Extracorporeal cellular therapy (ELAD) in severe alcoholic hepatitis: A multinational, prospective, controlled, randomized trial.

Severe alcoholic hepatitis (sAH) is associated with a poor prognosis. There is no proven effective treatment for sAH, which is why early transplantation has been increasingly discussed. Hepatoblastoma-derived C3A cells express anti-inflammatory proteins and growth factors and were tested in an extracorporeal cellular therapy (ELAD) study to establish their effect on survival for subjects with sAH. Adults with sAH, bilirubin ≥8 mg/dL, Maddrey\u27s discriminant function ≥ 32, and Model for End-Stage Liver Disease (MELD) score ≤ 35 were randomized to receive standard of care (SOC) only or 3-5 days of continuous ELAD treatment plus SOC. After a minimum follow-up of 91 days, overall survival (OS) was assessed by using a Kaplan-Meier survival analysis. A total of 203 subjects were enrolled (96 ELAD and 107 SOC) at 40 sites worldwide. Comparison of baseline characteristics showed no significant differences between groups and within subgroups. There was no significant difference in serious adverse events between the 2 groups. In an analysis of the intent-to-treat population, there was no difference in OS (51.0% versus 49.5%). The study failed its primary and secondary end point in a population with sAH and with a MELD ranging from 18 to 35 and no upper age limit. In the prespecified analysis of subjects with MELD \u3c 28 (n = 120), ELAD was associated with a trend toward higher OS at 91 days (68.6% versus 53.6%; P = .08). Regression analysis identified high creatinine and international normalized ratio, but not bilirubin, as the MELD components predicting negative outcomes with ELAD. A new trial investigating a potential benefit of ELAD in younger subjects with sufficient renal function and less severe coagulopathy has been initiated. Liver Transplantation 24 380-393 2018 AASLD

A decade of rising alcoholic liver disease hospital admissions and deaths in Irish hospitals, 2007-2016: a retrospective cross-sectional analysis.

BACKGROUND Alcoholic liver disease (ALD) is a major cause of both liver cirrhosis and hepatocellular carcinoma (HCC) in Ireland. AIMS The aim of the study was to identify the epidemiological profile, temporal trends, development of complications and mortality arising from inpatient care episodes linked to ALD in Ireland from 2007 to 2016. METHODS This was a national retrospective study that analysed data on patient discharges from hospitals across Ireland. The Hospital Inpatient Enquiry System was used to gather this data. The main outcome measures were the number of hospital discharges for patients with ALD or HCC, also expressed per 100 000 population, the mortality rate associated with ALD and the prevalence of complications associated with ALD. RESULTS A total of 33 794 hospital discharges were examined. There was a 38% increase in hospital discharges and 300% increase in HCC coding for patients with ALD between 2006 and 2016. There were 73 hospital discharges with ALD per 100 000 population in 2016. That year, 40 482 bed days were required for inpatient management equating to 120 beds per day. Deaths from ALD rose by 29% over the 10-year period. Cirrhosis was diagnosed in 57% and 24% had ascites. Mortality was 9.8% rising to 16% with variceal bleeding and 42% with acute kidney injury. Only 31% were under the care of a gastroenterologist or hepatologist. CONCLUSION Ireland is seeing a rise in ALD-related hospital admissions and deaths, including HCC which increased three-fold. ALD is a preventable disease, and public health interventions are of proven benefit and required to reverse this trend