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

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.

Treatment eligibility in Alaska Native and American Indian persons with hepatitis C virus infection.

OBJECTIVES: Treatment with pegylated interferon and ribavirin may prevent progression of liver disease among patients with chronic hepatitis C virus infection (HCV). Treatment initiation is based on published clinical eligibility criteria, patients' willingness to undergo treatment and likelihood of success. We examined treatment eligibility in a cohort of Alaska Native and American Indian persons with chronic HCV infection. STUDY DESIGN: Retrospective cohort study. METHODS: Medical records of all treatment naïve HCV RNA positive patients given an appointment by hepatology specialty clinic staff in 2003 and 2007 were evaluated by a hepatology provider to investigate documented reasons for treatment deferral. RESULTS: Treatment was initiated in 4 of 94 patients (4%) in 2003 and 14 of 146 patients (10%) in 2007. Major reasons for treatment deferral in 2003 versus 2007 included inconsistent appointment attendance (36% of deferrals vs. 18%), active substance abuse (17% vs. 22%), patient decision (17% vs. 27%), liver biopsy without fibrosis or normal ALT (8% vs. 3%), uncontrolled psychiatric condition (7% vs. 7%) and concurrent medical condition (6% vs. 9%). There was significant improvement in proportion of appointments attended in 2007 versus 2003 (76% vs. 67%, p = 0.04) and the percentage of patients attending at least 1 appointment (84% vs. 66%, p = 0.002). CONCLUSIONS: Multiple reasons for treatment deferral were documented. Despite a significant improvement in hepatology clinic attendance and an increase in the number of patients started on treatment in 2007 compared to 2003, the overall percentage of those treated remained low.

Early radiographic and clinical features associated with bronchiectasis in children.

Bronchiectasis among children living in developing regions is associated with respiratory infections during early childhood, but specific risk factors that precede childhood bronchiectasis are not fully characterized. We hypothesized that severe respiratory syncytial viral (RSV) infection in infancy would increase the risk of bronchiectasis among Alaska Native children in rural Alaska. This was a follow-up cohort study of a 1993-1996 case-control study of RSV-hospitalized case patients and their controls. For each 5-8-year-old former case-patient and control subject, we reviewed medical records, interviewed parents, performed physical examinations and spirometry, collected sera, and analyzed all historical chest radiographs. Ten (11%) RSV cases and 10 (9%) controls had radiographic evidence of bronchiectasis. The mean age at radiographic diagnosis of bronchiectasis was 3.3 years (range, 1.2-6.1 years). Children were more likely to develop bronchiectasis if their chest radiographs, when they were < 2 years of age, showed lung parenchymal densities (RR = 3.9, P < 0.013), persistent parenchymal densities > 6 months' duration (RR = 3.0, P = 0.02), or infiltrates on multiple episodes (test for trend, P = 0.003). Radiographic features of hyperinflation and atelectasis among children < 2 years old were not associated with eventual bronchiectasis. A single severe infection with RSV alone did not predispose Alaska Native infants to bronchiectasis. Childhood bronchiectasis was associated with lung and hence airway injury, manifested on radiographs by parenchymal densities or "pneumonia" rather than by hyperinflation or atelectasis.