Barriers to hepatitis C treatment in the era of direct-acting anti-viral agents.

BACKGROUND: Direct-acting anti-virals (DAA) are safe, effective treatment of hepatitis C virus (HCV). Suboptimal linkage to specialists and access to DAAs are the leading barriers to treatment; however, data are limited. AIM: To determine predictors of follow-up, receipt of DAAs, and reasons for the lack thereof. METHODS: We used clinical data from retrospective cohort of HCV-infected patients with previously established HCV care in the US Department of Veterans Affairs to examine predictors of follow-up in HCV clinics and DAA treatment (during 12/1/2013-4/30/2015). We then conducted a structured review of medical charts of HCV patients to determine reasons for lack of follow-up and treatment. RESULTS: We identified 84 221 veterans who were previously seen in HCV clinics during the pre-DAA era. Of these, 47 165 (56.0%) followed-up in HCV specialty clinics, 13 532 (28.7%) of whom received DAAs. Older age, prior treatment, presence of cirrhosis or HCC, HIV/HBV co-infection and psychiatric illness were predictors of follow-up. Alcohol/drug abuse and medical co-morbidity were predictors of lack of treatment. Of the 905 prospectively recruited patients, 56.2% patients had a specialist visit and 28% received DAAs. Common reasons for lack of follow-up were relocation (n = 148, 37.4%) and missed/cancelled appointments (n = 63, 15.9%). Reasons for lack of treatment included waiting for newer therapy (n = 99, 38.8%), co-morbidities (n = 66, 25.9%) and alcohol/drug abuse (n = 63, 24.7%). CONCLUSIONS: Half of patients with established HCV care were followed-up in the DAA era and only 29% received DAAs. Targeted efforts focusing on patient and system-levels may improve the reach of treatment with the new DAAs.

The association between serological and dietary vitamin D levels and hepatitis C-related liver disease risk differs in African American and white males.

BACKGROUND: Vitamin D may affect the severity of HCV-related liver disease. AIM: To examine the association between serum vitamin D levels and advanced liver disease in a multiethnic US cohort of HCV patients, and account for dietary and supplemental intake. METHODS: We measured serum 25-hydroxyvitamin D levels and used FibroSURE-ActiTest to assess hepatic pathology in a cohort of HCV-infected male veterans. We estimated and adjusted for daily intake of vitamin D from diet using a Dietary History Questionnaire, and dispensed prescriptions prior to study enrolment. We used race-stratified logistic regression analyses to evaluate the relationship between serum vitamin D levels and risk of advanced fibrosis (F3/F4-F4) and advanced inflammation (A2/A3-A3). RESULTS: A total of 163 African American (AA) and 126 White non-Hispanics were studied. Overall, ~44% of AAs and 15% of Whites were vitamin D deficient (<12 ng/mL) or insufficient (12-19 ng/mL); 4% of AAs and 9% of White patients had an elevated level (>50 ng/mL). Among AAs, patients with elevated serum vitamin D levels had significantly higher odds of advanced fibrosis (OR = 12.91, P = 0.03) than those with normal levels. In contrast, AAs with insufficient or deficient levels had > two-fold excess risk of advanced inflammation (P = 0.06). Among White males there was no association between vitamin D levels and advanced fibrosis (F3/F4-F4) or inflammation (A2/A3-A3) risk. CONCLUSIONS: We observed potential differences in the association between vitamin D levels and degree of HCV-related hepatic fibrosis between White and African American males. Additional research is necessary to confirm that high serum vitamin D levels may be associated with advanced fibrosis risk in African American males, and to evaluate whether racial differences exist in HCV-infected females.

Lymphocytosis as a predictor of poor response to treatment of hepatitis C.

BACKGROUND/AIMS: Identification of factors predicting response to therapy is critical in the management of hepatitis C. This study assessed significance of lymphocytosis as a predictor of sustained virological response (SVR). METHODS: Retrospective analysis of lymphocytosis and its correlation with virologic response was performed in 110 subjects with chronic HCV infection, who underwent interferon based therapy. Lymphocytosis was defined as ratio of lymphocytes to neutrophils (L/N) above 0.6. L/N ratios were calculated to avoid the impact of hypersplenism and constitutional leukopenia seen in African Americans (AA). RESULTS: At baseline, L/N of HCV subjects (0.86) as compared to Hepatitis B controls (0.56) was significantly higher (P < 0.01). More AA HCV subjects (81.8%) had lymphocytosis at baseline when compared to Caucasian Americans subjects with HCV (37.9%) or AA controls (39.4%). Nonresponders had a higher frequency of lymphocytosis at baseline compared to subjects that achieved SVR (61.4% vs. 36.0%, p<0.05). More HCV subjects without lymphocytosis at baseline achieved SVR (33.3%) compared to HCV subjects with lymphocytosis (15%). At week 12 of therapy, nonresponders had higher L/N (1.02 vs. 0.86) and frequency of lymphocytosis (73% vs. 48%) compared to subjects that achieved SVR (p<0.05 for both). Only 17.2% of subjects with lymphocytosis at 12 weeks achieved SVR compared to 37.5% without lymphocytosis (p < 0.05). All responders exhibited significant normalization of lymphocytosis after treatment. CONCLUSIONS: HCV induces lymphocytosis, especially in AA, and is associated with lower rate of SVR. Furthermore, lymphocytosis may serve as an inexpensive pre-treatment tool to predict poor virologic response to HCV therapy.

Utility of a depression score to predict candidacy for hepatitis C virus therapy in veterans: a prospective longitudinal study.

BACKGROUND: The frequency and determinants of receipt of antiviral therapy once a diagnosis of a mood disorder is established in hepatitis C virus (HCV)-infected patients remains unknown. AIM: To examine the incidence and determinants of receiving antiviral therapy in HCV-infected veterans with abnormal scores of Zung Self-Rating Depression Scale (SDS). METHODS: We systematically evaluated the presence of psychiatric disorders among HCV-infected patients with initial referral between September 2000 and May 2002. We reviewed medical records, obtained history, and administered Zung SDS to evaluate for depressive symptoms. Patients with psychiatric disorders were referred for psychiatric evaluation. The primary outcome was the receipt of antiviral therapy during and after the initial evaluation up to December 1, 2003. The association between SDS scores and receipt of antiviral therapy was examined in a multivariate Cox proportional hazards regression. RESULTS: A total of 424 patients completed a Zung SDS. The scores were normal in only 43% of all patients, and were impaired mildly in 25%, moderately in 23%, and severely in 9%. Zung SDS scores were significantly higher in patients who served during the Vietnam War era, participated in combat, or had lower albumin levels. At the end of the first visit, 180 (42%) had psychiatric disorders. An abnormal Zung score (>55) was the only reason for referral to psychiatry in 83 of 180 patients; and in those 78 (94%) a formal psychiatric evaluation confirmed depressive disorder. Psychiatric disorders were the sole contraindication to therapy in 145 (34%) patients in whom eligibility for antiviral therapy was achieved in 42 (29%) during a mean follow-up duration of 27 months. CONCLUSIONS: Approximately one-quarter of patients with psychiatric disorders may become eligible for antiviral therapy following subsequent management of these disorders. The Zung self-screening test is an easy, valid method for detecting mood disorders in HCV-infected veterans.