Search

Chronic hepatitis C virus (HCV) is widely prevalent in the Virginia Department of Corrections (DOC). However, sustained virologic response (SVR) with all oral direct-acting antiviral (DAA) therapy is unknown. HCV treatment was provided through telemedicine following guidelines of the American Association for the Study of Liver Diseases and Infectious Diseases Society of America. SVR12 in the DOC was compared in two control groups: privately insured and indigent patients receiving care in HCV treatment clinics by the same providers during the same time period. Of 220 DOC patients, 180 were started on therapy (158 genotype [GT] 1, 15 GT2, and 10 GT3). SVR12 data on GT1 patients who received ledipasvir/sofosbuvir with or without ribavirin (RBV) were 96%, similar to our indigent (95%) and private clinic (93%) patients despite differences in age, gender, treatment experience, FIB-4, and use of RBV. Multiple logistic regression of GT1 patients identified lower FIB-4 (p = .008) and treatment clinic (p = .01) as independent predictors of SVR12. HCV treatment in the DOC by telemedicine with DAA is not only feasible but has a very high SVR12 similar to published trials. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Chronic hepatitis C virus (HCV) is common in the correctional setting and there are few data on the use of interferon (IFN)/ribavirin(RVN) combination therapy in this population. Given the high proportion of African Americans (AA) in correctional facilities, which may be associated with reduced response rates, the correctional setting allows a unique opportunity to compare the response rates of AA to Caucasians (CA). The present study describes our experience of treating HCV in the inmate population of the Virginia Department of Corrections.METHODS: Of the 119 inmates evaluated between 1998 and 2000, a retrospective analysis of 59 consecutive inmates (mean age 41, 83% male, 55% CA, 73% genotype (GT)1, and 41% with advanced fibrosis) who underwent HCV therapy with IFN a-2b (3 MU TIW) and RVN (1,000–1,200 mg/d) under direct observation was performed. Patients were followed by telemedicine and the primary endpoint was sustained virologic response (SVR) defined as an undetectable HCV RNA at least 24 wk after completion of therapy.RESULTS: All but one patient completed at least 12 wk of therapy and no patient required dose reduction. By wk 24, 34 inmates (58%) responded (negative HCV RNA) which was higher in CA compared to AA (70%vs40%;p= 0.037). Although overall SVR was higher in CA compared to AA (41%vs28%;p= ns), we observed no difference in SVR when comparing only GT 1 CA to AA (33%vs29%).CONCLUSIONS: HCV can be effectively treated in the correctional setting with response rates similar to, if not better than the published literature. In this controlled setting of direct observational therapy, we observed similar SVR in CA and AA. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to determine the effect of comorbidities on covert hepatic encephalopathy (CHE) diagnosis and overt hepatic encephalopathy (OHE) development., Methods: Cirrhotic outpatients underwent CHE testing and 2-year follow-up. Cox regression was performed for time to OHE. In total, 700 patients (60 years, 84% men, model for end-stage liver disease 11) and 33% prior OHE underwent testing and follow-up., Results: Major comorbidities were hypertension (54%), diabetes (35%), and depression (29%). Common medications were proton pump inhibitor (49%), beta-blockers (32%), and opioids (21%). Approximately 90 (40%) prior-OHE patients developed recurrence 93 (30,206) days post-testing predicted only by liverrelated variables., Discussion: Demographics, cirrhosis characteristics, and opioid use, but not other comorbid conditions, were associated with CHE diagnosis and OHE progression., (Copyright © 2021 by The American College of Gastroenterology.)

Background: Alcoholic hepatitis (AH) is a severe and life-threatening alcohol-associated liver disease. Only a minority of heavy drinkers acquires AH and severity varies among affected individuals, suggesting a genetic basis for the susceptibility to and severity of AH., Methods: A cohort consisting of 211 patients with AH and 176 heavy drinking controls was genotyped for five variants in five candidate genes that have been associated with chronic liver diseases: rs738409 in patatin-like phospholipase domain-containing protein 3 (PNPLA3), rs72613567 in hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13), rs58542926 in transmembrane 6 superfamily member 2 (TM6SF2), rs641738 in membrane bound O-acyltransferase domain containing 7 (MBOAT7), and a copy number variant in the haptoglobin (HP) gene. We tested the effects of individual variants and the combined/interacting effects of variants on AH risk and severity., Results: We found significant associations between AH risk and the risk alleles of rs738409 (p = 0.0081) and HP (p = 0.0371), but not rs72613567 (p = 0.3132), rs58542926 (p = 0.2180), or rs641738 (p = 0.7630), after adjusting for patient's age and sex. A multiple regression model indicated that PNPLA3 rs738409:G [OR = 1.59 (95% CI: 1.15-2.22), p = 0.0055] and HP*2 [OR = 1.38 (95% CI: 1.04-1.82), p = 0.0245], when combined and adjusted for age and sex also had a large influence on AH risk among heavy drinkers. In the entire cohort, variants in PNPLA3 and HP were associated with increased total bilirubin and Model for End-stage Liver Disease (MELD) score, both measures of AH severity. The HSD17B13 rs72613567:AA allele was not found to reduce risk of AH in patients carrying the G allele of PNPLA3 rs738409 (p = 0.0921)., Conclusion: PNPLA3 and HP genetic variants increase AH risk and are associated with total bilirubin and MELD score, surrogates of AH severity., (© 2021 by the Research Society on Alcoholism.)

Objectives: Cirrhosis is associated with gut microbial dysbiosis, high readmissions and proton pump inhibitor (PPI) overuse, which could be inter-linked. Our aim was to determine the effect of PPI use, initiation and withdrawl on gut microbiota and readmissions in cirrhosis., Methods: Four cohorts were enrolled. Readmissions study: Cirrhotic inpatients were followed throughout the hospitalization and 30/90-days post-discharge. PPI initiation, withdrawal/continuation patterns were analyzed between those with/without readmissions. Cross-sectional microbiota study: Cirrhotic outpatients and controls underwent stool microbiota analysis. Beneficial autochthonous and oral-origin taxa analysis vis-à-vis PPI use was performed. Longitudinal studies: Two cohorts of decompensated cirrhotic outpatients were enrolled. Patients on chronic unindicated PPI use were withdrawn for 14 days. Patients not on PPI were started on omeprazole for 14 days. Microbial analysis for oral-origin taxa was performed pre/post-intervention., Results: Readmissions study: 343 inpatients (151 on admission PPI) were enrolled. 21 were withdrawn and 45 were initiated on PPI resulting in a PPI use increase of 21%. PPIs were associated with higher 30 (p = 0.002) and 90-day readmissions (p = 0.008) independent of comorbidities, medications, MELD and age. Cross-sectional microbiota: 137 cirrhotics (59 on PPI) and 45 controls (17 on PPI) were included. PPI users regardless of cirrhosis had higher oral-origin microbiota while cirrhotics on PPI had lower autochthonous taxa compared to the rest. Longitudinal studies: Fifteen decompensated cirrhotics tolerated omeprazole initiation with an increase in oral-origin microbial taxa compared to baseline. PPIs were withdrawn from an additional 15 outpatients, which resulted in a significant reduction of oral-origin taxa compared to baseline., Conclusions: PPIs modulate readmission risk and microbiota composition in cirrhosis, which responds to withdrawal. The systematic withdrawal and judicious use of PPIs is needed from a clinical and microbiological perspective in decompensated cirrhosis.

Nonalcoholic fatty liver disease is associated with cardiovascular disease (CVD) in the general population. Despite a high prevalence of de novo hepatic steatosis after liver transplantation (LT), there are no data exploring the association between hepatic steatosis after LT and atherogenic risk. The aim of the study was to explore the impact of hepatic steatosis on serum atherogenic markers in liver transplantation recipients (LTRs). Biomarkers of CVD risk were compared in 89 LTRs with no known history of dyslipidemia, ischemic heart disease, or graft cirrhosis. To avoid potential confounders, LTRs on oral hypoglycemic agents, exogenous insulin, corticosteroids, or lipid-lowering therapy were excluded. Only patients for whom histological assessment was available after LT were included in the study. Thirty-five LTRs had de novo hepatic steatosis after LT, whereas 54 did not. Both cohorts were similar with regards to age, sex, ethnicity, and follow-up from LT. Additionally, the traditional lipid profile was similar between the 2 cohorts. LTRs with hepatic steatosis had higher serum concentrations of small-dense low-density lipoprotein cholesterol (sdLDL-C; 34.8 ± 16.9 versus 22.7 ± 11.2 mg/dL; P < 0.001), sdLDL-C to low-density lipoprotein cholesterol ratio (32.6 ± 11.6 versus 24.6 ± 10.2; P < 0.01), small-dense low-density lipoprotein particle concentration (sdLDL-P; 770 ± 440 versus 486 ± 402 nmol/L; P < 0.01), very low density lipoprotein particle concentration (VLDL-P; 7.90 ± 7.91 versus 3.86 ± 3.18 nmol/L; P < 0.01), and very low density lipoprotein size (VLDL-size; 51.9 ± 6.4 versus 48.7 ± 6.3 nm; P = 0.06). LTRs with hepatic steatosis had higher serum insulin concentrations (27.8 ± 41.8 versus 11.7 ± 7.8 uU/mL; P < 0.01) but similar fasting glucose and hemoglobin A1c. Steatosis grade was directly related to sdLDL-C, sdLDL-P, insulin, VLDL-P, and VLDL-size. In multivariate analysis, the association between steatosis grade and sdLDL-C (β = 0.03; P = 0.029), VLDL-size (β = 0.316; P = 0.04), and low-density lipoprotein particle size (β = -0.27; P = 0.05) was independent of sex, body mass index, age, diabetes mellitus, time from transplant, and indication for LT. In conclusion, de novo hepatic steatosis after LT is associated with atherogenic lipoproteins and independent of traditional CVD risk factors., (© 2015 American Association for the Study of Liver Diseases.)

Poor brain reserve in alcoholic cirrhosis could worsen insight regarding disease severity and increase the patients' vulnerability toward further deterioration. The aim of this study was to analyze brain reserve in abstinent alcoholic cirrhotic (Alc) patients compared to nonalcoholic cirrhotic (Nalc) patients in the context of hepatic encephalopathy (HE) and to evaluate relative change in brain reserve between groups over time and before and after elective transjugular intrahepatic portosystemic shunt (TIPS) placement. The cross-sectional study included 46 Alc and 102 Nalc outpatients with or without HE. Cognitive tests were followed by magnetic resonance imaging (MRI), including proton magnetic resonance spectroscopy (1 H-MRS), diffusion tensor imaging, and T1-weighted imaging. The prospective study included 1H-MRS on a subset of 10 patients before and after TIPS placement. Another subset of 26 patients underwent (1) H-MRS at least 1 year apart. For the cross-sectional study, Alc patients were worse on cognitive tests than Nalc patients. MRI results suggest a greater effect of hyperammonemia, brain edema, and significantly higher cortical damage in Alc as compared to Nalc patients. The effect of HE status on cognitive tests and brain reserve was more marked in the Nalc than in the Alc group. For the TIPS study, Nalc patients showed a greater adverse relative change after TIPS compared to the Alc group. At 1-year follow-up, both groups remained stable between the 2 visits. However, Alc patients continued to show poor brain reserve compared to Nalc patients over time. In conclusion, Alc patients, despite abstinence, have a poor brain reserve, whereas Nalc patients have a greater potential for brain reserve deterioration after HE and TIPS. Information regarding the brain reserve in cirrhosis could assist medical teams to refine their communication and monitoring strategies for different etiologies., (© 2015 American Association for the Study of Liver Diseases.)

Orthotopic liver transplantation (OLT) is the only effective treatment for end-stage liver disease. Although most patients do well and are discharged promptly, some require prolonged length of stay (PLOS). The prevalence of PLOS, associated factors, and their impact on survival are not well defined. We reviewed our adult OLT database for patients who survived > 30 days. PLOS was defined as hospitalization > 30 days following OLT. Of 521 OLT recipients, 68 (13%) had PLOS with a median duration of 50 days versus only 10 days for patients discharged within 30 days. Significant differences in pre-OLT variables between patients with and without PLOS included the mean wait list time (P = 0.001), hospitalization at the time of OLT (P = 0.001), and prior OLT (P = 0.041). Factors independently associated with PLOS included intensive care unit status at the time of OLT [odds ratio (OR), 4; 95% confidence interval (CI), 1.6-10.4], OLT prior to Model for End-Stage Liver Disease implementation (OR, 2.27; 95% CI, 1.04-5.26), in-hospital post-OLT bacterial infection (OR, 9.34; 95% CI, 4.65-18.86), gastrointestinal bleeding (OR, 4.34; 95% CI, 1.4-14.08), renal failure (OR, 10.86; 95% CI, 5.07-23.25), and allograft rejection (OR, 3.7; 95% CI, 1.23-11.11). One-year graft survival and patient survival were significantly less in those with PLOS (for both, P < 0.0001). Among PLOS patients, factors independently associated with increased 1-year mortality were donor age (OR, 1.07; 95% CI, 1.009-1.13), primary diagnosis of hepatitis C virus (OR, 6.89; 95% CI, 1.40-34.48), in-hospital post-OLT bacterial infection (OR, 13.3; 95% CI, 2.11-83.33), and cardiac complications (OR, 20.4; 95% CI, 1.51-250; c-statistic for the model, 0.85). In conclusion, PLOS following OLT is associated with a significant decrease in survival despite a marked increase in cost and resource utilization. Efforts to modify those factors that contribute to PLOS may reduce this event, improve survival, and reduce OLT-associated costs.

Background and Objective: Chronic hepatitis C virus (HCV) is common in the inmate population of the United States. Long-standing HCV can progress to cirrhosis, which can contribute to significant morbidity and mortality. However, those inmates with histologically mild disease are unlikely to develop liver-related morbidity or mortality during their period of incarceration. Our objective was to develop an economic strategy for evaluation and treatment of inmates with chronic HCV., Methods and Measures: A retrospective cohort analysis of 302 inmates within the Virginia Department of Corrections (VDOC) who underwent liver biopsy for chronic HCV at the Virginia Commonwealth University Health System between 1998 and 2002 was performed. The data from this analysis was to utilized to develop a cost model for treatment of chronic HCV in this population based upon biochemical or histologic criteria. We used the perspective of the VDOC using actual costs paid to providers, hospitals, and pharmacies. The primary endpoint was cost-effectiveness of HCV treatment., Results: Eighty percent of inmates with chronic HCV were genotype 1, 49% had a normal value for serum ALT at the time of evaluation, 30% had no fibrosis, and 24% had bridging fibrosis or cirrhosis. The cost to evaluate and treat 100 consecutive inmates with peginterferon and ribavirin regardless of serum ALT and liver histology was calculated to be $1,775,900 or $35,500 per sustained virologic response (SVR). Although the cost declined by 50% if only those patients with an elevated serum ALT were treated, 45% of those inmates with varying degrees of fibrosis, and 21% with cirrhosis would not have received therapy utilizing this scenario. In contrast, the cost of performing liver biopsy and treating only those patients with any degree of fibrosis was $1,367,043; a savings of slightly more than $400,000 per 100 patients evaluated. The overall cost of treatment was most influenced by the price of peginterferon and ribavirin, which declined as the histologic criteria utilized for treatment increased., Conclusions: A strategy in which inmates with chronic HCV are evaluated and a decision regarding treatment is based upon either biochemical or histologic criteria, which appears to balance both the health-care rights of the inmate and the impact of treating this disease on the financial and other resources of the correctional system.

Background & Aims: Differences in hepatitis C virus (HCV)-related liver disease between Caucasians and African Americans remain controversial., Methods: We performed a retrospective analysis of 302 consecutive inmates in the Virginia Department of Corrections evaluated for HCV between October 1998 and July 2002. All subjects were anti-HCV positive, HCV treatment naive, human immunodeficiency virus and HBV negative, and had compensated liver disease., Results: The mean age of the cohort was 41 years; they were 91% male and 51% Caucasian. The mean ALT level was 94 U/L, 49% had a normal ALT level, and 80% were genotype 1. The mean Knodell histologic activity index (HAI) was 7.03, with bridging fibrosis in 18% and cirrhosis in 6%. When analyzed by race, the mean ALT level (106 vs. 79 U/L; P = 0.01), proportion with normal ALT level (46% vs. 57%; P = 0.06), and proportion with genotype 1 (67% vs. 94%; P < 0.001) were different between Caucasians and African Americans, respectively. Although the HAI and proportion with bridging fibrosis/cirrhosis were similar between groups, African Americans had lower piecemeal necrosis (1.41 vs. 1.72; P = 0.034) and fibrosis (1.12 vs. 1.40; P = 0.047) scores compared to Caucasians. Multivariate analysis demonstrated that age, ALT, and race were significant independent variables associated with total HAI, piecemeal necrosis, and fibrosis scores., Conclusions: Although the overall spectrum of liver disease is similar, African Americans have less piecemeal necrosis and lower fibrosis scores independent of age and ALT compared with Caucasians.