Evaluating the safety and efficacy of seladelpar for adults with primary biliary cholangitis.

INTRODUCTION: Seladelpar (MBX-8025) is a once-daily administered highly specific PPAR-δ agonist in Phase 3 and extension trials for use in patients with primary biliary cholangitis (PBC). AREAS COVERED: This review provides background on current treatment options for PBC, and summarizes clinical trial data regarding the safety and effectiveness of seladelpar within the context of these treatments. EXPERT OPINION: Clinical trials results demonstrate the safety and tolerability of seladelpar use for PBC, including in patients with cirrhosis. The primary composite endpoint (ALP <1.67 times ULN, decrease ≥ 15% from baseline, and TB ≤ULN) was met in 61.7% of the patients treated with seladelpar and in 20% receiving placebo (p < 0.001). Moreover, pruritus - a cardinal and often intractable symptom of PBC - was improved with seladelpar treatment, as were overall quality of life measurements. Improvements in markers of inflammation were likewise observed. These biochemical and clinical findings therefore represent landmark developments in PBC treatment and offer a therapeutic option for PBC.

The Changing Global Epidemiology of Hepatocellular Carcinoma.

Hepatocellular carcinoma is among the leading causes of morbidity and mortality. Owing to the current epidemic of metabolic syndrome, the population affected by nonalcoholic fatty liver disease/nonalcoholic steatohepatitis continues to increase and now comprises a significant portion with those with hepatocellular carcinoma. The World Health Organization goal of obtaining universal hepatitis B virus vaccination has led to a global effort to improve vaccination, prevent mother-to-child transmission, and implement linkage to care to avoid the development of hepatocellular carcinoma. In contrast with the decreased burden of chronic hepatitis C virus, there has been an increase in new-onset acute hepatitis C virus.

Association Between Race/Ethnicity and Insurance Status with Outcomes in Patients with Hepatocellular Carcinoma.

BACKGROUND: Racial/ethnic disparities in prognosis have been reported in patients with hepatocellular carcinoma (HCC); however, few studies have evaluated racial/ethnic disparities in the context of insurance status. AIMS: Characterize racial/ethnic and insurance status in early tumor detection, receipt of curative therapy and overall survival in a multicenter diverse cohort of HCC patients from the USA. STUDY: We included patients with HCC diagnosed between June 2012 and May 2013 at four centers in the USA. Generalized linear mixed effects models were used to compare early tumor detection (defined using Milan Criteria) and curative treatment receipt (liver transplantation, surgical resection, or local ablation) as a function of patient race/ethnicity and insurance status. A multivariable frailty survival model was used to compare risk of death between patient groups. RESULTS: Of 379 HCC patients (52.8% non-Hispanic White, 19.5% Hispanic White, 19.8% Black), 46.4% and 48.0% were found at an early stage and underwent curative therapy, respectively, and median overall survival of the cohort was 25.7 months. Early detection of HCC was associated with gastroenterology subspecialty care and receipt of HCC surveillance but not race/ethnicity or insurance status in adjusted models. However, commercial insurance was significantly associated with higher odds of curative treatment receipt, which in turn was the strongest correlate for overall survival. After adjusting for health system and insurance status, race/ethnicity was not associated with curative treatment receipt or overall survival. CONCLUSIONS: Insurance status and access to gastroenterology subspecialty care may be important drivers of racial/ethnic disparities in prognosis among HCC patients.

Drug Hepatotoxicity: Causality Assessment.

Drug induced liver injury is a diagnosis that relies on the patterns of injury associated with specific medications and toxins. The process by which a clinician determines which agent is the likely culprit of the liver injury is called causality assessment. The Roussel Uclaf Causality Assessment Method (RUCAM) and additional causality assessment methods have been developed with the goal of providing a more standardized, less subjective approach to causality assessment. RUCAM remains the most used standardized method, however many physicians continue to rely on their experience for causality assessment.

Early Hospital Readmissions and Mortality in Patients With Decompensated Cirrhosis Enrolled in a Large National Health Insurance Administrative Database.

BACKGROUND: Patients with decompensated cirrhosis have high rates of morbidity and mortality and frequently require hospital admission. Few studies have examined early readmission as an indicator of 90 day and overall mortality. Analysis of large databases is needed to evaluate the association between early readmission and mortality in decompensated cirrhosis. METHODS: We analyzed 5 years of private, employer-based, health insurance claims data associated with HealthCare Services Corporation on 13.5 million members over 4 states from 2010 to 2014. We defined early readmission as an admission to a general acute care hospital within 30 days of an index hospitalization and compared mortality to those who were readmitted after 30 days (late readmission). Univariable analysis was used to compare clinical and patient characteristics associated with early readmission. Cox proportional hazard models with time-varying covariates were used to assess if an early readmission was an independent risk factor for death. RESULTS: A total of 16,107 patients with decompensated cirrhosis were analyzed. During the study period, 82% of patients with decompensated cirrhosis were hospitalized at least once. Over 50% of hospitalized patients experienced an early readmission. Patients with an early readmission received blood transfusions, transjugular intrahepatic portosystemic shunt, paracentesis, thoracentesis, and upper endoscopies more frequently than those with a late readmission. Cirrhotics with an early readmission had higher rates of hepatorenal syndrome, sepsis, hepatocellular carcinoma, hepatic encephalopathy, and ascites. Patients experiencing an early readmission had greater 90 day, 1 year and overall mortality. Early readmission was an independent predictor of worse survival when adjusting for other conditions associated with mortality in patients with cirrhosis, but the impact of an early readmission dissipated after 1 year. CONCLUSIONS: Patients with decompensated cirrhosis have high rates of hospitalization and frequently experience an early readmission. An early readmission to an acute care hospital is an independent predictor of mortality in patients with decompensated cirrhosis for at least 1 year following initial hospitalization.