Association Between Sustained Virological Response and All-Cause Mortality Among Patients With Chronic Hepatitis C and Advanced Hepatic Fibrosis

Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 12/2012; 308(24):2584-93. DOI: 10.1001/jama.2012.144878
Source: PubMed


Chronic hepatitis C virus (HCV) infection outcomes include liver failure, hepatocellular carcinoma (HCC), and liver-related death.
To assess the association between sustained virological response (SVR) and all-cause mortality in patients with chronic HCV infection and advanced hepatic fibrosis.
An international, multicenter, long-term follow-up study from 5 large tertiary care hospitals in Europe and Canada of 530 patients with chronic HCV infection who started an interferon-based treatment regimen between 1990 and 2003, following histological proof of advanced hepatic fibrosis or cirrhosis (Ishak score 4-6). Complete follow-up ranged between January 2010 and October 2011.
All-cause mortality. Secondary outcomes were liver failure, HCC, and liver-related mortality or liver transplantation.
The 530 study patients were followed up for a median (interquartile range [IQR]) of 8.4 (6.4-11.4) years. The baseline median (IQR) age was 48 (42-56) years and 369 patients (70%) were men. The Ishak fibrosis score was 4 in 143 patients (27%), 5 in 101 patients (19%), and 6 in 286 patients (54%). There were 192 patients (36%) who achieved SVR; 13 patients with SVR and 100 without SVR died (10-year cumulative all-cause mortality rate, 8.9% [95% CI, 3.3%-14.5%] with SVR and 26.0% [95% CI, 20.2%-28.4%] without SVR; P < .001). In time-dependent multivariate Cox regression analysis, SVR was associated with reduced risk of all-cause mortality (hazard ratio [HR], 0.26; 95% CI, 0.14-0.49; P < .001) and reduced risk of liver-related mortality or transplantation (HR, 0.06; 95% CI, 0.02-0.19; P < .001), the latter occurring in 3 patients with SVR and 103 without SVR. The 10-year cumulative incidence rate of liver-related mortality or transplantation was 1.9% (95% CI, 0.0%-4.1%) with SVR and 27.4% (95% CI, 22.0%-32.8%) without SVR (P < .001). There were 7 patients with SVR and 76 without SVR who developed HCC (10-year cumulative incidence rate, 5.1%; 95% CI, 1.3%-8.9%; vs 21.8%; 95% CI, 16.6%-27.0%; P < .001), and 4 patients with SVR and 111 without SVR experienced liver failure (10-year cumulative incidence rate, 2.1%; 95% CI, 0.0%-4.5%; vs 29.9%; 95% CI, 24.3%-35.5%; P < .001).
Among patients with chronic HCV infection and advanced hepatic fibrosis, sustained virological response to interferon-based treatment was associated with lower all-cause mortality.

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    • "More likely, this association may have been accounted for by the known relationship between overweight (leading to steatosis) and HCC [29]. On the other hand, HCV genotype 3 infection is indeed associated with an increased risk for HCC [21] [30] [31], but whether this is due to viral steatosis is unknown. Association does not imply causation and, besides, steatosis is often reduced or absent in late stages of liver disease, i.e., at the time HCC occurs [32] [33] [34]. "
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    ABSTRACT: The hepatitis C virus (HCV) is a major cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma worldwide. A significant portion of the morbidity and mortality associated with HCV is a consequence of numerous HCV-associated comorbidities. Type 2 diabetes and atherosclerosis, two known complications of the metabolic syndrome, are noteworthy, because HCV has been suggested to play a role in their pathogenesis. In addition, HCV also causes steatosis, which may increase the risk of cardiovascular events. This review summarizes the evidence supporting the association between HCV and steatosis, insulin resistance/type 2 diabetes and cardiovascular morbidity and mortality. Their diagnostic, prognostic and management aspects are discussed.
    Preview · Article · Nov 2014 · Journal of Hepatology
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    • "It must be added that HCV is widely under documented on death certificates [8] and therefore a true appreciation of the HCV-related health burden is lacking. In addition, the clinical impact of some extrahepatic disorders, leading to renal, cardiac and cerebrovascular outcomes associated with cryoglobulinemia and diabetes, has been emphasized only recently [4] [5] [9] [10] and traditionally neglected in cost-effectiveness analyses. Safe and effective drugs are now available, although their cost will impose prioritization in their allocation. "
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    ABSTRACT: The advent of potent and safe direct-acting antivirals against the hepatitis C virus has the potential of fulfilling the dream of eliminating this infection and its impact on global public health. However, even if effective drugs are at hand, most patients remain unaware of their infection, which may be recognized only in late stages when dire complications have occurred. Europe is not spared by this scourge, with its estimated 19,000,000 persons infected, and knowledge of the epidemiology of HCV and its drivers is a critical tool in fighting this virus. A thorough review is provided on the extent of the HCV epidemic across Europe, with a discussion of the most important subgroups affected, and of the risk factors of infection, both traditional and new.
    Preview · Article · Oct 2014 · Digestive and Liver Disease
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    • "Antiviral treatment of chronic HCV aims to produce a sustained virological response (SVR), defined as undetectable levels of HCV RNA 12 or 24 weeks after treatment. SVR is associated with reduced all-cause [5] and liver-related mortality [5,6], and HCC rates [7]. Dual therapy with pegylated interferon (peg-IFN) and ribavirin produces SVR in approximately 80% of genotype 2 and 3 infections and 40-50% for genotype 1 [8,9]. "
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    ABSTRACT: Background The societal, clinical and economic burden imposed by the complications of chronic hepatitis C virus (HCV) infection - including cirrhosis and hepatocellular carcinoma (HCC) - is expected to increase over the coming decades. However, new therapies may improve sustained virological response (SVR) rates and shorten treatment duration. This study aimed to estimate the future burden of HCV-related disease in England if current management strategies remain the same and the impact of increasing diagnosis and treatment of HCV as new therapies become available. Methods A previously published model was adapted for England using published literature and government reports, and validated through an iterative process of three meetings of HCV experts. The impact of increasing diagnosis and treatment of HCV as new therapies become available was modelled and compared to the base-case scenario of continuing current management strategies. To assess the ‘best case’ clinical benefit of new therapies, the number of patients treated was increased by a total of 115% by 2018. Results In the base-case scenario, total viraemic (HCV RNA-positive) cases of HCV in England will decrease from 144,000 in 2013 to 76,300 in 2030. However, due to the slow progression of chronic HCV, the number of individuals with cirrhosis, decompensated cirrhosis and HCC will continue to increase over this period. The model suggests that the ‘best case’ substantially reduces HCV-related hepatic disease and HCV-related liver mortality by 2020 compared to the base-case scenario. The number of HCV-related HCC cases would decrease 50% by 2020 and the number progressing from infection to decompensated cirrhosis would decline by 65%. Therefore, compared to projections of current practices, increasing treatment numbers by 115% by 2018 would reduce HCV-related mortality by 50% by 2020. Conclusions This analysis suggests that with current treatment practices the number of patients developing HCV-related cirrhosis, decompensated cirrhosis and HCC will increase substantially, with HCV-related liver deaths likely to double by 2030. However, increasing diagnosis and treatment rates could optimise the reduction in the burden of disease produced by the new therapies, potentially halving HCV-related liver mortality and HCV-related HCC by 2020.
    Full-text · Article · Aug 2014 · BMC Gastroenterology
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