Long-term Outcome of Chronic Hepatitis C After Sustained Virological Response to Interferon-based Therapy

C. Koh; T. Heller; V. Haynes-Williams; K. Hara, X. Zhao; J. J. Feld; D. E. Kleiner; Y. Rotman; M. G. Ghany; T. J. Liang; J. H. Hoofnagle


Aliment Pharmacol Ther. 2013;37(9):887-894. 

In This Article

Abstract and Introduction


Background Although the short-term benefits of a sustained virological response (SVR) to interferon-based therapies of chronic hepatitis C (CHC) are well known, the long-term consequences of SVR are less clear.

Aim To assess changes in markers of disease activity and fibrosis in patients followed up to 23 years post-SVR.

Methods The first 103 SVR patients (from 1984 to 2003) at the National Institutes of Health Clinical Center were evaluated. Serum markers before treatment and at the last visit were compared. Evaluations after 2007 included transient elastography (TE).

Results Of 103 patients, three subsequently relapsed 0.7, 6.3 and 6.5 years post therapy. The remaining 100 patients (56 men, mean age 56 years) maintained SVR at final follow-up. No patients developed hepatic decompensation, but one with pre-treatment cirrhosis died 12 years post SVR of hepatocellular carcinoma. In comparison to pre-treatment values, markers improved at follow-up, including mean ALT (152–27 U/L), AST (87–24 U/L), alkaline phosphatase (78–69 U/L), IgG (1463–1113 mg/dL), platelet count (209 000–239 000/μL) and AST to platelet count ratio index (APRI: 1.31–0.33). TE was performed in 69 patients and was normal (<7.0 kPA) in 60%, moderately elevated (7.1–13.8) in 31% and cirrhotic range (>13.8) in 9%. TE and platelet counts at follow-up correlated with fibrosis on pre-treatment liver biopsy (P < 0.001).

Conclusions In 97% of patients with CHC, SVR is durable without evidence of disease progression, although some degree of hepatic fibrosis may persist and patients with pre-treatment cirrhosis are at continuing low risk for hepatocellular carcinoma.


Chronic hepatitis C virus (HCV) infection is estimated to affect 180 million persons worldwide and at least 3.2 million Americans.[1,2] This disease is the most common cause of chronic hepatitis and cirrhosis, end-stage liver disease and hepatocellular carcinoma in the United States and the developed world.[3,4] It is also the single most common reason for liver transplantation.[4] Therapy for HCV has evolved during the last 20 years from use of interferon alone to the combination of interferon and ribavirin followed by the combination of peginterferon with ribavirin.[5–7] Recently direct-acting antiviral agents have been developed for HCV that have increased the response rate substantially.[8–13] The endpoint for assessing efficacy of antiviral therapy has been the loss of HCV RNA from serum which, if sustained for at least 6 months after stopping treatment, is referred to as a sustained virological response (SVR).[14] The durability of a 6-month SVR is above 95%, but the long-term clinical benefits of this outcome have not been well defined.[15,16]

Although achievement of an SVR has been associated with clinical, laboratory and histological improvements in chronic HCV, this endpoint is a surrogate for the ultimate aim of therapy, which is prevention of progression to cirrhosis, end-stage liver disease, hepatocellular carcinoma and death from liver disease.[17–26] These 'hard' endpoints, however, generally take years or decades to evolve and following patients randomised to treatment or observation with these dire outcomes has not been practical and has been considered ethically untenable. Thus, while SVR is associated with improvements in serum aminotransferase levels and liver histology, its role in preventing progression of disease and disability or death from chronic liver disease is uncertain and currently controversial.

At the Clinical Center of the National Institutes of Health (NIH), we have conducted a series of prospective controlled and uncontrolled studies of therapy of chronic HCV beginning in 1984.[26–31] All patients who achieved an SVR as a part of these studies have been followed on a long-term basis to assess the natural history and outcome of this virological response. As a consequence, we have a cohort of SVR patients that have been followed up for up to 23 years. We report the follow-up of the initial 103 patients who achieved an SVR between the years 1986 and 2003.