Early liver biopsy, intraparenchymal cholestasis, and prognosis in patients with alcoholic steatohepatitis.
BACKGROUND
Alcoholic steatohepatitis (ASH) is a serious complication of alcoholic liver disease. The diagnosis of ASH requires the association of steatosis, evidence of hepatocellular injury with ballooning degeneration, and polynuclear neutrophil infiltration on liver biopsy. Whether these lesions, in addition to other histological features observed in liver tissue specimens, have prognostic significance is unclear.


METHODS
We studied 163 patients (age 55 yrs [35-78], male/female 102/61) with recent, heavy (> 80 gr/day) alcohol intake, histologically-proven ASH (97% with underlying cirrhosis, Maddrey's score 39 [13-200], no sepsis), who had a liver biopsy performed 3 days [0-10] after hospital admission for clinical decompensation. A semi-quantitative evaluation of steatosis, hepatocellular damage, neutrophilic infiltration, periportal ductular reaction, intraparenchymal cholestasis, and iron deposits was performed by two pathologists. All patients with a Maddrey's score ≥ 32 received steroids. The outcome at 3 months was determined. Statistical analysis was performed using the Wilcoxon and Fisher's exact tests, Kaplan-Meier method, and the Cox proportional hazard model.


RESULTS
43 patients died after 31 days [5-85] following biopsy. The 3-month survival rate was 74%. Mean kappa value for histological assessment by the two pathologists was excellent (0.92). Univariate analysis identified age, the Maddrey's score, the Pugh's score, the MELD score and parenchymal cholestasis, but not other histological features, as factors associated with 3-month mortality. At multivariate analysis, age (p = 0.029, OR 2.83 [1.11-7.2], intraparenchymal cholestasis (p = 0.001, OR 3.9 [1.96-7.8], and the Maddrey's score (p = 0.027, OR 3.93 [1.17-13.23] were independent predictors of outcome. Intraparenchymal cholestasis was more frequent in non survivors compared to survivors (70% versus 25%, p < 0.001). Serum bilirubin was higher in patients with severe compared to those with no or mild intraparenchymal cholestasis (238 [27-636] versus 69 [22-640] umol/l, p < 0.001).


CONCLUSIONS
In this large cohort of patients with histologically documented ASH early after admission and no sepsis, liver biopsy identified marked intraparenchymal cholestasis as an independent predictor of poor short term outcome together with age and the Maddrey's score. It may be hypothesized that incorporation of this particular variable into existing disease severity scores for ASH would improve their performance.
Gastroenterology and Hepatology, Specialities Department, University Hospitals of Geneva, 4, Rue Gabrielle Perret-Gentil, CH-1211 Geneva, Switzerland. laurent.spahr@hcuge.ch
Laurent
L
Spahr
Laura
L
Rubbia-Brandt
Muriel
M
Genevay
Antoine
A
Hadengue
Emiliano
E
Giostra
D000328:Adult; D000367:Age Factors; D000368:Aged; D001663:Bilirubin / Q000097:blood; D044963:Biopsy, Fine-Needle; D002780:Cholestasis, Intrahepatic / Q000150:complications* / Q000401:mortality / Q000473:pathology; D015331:Cohort Studies; D005235:Fatty Liver, Alcoholic / Q000150:complications* / Q000401:mortality* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008099:Liver / Q000473:pathology*; D008104:Liver Cirrhosis, Alcoholic / Q000150:complications* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D012720:Severity of Illness Index; D015996:Survival Rate
D001663:Bilirubin