Background & Aims
There is no histologic classification system to determine prognoses
of patients with alcoholic hepatitis (AH). We identified histologic features
associated with disease severity and created a histologic scoring system to
predict short-term (90 day) mortality.
Methods
We analyzed data from 121 patients admitted to the Liver Unit
(Hospital Clinic, Barcelona, Spain) from January 2000 through January 2008
with features of AH, and developed a histologic scoring system to determine
risk of death using logistic regression. The system was tested and updated
in a test set of 96 patients from 5 academic centers in the US and Europe,
and a semi-quantitative scoring system was developed, called the alcoholic
hepatitis histologic score (AHHS). The system was validated in an
independent set of 109 patients. Inter-observer agreement was evaluated by
weighted statistic analysis.
Results
Degree of fibrosis, neutrophil infiltration, type of
bilirubinostasis, and presence mega-mitochondria were independently
associated with 90 day mortality. We used these 4 parameters to develop the
AHHS to identify patients with low (0–3 points), moderate
(4–5 points), and high (6–9 points) risks of death within 90
days (3%, 19%, and 51%, respectively;
P<.0001). The AHHS estimated 90 day
mortality in the training and test sets with an area under the receiver
operating characteristic value of 0.77 (95% confidence interval,
0.71–0.83). Inter-rate agreement values were 0.65 for fibrosis, 0.86
for bilirubinostasis, 0.60 for neutrophil infiltration, and 0.46 for
megamitochondria. Interestingly, the type of bilirubinostasis predicted the
development of bacterial infections.
Conclusions
We identified histologic features associated with severity of AH and
developed a patient classification system that might be used in clinical
decision making.
on behalf of the RELIEF study group Acute-on-chronic liver failure (ACLF) is a frequent cause of death in cirrhosis. Albumin dialysis with the molecular adsorbent recirculating system (MARS) decreases retained substances and improves hemodynamics and hepatic encephalopathy (HE). However, its survival impact is unknown. In all, 189 patients with ACLF were randomized either to MARS (n 5 95) or to standard therapy (SMT) (n 5 94). Ten patients (five per group) were excluded due to protocol violations. In addition, 23 patients (MARS: 19; SMT: 4) were excluded from per-protocol (PP) analysis (PP population n 5 156). Up to 10 6-8-hour MARS sessions were scheduled. The main endpoint was 28-day ITT and PP survival. There were no significant differences at inclusion, although the proportion of patients with Model for Endstage Liver Disease (MELD) score over 20 points and with spontaneous bacterial peritonitis (SBP) as a precipitating event was almost significantly greater in the MARS group. The 28-day survival was similar in the two groups in the ITT and PP populations (60.7% versus 58.9%; 60% versus 59.2% respectively). After adjusting for confounders, a significant beneficial effect of MARS on survival was not observed (odds ratio [OR]: 0.87, 95% confidence interval [CI] 0.44-1.72). MELD score and HE at admission and the increase in serum bilirubin at day 4 were independent predictors of death. At day 4, a greater decrease in serum creatinine (P 5 0.02) and bilirubin (P 5 0.001) and a more frequent improvement in HE (from grade II-IV to grade 0-I; 62.5% versus 38.2%; P 5 0.07) was observed in the MARS group. Severe adverse events were similar. Conclusion: At scheduled doses, a beneficial effect on survival of MARS therapy in patients with ACLF could not be demonstrated. However, MARS has an acceptable safety profile, has significant dialysis effect, and nonsignificantly improves severe HE.
Infections ACLF Death Different clinical courses of acutely decompensated cirrhosis Pre-ACLF Unstable decompensated cirrhosis Stable decompensated cirrhosis 0 90 180 270 360 Days Highlights Patients with acutely decompensated cirrhosis without ACLF develop 3 different clinical courses. Patients with pre-ACLF develop ACLF within 90 days and have high systemic inflammation and mortality. Patients with unstable decompensated cirrhosis suffer from complications of severe portal hypertension. Patients with stable decompensated cirrhosis have less frequent complications and lower 1-year mortality risk.
Financial support: The study was supported by the European Foundation for the Study of Chronic Liver Failure (EF-Clif). EF-Clif received unrestricted donations from Grifols and Cellex Foundations and is partner or contributor in several projects of the EU Horizon 2020 research program. Maria Papp was supported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Science (BO/00232/17/5) and the New National Excellence Program of the Ministry of Human Capacities (ÚNKP-18-4 Bolyai Plus). Pere Ginès is a recipient of the ICREA ACADEMIA AWARD (2015-2020). Disclosures The EASL-CLIF Consortium is a network of 101 European University hospitals supported by the EF-Clif. EF-Clif is a private non-profit organization aimed at improving clinical and translational research in cirrhosis. The scientific agenda of the EASL-CLIF Consortium and the specific research protocols are made exclusively by the Steering Committee members without any participation of pharmaceutical companies.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.