The use of cyclosporine for recurrent hepatitis C after liver transplant: a randomized pilot study.

BACKGROUND: Cyclosporine has antiviral activity in vitro against hepatitis C (HCV). We performed a pilot study to prospectively determine the antiviral effect of cyclosporine during therapy with PEGalfa-2a and ribavirin in liver transplant recipients with recurrent HCV infection. METHODS: Patients with HCV recurrence (Ishak Fibrosis Stage > or = 2) were enrolled for 2 years at the University of Florida. Thirty-eight patients were randomized to continued tacrolimus or switched to cyclosporine. Both groups received PEGalfa-2a and ribavirin. RESULTS: Twenty patients received tacrolimus and 18 cyclosporine, with a mean age of 53. Eighty-two percent were men, 84% Caucasian, and 90% genotype 1. In patients switched from tacrolimus to cyclosporine, HCVRNA levels decreased by a mean of 0.39 million IU/ml during the 1 month prior to initiating PEG/RBV. Sustained viral response for cyclosporine was higher than in patients on tacrolimus receiving PEG/RBV therapy. CONCLUSIONS: This randomized controlled pilot study is the first in vivo study evaluating cyclosporine versus tacrolimus in liver transplant recipients undergoing antiviral therapy. Change from tacrolimus to cyclosporine led to a modest HCV RNA drop and appeared to enhance the antiviral response of PEG/RBV. A larger randomized study is necessary to see if cyclosporine offers any advantage over tacrolimus.

Factors predicting survival after transjugular intrahepatic portosystemic shunt creation: 15 years' experience from a single tertiary medical center.

PURPOSE: This retrospective analysis was conducted to identify factors predictive of survival after transjugular intrahepatic portosystemic shunt (TIPS) creation. MATERIALS AND METHODS: Patients who underwent TIPS creation between January 1991 and December 2005 at a tertiary-care center were identified. Log-rank tests were used to compare the cumulative survival functions among groups of patients who underwent TIPS creation for various indications. Thirty-day mortality after TIPS creation was examined by logistic regression. Cox proportional-hazards analyses were performed to analyze the cumulative 90-day and 1-year survival. Selected variables such as creatinine, bilirubin, and International Normalized Ratio (INR) were assessed with respect to survival. RESULTS: The study included 352 patients, of whom 229 (65.1%) were male. The mean age at the time of TIPS creation was 53.6 years (range, 21-82 y). A Model for End-stage Liver Disease (MELD) score greater than 15 was significantly associated with poor survival (P < .05) at 30 days, 90 days, and 1 year after TIPS creation. Independently, a serum total bilirubin level greater than 2.5 mg/dL, an INR greater than 1.4 (P < .05), and a serum creatinine level greater than 1.2 mg/dL were predictive of poor survival. Finally, age greater than 70 years was associated with poor survival at 90 days and 1 year after TIPS creation (P < .05). CONCLUSION: The choice to create a TIPS in individuals whose MELD score is greater than 15 and/or whose age is greater than 70 years should involve a careful consideration of risk/benefit ratio, taking into account the finding that such patients have significantly poorer survival after TIPS creation.

Burden of nonalcoholic fatty liver disease and advanced fibrosis in a Texas Hispanic community cohort.

AIM: To investigate the potential burden of nonalcoholic steatohepatitis (NASH) and advanced fibrosis in a hispanic community. METHODS: Four hundred and forty two participants with available ultrasonography data from the Cameron County Hispanic Cohort were included in this study. Each participant completed a comprehensive questionnaire regarding basic demographic information, medical history, medication use, and social and family history including alcohol use. Values of the nonalcoholic fatty liver disease fibrosis score (NFS), FIB4 index, BARD score, and Aspartate aminotransferase to Platelet Ratio Index (APRI) were computed using the blood samples collected within 6 mo of liver ultrasonography from each participant. Hepatic steatosis was determined by ultrasonography. As part of univariable analysis, for continuous variables, comparisons among groups were performed with student-t test, one way analysis of variance, and Mann-Whitney test. Pearson χ(2) and the Fisher exact test are used to assess differences in categorical variables. For multivariable analyses, logistic regression analyses were performed to identify characteristics associated with hepatic steatosis. All reported P values are based two-sided tests, and a P value of less than 0.05 was considered to indicate statistical significance. RESULTS: The mean age and body mass index (BMI) of the study participants were 49.1 years and 31.3 kg/m(2), respectively. Among them, 65.6% were females, 52% had hepatic steatosis, 49.5% had metabolic syndrome, and 29% had elevated aminotransferases. Based on established cut-offs for diagnostic panels, between 17%-63% of the entire cohort was predicted to have NASH with indeterminate or advanced fibrosis. Participants with hepatic steatosis had significantly higher BMI (32.9 ± 5.6 kg/m(2) vs 29.6 ± 6.1 kg/m(2), P < 0.001) and higher prevalence rates of elevation of ALT (42.2% vs 14.6%, P < 0.001), elevation of aspartate aminotransferase (38.7% vs 18.9%, P < 0.001), and metabolic syndrome (64.8% vs 33%, P < 0.001) than those without hepatic steatosis. The NFS scores (P = 0.002) and the APRI scores (P = 0.002) were significantly higher in those with steatosis but the scores of the FIB4 index and BARD were similar between the two groups. After adjusting for age, gender and BMI, elevated transaminases, metabolic syndrome and its components, intermediate NFS and APRI scores were associated hepatic steatosis in multivariable analysis. CONCLUSION: The burden of NASH and advanced fibrosis in the Hispanic community in South Texas may be more substantial than predicted from referral clinic studies.

Associations between smoking and tooth loss according to the reason for tooth loss: the Buffalo OsteoPerio Study.

BACKGROUND: Smoking is associated with tooth loss. However, smoking's relationship to the specific reason for tooth loss in postmenopausal women is unknown. METHODS: Postmenopausal women (n = 1,106) who joined a Women's Health Initiative ancillary study (The Buffalo OsteoPerio Study) underwent oral examinations for assessment of the number of missing teeth, and they reported the reasons for tooth loss. The authors obtained information about smoking status via a self-administered questionnaire. The authors calculated odds ratios (ORs) and 95 percent confidence intervals (CIs) by means of logistic regression to assess smoking's association with overall tooth loss, as well as with tooth loss due to periodontal disease (PD) and with tooth loss due to caries. RESULTS: After adjusting for age, education, income, body mass index, history of diabetes diagnosis, calcium supplement use and dental visit frequency, the authors found that heavy smokers (≥ 26 pack-years) were significantly more likely to report having experienced tooth loss compared with never smokers (OR = 1.82; 95 percent CI, 1.10-3.00). Smoking status, packs smoked per day, years of smoking, pack-years and years since quitting smoking were significantly associated with tooth loss due to PD. For pack-years, the association for heavy smokers compared with that for never smokers was OR = 6.83 (95 percent CI, 3.40 -13.72). The study results showed no significant associations between smoking and tooth loss due to caries. CONCLUSIONS AND PRACTICAL IMPLICATIONS: Smoking may be a major factor in tooth loss due to PD. However, smoking appears to be a less important factor in tooth loss due to caries. Further study is needed to explore the etiologies by which smoking is associated with different types of tooth loss. Dentists should counsel their patients about the impact of smoking on oral health, including the risk of experiencing tooth loss due to PD.

Recurrent hepatocellular carcinoma in liver transplant recipients with hepatitis C.

PURPOSE: Hepatitis C (HCV) is the most common liver disease in patients transplanted with hepatocellular carcinoma (HCC) in the West. We examined predictors of HCC recurrence in liver transplant recipients with HCV. METHODS: From 1997 to 2006, 53 patients with HCC and HCV underwent liver transplantation. Pre-and post-operative data (including liver biopsies 4 months post-transplant) were collected. Differences between HCC recurrence and non-recurrence groups were detected by Student's t test or chi-square test. Data were analyzed as predictors of HCC recurrence by logistic regression multivariate analysis. Cumulative survival was analyzed by Kaplan-Meier curves and compared by the log-rank test. RESULTS: Eleven of 53 patients (20.8%) developed HCC recurrence at a median interval of 15 months (2 to 55 months). Median Histology Activity Index (HAI) of liver biopsies, AST, and ALT at 4 months were significantly greater in patients with HCC recurrence. Independent predictors of HCC recurrence were HAI ≥ 4 at 4 months, ALT ≥ 100 at 4 months, and vascular invasion. Patients with HCC recurrence had significantly decreased survival. CONCLUSIONS: In this preliminary study, Histology Activity Index and ALT at 4 months, as well as vascular invasion, predicted HCC recurrence in liver transplant recipients with HCV.

Asymptomatic primary biliary cirrhosis is not associated with increased frequency of cardiovascular disease.

AIM: To estimate the prevalence of cardiovascular events in Primary biliary cirrhosis (PBC) and to determine whether this risk is higher within specific subgroups of patients with PBC. METHODS: We included 180 patients with PBC (cases) and 151 patients seen for HCV infection (controls). Medical records were reviewed and statistical analyses were performed as appropriate. RESULTS: When compared to controls, PBC patients were older, leaner and had higher serum levels of total cholesterol, high density lipoprotein and low density cholesterol. There were more females in the PBC group (91.7% vs 43%, P < 0.001). More control subjects had smoked than the PBC patients (63.6% vs 35%, P < 0.001). The prevalence of hypertension, diabetes, coronary artery disease and stroke was similar between the two groups. Seven percent of controls and 10% of cases developed any type of cardiovascular disease (P = 0.3). Only 36.7% were asymptomatic at diagnosis. Three cardiovascular events were documented among asymptomatic patients (4.5%) and fifteen among symptomatic patients (13.2%; P = 0.06). Among PBC patients with fatigue, 10 (13.5%) had a cardiovascular event compared to 7 (6.7%) among patients without fatigue (P = 0.1). CONCLUSION: Asymptomatic PBC patients do not have a greater frequency of cardiovascular disease; nor do patients suffering with fatigue.