Determinants of Outcome in Severe Alcoholic Hepatitis
Determinants of Outcome in Severe Alcoholic Hepatitis
Our institute is a large teaching hospital in South East England with a referral base of ~300 000 patients. In our region, alcohol-related hospital admissions have doubled over the last 7 years (855/100 000 in 2003/04 to 1986.5/100 000 in 2010/11) and our primary care trust (PCT) ranks in the top quartile of PCTs for alcohol-specific mortality with death from chronic liver disease (CLD) being higher than the national average.
The study period was from January 2006 until August 2011, the starting time point chosen due to the availability of electronic pathology records. Those with a primary coded diagnosis of ALD (all 'K70' ICD-10 codes) were identified from the hospital's database of in-patient admissions. Medical and electronic records of consecutive patients admitted with a coded diagnosis of ALD were then retrospectively reviewed to identify those with SAH as their index presentation of liver disease.
SAH was defined by:
Patients with any other form of coexistent chronic liver disease (viral hepatitis, iron overload, biliary or autoimmune disease) or history of jaundice ≥3 months were excluded.
In the context of SAH management, the need for histological confirmation is controversial and the frequency of liver biopsy varies according to local facilities and expertise. A minority of our cohort (n = 12, 11.0%) had biopsy-proven AH, reflective of clinical practice in most UK centres. A clinical diagnosis of SAH proves correct in 96% of cases, provided a threshold bilirubin ≥80 μmol/L is applied, a criterion fulfilled by all our patients. Our short-term outcomes (see below) were comparable to studies mandating histological confirmation of alcoholic hepatitis.
A retrospective review of clinical records was performed and the following data obtained: patient demographics, nature, duration and quantity of alcohol consumption, presence of cirrhosis, ascites, infections, hepatorenal syndrome (HRS), hepatic encephalopathy (HE) and portal hypertension-related gastrointestinal (GI) haemorrhage. The following prognostic scores were calculated at admission: Child–Pugh Score (CPS), DF, Glasgow Alcoholic Hepatitis Score (GAHS), Model for End-stage Liver Disease (MELD) and MELD-sodium (MELD-Na).
At our institute, medical therapy for SAH is prescribed at the discretion of the treating hepatologist, although it usually comprises corticosteroids (CS) (prednisolone 30 mg or 40 mg daily) and/or pentoxifylline (PTX) 1200 mg daily for 4 weeks. HRS was treated with terlipressin and albumin. All patients received dietetic input and were offered referral to alcohol liaison counsellors.
Spontaneous bacterial peritonitis (SBP) and HRS: as previously described.
Cirrhosis: any one of the following: corroborative histology, nodular liver margin or splenomegaly on imaging.
Recidivism: defined as any amount of regular alcohol use after index hospitalisation with SAH. This was largely determined from self-reported alcohol consumption in hospital records, including documentation from Emergency Department and out-patient clinic visits, subsequent in-patient admissions and correspondence from primary care physicians. Patients were classified into four groups according to drinking behaviour following index hospitalisation:
In view of the small number of patients in group 4, for purposes of data analysis, these cases were included in group 1.
Overall survival was calculated from the date of hospitalisation with SAH and censored at death or last hospital follow-up, determined as of July 2012. Cause of death was obtained from hospital, Coroner and primary care records. Deaths arising from hepatocellular carcinoma (HCC), liver failure and portal hypertension-related GI bleeding were deemed to constitute liver-related mortality (LRM). In those surviving the index hospitalisation, the number of subsequent admissions and need for liver transplantation (LT) were recorded. Those undergoing LT were censored alive at the date of transplantation.
Data are presented as mean ± standard deviation, median (interquartile range) or number (%) and all reported P values are two-tailed. The Mann–Whitney U- and Student's t-tests were used to compare nonparametric and parametric continuous variables, respectively, and categorical data were compared using the χ test. Kaplan–Meier (KM) survival tables and curves were generated and factors compared using the log rank test. Cox proportional hazards survival analysis was performed to identify factors associated with long-term mortality. Parameters with P value <0.10 in univariate analysis were selected for inclusion in a multivariable Cox regression model to determine independent predictors of survival. Survival analyses were performed in the whole cohort and then repeated to include only those who survived index hospitalisation. Receiver operator characteristic (ROC) curves were generated to evaluate the use of prognostic scores in predicting outcome beyond 12 months and compared using area under the curve (AUROC) analysis. In light of the anticipated high short-term mortality, the median follow-up time was calculated using the reverse KM method. Statistical analyses were undertaken using spss version 19.0 (SPSS Inc., Chicago, IL, USA) and figures produced using Prism Version 5 (GraphPad, San Diego, CA, USA).
This study was classified as service evaluation by both our institute's Research and Development Department and the National Research Ethics Service, and consequently formal ethics approval was not deemed necessary.
Patients and Methods
Our institute is a large teaching hospital in South East England with a referral base of ~300 000 patients. In our region, alcohol-related hospital admissions have doubled over the last 7 years (855/100 000 in 2003/04 to 1986.5/100 000 in 2010/11) and our primary care trust (PCT) ranks in the top quartile of PCTs for alcohol-specific mortality with death from chronic liver disease (CLD) being higher than the national average.
The study period was from January 2006 until August 2011, the starting time point chosen due to the availability of electronic pathology records. Those with a primary coded diagnosis of ALD (all 'K70' ICD-10 codes) were identified from the hospital's database of in-patient admissions. Medical and electronic records of consecutive patients admitted with a coded diagnosis of ALD were then retrospectively reviewed to identify those with SAH as their index presentation of liver disease.
SAH was defined by:
Presence of jaundice (bilirubin >80 μmol/L) and coagulopathy (INR ≥1.5) with admission Discriminant Function (DF) ≥32.
Long-standing alcohol excess (>50 g/day in women and >70 g/day in men until at least 6 weeks prior to admission).
plus any one of the following additional criteria:
AST:ALT ratio >2.
Enlarged, tender liver with peripheral blood leucocytosis.
Presence of hepatic encephalopathy at presentation.
Corroborative liver biopsy, where available.
Patients with any other form of coexistent chronic liver disease (viral hepatitis, iron overload, biliary or autoimmune disease) or history of jaundice ≥3 months were excluded.
In the context of SAH management, the need for histological confirmation is controversial and the frequency of liver biopsy varies according to local facilities and expertise. A minority of our cohort (n = 12, 11.0%) had biopsy-proven AH, reflective of clinical practice in most UK centres. A clinical diagnosis of SAH proves correct in 96% of cases, provided a threshold bilirubin ≥80 μmol/L is applied, a criterion fulfilled by all our patients. Our short-term outcomes (see below) were comparable to studies mandating histological confirmation of alcoholic hepatitis.
Data Collection
A retrospective review of clinical records was performed and the following data obtained: patient demographics, nature, duration and quantity of alcohol consumption, presence of cirrhosis, ascites, infections, hepatorenal syndrome (HRS), hepatic encephalopathy (HE) and portal hypertension-related gastrointestinal (GI) haemorrhage. The following prognostic scores were calculated at admission: Child–Pugh Score (CPS), DF, Glasgow Alcoholic Hepatitis Score (GAHS), Model for End-stage Liver Disease (MELD) and MELD-sodium (MELD-Na).
At our institute, medical therapy for SAH is prescribed at the discretion of the treating hepatologist, although it usually comprises corticosteroids (CS) (prednisolone 30 mg or 40 mg daily) and/or pentoxifylline (PTX) 1200 mg daily for 4 weeks. HRS was treated with terlipressin and albumin. All patients received dietetic input and were offered referral to alcohol liaison counsellors.
Study Definitions
Spontaneous bacterial peritonitis (SBP) and HRS: as previously described.
Cirrhosis: any one of the following: corroborative histology, nodular liver margin or splenomegaly on imaging.
Recidivism: defined as any amount of regular alcohol use after index hospitalisation with SAH. This was largely determined from self-reported alcohol consumption in hospital records, including documentation from Emergency Department and out-patient clinic visits, subsequent in-patient admissions and correspondence from primary care physicians. Patients were classified into four groups according to drinking behaviour following index hospitalisation:
Consistent abstainers: continued abstinence following discharge sustained until last follow-up.
Continued drinkers: evidence of early return (within 3 months of discharge) to regular alcohol use of any quantity, ongoing at last follow-up.
Relapsers: those who abstained for at least 3 months after discharge, although subsequently relapsed, with ongoing alcohol use at last follow-up.
Eventual abstainers: those who initially resumed drinking, although had been abstinent for ≥3 months at last follow-up.
In view of the small number of patients in group 4, for purposes of data analysis, these cases were included in group 1.
Overall survival was calculated from the date of hospitalisation with SAH and censored at death or last hospital follow-up, determined as of July 2012. Cause of death was obtained from hospital, Coroner and primary care records. Deaths arising from hepatocellular carcinoma (HCC), liver failure and portal hypertension-related GI bleeding were deemed to constitute liver-related mortality (LRM). In those surviving the index hospitalisation, the number of subsequent admissions and need for liver transplantation (LT) were recorded. Those undergoing LT were censored alive at the date of transplantation.
Statistical Analysis
Data are presented as mean ± standard deviation, median (interquartile range) or number (%) and all reported P values are two-tailed. The Mann–Whitney U- and Student's t-tests were used to compare nonparametric and parametric continuous variables, respectively, and categorical data were compared using the χ test. Kaplan–Meier (KM) survival tables and curves were generated and factors compared using the log rank test. Cox proportional hazards survival analysis was performed to identify factors associated with long-term mortality. Parameters with P value <0.10 in univariate analysis were selected for inclusion in a multivariable Cox regression model to determine independent predictors of survival. Survival analyses were performed in the whole cohort and then repeated to include only those who survived index hospitalisation. Receiver operator characteristic (ROC) curves were generated to evaluate the use of prognostic scores in predicting outcome beyond 12 months and compared using area under the curve (AUROC) analysis. In light of the anticipated high short-term mortality, the median follow-up time was calculated using the reverse KM method. Statistical analyses were undertaken using spss version 19.0 (SPSS Inc., Chicago, IL, USA) and figures produced using Prism Version 5 (GraphPad, San Diego, CA, USA).
This study was classified as service evaluation by both our institute's Research and Development Department and the National Research Ethics Service, and consequently formal ethics approval was not deemed necessary.