Acute Alcoholic Hepatitis: Natural History and Predictors of Mortality Using a Multicenter Prospective Study

Abstract

Objective: To examine the natural history of acute alcoholic hepatitis (AH) and identify predictors of mortality for AH using data from a prospective multicenter observational study.

Participants and methods: We analyzed data from 164 patients with AH and 131 heavy-drinking controls with no liver disease. Participants underwent clinical/laboratory assessment at baseline and 6 and 12 months after enrollment. Multivariable analyses were conducted to identify variables associated with mortality and examine the association between coffee drinking and risk of AH.

Results: Thirty-six patients with AH died during follow-up, with estimated 30-day, 90-day, 180-day, and 1-year survival of 0.91 (95% CI, 0.87-0.96), 0.85 (95% CI, 0.80-0.91), 0.80 (95% CI, 0.74-0.87), and 0.75 (95% CI, 0.68-0.83), respectively. In the multivariable analysis, higher serum bilirubin level (hazard ratio [HR]=1.059; 95% CI, 1.022-1.089), lower hemoglobin level (HR=1.263; 95% CI, 1.012-1.575), and lower platelet count (HR=1.006; 95% CI, 1.001-1.012) were independently associated with mortality in AH. Compared with controls, fewer patients with AH regularly consumed coffee (20% vs 44%; P<.001), and this association between regular coffee drinking and lower risk of AH persisted after controlling for relevant covariates (odds ratio=0.26; 95% CI, 0.15-0.46). Time-dependent receiver operating characteristic curve analysis revealed that Model for End-Stage Liver Disease; Maddrey Discriminant Function; age, serum bilirubin, international normalized ratio, and serum creatinine; and Child-Pugh scores all provided similar discrimination performance at 30 days (area under the curve=0.73-0.77).

Conclusion: Alcoholic hepatitis remains highly fatal, with 1-year mortality of 25%. Regular coffee consumption was associated with lower risk of AH in heavy drinkers.

Keywords: ABIC, age, serum bilirubin, international normalized ratio, and serum creatinine; AH, alcoholic hepatitis; AIC, Akaike Information Criterion; ALT, alanine aminotransferase; AST, aspartate aminotransferase; AUC, area under the curve; BMI, body mass index; CP, Child-Pugh; HR, hazard ratio; INR, international normalized ratio; IQR, interquartile range; MELD, Model for End-Stage Liver Disease; NA, not applicable; OR, odds ratio; ROC, receiver operating characteristic; STOPAH, Steroids or Pentoxifylline for Alcoholic Hepatitis; TREAT, Translational Research and Evolving Alcoholic Hepatitis Treatment; WBC, white blood cell; mDF, Maddrey Discriminant Function.

Figure 1

Consort diagram describing the cohort experience through 12-month follow-up. Completed indicates completed the visit (regardless of whether completed inside or outside the 3-month window); in window, individual still in window but not completed (3-9 months for the 6-month visit, 9-15 months for the 12-month visit); not yet in window, follow-up time less than 3 months for the 6-month visit and less than 9 months for the 12-month visit; missing visit, past the window/missed the visit.

Figure 2

Kaplan-Meier curve for survival of 164 patients with alcoholic hepatitis. Solid line represents mean survival; dotted lines, 95% CI.

Figure 3

Receiver operating characteristic (ROC) curves for Model for End-Stage Liver Disease (MELD); Maddrey Discriminant Function (mDF); age, serum bilirubin, international normalized ratio, and serum creatinine (ABIC); and Child-Pugh (CP) scores for predicting 30-day, 90-day, 180-day, and 1-year mortality rates. A, The ROC curve for MELD scores. The area under the curve (AUC) for 30-day mortality is 0.76 (95% CI, 0.67-0.85); 90-day mortality, 0.73 (95% CI, 0.64-0.82); 180-day mortality, 0.69 (95% CI, 0.58-0.79); and 1-year mortality, 0.62 (95% CI, 0.51-0.73). B, The ROC curve for mDF scores. The AUC for 30-day mortality is 0.75 (95% CI, 0.67-0.84); 90-day mortality, 0.73 (95% CI, 0.65-0.82); 180-day mortality, 0.71 (95% CI, 0.62-0.81); and 1-year mortality, 0.65 (95% CI, 0.55-0.76). C, The ROC curve for ABIC scores. The AUC for 30-day mortality is 0.73 (95% CI, 0.59-0.87); 90-day mortality, 0.71 (95% CI, 0.6-0.82); 180-day mortality, 0.71 (95% CI, 0.61-0.81); and 1-year mortality, 0.64 (95% CI, 0.53-0.76). D, The ROC curve for CP scores. The AUC for 30-day mortality is 0.77 (95% CI, 0.64-0.89), 90-day mortality, 0.69 (95% CI, 0.56-0.83); 180-day mortality, 0.7 (95% CI, 0.58-0.81); and 1-year mortality, 0.7 (95% CI, 0.6-0.8).

Figure 4

Kaplan-Meier survival curves for 4 risk stratification models stratified by optimal cutoff points (90-day interval). A, Model for End-Stage Liver Disease (MELD) score (<22 vs ≥22). B, Maddrey Discriminant Function (mDF) score (<44.62 vs ≥44.62). C, Age, serum bilirubin, international normalized ratio, and serum creatinine (ABIC) score (<7.603 vs ≥7.603). D, Child-Pugh (CP) score (<9 vs ≥9).