Attacking the public health crisis of hepatocellular carcinoma at its roots.

As the third most common cause of cancer-related death worldwide with significant mortality rates in the United States, hepatocellular carcinoma has strong association with cirrhosis and chronic hepatitis B virus (HBV) with a growing at-risk population from the rise in chronic liver disease from alcohol use and nonalcoholic fatty liver disease. Despite this, progress in identifying at-risk individuals and early detection of HCC in these populations have lagged behind treatment advances.The lack of consensus may undermine widespread adoption of surveillance programs, thus preventing HCC detection at a curable stage. This public policy corner piece focuses on opportunities for prevention of HCC by focusing on its principal risk factors: viral hepatitis, NAFLD, and alcohol-related liver disease, and three key action points to reverse the course of this public health crisis: 1) Awareness and education; 2) Screening and diagnosis, and 3) Partnerships and advocacy.

Prevalence and correlates of hepatitis C virus-associated inflammatory arthritis in a population-based cohort.

OBJECTIVES: The objectives of this study were to determine the prevalence of hepatitis C virus-associated inflammatory arthritis, to describe its clinical and immunologic correlates, and to identify features that are characteristic of arthritis in chronic hepatitis C. METHODS: Participants with chronic hepatitis C infection enrolled in a population-based cohort study in Alaska and who had not received anti-viral treatment for hepatitis C were recruited. In a cross-sectional study, we assessed joint symptoms and signs, performed autoantibody and cytokine testing, and abstracted medical records for features of hepatitis C and arthritis. RESULTS: Of the 117 enrolled participants, 8 (6.8%) had hepatitis C-associated arthritis. The participants with arthritis were younger than those without (median age: 45 vs. 52, p = 0.02). Rheumatoid factor was commonly present among patients with hepatitis C-associated arthritis. The only studied autoantibody found more commonly in patients with HCV arthritis than those without arthritis was anti-nuclear antibody (63% vs. 23%, p = 0.026). The only joint symptom significantly more common in hepatitis C arthritis was self-reported joint swelling (75% vs. 26%, p = 0.007). Features of fibromyalgia were more common and functional status was worse in those with arthritis than those without. No cytokines differed in patients with and without arthritis. There were no associations of arthritis or autoantibodies with liver-related outcomes. CONCLUSIONS: In this study of a cohort of individuals with chronic HCV infection, HCV-associated arthritis was present in less than 10%. Few serologic features distinguished participants with or without arthritis, but self-reported joint swelling was more common in those with arthritis.

Results of interferon-based treatments in Alaska Native and American Indian population with chronic hepatitis C.

BACKGROUND: There have been few reports of hepatitis C virus (HCV) treatment results with interferon-based regimens in indigenous populations. OBJECTIVE: To determine interferon-based treatment outcome among Alaska Native and American Indian (AN/AI) population. DESIGN: In an outcomes study of 1,379 AN/AI persons with chronic HCV infection from 1995 through 2013, we examined treatment results of 189 persons treated with standard interferon, interferon plus ribavirin, pegylated interferon plus ribavirin and triple therapy with a protease inhibitor. For individuals treated with pegylated interferon and ribavirin, the effect of patient characteristics on response was also examined. RESULTS: Sustained virologic response (SVR) with standard interferon was 16.7% (3/18) and with standard interferon and ribavirin was 29.7% (11/37). Of 119 persons treated with pegylated interferon and ribavirin, 61 achieved SVR (51.3%), including 10 of 46 with genotype 1 (21.7%), 38 of 51 with genotype 2 (74.5%) and 13 of 22 with genotype 3 (59.1%). By multivariate analysis, SVR in the pegylated interferon group was associated with female sex (p=0.002), estimated duration of infection (p=0.034) and HCV genotype (p<0.0001). There was a high discontinuation rate due to side effects in those treated with pegylated interferon and ribavirin for genotype 1 (52.2%). Seven of 15 genotype 1 patients treated with pegylated interferon, ribavirin and telaprevir or boceprevir achieved SVR (46.7%). CONCLUSIONS: We had success with pegylated interferon-based treatment of AN/AI people with genotypes 2 and 3. However, there were low SVR and high discontinuation rates for those with genotype 1.

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.

Factors associated with the progression of fibrosis on liver biopsy in Alaska Native and American Indian persons with chronic hepatitis C.

BACKGROUND: Various factors influence the development and rate of fibrosis progression in chronic hepatitis C virus (HCV) infection. OBJECTIVES: To examine factors associated with fibrosis in a longterm outcomes study of Alaska Native/American Indian persons who underwent liver biopsy, and to examine the rate of fibrosis progression in persons with subsequent biopsies. METHODS: A cross-sectional analysis of the demographic, inflammatory and viral characteristics of persons undergoing liver biopsy compared individuals with early (Ishak fibrosis score of lower than 3) with those with advanced (Ishak score of 3 or greater) fibrosis. Persons who underwent two or more biopsies were analyzed for factors associated with fibrosis progression. RESULTS: Of 253 HCV RNA-positive persons who underwent at least one liver biopsy, 76 (30%) had advanced fibrosis. On multivariate analysis, a Knodell histological activity index score of 10 to 14 and an alpha-fetoprotein level of 8 ng/mL or higher were found to be independent predictors of advanced liver fibrosis (P<0.0001 for each). When surrogate markers of liver inflammation (alanine aminotransferase, aspartate aminotransferase/alanine aminotransferase ratio and alpha-fetoprotein) were removed from the model, type 2 diabetes mellitus (P=0.001), steatosis (P=0.03) and duration of HCV infection by 10-year intervals (P=0.02) were associated with advanced fibrosis. Among 52 persons who underwent two or more biopsies a mean of 6.2 years apart, the mean Ishak fibrosis score increased between biopsies (P=0.002), with progression associated with older age at initial biopsy and HCV risk factors. CONCLUSIONS: The presence of type 2 diabetes mellitus, steatosis and duration of HCV infection were independent predictors of advanced fibrosis in the present cohort, with significant fibrosis progression demonstrated in persons who underwent serial biopsies.