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DDW: Interferon Has Long-Term Histo Benefits in HCV

CHICAGO, June 3 -- A single course of interferon-based therapy, with or without ribavirin, produces long-term improvements in liver histology in patients with hepatitis C (HCV) who completely clear the virus, researchers found.

Patients who had a sustained virologic response had significant reductions in inflammation and fibrosis of the liver five or six years after receiving treatment, Mitchell Shiffman, M.D., of Virginia Commonwealth University , reported at Digestive Disease Week here.

Even half of the patients who had cirrhosis improved if they responded to therapy.

"We used to think that once you had cirrhosis, it was sort of a done deal, and no matter what happened, you couldn't get any improvement," said co-investigator Richard Sterling, M.D., also at Virginia Commonwealth . "But this study now confirms that some of those patients can actually resolve their liver scarring and inflammation."

Conversely, patients who declined or did not respond to treatment had significantly more inflammation and worsened fibrosis on a follow-up biopsy.

Several studies have shown that patients with chronic HCV can develop increased liver fibrosis over time. But the long-term impact of interferon-based therapy (in patients with and without a sustained virologic response) remained unknown, Dr. Sterling said.

Uncontrolled studies have shown that patients with a sustained virologic response have improvements in liver histology following a single course of interferon-based therapy, he said.

There has even been some suggestion that patients who do not have a response to therapy have reduced scarring in the short term, he said.

To explore the issue, Drs. Shiffman and Sterling and their colleagues began a prospective, longitudinal cohort study in 1991.

They included all patients who had a liver biopsy and either declined treatment (46 patients) or received a single course of interferon-based therapy, with or without ribavirin (287 patients).

All patients received a follow-up biopsy five or six years later. Most studies looking at the effect of therapy on liver histology have only followed up at 24 or 48 weeks, Dr. Sterling said.

The patients who decided not to undergo treatment generally had mild disease, as indicated by lower inflammation and fibrosis scores and lower serum alanine aminotransferase.

Of those who underwent treatment, 185 did not have a sustained virologic response and 102 did.

Patients who declined treatment and those who underwent treatment but failed to respond had similar increases in both inflammation and fibrosis of the liver (P<0.001 for all comparisons). There were no differences between the two groups at follow-up.

Factors that predicted fibrosis progression were the changes in total inflammation and interface hepatitis from baseline (P<0.005 for both), and the degree of interface hepatitis at baseline (P<0.05).

The findings remained the same regardless of the degree of scarring at baseline.

In patients who had a sustained virologic response, inflammation and fibrosis of the liver both improved over time.

Of patients who had early scarring, or portal fibrosis, at baseline and had a sustained virologic response, 73% lacked any fibrosis at follow-up while 20% remained unchanged.

Of patients who had bridging fibrosis on the first biopsy and had a sustained virologic response, 35% were free from fibrosis at follow-up. Some 23% had reduced fibrosis, while 38% remained unchanged, and 4% progressed to cirrhosis.

And of patients who started out with cirrhosis and had a sustained virologic response, half improved: 10% had no fibrosis at follow-up. while 10% had improved to portal fibrosis, and 30% had improved to bridging fibrosis.

"The results of our study show that in patients who respond to treatment, the use of interferon or peginterferon in addition to ribavirin is very effective," Dr. Sterling said.

Shiffman M, et al "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.

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