Impact of Hepatitis C Virus Infection on the in-Hospital Mortality of Patients with Alcoholic Hepatitis

Background and Aim: There is limited data on the impact of hepatitis C virus (HCV) infection on alcoholic hepatitis (AH). The present study was performed to assess the effect of HCV on inhospital mortality of AH. Methods: Using Nationwide Inpatient Sample (1998-2007), AH admissions were stratified based on the presence or absence of HCV. Results: Of 111,726 AH admissions, 7,240 (6.5%) were HCV +ve. These patients were different from HCV –ve subjects in age, race, Charlston Comorbidity index, pay source, hospital characteristics, complications, and interventions needed. In-hospital mortality from AH was higher in presence of HCV (3.8% vs. 3.1%; P=0.001). On multivariate logistic regression, HCV infection independently predicted in-hospital mortality of AH after controlling for other variables including calendar year [OR 1.29 (CI: 1.12-1.49; P=0.0005)]. Other strong predictors were hepatic encephalopathy and renal failure. Conclusion: Concomitant HCV infection is an important risk factor for in-hospital mortality in AH. Further studies with longer follow up are needed to assess the impact of HCV on AH patients at 6 months and at one year.


Introduction
Hepatitis C virus (HCV) infection and alcohol are the two most common causes of liver disease in the United States (US) (Anonymous 2002).It is well established that alcoholics with HCV infection develop cirrhosis and hepatocellular carcinoma more frequently than alcoholics without HCV infection (Peters and Terrault 2002;A. K. Singal and Anand, 2007).However, there is limited data on the effect of CHC on the outcome of alcoholic hepatitis (AH).We conducted the present study using the National Inpatient Sample (NIS) dataset to examine the impact of HCV on the inhospital mortality in patients with AH.The study was approved by the Institutional review board.

Methods
The Nationwide Inpatient Sample (NIS) dataset with details of about 8 million hospital discharges (with up to 15 diagnosis and 15 procedure codes) from over 1,050 hospitals in 42 states in the US.Discharges with a primary or secondary Journal of Virology & Microbiology 2 diagnosis of AH (ICD-9-CM code 571.1) were stratified based on their HCV status (ICD-9-CM code 070.41, 070.44, 070.51, 070.54, 070.70, 070.71).The primary outcome measure was in-hospital mortality.Two groups of AH patients (HCV +ve and HCV -ve) were compared with respect to patient demographics, Charlston Comorbidity Index (CCI) (Quan et al. 2005), admission type (elective vs. emergency), pay source (self employed or medicaid payment), hospital characteristics (urban or rural, teaching or non-teaching, bed size and geographical location), length of hospital stay, liver disease complications, diagnostic or therapeutic interventions, and outcome.Specific codes were used to identify each of these variables in the dataset (Table 1).

Results
A total of 111,726 AH admissions (6.5% with concomitant HCV infection) between 1998 and 2007 were analyzed.Patients with AH and concomitant HCV infection were younger, required admission on an emergent basis, were of black or Hispanic ethnicity, had a higher CCI score, were on Medicaid pay source, were more likely to be in a large, urban teaching hospital, located in the Western region of the country, and more frequently had liver related complications (Table 2).Although, overall mean length of hospital stay was similar between HCV positive and HCV negative groups (6.0±5.8 vs. 5.5±39 days; P=0.28), the proportion of patients staying in the hospital for more than 7 days was higher in HCV +ve AH admissions (23% vs. 21%; P<0.0001).
A total of 3,541 (3.2%) patients died (higher with HCV: 3.8% vs. 3.1%; P=0.001) during the hospital stay.In-hospital mortality decreased at about 7% per year [OR 0.93 (CI: 0.91-0.94;P<0.0001)] over the last decade.After controlling for other confounding variables including the calendar year, HCV was an independent predictor of in-hospital mortality in patients admitted with AH (Table 3).Patients with AH and concomitant HCV infection had worse outcome with a higher in-hospital mortality.This is reflected with higher rate of complications amongst patients with concomitant HCV infection.Several studies in the past have assessed the impact of HCV on alcoholic cirrhosis.However, the effect of HCV on the outcome of AH has not been examined properly.A previous study observed that patients with AH had a worse outcome at 6 months follow-up in the presence of HCV infection compared to patients without HCV (A. S. Singal, S; Kuo, YF; Weinman, SA. 2011).However, this was a small retrospective study from a single institution.
AH is a serious medical condition with a mortality of about 40% at 6 months in patients with severe disease despite treatment with corticosteroids and/or pentoxifylline (Lucey et al. 2009).In the present study, the overall in-hospital mortality was only 3.2%.Being a data set analysis, rigorous clinical criteria for the diagnosis of AH can't be applied.It is possible that this may have resulted in a more heterogeneous data collection and included patients with relatively milder forms of disease.The lack of availability of laboratory parameters in this data set limits determination of disease severity.However, we believe that the large sample size from a nationally representative database should overcome this limitation to a great extent.Since the number of admissions was the denominator for estimating the mortality, this may also have falsely lowered the inpatient mortality from AH as a patient may have been admitted several times prior to mortality.Furthermore, the lack of follow-up data after discharge from the hospital, limits the long-term outcome analysis of these patients.
In summary, our study indicates that inhospital mortality of patients admitted with AH is low.However, the presence of concomitant HCV infection is associated with higher in-hospital mortality.If these findings are confirmed in prospective studies and from databases with outpatient follow up, HCV infection in patients admitted with AH may be incorporated into scoring systems designed for the assessment of disease severity and mortality.

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ventilation, endotracheal intubation Continuous variables were compared using t-test and categorical variables using Chisquare test.Logistic regression model was built to study the independent association of HCV and in-hospital mortality.Variables which could have confounded the outcome were entered into the model.The results of logistic regression were described as odds ratio (OR) with 95% confidence interval (95% CI).