Risk Of Developing Liver Cancer After HCV Treatment

Wednesday, July 31, 2013

Durability of sustained virologic response in chronic hepatitis C.

Gut Liver. 2013 Jul;7(4):458-61. doi: 10.5009/gnl.2013.7.4.458. Epub 2013 Jun 20.

Durability of sustained virologic response in chronic hepatitis C

Uyanikoglu A, Kaymakoglu S, Danalioglu A, Akyuz F, Ermis F, Pinarbasi B, Demir K, Besisik F, Cakaloglu Y.

Source
Department of Gastroenterology, Harran University Faculty of Medicine, Sanliurfa, Turkey.

Abstract
BACKGROUND/AIMS:

The aim of this study is to investigate the rate of sustained virologic response (SVR) in chronic hepatitis C patients receiving antiviral treatment.

METHODS:
The files of patients with chronic hepatitis C treated with interferon±ribavirin between 1995 and 2009 were reviewed retrospectively. Six months after the end of treatment, patients with negative hepatitis C virus (HCV)-RNA (<50 IU/mL, as determined by the polymerase chain reaction method) were enrolled in the study.

RESULTS:
The mean age of 196 patients (89 males) was 46.13±11.10 years (range, 17 to 73 years). In biopsies, the mean stage was 1.50±0.94; histological activity index was 7.18±2.43. In total, 139 patients received pegylated interferon (IFN)+ribavirin, 21 patients received classical IFN+ribavirin, and 36 patients received IFN alone. The HCV genotypes of 138 patients were checked: 77.5% were genotype 1b, and 22.5% were other genotypes. After achievement of SVR, the median follow-up period was 33.5 months (range, 6 to 112 months), and in this period relapse was only detected in two patients (1.02%) at 18 and 48 months after treatment.

CONCLUSIONS:
In total, 98.9% of patients with SVR in chronic hepatitis C demonstrated truly durable responses over the long-term follow-up period of 3 years; relapsed patients had intermittent or low-grade viremia.

KEYWORDS:
Chronic hepatitis C, Interferons
PMID: 23898387 [PubMed]

Discussion Only
Full Text Available Here

Regular and long-term follow-up of patients with SVR was not well documented. The current study evaluates the long term results of SVR. In standard interferon or IFN/ribavirin combination therapies, HCV-RNA was negative for 92% to 100% of patients during the follow-up of 1 to 12 years following SVR in patients with chronic hepatitis C.

Recent studies reported that cure for HCV infection was achieved with SVR. Additionally, histological improvement was detected in 94% of the patients and persistently normal ALT levels were detected in 93%.

Our results also confirmed these data and HCV-RNA level was not detectable in the long term for 99.4% of the patients. ALT was determined to be within normal limits for 153 patients (94%) in the final control.

The available data was relatively less for PEG-IFN/ribavirin combination. In a study by Swain et al follow-up of 845 patients who achieved SVR with interferon alpha 2a±ribavirin revealed that HCV-RNA was detected in only seven patients (<1%) within 391 to 1,076 days after treatment. For treatments based on PEG-IFN, it was concluded that late relapse was rare after achievement of SVR. More than half (65%) of our patients received PEG-IFN/ribavirin treatment, with results supporting this study. PEG-IFN + ribavirin treatment appears to have good long term results.

In chronic hepatitis C treatment, it is still uncertain whether complete elimination is achieved as a result of the treatment or whether a small number of viruses persist. In former studies using less sensitive tests, 95% of the patients with SVR had undetectable levels of HCV-RNA in the liver within 1 to 2 years after treatment. Only two of the seven patients with HCV-RNA detected in the liver after treatment relapsed after 4 years. In another study, none of the 17 patients with negative HCV-RNA detected in the liver after treatment relapsed at the end of 12 years.

On the other hand, only two of the 17 patients with negative HCV-RNA resulting from IFN+ribavirin had negative HCV-RNA in all of their body components including hepatocyte, serum, peripheral blood mononuclear cell, lymphocyte, and macrophage cultures. This suggests that there is a probability of relapse after many years.

The clinical significance of low-level HCV-RNA persistence is unknown and further studies must be performed for this issue. For two of our 196 patients with SVR, HCV-RNA was determined to be positive at a low level at months 18 and 48; however, when both observations were repeated after 3 months they were noted to be negative. The exact reason for transient positivity of HCV-RNA was not clear. It was determined that patients with SVR demonstrated truly durable viral responses and relapsed patients had intermittent and low-grade viraemia.

SVR presumably prevents HCC development. None of our patients with SVR demonstrated HCC on long term follow-up. Improvements in liver fibrosis, biochemical indicators, fatigue, and life quality
were detected with SVR. In our batch, no data was available concerning improvements in fibrosis, as there were no adequate end-of-therapy control liver biopsies.

When pretreatment ALT levels were compared with ALT on the last control (101.72±78.84 IU/mL [range, 12 to 465 IU/mL] vs 22.52±11.73 IU/mL [range, 8 to 84 IU/mL]), further improvement was observed (p<0.05).

In conclusion, it was found that patients with SVR in chronic hepatitis C demonstrated truly durable responses in the long term follow-up period of 3 years on average and that there was no complication related with liver disease throughout this period

Gut and Liver 2013 Jul; 7(4): 458-461/ Download Full Text

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