What is Killing People With Hepatitis C Virus Infection?

JasonGrebely, B.Sc., Ph.D.; Gregory J.Dore, M.B.B.S., Ph.D., F.R.A.C.P., M.P.H.

Disclosures

Semin Liver Dis. 2011;31(4):331-339. 

In This Article

Abstract and Introduction

Abstract

The burden of hepatitis C virus (HCV)-related morbidity and mortality continues to rise. Progression to advanced liver disease among HCV-infected individuals generally requires decades, but we are entering an era where those infected with HCV in the 1970s and 1980s are at significant risk of mortality. Liver disease has overtaken drug-related harm as the major cause of mortality in HCV-infected individuals in many settings. Direct-acting antiviral therapies have provided renewed optimism, but HCV treatment uptake will need to increase markedly to reduce liver disease mortality. This review provides updated information on the natural history of HCV, disease-specific causes of mortality among people with HCV, estimates and projections of HCV-related disease burden and mortality and individual and population-level strategies to reduce mortality. The considerable variability in mortality rates within subpopulations of people with HCV will be outlined, such as in people who inject drugs and those with HIV co-infection.

Introduction

The next decade will be a crucial period in the public health response to hepatitis C virus (HCV) infection. The rapid development of direct-acting antiviral (DAA) therapy for chronic HCV infection has brought considerable optimism to the HCV sector,[1] with the realistic hope that therapeutic intervention will soon be more effective and offer shorter treatment duration. The initial phase of combination pegylated interferon (PEG-IFN), ribavirin, and one or more DAA agents will be associated with increased toxicity and complexity of therapeutic management,[1] but over the course of this decade, strategies including interferon-free regimens with enhanced tolerability, dosing schedules, and simplified monitoring protocols should emerge.

These therapeutic advances are urgently required, as a high HCV incidence 20 to 30 years ago is now reflected in a growing burden of advanced HCV-related liver disease.[2–8] Without effective therapeutic intervention, the projected liver disease burden will continue to rise in many countries,[9–14] for at least the next one to two decades, and beyond in those settings that have experienced ongoing high-level HCV transmission.

Despite the prospect of greatly improved therapies, the challenges ahead for HCV infection are considerable. HCV treatment uptake is very low in many countries[12,15,16] and within marginalized subpopulations in countries with higher treatment uptake.[16–20] The explanations for low uptake are multifactorial[21] and not the focus of this review, but interferon-related toxicity, lack of HCV treatment infrastructure, suboptimal government subsidization programs and medical insurance coverage, as well as competing patient health and social priorities are likely to remain as contributing factors in the near future.

An improved understanding of morbidity and mortality among people with HCV infection will guide clinical management and therapy decision-making, both at the individual patient and population strategic levels. This review will provide updated information on the natural history of HCV infection, disease-specific causes of mortality among people with HCV infection, estimates and projections of HCV-related disease burden and mortality, the potential impact of HCV treatment on disease burden, and individual and population-level strategies to reduce mortality. The considerable variability in mortality rates within subpopulations of people with HCV will be outlined, and a particular focus given to the issue of competing mortality risk among people who inject drugs and those with human immunodeficiency virus (HIV) co-infection.

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