Effects of interferon therapy in “non responder” patients with chronic hepatitis C

Poynard, Thierry; Moussali, Joseph; Ratziu, Vlad; Regimbeau, C.; Opolon, P

doi:10.1016/s0168-8278(99)80397-3

Cited by 24 publications

(20 citation statements)

References 34 publications

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“…Although a biochemical sustained response without clearance of HCV-RNA is regarded as an ephemeral result portending future relapse of disease, the prolonged improvement of cytolysis induced by re-treatment in some patients may nevertheless be of clinical benefit in reducing progression to cirrhosis. [20][21][22] In accordance with previous reports, 23,24 our study showed that young age and genotype other than 1 are strong predictive factors of sustained response; we also confirmed 17 that the beneficial effect of combination therapy is extended to patients with advanced fibrosis or cirrhosis.…”

Section: Discussionsupporting

confidence: 91%

A Randomized 4–Arm Multicenter Study of Interferon Alfa-2B Plus Ribavirin in the Treatment of Patients With Chronic Hepatitis C Not Responding to Interferon Alone

et al. 2001

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To determine whether a higher dosage of interferon (IFN) associated with ribavirin and/or prolonged time of administration may improve therapeutic efficacy, we conducted a 4-arm randomized trial on patients with chronic hepatitis C not responding to one or more previous treatment courses with IFN monotherapy. Group 1 (n ‫؍‬ 139) received 3 million units (MU) IFN-␣2b 3 times a week (t.i.w.) plus ribavirin 1,000 mg/d for 12 months; group 2 (n ‫؍‬ 162) received 5 MU t.i.w. plus ribavirin for 12 months; group 3 (n ‫؍‬ 142) received 3 MU t.i.w. plus ribavirin for 6 months; and group 4 (n ‫؍‬ 151) received 5 MU t.i.w. plus ribavirin for 6 months. The primary end point was hepatitis C virus (HCV)-RNA clearance at the end of 6-month follow-up. HCV-RNA was negative in 15% of group 1, 23% of group 2, 11% of group 3, 16% of group 4 (group 2 vs. group 3, P ‫؍‬ .04). Among patients with genotypes 1 and 4, sustained response was significantly higher in group 2 vs. group 3 (18% vs. 7%, P ‫؍‬ .03; group 1 ‫؍‬ 9%, group 4 ‫؍‬ 12%, P ‫؍‬ not significant [NS]). In patients with genotypes 2 and 3, sustained virologic response was not affected by the different regimens (group 1 ‫؍‬ 32%, group 2 ‫؍‬ 30%, group 3 ‫؍‬ 30%, group 4 ‫؍‬ 35%, P ‫؍‬ NS). In conclusion, about 23% of nonresponders to IFN monotherapy may achieve a sustained response if Combination therapy (interferon [IFN] plus ribavirin) is the first-line therapy for naive patients with chronic hepatitis C 1,2 ; patients who have relapsed after an initial treatment with IFN alone can also be re-treated with good results. 3 Unfortunately, there is no therapeutic option for patients who have not responded to IFN and to date consensus conferences 4,5 have not recommended any therapeutic schedule for IFN nonresponders; these patients nevertheless represent a high percentage of patients.Re-treatment of nonresponders with higher dosages of IFN and/or more aggressive approaches is ineffective 5 or induces a low rate of sustained responders 6 ; recent trials with IFN plus ribavirin combination protocols 7-11 have given disappointing results, but the small number of patients recruited into the studies and the low dosage of IFN used have made the results questionable.To address the question of whether higher than standard IFN dosages associated with ribavirin and/or prolonged time of administration may improve the rate of sustained responses, we conducted a 4-arm randomized trial on patients with chronic hepatitis C not responding to one or more previous treatment courses with IFN alone. The study was designed to compare the efficacy and safety of IFN given at 3 million units (MU) and 5 MU 3 times a week (t.i.w.) plus ribavirin 1,000 mg given daily over treatment durations of 6 and 12 months. PATIENTS AND METHODSDefinition of Nonresponse. According to the Consensus Conference held in Paris, February 26 to 27,1999, nonresponse to IFN monotherapy is defined by abnormal alanine transaminase (ALT) levels or by the presence of hepatitis C virus (HCV)-RNA during therapy; breakthroughs durin...

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Section: Discussionsupporting

confidence: 91%

A Randomized 4–Arm Multicenter Study of Interferon Alfa-2B Plus Ribavirin in the Treatment of Patients With Chronic Hepatitis C Not Responding to Interferon Alone

et al. 2001

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“…This is supported by the fact that in our study, treated patients with a virological or a biochemical response had better overall survival than treated patients without a virological or a biochemical response. This result, consistent with the results of similar studies previously reported in the literature (21,25,26), reinforces the hypothesis that survival is causally related to the effect of treatment and that the better survival observed in non-SVR patients than untreated patients is not due to a bias of indication.…”

Section: Discussionsupporting

confidence: 93%

Impact of Treatment against Hepatitis C Virus on Overall Survival of Naive Patients with Advanced Liver Disease

Kutala

Guedj

Asselah

et al. 2015

Antimicrob Agents Chemother

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The beneficial effect of achieving a sustained virological response (SVR) after antiviral treatment against hepatitis C virus is well established. However, it remains unclear whether unsuccessful treatment (non-SVR) also improves patient survival, especially in patients with advanced liver fibrosis. We retrospectively evaluated the incidence of death or liver transplantation in the 427 naive patients with a Child-Pugh score of A and advanced fibrosis newly admitted to the Hospital Beaujon between 2000 and 2010. Patients were followed for a median time of 5.5 years. The baseline characteristics of untreated (n ‫؍‬ 102) and treated (n ‫؍‬ 325) patients were largely similar, and there was no evidence of a bias of indication. Treated patients received a combination of interferon and ribavirin and had an SVR rate of 32%. The incidence of death or liver transplantation per 100 person-years was 1.00, 3.20, and 5.44 in SVR, non-SVR, and untreated patients, respectively. After adjusting for baseline characteristics, the risk of death or liver transplantation was significantly lower in SVR than in non-SVR patients and in non-SVR than in untreated patients (hazard ratios, 0.35 and 0.51, respectively; P ‫؍‬ 0.019 and 0.038, respectively). The effect of treatment in non-SVR patients was higher in patients who had a virological or a biochemical response than in those who did not have a virological or a biochemical response. The risk of death or liver transplantation was significantly lower in treated than in untreated patients. Moreover, there was a gradient of mortality between patients with SVRs, virological or biochemical responders, and untreated patients, suggesting that treatment, even in the absence of viral eradication, has a beneficial effect on survival.

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“…In addition, some studies have shown that treatment with interferon-alpha leads to improved liver histology, mainly reducing inflammation and having a lesser effect on fibrosis [6], especially in patients who show a sustained virological response [7,8]. On the other hand, the influence of the treatment on the improvement of hepatic histology in patients who do not have SVR has shown controversial results [9][10][11][12][13].…”

Section: It Is Known That Human Immunodeficiency Virus (Hiv) May Modimentioning

confidence: 99%

HCV virological response during treatment of chronic hepatitis C is associated with liver histological Improvement in patients with HCV/HIV co-infection

Castro¹,

Ramalho²,

Zucoloto³

et al. 2008

Braz J Infect Dis

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Liver histological improvement after treatment for chronic hepatitis C in patients co-infected with human immunodeficiency virus-1 (HIV-1) has been described. Paired liver biopsies in twenty six HCV/HIV co-infected patients were compared to determine factors possibly associated with histological improvement. The patients were submitted to a liver biopsy before treatment for hepatitis C and 25 months after the end of treatment. Fragments of the liver biopsy obtained before and after treatment were compared regarding the following parameters: histological activity index (HAI) and degree of fibrosis (Knodell); intensity of collagen deposits (Sirius Red staining) and degree of stellate cell activation (alpha-smooth muscle actin labeling). The ratios of the post and pre-treatment variables were related through logistic regression to body mass index (BMI), alcohol ingestion, HCV genotype, HCV viremia, presence of hepatic iron and pre-treatment hepatic steatosis. A negative RNA test in the 24 th week of treatment was associated with improvement in fibrosis, collagen deposits and stellate cell numbers. The other variables analyzed did not correlate to an improvement in hepatic histology after hepatitis C treatment. Reduction in HCV viremia during treatment may result in reduced hepatic fibrosis even in patients without a sustained virological response.

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Effects of interferon therapy in “non responder” patients with chronic hepatitis C

Cited by 24 publications

References 34 publications

A Randomized 4–Arm Multicenter Study of Interferon Alfa-2B Plus Ribavirin in the Treatment of Patients With Chronic Hepatitis C Not Responding to Interferon Alone

A Randomized 4–Arm Multicenter Study of Interferon Alfa-2B Plus Ribavirin in the Treatment of Patients With Chronic Hepatitis C Not Responding to Interferon Alone

Impact of Treatment against Hepatitis C Virus on Overall Survival of Naive Patients with Advanced Liver Disease

HCV virological response during treatment of chronic hepatitis C is associated with liver histological Improvement in patients with HCV/HIV co-infection

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