Long-Term Follow-up of Interferon Therapy up to 10 years after achieving sustained undetectable HCV-RNA

10-Year follow-up after interferon-alpha therapy for chronic hepatitis C

Hepatology 1998 Oct;28(4):1121-7
Lau DTY, Kleiner DE, Ghany MG, Park Y, Schmid P, Hoofnagle JH

Liver Diseases Section, Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA

Sustained responses to interferon-alpha occur in 10% to 25% of patients with chronic hepatitis C, but the long-term outcome is not well defined. We evaluated the long-term clinical, histological, and virological outcomes of10 patients with chronic hepatitis C who were treated between 1984 and 1987 with interferon-alpha-2b for 52 +/- 6 weeks (total doses of 492 +/- 116 MU).

Before therapy, all 10 had hepatitis C virus (HCV) RNA, elevations of serum aminotransferases, and chronic hepatitis with fibrosis on liver biopsy. Clinical follow up was 6 to 13 years, and liver biopsies were done 5 to 11 years after initiation of therapy. HCV RNA was assayed by qualitative and quantitative reverse transcriptase-polymerase chain reaction assays.

Among 5 patients who had a 6-month sustained response after therapy, all remained HCV RNA negative, and at last follow-up, 4 had normal and 1 minimally elevated serum aminotransferase levels. Liver biopsy specimens were nonreactive for HCV RNA, and all the patients showed improvements in both inflammation and fibrosis and were either normal or had mild, nonspecific inflammatory changes.

Among 5 patients without a sustained response, all continued to have HCV RNA in serum and persistent or intermittent aminotransferase elevations. Liver biopsy specimens showed little or no change in necrosis and inflammation; all except 1 patient had progression of fibrosis scores or cirrhosis. All 5 patients had symptoms of chronic hepatitis, 1 underwent liver transplantation, and another had progressive hepatic decompensation. In conclusion, patients with a 6-month posttreatment virological response have a favorable long-term clinical and histological outcome.

Long-term histologic improvement and loss of detectable intrahepatic HCV RNA in patients with chronic hepatitis C and sustained response to interferon-alpha therapy

Ann Intern Med 1997 Nov 15;127(10):875-81
Marcellin P, Boyer N, Gervais A, Martinot M, Pouteau M, Castelnau C, Kilani
A, Areias J, Auperin A, Benhamou JP, Degott C, Erlinger S

Hopital Beaujon, Clichy, France.

BACKGROUND: Less than 20% of patients with chronic hepatitis C have a sustained response to interferon-alpha therapy. The long-term benefit of interferon-alpha with regard to hepatic viral clearance and histologic improvement remains unknown. OBJECTIVE: To determine the long-term biochemical, virologic, and histologic outcomes in patients with chronichepatitis C who have a sustained response to interferon-alpha therapy.

DESIGN: Prospective cohort study. SETTING: University hospital.

PATIENTS: 80 patients who had chronic hepatitis C, had a sustained biochemical and virologic response to interferon-alpha therapy, and were followed for at least 12-months.

MEASUREMENTS: Serum hepatitis C virus (HCV) RNA detected by polymerase chain reaction (PCR); HCV genotyping determined by line probe assay; liver histologic studies; liver HCV RNA detected by PCR on frozen liver tissue samples (in 27 patients); and repeated measurements of serum alanine aminotransferase (ALT) levels. Liver biopsy was done before treatment in all 80 patients, and at least one biopsy was done in 69 patients 1 to 6 years after treatment.

RESULTS: The 80 patients had follow-up 1 to 7.6 years (mean +/- SD, 4.0 +/- 2.0 years) after interferon-alpha treatment. The follow-up period was 1, 2, 3, 4, 5, 6, and more than 6 years in 11, 13, 14, 18, 10, 12, and 2 patients, respectively, after the end of therapy. During the entire follow-up period, 93% (95% CI, 84% to 97%) of patients had persistently normal serum ALT levels. Serum HCV RNA remained undetectable in 96% (CI, 89% to 99%) of patients. A comparison of liver histologic findings before and 1 to 6.2 years after interferon-alpha treatment showed a clear improvement in 94% (CI, 83% to 99%) of patients. In 62% of patients, the last biopsy done showed normal or nearly normal histologic findings. Liver HCV RNA was detectable before treatment in all 13 patients tested and was undetectable 1 to 5 years after treatment in all 27 patients tested.

CONCLUSIONS: In patients with chronic hepatitis C who have persistently normal serum ALT levels and no detectable serum HCV RNA 6 months after interferon-alpha therapy, a long-term sustained biochemical and virologic response is generally seen. This response is associated with an absence of detectable intrahepatic HCV RNA and marked histologic improvement.