A Sustained Virologic Response Is Durable in Patients With Chronic Hepatitis C Treated With Peginterferon Alfa-2a and Ribavirin

doi:10.1053/j.gastro.2010.07.009

Gastroenterology

Volume 139, Issue 5, November 2010, Pages 1593-1601

https://doi.org/10.1053/j.gastro.2010.07.009 Get rights and content

Background & Aims

A sustained virologic response (SVR) to therapy for hepatitis C virus (HCV) infection is defined as the inability to detect HCV RNA 24 weeks after completion of treatment. Although small studies have reported that the SVR is durable and lasts for long periods, it has not been conclusively shown.

Methods

The durability of treatment responses was examined in patients originally enrolled in one of 9 randomized multicenter trials (n = 1343). The study included patients who received pegylated interferon (peginterferon) alfa-2a alone (n = 166) or in combination with ribavirin (n = 1077, including 79 patients with normal alanine aminotransferase levels and 100 patients who were coinfected with human immunodeficiency virus and HCV) and whose serum samples were negative for HCV RNA (<50 IU/mL) at their final assessment. Patients were assessed annually, from the date of last treatment, for a mean of 3.9 years (range, 0.8–7.1 years).

Results

Most patients (99.1%) who achieved an SVR had undetectable levels of HCV RNA in serum samples throughout the follow-up period. Serum samples from 0.9% of the patients contained HCV RNA a mean of 1.8 years (range, 1.1–2.9 years) after treatment ended. It is not clear if these patients were reinfected or experienced a relapse.

Conclusions

In a large cohort of patients monitored for the durability of an SVR, the SVR was maintained for almost 4 years after treatment with peginterferon alfa-2a alone or in combination with ribavirin. In patients with chronic hepatitis C infection, the SVR is durable and these patients should be considered as cured.

Section snippets

Patients and Methods

Patients were eligible for the long-term follow-up study if they were previously enrolled in one of 10 clinical trials.16, 17, 20, 24, 25, 26, 27, 28, 29, 30

Patients were not eligible for inclusion in the long-term follow-up study if they had been treated with anti-HCV therapy other than those medications assigned in the original protocol since enrolling in the original trials; were unable or unwilling to provide informed consent or abide by the requirements of the study; and had a history or

Results

This long-term follow-up study recruited 1753 patients from 198 centers in 19 countries. The first patient was enrolled in May 2000, and the last patient's final visit was in February 2008.

Discussion

The present study represents the largest prospective cohort of patients followed up for the durability of SVR among patients previously treated for hepatitis C infection. The main finding of this long-term follow-up study in more than 1300 patients is that an SVR achieved with peginterferon alfa-2a, alone or in combination with ribavirin, is durable over the long-term and recurrence of HCV RNA is extremely rare. Overall, 99.1% of patients who achieved an SVR after treatment remained HCV RNA

Acknowledgments

The authors thank Health Interactions for editorial support.

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2023, Comprehensive Guide to Hepatitis Advances
Hepatitis C remains a major global health problem, with an estimated 58 million people infected worldwide and 1.5 million new infections occurring every year (World Health Organisation, 2022) [1]. If left untreated, hepatitis C can establish chronic infection in the liver, leading to hepatitis, liver cirrhosis, and hepatocellular carcinoma (Westbrook and Dusheiko, 2014) [2]. Over the past 10 years, treatment of this condition has been revolutionized by the introduction of highly potent directly acting antivirals that can achieve a sustained virological response in over 95% of patients (Feld et al., 2015; Foster et al., 2015; Curry et al., 2015; Wei et al., 2020) [[3], [4], [5], [6]]. These agents are orally administered and have a favorable side-effect profile, but access remains limited in many low- and middle-income countries. Furthermore, inadequate screening programs and a global deficiency in quality-assured diagnostic tests mean that approximately 80% of infected individuals are currently unaware of their diagnosis (World Health Organisation, 2020) [7]. In response to these challenges, the World Health Organisation set out a Global Health Strategy with the aim of reducing new viral hepatitis infections by 90% by the year 2030 (World Health Organisation, 2016) [8]. In this chapter, we will describe the evolution of antiviral therapies over the past few decades, outline the treatment of special populations, and explore barriers to achieving the elimination of the virus on a global scale.
Risk of hepatitis C reinfection following successful therapy among people living with HIV: a global systematic review, meta-analysis, and meta-regression
2022, The Lancet HIV
Citation Excerpt :
In studies using end of treatment to indicate the beginning of the time at risk of HCV reinfection, HCV RNA recurrence was considered to be reinfection if HCV sequencing or genotype data were used to confirm detection of infection with an HCV strain, subtype, or genotype distinct from the virus before treatment. In the studies using sustained virological response to indicate the beginning of the time at risk of HCV reinfection, any HCV RNA recurrence was considered to be reinfection, given the low likelihood of viral relapse after sustained virological response.9,10 For each included study, the incidence of HCV reinfection was calculated using the reported number of reinfection cases and person-years of follow-up.
The benefits of direct-acting antivirals towards the elimination of hepatitis C virus (HCV) in people living with HIV are decreased when individuals are reinfected with HCV following treatment. We aimed to systematically review the existing evidence of HCV reinfection risk after treatment among people living with HIV, including people who inject drugs and men who have sex with men (MSM), and to identify the factors that explain heterogeneity in the incidence of HCV reinfection.
For this systematic review and meta-analysis, we searched PubMed, Scopus, Web of Science, Cochrane, PsycINFO, and conference presentations from date of database inception to Jan 10, 2022, for clinical trials and cohort studies providing data that could be used to calculate the incidence of HCV reinfection following HCV treatment. Random-effect meta-analysis models were used to calculate rate estimates. Study-level factors contributing to heterogeneity of reinfection estimates were assessed using meta-regression. This study is registered with PROSPERO, CRD42019146973.
41 studies, predominantly conducted in Europe, were included, with a total of 9024 participants. The incidence of reinfection was 3·76 cases per 100 person-years of follow-up (95% CI 2·80–5·05; I² 85·9%) among people living with HIV overall, 6·01 (4·54–7·95; 74·1%) among MSM, and 3·29 (2·01–5·39; 83·9%) among people who inject drugs. A similar incidence of reinfection was observed following interferon-based therapy (4·92 cases per 100 person-years of follow-up, 3·30–7·32; I² 78·3%) and direct-acting antiviral therapy (3·88, 2·51–6·01; 85·4%). A higher proportion (≥85%) of MSM in the study population (adjusted rate ratio 2·66, 95% CI 1·37–5·15) and recent HCV infection (2·22, 1·09–4·55) were associated with an increased incidence of reinfection; a longer duration of follow-up after treatment (0·97, 0·96–0·99) was associated with a decreased incidence.
Risk of HCV reinfection following treatment in people living with HIV was highest among MSM and those with recent HCV infection. Continued scale-up of HCV treatment and ongoing HCV screening and treatment of infection in this patient population should reduce viraemic burden and risk of reinfection.
None.
Chronic Hepatitis B Virus in Patients with Chronic Hepatitis C Virus
2021, Clinics in Liver Disease
EASL recommendations on treatment of hepatitis C: Final update of the series<sup>☆</sup>
2020, Journal of Hepatology
Citation Excerpt :
In settings where sensitive HCV RNA assays are not available and/or not affordable, a qualitative assay with a lower limit of detection ≤1,000 IU/ml (3.0 Log10 IU/ml) can be used to assess SVR12 or SVR24. Long-term follow-up studies have shown that an SVR corresponds to a definitive cure of HCV infection in the vast majority of cases.5,93 In patients with advanced fibrosis (METAVIR score F3) and cirrhosis (F4), an SVR reduces the rate of decompensation and will also reduce, but not abolish, the risk of HCC.12
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease, with approximately 71 million chronically infected individuals worldwide. Clinical care for patients with HCV-related liver disease has advanced considerably thanks to an enhanced understanding of the pathophysiology of the disease, as well as developments in diagnostic procedures and improvements in therapy and prevention. These therapies make it possible to eliminate hepatitis C as a major public health threat, as per the World Health Organization target, although the timeline and feasibility vary from region to region. These European Association for the Study of the Liver recommendations on treatment of hepatitis C describe the optimal management of patients with recently acquired and chronic HCV infections in 2020 and onwards.
Hepatitis C reinfection after successful antiviral treatment among people who inject drugs: A meta-analysis
2020, Journal of Hepatology
Citation Excerpt :
In most studies, all cases of recurrent viraemia following SVR were considered as reinfection. Although post-SVR HCV relapse is rare,17,18 without using HCV sequencing it is not possible to fully distinguish reinfection from late relapse. In several studies, reinfection was diagnosed on the basis of detection of recurrent viraemia with different HCV genotype/subtype.
HCV reinfection following successful treatment can compromise treatment outcomes. This systematic review assessed the rate of HCV reinfection following treatment among people with recent drug use and those receiving opioid agonist therapy (OAT).
We searched bibliographic databases and conference abstracts for studies assessing post-treatment HCV reinfection rates among people with recent drug use (injecting or non-injecting) or those receiving OAT. Meta-analysis was used to cumulate reinfection rates and meta-regression was used to explore heterogeneity across studies.
Thirty-six studies were included (6,311 person-years of follow-up). The overall rate of HCV reinfection was 5.9/100 person-years (95% CI 4.1–8.5) among people with recent drug use (injecting or non-injecting), 6.2/100 person-years (95% CI 4.3–9.0) among people recently injecting drugs, and 3.8/100 person-years (95% CI 2.5–5.8) among those receiving OAT. Reinfection rates were comparable following interferon-based (5.4/100 person-years; 95% CI 3.1–9.5) and direct-acting antiviral (3.9/100 person-years; 95% CI 2.5–5.9) therapy. In stratified analysis, reinfection rates were 1.4/100 person-years (95% CI 0.8–2.6) among people receiving OAT with no recent drug use, 5.9/100 person-years (95% CI 4.0–8.6) among people receiving OAT with recent drug use, and 6.6/100 person-years (95% CI 3.4–12.7) among people with recent drug use not receiving OAT. In meta-regression analysis, longer follow-up was associated with lower reinfection rate (adjusted rate ratio [aRR] per year increase in mean/median follow-up 0.77; 95% CI 0.69–0.86). Compared with people receiving OAT with no recent drug use, those with recent drug use receiving OAT (aRR 3.50; 95% CI 1.62–7.53), and those with recent drug use not receiving OAT (aRR 3.96; 95% CI 1.82–8.59) had higher reinfection rates.
HCV reinfection risk following treatment was higher among people with recent drug use and lower among those receiving OAT. The lower rates of reinfection observed in studies with longer follow-up suggested higher reinfection risk early post-treatment.
Our findings demonstrate that although reinfection by hepatitis C virus occurs following successful treatment in people with recent drug use, the rate of hepatitis C reinfection is lower than the rates of primary infection reported in the literature for this population – reinfection should not be used as a reason to withhold therapy from people with ongoing injecting drug use. The rate of hepatitis C reinfection was lowest among people receiving opioid agonist therapy with no recent drug use. These data illustrate that harm reduction services are required to reduce the reinfection risk, while regular post-treatment hepatitis C assessment is required for early detection and retreatment.
Trends in long-term outcomes of patients with HCV-associated hepatocellular carcinoma after hepatectomy: A comparison before and after introduction of direct-acting antivirus therapy
2024, Annals of Gastroenterological Surgery

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: Conflicts of interest The authors disclose the following: Prof Swain has served on advisory boards for Roche and Gilead and received research or grant support from Roche, Gilead, Bristol-Myers Squibb, Novartis, Merck, Schering-Plough, Intercept Pharma, and Boehringer Ingelheim. Prof Shiffman has served on advisory committees or review panels for Gilead, Schering-Plough, Anadys, Vertex, Biolex, Human Genome Sciences, Novartis, and ZymoGenetics; served as a consultant for Roche and Pfizer; received research grant support from Roche, Schering-Plough, Vertex, Biolex, GlaxoSmithKline, GlobeImmune, Human Genome Sciences, Idenix, Tibotec, ZymoGenetics, and Gilead; and served on the speaker's bureau for Roche and Schering-Plough. Prof Cooksley has served on the speaker's bureau for Roche. Prof Zeuzem has served as a consultant for Roche and Novartis/Human Genome Sciences, on advisory boards for Roche and Novartis/Human Genome Sciences, and on the speaker's bureau for Roche and Schering-Plough. Prof Dieterich has served on advisory boards, on the speaker's bureau, and as a consultant for Roche, Gilead, Boehringer Ingelheim, Novartis, and Bristol-Myers Squibb. Prof Abergel's research is supported by Roche. Prof Pessôa has served as a consultant for Roche, Bristol-Myers Squibb, and Novartis; served on advisory boards for Roche, Bristol-Myers Squibb, and Novartis; served on the speaker's bureau for Roche and Bristol-Myers Squibb; and received research and travel grants from Roche, Bristol-Myers Squibb, and Novartis. Dr Lin, Dr Tietz, and Dr Connell are employees of Roche. Prof Lai and Prof Diago disclose no conflicts.

: Funding Supported by Roche (Basel, Switzerland).

^†: Deceased.

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Clinical Advances in Liver, Pancreas, and Biliary TractA Sustained Virologic Response Is Durable in Patients With Chronic Hepatitis C Treated With Peginterferon Alfa-2a and Ribavirin

Background & Aims

Methods

Results

Conclusions

Section snippets

Patients and Methods

Results

Discussion

Acknowledgments

Hepatology

J Hepatol

Gastroenterology

J Hepatol

J Hepatol

Gastroenterology

Hepatology

J Hepatol

Sustained virological response to interferon plus ribavirin reduces liver-related complications and mortality in patients coinfected with human immunodeficiency virus and hepatitis C virus

Hepatology

Effect of peginterferon alfa-2a on liver histology in chronic hepatitis C: a meta-analysis of individual patient data

Hepatology

Effects of interferon treatment response on liver complications of chronic hepatitis C: 9-year follow-up study

Am J Gastroenterol

Clinical, virologic, histologic, and biochemical outcomes after successful HCV therapy: a 5-year follow-up of 150 patients

Hepatology

Long-term effect of interferon alpha-2b plus ribavirin therapy on incidence of hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis

J Viral Hepat

Interferon treatment improves survival in chronic hepatitis C patients showing biochemical as well as virological responses by preventing liver-related death

J Viral Hepat

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

Long term clinical outcome of chronic hepatitis C patients with sustained virological response to interferon monotherapy

Gut

Sustained responders have better quality of life and productivity compared with treatment failures long after antiviral therapy for hepatitis C

Am J Gastroenterol

Diagnosis, management, and treatment of hepatitis C: an update

Hepatology

National Institutes of Health Consensus Development Conference Statement: management of hepatitis C: 2002–June 10-12, 2002

Hepatology

Diagnosis, management, and treatment of hepatitis C

Hepatology

Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection

N Engl J Med

Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose

Ann Intern Med

Role of weight-based ribavirin dosing and extended duration of therapy in chronic hepatitis C in HIV-infected patients: the PRESCO trial

AIDS Res Hum Retroviruses

Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients

N Engl J Med

Clinical Advances in Liver, Pancreas, and Biliary Tract
A Sustained Virologic Response Is Durable in Patients With Chronic Hepatitis C Treated With Peginterferon Alfa-2a and Ribavirin