Greater Transplant-Free Survival in Patients Receiving Obeticholic Acid for Primary Biliary Cholangitis in a Clinical Trial Setting Compared to Real-World External Controls.

BACKGROUND & AIMS: The Primary Biliary Cholangitis (PBC) Obeticholic Acid (OCA) International Study of Efficacy (POISE) randomized, double-blind, placebo-controlled trial demonstrated that OCA reduced biomarkers associated with adverse clinical outcomes (ie, alkaline phosphatase, bilirubin, aspartate aminotransferase, and alanine aminotransferase) in patients with PBC. The objective of this study was to evaluate time to first occurrence of liver transplantation or death in patients with OCA in the POISE trial and open-label extension vs comparable non-OCA-treated external controls. METHODS: Propensity scores were generated for external control patients meeting POISE eligibility criteria from 2 registry studies (Global PBC and UK-PBC) using an index date selected randomly between the first and last date (inclusive) on which eligibility criteria were met. Cox proportional hazards models weighted by inverse probability of treatment assessed time to death or liver transplantation. Additional analyses (Global PBC only) added hepatic decompensation to the composite end point and assessed efficacy in patients with or without cirrhosis. RESULTS: During the 6-year follow-up, there were 5 deaths or liver transplantations in 209 subjects in the POISE cohort (2.4%), 135 of 1381 patients in the Global PBC control (10.0%), and 281 of 2135 patients in the UK-PBC control (13.2%). The hazard ratios (HRs) for the primary outcome were 0.29 (95% CI, 0.10-0.83) for POISE vs Global PBC and 0.30 (95% CI, 0.12-0.75) for POISE vs UK-PBC. In the Global PBC study, HR was 0.20 (95% CI, 0.03-1.22) for patients with cirrhosis and 0.31 (95% CI, 0.09-1.04) for those without cirrhosis; HR was 0.42 (95% CI, 0.21-0.85) including hepatic decompensation. CONCLUSIONS: Patients treated with OCA in a trial setting had significantly greater transplant-free survival than comparable external control patients.

Epidemiologic features of a large hepatitis C cohort evaluated in a major health system in the western United States.

INTRODUCTION AND AIM: Real-world epidemiologic data to guide hepatitis C virus (HCV)-related public health initiatives are lacking. The aim of this study was to describe the prevalence and epidemiological characteristics of a large cohort of patients with an HCV diagnosis evaluated in one of the largest health systems in the United States. MATERIALS AND METHODS: De-identified demographic and clinical data were extracted from the electronic health record for patients actively followed within the Providence Health & Services health care system. Rates of HCV prevalence and co-morbid illnesses among HCV-infected patients were determined. RESULTS: Among 2,735,511 active patients, 23,492 (0.86%) were found to have evidence of HCV infection, the majority of which were Caucasian (78.2%) and born between the years 1945 and 1965 (68.3%). In comparison to Caucasians, higher rates of HCV infection were found among Native Americans (2.5% vs. 0.95%, p<0.001). Compared to HCV-negative patients, a greater proportion of HCV-positive patients had diabetes mellitus (18.7 vs. 8.9%, p<0.0001), chronic kidney disease (4.4 vs. 1.8%, p<0.0001), end-stage renal disease necessitating hemodialysis (2.6 vs. 0.6%, p<0.0001), and HIV co-infection (2.4 vs. 0.2, p<0.0001). Nearly two-thirds (62.1%) of HCV patients had government-sponsored insurance, and 93.0% of treated patients resided in urban settings. CONCLUSION: The prevalence of HCV infection in this large health care system serving the Pacific Northwest, Alaska, and California was lower than prior population-based estimates and may reflect real-world prevalence rates among patients not selected for risk-based screening. Native Americans are disproportionately affected by HCV and may warrant targeted screening.

Nutritional Approaches to Achieve Weight Loss in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) can range in spectrum from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), which is characterized by lipotoxicity, hepatocellular ballooning, and inflammation and can progress to cirrhosis. Weight loss is the cornerstone treatment for NAFLD and NASH. Various randomized controlled trials have shown that weight loss of ≥5-10% leads to significant improvements in hepatic steatosis. Diets high in sodium and fructose have been implicated in the pathogenesis of NAFLD. Although some clinical studies suggest that an isocaloric high-fructose diet does not worsen NAFLD, these clinical studies are often short in duration. More recently, the Dietary Approaches to Stop Hypertension diet, a sodium-restricted diet, has been associated with less prevalence of NAFLD and has been shown to improve NAFLD. In addition, the Mediterranean diet has been promising in improving hepatic steatosis, and a larger randomized controlled trial is currently enrolling subjects. For those who are unable to pursue weight loss through dietary approaches, bariatric surgery has been shown to improve hepatic steatosis and steatohepatitis. This method has been variable in improving hepatic fibrosis. In conclusion, weight loss is crucial to the improvement of NAFLD and NASH, and patients should attempt various diets in an attempt to achieve weight loss.

Gastric graft-versus-host disease revisited: does proton pump inhibitor therapy affect endoscopic gastric biopsy interpretation?

Accurate diagnosis of gastrointestinal graft-versus-host disease (GvHD) is important, as it contributes significantly to postallogeneic stem cell transplant (SCT) morbidity and mortality. To test the hypothesis that proton pump inhibitor (PPI) therapy may interfere with histologic evaluation of gastric GvHD by inducing apoptosis, we evaluated epithelial apoptotic body counts in antral and fundic biopsies from SCT recipients and control patients, both taking and not taking PPIs at the time of endoscopic biopsy. Hematoxylin and eosin-stained slides of gastric biopsies from 130 patients (75 allogeneic SCT with GvHD on clinical and histologic grounds, and a comparison group of 55 age- and sex-matched nontransplant patients with histologically normal gastric biopsies) were reviewed. The groups were further stratified into patients taking (PPI+) and not taking PPIs (PPI-) at the time of biopsy. Apoptotic bodies (AB)/10 (400 x) high power fields (HPF) were quantified for each case. Mean apoptotic body counts were then calculated for each case group. Seventy antral cases (31 control and 39 transplant) were also evaluated via gastrin immunohistochemistry, and the mean number of gastrin positive cells/400 x HPF calculated. In the PPI- groups, apoptosis was increased in biopsies from transplant patients, compared with controls, both in antral and fundic mucosa. In PPI+ patients, there was significantly more apoptosis in the gastric body in transplant patients than in controls. However, comparing antral biopsies from control and transplant PPI+ patients, there was no significant difference in AB quantitation. More apoptosis was seen in antral biopsies from PPI+ control patients when compared with PPI- control patients (P = 0.009). Mean numbers of gastrin positive cells/400 x HPF were increased in both control and transplant patients taking PPIs (85 and 58, respectively) compared with samples from those patients not taking PPIs (48 and 51, respectively). PPI therapy is associated with increased apoptosis in antral biopsies and may interfere with the evaluation of GvHD in biopsies from this site. A similar increase in apoptosis was not seen in fundic biopsies; biopsy of the gastric fundus rather than antrum may be preferable for the diagnosis of upper gastrointestinal GvHD.

Miliary tuberculosis as a cause of acute empyema.

Adult respiratory distress syndrome (ARDS) and sepsis are known, life-threatening complications of miliary tuberculosis. This report describes a patient with miliary tuberculosis who rapidly developed an acute tuberculous empyema. She had a fulminant course culminating in ARDS, sepsis and subsequent death. This case highlights the rare association of acute empyema with miliary tuberculosis.