Clinical

High-dose interferon alpha provides lasting benefit in chronic hepatitis D

Last Updated: 2004-07-05 10:00:02 -0400 (Reuters Health)

By Megan Rauscher

NEW YORK (Reuters Health) - For patients with chronic hepatitis D, high-dose interferon alpha offers the best chance of long-term survival, even among those who have cirrhosis before treatment is initiated, results of a long-term follow up study indicate.

Researchers followed 36 patients with chronic hepatitis D who were treated in the early 1990s with a 48-week course of either high-dose (9 million units) or low-dose (3 million units) interferon alpha or with no therapy for an additional 2 to 14 years.

"A beneficial effect of high doses of interferon was already evident at the end of the treatment period, with disappearance of signs of liver damage in a significant proportion and a slowly progressive decrease of virus replication," Dr. Patrizia Farci from the University of Cagliari in Italy told Reuters Health.

During follow up, patients in the high dose interferon-alpha group survived significantly longer than patients in the low-dose interferon alpha (p = 0.019) or untreated control group (p = 0.003). Survival did not differ between untreated controls and those treated with low-dose interferon alpha.

"It is remarkable," the team notes in the June issue of Gastroenterology, "that half the patients who had a biochemical response at the end of treatment with 9 million units of interferon (for 48 weeks) continued to have normal ALT for up to 14 years after the termination of therapy."

"Interestingly," they write, all patients who had persistently normal ALT levels had a decline in antibody titer and ultimately lost serum IgM antibody to hepatitis delta antigen, "which is considered to be the best marker of resolution of disease activity." The "sustained decrease" in HDV replication in the high dose group led to clearance of HDV RNA and eventually hepatitis B virus in some patients.

"But the most striking finding was obtained from the liver histology study," Dr. Farci told Reuters Health. "Several patients treated with interferon at the high dose showed a complete regression of liver fibrosis, which is the major histopathological change underlying liver cirrhosis, resulting in a normal-appearing liver tissue."

"Our study rebuts the dogma that cirrhosis is an irreversible process," Dr. Farci said.

According to Dr. Farci, the clinical, virological, and histopathological findings in this study "clearly demonstrate that treatment with high doses of interferon can dramatically change the natural history of chronic hepatitis D, the most severe form of chronic viral hepatitis."

Gastroenterology 2004;126:1740-1749.