The Worsening Profile of Alcoholic Hepatitis in the United States

Abstract

Background: Alcoholic hepatitis (AH) is a major cause of liver-related hospitalization. The profile, treatment patterns, and outcomes of subjects admitted for AH in routine clinical practice are unknown. Also, it is not known whether these are changing over time. This study is thus aimed to identify temporal trends in hospitalization rates, clinical characteristics, treatment patterns, and outcomes of subjects admitted for AH in a routine clinical setting.

Methods: A retrospective analysis of adults admitted for AH from 2000 to 2011 was performed using an anonymized EMR database of patient-level data from 169 U.S. medical centers.

Results: (i)

Epidemiology: The proportion of baby boomers admitted for AH increased from 2000 to 2011 (26 to 31%, p < 0.0001). (ii)

Clinical: The median Model for End-Stage Liver Disease (MELD) score increased over time from 12 to 14 (p = 0.0014) driven mainly by increased international normalized ratio (1.2 to 1.4, p < 0.0001). The median Charlson Comorbidity Index increased from 0 to 1 (p < 0.0001) with increased diabetes, chronic obstructive pulmonary disease, and heart disease. (iii)

Complications: The following increased from 2001 to 2011: Gastrointestinal bleed-7 to 10% (p = 0.03); hepatic encephalopathy-7 to 13% (p < 0.0001); hepatorenal syndrome-1.8 to 2.8% (p = 0.0003); sepsis-0 to 6% (p < 0.0001); and pancreatitis-11 to 16% (p = 0.0061). (iv) Treatment patterns and mortality: Eight to 9% of subjects received steroids while pentoxifylline use increased to 2.2%. In those with MELD ≥ 22, mortality remained between 19 and 20% and only steroids modestly improved survival in this subset.

Conclusions: Severe AH continues to have a high mortality. The severity and comorbidities and complications associated with AH have worsened. Drug therapy remains suboptimal.

Keywords: Alcohol-Induced Cirrhosis; Alcoholic Hepatitis; Cirrhosis; Lille Score; Liver Failure; Model for End-Stage Liver Disease; Pentoxifylline; Prednisolone; Sepsis; Steroids.

Fig. 1

The median Charlson Comorbidity Index with upper and lower quartiles from 2000 to 2011. The median increased significantly (p < 0.001) from 2000 to 2011.

Fig. 2

Mortality in hospitalized subjects with alcoholic hepatitis: 2.3% of those with a Model for End-Stage Liver Disease (MELD) score < 22 died, while 19.3% of those with a MELD ≥ 22 died during the first hospitalization (p < 0.0001). Also, 0.7 and 5.6% of those below and above these MELD thresholds, respectively, were sent to hospice for terminal care, and the overall composite endpoints of death or transfer to hospice for terminal care in these groups were 2.6 and 20.8%, respectively. Of all deaths (inset), 71.2% occurred in those with MELD ≥ 22 whereas 29.8% occurred in those with lower MELD scores.

Fig. 3

Effectiveness of drug therapy in routine clinical practice: Mortality and a composite end point including in-hospital mortality and transfer to hospice are shown for subjects with alcoholic hepatitis and Model for End-Stage Liver Disease (MELD) ≥ 22. Those receiving any drug therapy had a significantly improved in-hospital mortality and the composite end point compared to MELD-matched controls who did not receive these drugs. Steroids improved mortality but only produced a trend toward improved composite end point. On the other hand, pentoxifylline was not associated with either significantly improved in-hospital mortality or the composite end point.