High-dose Interferon alfa-2a therapy was effective in chronic hepatitis D
ACP J Club. 1994 May-June;120:68. doi:10.7326/ACPJC-1994-120-3-068
Farci P, Mandas A, Coiana A, et al. Treatment of chronic hepatitis D with interferon alfa-2a. N Engl J Med. 1994 Jan 13;330:88-94.
To compare the use of high- or low-dose interferon alfa with no treatment in patients with chronic hepatitis D.
Randomized controlled trial with a mean follow-up of 32 months.
Hepatitis clinic in Italy.
42 patients between 18 and 60 years of age who had serum hepatitis B surface antigen (HBsAg), serum antibody to hepatitis delta antigen of the IgG and IgM classes, and serum hepatitis delta virus (HDV) RNA recorded on 3 occasions within 6 months before enrollment; serum levels of alanine aminotransferase at least twice the upper limit of normal 6 months before enrollment; histologic evidence of chronic hepatitis; and a positive test for intrahepatic HDV antigen. Exclusion criteria were a course of antiviral or immunosuppressive therapy within 6 months before enrollment, pregnancy or lactation, advanced or decompensated cirrhosis, clotting abnormalities precluding a liver biopsy, hepatocellular carcinoma, leukocyte count < 3 × 109/L, platelet count < 100 × 109/L, hemophilia, drug abuse, presence of antibodies to human immunodeficiency virus type 1, and other serious medical illnesses. Follow-up was 93%.
Patients were assigned to receive either 9 million units (n = 14) or 3 million units (n = 14) of recombinant interferon alfa or no treatment (n = 14) . Interferon was given intramuscularly 3 times/wk for 48 weeks.
Main outcome measures
Biochemical response defined as normal levels of serum alanine aminotransferase; virologic response defined as absence of serum HDV RNA; and histologic findings.
Serum alanine aminotransferase reached normal levels in more patients receiving 9 million units of interferon than in patients receiving no treatment (Table);no difference existed between patients receiving 3 million units (29% reached normal serum alanine aminotransferase levels) and untreated patients. Serum HDV RNA was absent in 71% of patients in the high-dose group compared with none of the untreated patients (P = 0.001). Both normal alanine transferase levels and absence of serum HDV RNA was achieved in 50% of patients in the high-dose group compared with none of the untreated patients (P = 0.004). The high-dose group showed greater histologic improvement than untreated patients (P = 0.02).
Rates of biochemical and virologic responses were greatest for high-dose interferon alfa therapy compared with low-dose therapy or no treatment in patients with chronic hepatitis D. Improvement was seen in approximately 50% of patients.
Source of funding: Not stated.
For article reprint: Dr. P. Farci, The Hepatitis Viruses Section, Laboratory of Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA. FAX 301-402-0524.
Table. Treatment with 9 million units interferon vs no treatment in chronic hepatitis D*
|Outcome at 48 wk||9 million units interferon treatment||No treatment||RBI (95% CI)||NNT (CI)|
|Normal serum alanine aminotransferase levels||71%||8%||829% (100 to 5209)||2 (1 to 4)|
*Abbreviations defined in Glossary; RBI, NNT, and CI calculated from data in article.
Chronic hepatitis D is a serious and often progressive liver disorder, exacerbating liver disease in patients who are chronic carriers of HBsAg. In the past decade, several controlled trials have shown the effectiveness of interferon alfa in the treatment of chronic hepatitis B and chronic hepatitis C. Uncertainty exists about the role of interferon alfa in the treatment of chronic hepatitis D.
The controlled trial done by Farci and colleagues contributes to our understanding of the role of interferon in chronic hepatitis D infection. In this well-done trial, the authors compared the efficacy of high- and low-dose interferon alfa with no treatment during 48 weeks. The authors provided evidence that the efficacy of interferon alfa as a treatment for chronic hepatitis D is related to the dose and not to the duration of treatment. Relapse, however, was noted in both groups after the treatment had stopped. The effect of the high-dose interferon alfa on liver histology was statistically significant when compared with the control group but less dramatic than its effects on biochemical tests. The effects on viral replication were not sustained.
This study shows the efficacy of short-term treatment of chronic hepatitis D with interferon alfa at a high dose. Whether or not interferon alfa changes the natural history of chronic hepatitis D or has a role in the maintenance treatment is, however, still unclear. Additional long-term clinical studies that examine the safety and efficacy of maintenance therapy after high-dose interferon therapy are needed before interferon alfa can be fully established as a treatment for chronic hepatitis D.
Young-Mee Lee, MD
Tufts University School of MedicineBoston, Massachusetts, USA