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.
Alcoholic hepatitis (AH) frequently progresses to multiple organ failure (MOF) and death. However, the driving factors are largely unknown. At admission, patients with AH often show criteria of systemic inflammatory response syndrome (SIRS) even in the absence of an infection. We hypothesize that the presence of SIRS may predispose to MOF and death. To test this hypothesis, we studied a cohort including 162 patients with biopsy-proven AH. The presence of SIRS and infections was assessed in all patients, and multivariate analyses identified variables independently associated with MOF and 90-day mortality. At admission, 32 (19.8%) patients were diagnosed with a bacterial infection, while 75 (46.3%) fulfilled SIRS criteria; 58 patients (35.8%) developed MOF during hospitalization. Short-term mortality was significantly higher among patients who developed MOF (62.1% versus 3.8%, P <0.001). The presence of SIRS was a major predictor of MOF (odds ratio = 2.69, P=0.025) and strongly correlated with mortality. Importantly, the course of patients with SIRS with and without infection was similar in terms of MOF development and short-term mortality. Finally, we sought to identify serum markers that differentiate SIRS with and without infection. We studied serum levels of high-sensitivity C-reactive protein, procalcitonin, and lipopolysaccharide at admission. All of them predicted mortality. Procalcitonin, but not high-sensitivity C-reactive protein, serum levels identified those patients with SIRS and infection. Lipopolysaccharide serum levels predicted MOF and the response to prednisolone.
Conclusion
In the presence or absence of infections, SIRS is a major determinant of MOF and mortality in AH, and the mechanisms involved in the development of SIRS should be investigated; procalcitonin serum levels can help to identify patients with infection, and lipopolysaccharide levels may help to predict mortality and the response to steroids.
Complete abstinence after an episode of AH positively impacts long-term survival. The combination of 2 variables easily obtained at admission might be useful to predict long-term abstinence after an episode of AH. Strategies aimed at promoting alcohol abstinence in these patients are necessary. (Hepatology 2017;66:1842-1853).
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