Infection With Hepatitis C Virus Genotype 3 Is an Independent Risk Factor for End-Stage Liver Disease, Hepatocellular Carcinoma, and Liver-Related Death

doi:10.1016/j.cgh.2016.10.012

Clinical Gastroenterology and Hepatology

Volume 15, Issue 3, March 2017, Pages 431-437.e2

https://doi.org/10.1016/j.cgh.2016.10.012 Get rights and content

Background & Aims

Few studies have examined factors associated with disease progression in hepatitis C virus (HCV) infection. We examined the association of 11 risk factors with adverse outcomes in a population-based prospective cohort observational study of Alaska Native/American Indian persons with chronic HCV infection.

Methods

We collected data from a population-based cohort study of liver-related adverse outcomes of infection in American Indian/Alaska Native persons with chronic HCV living in Alaska, recruited from 1995 through 2012. We calculated adjusted hazard ratios (aHR) and 95% confidence intervals (CIs) for end-stage liver disease (ESLD; presence of ascites, esophageal varices, hepatic encephalopathy, or coagulopathy), hepatocellular carcinoma (HCC), and liver-related death using a Cox proportional hazards model.

Results

We enrolled 1080 participants followed up for 11,171 person-years (mean, 10.3 person-years); 66%, 19%, and 14% were infected with HCV genotypes 1, 2, and 3, respectively. On multivariate analysis, persons infected with HCV genotype 3 had a significantly increased risk of developing all 3 adverse outcomes. Their aHR for ESLD was 2.1 (95% CI, 1.5–3.0), their aHR for HCC was 3.1 (95% CI, 1.4–6.6), and their aHR for liver-related death was 2.4 (95% CI, 1.5–4.0) compared with genotype 1. Heavy alcohol use was an age-adjusted risk factor for ESLD (aHR, 2.2; 95% CI, 1.6–3.2), and liver-related death (aHR, 2.9; 95% CI, 1.8–4.6). Obesity was a risk factor for ESLD (aHR, 1.4; 95% CI, 1.0–1.9), and diabetes was a risk factor for ESLD (aHR, 1.5; 95% CI, 1.1–2.2). Male sex was a risk factor for HCC (aHR, 3.6; 95% CI, 1.6–8.2).

Conclusions

In a population-based cohort study of American Indian/Alaska Native persons with chronic HCV infection, we found those infected with HCV genotype 3 to be at high risk for ESLD, HCC, and liver-related death.

Section snippets

Methods

The Alaska Native Tribal Health Consortium coordinates Alaska Tribal Health System health care throughout the state of Alaska. Further details of the population and health care delivery system have been described previously and in the Supplementary Tables 1 and 2.⁴ Electronic health records are used in these statewide Tribal facilities. Testing for anti-HCV was conducted at the laboratory at the Alaska Native Medical Center (ANMC); all positive results were reflexed automatically for HCV RNA

Results

Among 1132 persons found to have chronic HCV through 2012, 1080 (95.4%) were enrolled. Table 1 provides the demographic, risk factors, clinical, social, and laboratory characteristics of this cohort. Two thirds of participants (66%) were infected with HCV genotype 1, 90% were infected with HCV genotype 1a, and 19% and 14% were infected with HCV genotypes 2 and 3, respectively. At study entry, 22% of genotype 3 patients had an increased APRI score (≥1.5), which did not differ from 21% and 23% in

Discussion

The AK-HEPC study was a large and long population-based cohort study to examine the long-term outcome of chronic HCV infection. This population-based study of more than 1000 participants (94% of the known Alaska Native persons with chronic HCV infection in the state), followed up for 11,171 person-years, a mean of more than 10 years, was designed to examine prospectively the adverse events resulting from HCV infection. The study encompassed a large amount of clinical and laboratory data coupled

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: Conflicts of interest These authors disclose the following: Brenna Simons, James Gove, Julia Plotnik, and Youssef Barbour have received research support from Gilead Sciences. The remaining authors disclose no conflicts.

: Funding This work was supported by the Centers for Disease Control and Prevention (U01 PS001097). The findings and conclusions in this article are those of the authors and do not necessarily represent the official positions of the US Centers for Disease Control and Prevention.

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Original articlePancreas, biliary tract, and liverInfection With Hepatitis C Virus Genotype 3 Is an Independent Risk Factor for End-Stage Liver Disease, Hepatocellular Carcinoma, and Liver-Related Death

Background & Aims

Methods

Results

Conclusions

Section snippets

Methods

Results

Discussion

Gastroenterology

Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence

Hepatology

The increasing burden of mortality from viral hepatitis in the United States between 1999 and 2007

Ann Intern Med

The prevalence of hepatitis C virus infection in the United States, 1988 through 1994

N Engl J Med

Epidemiology and risk factors for hepatitis C in Alaska natives

Hepatology

Adverse outcomes in Alaska natives who recovered from or have chronic hepatitis C infection

Gastroenterology

An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011 Practice Guideline by the American Association for the Study of Liver Diseases

Hepatology

Original article
Pancreas, biliary tract, and liver
Infection With Hepatitis C Virus Genotype 3 Is an Independent Risk Factor for End-Stage Liver Disease, Hepatocellular Carcinoma, and Liver-Related Death