Sustained virological response after treatment in chronic hepatitis C - five year follow up

Sustained virological response after treatment in patients with chronic hepatitis C infection - a five year follow up

DOI: http://dx.doi.org/10.3329/bmrcb.v39i1.15791

Rahman MZ1, Ahmed DS1, Masud H1, Parveen S2, Rahman MA1, Chowdhury MS1, Barua R1, Ishaque SM1 1Department of Gastroenterology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, 2Department of Paediatrics, BSMMU, Dhaka.

Vol 39, No 1 (2013)

Abstract
Peginterferon α-2a and ribavirin combination therapy achieves a sustained virological response (SVR) in patients with chronic hepatitis C. Little is know about long-term durability of hepatitis C virus – Ribonucleic acid (HCV-RNA) negativity in patient treated with pegylated interferon and ribavirin therapy.

Aim of this study was to evaluate the durability of virologic response in patients with SVR to anti-viral therapy treated at our centre. A total of 52 patients with chronic hepatitis C virus infection who had obtained SVR after Peginterferon α-2a and ribavirin combination therapy were followed up to 5 years with annual HCV-RNA testing. During this follow up period, 4 of 52 patients with initial SVR developed late relapse of hepatitis C virus infection. Relapse was more common in patients who has cirrhosis (3/6 [50%]) vs (1/46 [2.17%]) without cirrhosis.

In conclusion, SVR is durable in most patients, but some patients do have late relapse; long term follow up may be particularly important in a subset of patients with hepatitis C virus infection who have liver cirrhosis.

Discussion Only
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Infection with hepatitis C virus is a leading cause of liver disease worldwide1,2. Progression to chronic hepatitis C occurs in most people acutely infected with HCV and persistent infection is an important cause of cirrhosis, end stage liver disease and hepatocellular carcinoma. Thus, early detection and treatment is of great importance. The goal of treatment is to prevent complications of HCV infection3,4.

There have been substantial improvements in the success of HCV treatment and there are currently several treatment regimens approved by the FDA. In randomized clinical trials, the highest overall SVR rated have been achieved with the combination of weekly subcuataneous injection of long acting peginterferon α-2a and daily oral ribavirin, which represents the current standard of care12-14. Nevertheless, little is known on the outcome of patients treated with PEG-IFN/ribavirin combination therapy.

Recently, swain et al. evaluated the durability of SVR after the treatment with peginterferon α-2a ± ribavirin in 845 patients, who had participated in pivotal trials15 and achieved SVR.

Only in seven patients (<1%), HCV-RNA was detected (after 391-1076 days of treatment). All these data indicate that the late relapse after SVR in chronic hepatitis C patients following anIFN-based anti-viral therapy is rare16-19.

This is the first study from Bangladesh on long term outcomes of anti-viral therapy for chronicHCV infection.

Our study shows that SVR is durable in a majority of patients but late relapses do occur. These relapses occur more commonly in patients with cirrhosis. Our study revealed late relapses in 7.69% over 5 year follow up. One reason for high late relapse in our study could be due to presence of poor baseline predictors of response: obesity i.e., BMI>30 (n=3), alcohol intake (n=1) and cirrhosis (n=3). In addition, on retrospective analysis we found that mean dose of ribavirin and peginterferon used in these patients was suboptimal as dose reductions were required more frequently due to severe adverse effects.

A theoretical explanation for late relapse could be persistence of undetected occult hepatitis C virus in hepatocytes, PBMCs, lymphocytes or macrophages.

There are several limitations of the study. Liver biopsy was not done. So histological relapse could not be seen. Similarly, retesting of genotype/sequencing was not done and possibility of reinfection cannot be ruled out.

SVR once achieved is sustained in majority of patients. The treating hepatologist need to be aware of occurrence of late relapses in patients with chronic HCV infection with cirrhosis.

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Of Interest - July 2013
Durability of sustained virologic response in chronic hepatitis C.