Shahriar Tavakoli-Tabasi

Physical and psychosocial contributors to quality of life in veterans with hepatitis C not on antiviral therapy

Background and Aims: Treatment-naive hepatitis C virus (HCV)-infected patients report impaired health-related quality of life (HRQOL), although causes are unclear. Psychosocial factors may be major determinants of HRQOL. Methods: We administered a general (Short Form-36; SF-36) and a liver-specific (Chronic Liver Disease Questionnaire; CLDQ) HRQOL measure to 62 HCV-infected veterans being considered for antiviral therapy. Psychosocial assessment included the Structured Clinical Interview for DSM-IV Axis I Disorders/Non-Patient (SCID-I/NP), Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), Abbreviated Cook-Medley (ACM) anger measure, and Medical Outcomes Study Social Support Measure (SSM). We examined the potential determinants of HRQOL, including psychosocial measures, demographic measures (age, sex, race/ethnicity), clinical measures (presence of cirrhosis, comorbid medical conditions), and viral data (quantitative PCR). Results: SF-36 scores were significantly lower in HCV-infected patients than published U.S. population norms but similar to those reported by previous studies of HCV-infected samples. CLDQ scores were very similar to those reported by previous studies. Demographic, clinical, and viral indicators were not statistically associated with HRQOL, and neither was the presence of a substance abuse or psychotic disorder. Lower BDI-II and BAI scores were associated with better general and disease-specific HRQOL. Lower SSM scores were associated with lower scores on SF-36 but not CLDQ; however, this effect did not persist in multiple linear regression analyses. In these, BDI-II was the strongest independent predictor of both SF-36 and CLDQ. Conclusions: Psychosocial factors, especially depression, are strong indicators of impaired HRQOL for HCV-infected veterans not receiving antiviral therapy. Screening and treatment of psychosocial factors is recommended.

Coffee and Caffeine Are Associated With Decreased Risk of Advanced Hepatic Fibrosis Among Patients With Hepatitis C

BACKGROUND & AIMS Coffee or caffeine has been proposed to protect against hepatic fibrosis, but few data are available on their effects in patients with chronic hepatitis C virus (HCV) infection. METHODS We conducted a cross-sectional study of veterans with chronic HCV infection to evaluate the association between daily intake of caffeinated and decaffeinated coffee, tea, and soda, and level of hepatic fibrosis, based on the FibroSURE test (BioPredictive, Paris, France) (F0-F3, mild [controls] vs. F3/F4-F4, advanced). Models were adjusted for multiple potential confounders including age, alcohol abuse, and obesity. RESULTS Among 910 patients with chronic HCV infection, 98% were male and 38% had advanced hepatic fibrosis. Daily intake of caffeinated coffee was higher among controls than patients with advanced fibrosis (1.37 vs. 1.05 cups/d; P = .038). In contrast, daily intake of caffeinated tea (0.61 vs. 0.56 cups/d; P = .651) or soda (1.14 vs. 0.95 cans/d; P = .106) did not differ between the groups. A higher percentage of controls (66.0%) than patients with advanced fibrosis (57.9%) consumed 100 mg or more of caffeine daily from all sources (P = .014); controls also received a larger proportion of their caffeine from coffee (50.2% vs. 43.0%; P = .035). Hepatoprotective effects of an average daily intake of 100 mg or more of caffeine (adjusted odds ratio, 0.71; 95% confidence interval, 0.53-0.95; P = .020) and 1 cup or more of caffeinated tea by non-coffee drinkers (adjusted odds ratio, 0.56; 95% confidence interval, 0.34-0.94; P = .028) persisted after adjustment for confounders, including insulin resistance. CONCLUSIONS A modest daily caffeine intake (as little as 100 mg) may protect against advanced hepatic fibrosis in men with chronic HCV infection. Additional research is needed to confirm these findings in women and in people with other chronic liver diseases.

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.

WNT Signaling Pathway Gene Polymorphisms and Risk of Hepatic Fibrosis and Inflammation in HCV-Infected Patients

Background Chronic hepatitis C infection is the leading cause of hepatocellular carcinoma (HCC), a highly lethal malignancy with rapidly increasing prevalence in the United States. Little is known about genetic variations and HCC risk. This study aimed to determine if genetic variation in Wnt signaling pathway genes are associated with advanced hepatic fibrosis and inflammation risk in a hepatitis C virus (HCV) infected population. Methods We performed a genetic association cross-sectional study evaluating single nucleotide polymorphisms (SNPs) in 58 candidate genes and risk of FibroSURE-Acti Test determined advanced fibrosis (F3/F4-F4 advanced cases vs. F0-F3 mild controls) and inflammation (A2/A3-A3 advanced cases vs. A0-A2 mild controls). We calculated odds ratios (ORs) and 95% confidence intervals (CIs) employing multivariate logistic regression. Haplotypes were inferred by the HAPLO.STAT program, interactions were evaluated using multifactor dimensionality reduction (MDR) analysis. Results Among 425 chronically HCV-infected male veterans, 155 (37%) had advanced fibrosis and 180 (42%) had advanced inflammation. Of 3016 SNPs evaluated, eight were significantly associated with fibrosis risk (e.g., SFRP2 rs11937424: OR = 2.19, 95% CI 1.48-3.23, P = 0.00004), and seven were significantly associated with inflammation risk (e.g., SFRP1 rs16890282: OR = 2.15, 95% CI 1.39-3.16, P = 0.0004). MDR analysis identified overweight/obese, SOST rs1405952, SFRP2 rs11937424, and FZD4 rs11234870 as the best interaction model for predicting risk of fibrosis; whereas race/ethnicity, FZD1 rs1346665, and TBX3 rs1520177 as the best interaction model for predicting risk of inflammation. Conclusions Polymorphisms in several genes involved in the Wnt signaling pathway were associated with hepatic fibrosis or inflammation risk in HCV-infected males. Additional studies in other multi-ethnic HCV cohorts are needed to validate our findings in males and to assess if similar associations exist in chronically HCV-infected females.

A longitudinal cohort study of mucocutaneous drug eruptions during interferon and ribavirin treatment of hepatitis C.

Goals: To describe dermatologic side effects encountered during treatment of patients with chronic hepatitis C, and analyze factors predisposing to such reactions. Background: Treatment of hepatitis C virus (HCV) infection with interferon (IFN) and ribavirin is associated with a number of mucocutaneous adverse reactions that have not been adequately studied. Study: A retrospective cohort study design was used to longitudinally describe mucocutaneous drug eruptions during IFN and ribavirin therapy in HCV-infected patients. Factors predictive of mucocutaneous eruptions were analyzed by the use of Kaplan-Meier curves and Cox proportional hazard model. Results: A total of 286 HCV-infected consecutive patients were treated with one of the IFN&agr; formulations plus ribavirin. The mean age was 51.1 years (SD 5.6). There were 6 female patients. There were 5 patients who were also infected with human immunodeficiency virus (HIV). Fifty-six percent of the patients were white, 37% were African American, and 14% were Hispanic. Twenty-one percent of all study patients developed mucocutaneous drug eruptions. The most common drug eruptions were eczematous drug eruptions (48%), seborrheic dermatitis (11%), and xerosis (8%). Dermatologic eruptions were a contributing factor in the decision to discontinue antiviral treatment in 10% of cases. Use of Pegylated IFN formulations (hazard ratio=1.86; 95% confidence interval, 1.04-3.34) and presence of HIV coinfection (hazard ratio=4.46; 95% confidence interval, 1.61-12.92) were associated with increased rate of skin reactions. Conclusions: Mucocutaneous reactions during IFN and ribavirin treatment of hepatitis C are common and are associated with HIV infection and use of Pegylated IFN.

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

Vitamin D may affect the severity of HCV‐related liver disease.

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

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.

Dietary fructose intake and severity of liver disease in hepatitis C virus-infected patients.

Background and Goals: Dietary fructose intake in the United States has been increasing, and fructose intake has been associated with the metabolic syndrome and hepatic steatosis. This study aimed to determine whether dietary fructose intake is associated with advanced hepatic fibrosis and inflammation in an hepatitis C virus (HCV)-infected male population. Study: We conducted a cross-sectional study of HCV-infected male veterans. The main exposure variable was daily dietary fructose calculated from the National Cancer Institute Diet History Questionnaire and the main outcome variables were FibroSURE-ActiTest determined hepatic fibrosis (F0-F3=mild vs. F3/F4-F4=advanced) and inflammation (A0-A2=mild vs. A2/A3-A3=advanced). We examined this association in logistic regression adjusting for demographic, clinical, and other dietary variables. Results: Among 313 HCV+ males, 103 (33%) had advanced fibrosis and 89 (28%) had advanced inflammation. Median daily fructose intake was 46.8 g (interquartile range, 30.4 to 81.0). Dietary fructose intake across quartiles among males with advanced versus mild fibrosis was 21.4% versus 25.2%, 32.0% versus 24.8%, 24.3% versus 25.2%, and 22.3% versus 24.8%, respectively, and among males with advanced versus mild inflammation was 20.2% versus 25.5%, 41.6% versus 21.4%, 22.5% versus 25.9%, and 15.7% versus 27.2%, respectively. In multivariate analysis, there were no significant associations between daily fructose intake and advanced fibrosis. There was a significant association only between the second quartile of daily fructose intake (30 to 48 g) and advanced inflammation. Conclusions: There were no significant associations between dietary fructose intake and hepatic fibrosis risk, as assessed by FibroSURE, in HCV-infected males. Additional research is needed to clarify the potential role of fructose intake and HCV-related hepatic inflammation.

Mortality in Patients Admitted for Concurrent COPD Exacerbation and Pneumonia.

ABSTRACT It is unclear whether concurrent pneumonia and chronic obstructive pulmonary disease (COPD) have a higher mortality than either condition alone. Further, it is unknown how this interaction changes over time. We explored the effect of pneumonia and COPD on inpatient, 30-day and overall mortality. We used a Veterans Health Affairs database to compare patients who were hospitalized for a COPD exacerbation without pneumonia (AECOPD), patients hospitalized for pneumonia without COPD (PNA) and patients hospitalized for pneumonia who had a concurrent diagnosis of COPD (PCOPD). We studied records of 15,065 patients with the following primary discharge diagnoses: (a) AECOPD cohort (7,154 individuals); (b) PNA cohort (4,433 individuals); and (c) PCOPD (3,478 individuals), comparing inpatient, 30-day and overall mortality in the three study cohorts. We observed a stepwise increase in inpatient mortality for AECOPD, PNA and PCOPD (4.8%, 9.5% and 13.2%, respectively). These differences persisted at 30 days post-discharge (AECOPD = 6.7%, PNA = 12.4% and PCOPD = 14.6%; p < 0.0001), but not throughout the study period (median follow-up: 37 months). With time, the death rate rose disproportionally in patients who had been admitted for AECOPD (AECOPD = 64.5%; PNA = 57.4% and PCOPD 66.2%; p < 0.001). In multivariate analysis, PCOPD predicted the greatest inpatient mortality (p < 0.001). The data showed a progression in inpatient and 30-day mortality from AECOPD to PNA to PCOPD. Pneumonia and COPD differentially affected inpatient, 30-day and overall mortality with pneumonia affecting predominantly inpatient and 30-day mortality while COPD affecting the overall mortality.

Immune reconstitution inflammatory syndrome in a patient with progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is a severe opportunistic infection of the central nervous system. A 52-year-old man with HIV infection, recently started on antiretroviral therapy, presented with symptoms of mental cloudiness, blurry vision and ataxia. MRI of the brain showed nodular perivascular space enhancement with surrounding vasogenic oedema and midline shift. A lumbar puncture revealed non-inflammatory cerebrospinal fluid and was positive for JC virus. As the patient developed worsening symptoms in the setting of initiation of antiretroviral therapy with immune recovery, a diagnosis of JC virus-associated immune reconstitution inflammatory syndrome (IRIS) was made. With recent literature on the use of CCR5 antagonist maraviroc in PML, our patient was started on maraviroc and noted to have improvement in PML IRIS. This is the first case of an HIV-positive patient successfully treated for PML IRIS with maraviroc, as verified by our literature review; also, our case has clinical implications in improving outcome in PML IRIS.