV patients with [no fibrosis]," the investigators concluded.

"Patients with HCV who achieve SVR, including those with [cirrhosis], resolve fibrosis, and after 5 years liver histology returns to normal in most patients without pre-existing [cirrhosis]," they added.

Hepatology Section, Virginia Commonwealth University Medical Center, Richmond, VA; Department of Pathology, Virginia Commonwealth University Medical Center, Richmond, VA.

7/7/09

Reference
ML Shiffman, SB Hubbard, A Long, and others. The Long Term Effects of Interferon Based (IFNTx) Therapy on Hepatic Histology in Patients with Chronic Hepatitis C Virus. Results of a Five Year Prospective Evaluation on Fibrosis Progression and Fibrosis Regression. Digestive Disease Week (DDW 2009). Chicago. May 30-June 4, 2009. Abstract 7.

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Magnetic resonance elastography (MRE)

New diagnostic technique to detect liver fibrosis

Magnetic resonance elastography (MRE) can accurately measure the extent and severity of hepatic fibrosis, US researchers have announced during ‘Liver Week 2008’ – the annual meeting of the American Association for the Study of Liver Disease.

Results of a study designed to assess the performance of MRE from the Mayo Clinic and Foundation in Rochester, Minnesota, presented by principal investigator Dr. Jayant A. Talwalker, showed that MRE is accurate in detecting fibrosis caused by a broad spectrum of liver diseases.

The study involved 113 patients who had had liver biopsies within the previous year. MRE was performed and liver stiffness measured in all subjects.

Etiology of disease was non-alcoholic fatty liver disease (NAFLD) in 42%, hepatitis C virus infection in 24%, primary biliary cirrhosis (PBC) in 7%, primary sclerosing cholangitis (PSC) in 6% and alcoholic liver disease in 3%.

There was no fibrosis visible in 20% of patients, stage I fibrosis was found in 22%, stage II fibrosis in 13%, stage III in fibrosis in 13% and stage IV fibrosis was found in 28% of patients.

"Hepatic stiffness increased systematically with fibrosis stage," Dr. Talwalker noted.

"MRE shows a bigger picture [of the liver] than biopsy," he said. "Early fibrosis, especially, is a patchy disease. The biopsy can greatly underestimate or overestimate disease, depending on whether or not the biopsy takes tissue from a fibrotic area. Biopsy is restricted to the right lobe," he added, "MRE visualizes the whole liver."

"MRE can guide treatment decisions," concluded the Mayo Clinic investigators.

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