1. Background

Excessive alcohol consumption is a growing trend in the United States, Europe, and Israel, with approximately 87% of the general population older than 18 years in USA reporting some history of alcohol consumption and approximately 25% meeting the criteria for heavy drinking [1-3]. Acute Alcoholic hepatitis (AAH) is a unique syndrome in patients with alcoholic liver disease. It is associated with poor prognosis and incredibly high short-term mortality of 16% to 50% within 1 month of presentation, depending on initial disease severity [4-8]. AAH accounts for 0.7% of all hospital admissions in the United States, which is higher than that for myocardial infarction, or acute pancreatitis [9,10]. Very few studies have examined both demographic patterns and natural history of AAH, in USA, Europe and Israel.

The risk of alcoholic liver disease is related to the amount and duration of alcohol use and the gender (women seem to be more vulnerable than men even when drinking the same amounts) [11,12]. However, only a small proportion of heavy drinkers develop AAH, suggesting the significant role of host and environmental factors on the development of AAH [2,4,5,13-16], The main objectives of this study were

· To find out the typical population with AAH in Israel

· To reveal their type of drinking habits

· To evaluate the prognosis and mortality of patients with AAH in southern Israel

· To guide physicians for further evaluation regarding AAH.

2. Participants and Methods

This study is concerned with retrospective observational cohort study of patients with well-characterized AAH in the years 1998-2017.All medical files of patients with "Acute Alcoholic hepatitis " or "Alcoholic יHepatitis", "Alcoholic hepatitis with cirrhosis", etc., were evaluated by a resident. Ninety-nine patients with "Acute Alcoholic Hepatitis", were found. Information was obtained from computed medical file. Inclusion criteria included all patients that were hospitalized with diagnosis of "acute alcoholic hepatitis". Pregnant women and minors were not included.

Statistical information was summarized with SPSS (version 18). Data was summarized in "prevalence tables', summarized statistics and safety margins and standard p-value. All statistical tests were done with distinction of bilateral alfa=0.05. Distribution of continuous variables with normal distribution was presented as average and standard deviation (Table 1).

2.1. Drinking habits

3. Results

3.1. Demographic Details

The study included 99 patients admitted to Barzilai Medical Center in 2004-2017 due to “Acute Alcoholic Hepatitis”. Ninety-nine patients were diagnosed as c AAH. Mean age was 48, 72 (72.3%) were males and 27 were females (27.3%.). Seventy-eight patients were born in Russia. Eighty-eight patients (88.9%) were admitted originally to internal medicine departments. Hundred thousand admissions to ED and 30000 admissions for hospitalization per year. Mean number of patients with AAH 99:14years, 14.1: 30,000, 0.047% of admissions for hospitalization were due to AAH. Mean alcohol amount that was consumed by males was 80 grams of alcohol per day. The amount of alcohol that was consumed by females was 40 grams of alcohol per day. Vodka was the most common source of alcohol with beer and wine coming next.

3.2. Laboratory Examinations

Mean level of bilirubin was 13mg/dl, mean albumin level was 2.7g/dl. Mean transaminases levels was elevated and alkaline phosphatase was up to twice the upper level of norm. Leukocytosis and neutrophilia were also typical.

3.3. Treatment 

Corticosteroids and pentoxyphylline were the most common medicines with N-Acetyl Cysteine less common.

3.4. Prognosis

One-year survival was 60%. Most of the surviving patients were either transplanted or successfully withdrawn from alcohol.

4. Discussion

A recent NIH study showed steep increase in the rate of alcohol-related ER visits of 50% between 2006-14 [17]. The number of people in the USA who consumed alcohol and the amount of the alcohol consumed did not change much, but the rate of visits for acute alcohol consumption rose by 40%. The searchers suspect the increase in ED visits is related to the increase in the intensity of alcohol use among subset of drinkers. Alcoholic hepatitis may be caused by each day drinking, or a few days’ week, such as on weekends. Any type of alcohol may cause disease. A binge drinking pattern is becoming increasingly prevalent, mainly among young individuals, but little is known about the impact on liver disease. Liver cirrhosis is seen only in minority of subjects with high alcohol consumption. Less than 10% of the consumers of more than 120 grams of alcohol per day have cirrhosis [17]. The incidence of alcohol abuse in Israel is much lower than in USA or west Europe, actually Israel and Turkey has the lowest incidence of alcoholism among youth, in the OECD [18], while the biggest surge in youth drinking was seen in Russia.

There is a worsening in alcohol use among Former Soviet Union (FSU) immigrants [18-20]. First generation FSU and second generation Ethiopian adolescents were found to have higher levels of binge alcohol drinking [21]. However, the fact that most of our patients were from former USSR should alert for increasing rate of binge alcohol drinking and more alcoholic hepatitis. The incidence of AAH of 0.047% in our hospital is much lower than the incidence of AAH admissions of 0.7% among American hospital admissions [17]. The ratio of females (20-25%) was similar to our modest group (27%). Women appear to be more vulnerable than man to many adverse consequences of alcohol abuse. Women achieve higher concentrations of alcohol in the blood and are more vulnerable than man in the same amounts of alcohol [22]. Compared with men, women develop alcohol-induced liver disease over a shorter period of time consuming alcohol and are more likely to develop AAH and to die from cirrhosis [22-24].

This may be related not only to the difference in the level of alcohol dehydrogenase but also to the female reproductive hormone estrogen [23]. Among Americans 10 percent of women and 22 percent of men consumed two or more drinks per day on average [25-29]. Women’s drinking is most common between ages 26 and 34 and among women who are divorced or separated The number of alcohol consumers was too small to show any statistical significant increase in the overall incidence of AAH Oran increase incidence among females. A remarkable Dannish study followed 2000 patients with AAH during a decade and found an increasing incidence of AAH, both in males and females as well as an increase in mortality, both in the short term and in the long term [24]. The causes of death in AAH are primarily due to liver-related complications, suggesting that patients with AAH could benefit from continued follow-up by a hepatologist after the acute episode. Twenty percent of patients died within 3 months of admission and 31% within 10 years.

The short term mortality of AAH patients in our study was tremendous (40%) however not much different from mortality in western medical literature. Severe alcoholic hepatitis has 28 days’ mortality of 25% to 50% in most studies [23-25]. Our patients had severe disease with Madrey score>32, so the one-year mortality of 40% is similar to other studies. All patients were treated with steroids, pentoxyphyllin or both of them or even UDCA.

5. Conclusions

Acute Alcoholic Hepatitis is much less common in Israel than in other OECD countries.

AAH incidence is increasing among females in Israel but it is still less common than among males

AAH has bad prognosis among patients with one-year mortality of up to 40 percent.

1. Mandayam S, Jamal MM, Morgan TR (2004) Epidemiology of alcoholic liver disease. Semin Liver Dis 24: 217-232.
2. Singal AK, Anand BS (2013) Recent trends in the epidemiology of alcoholic liver disease. Clin Liver Dis 2: 53-56.
3. National Institute on Alcohol Abuse and Alcoholism Alcohol facts and statistics 2014.
4. Singal AK, Kamath PS, Gores GJ, Shah VH (2014) Alcoholic hepatitis: current challenges and future directions. ClinGastroenterolHepatol 12: 555-564.
5. Lucey MR, Mathurin P, Morgan TR (2009) Alcoholic hepatitis. N Engl J Med 360: 2758-2769.
6. World Health Organization. World Health Organization; Geneva, Switzerland: 2014. Global Status Report on Alcohol and Health 2014.
7. Substance Abuse and Mental Health Services Administration. Substance Abuse and Mental Health Services Administration; Rockville, MD: 2014. Results from the 2013 National Survey on Drug Use and Health: Summary of National Findings. NSDUH series H-48, HHS publication No. (SMA) 14-4863.
8. Thursz MR, Richardson P, Allison M (2015) Prednisolone or pentoxifylline for alcoholic hepatitis. N Engl J Med 372: 1619-1628.
9. Jinjuvadia R, Liangpunsakul S (2015) Translational Research and Evolving Alcoholic Hepatitis Treatment Consortium Trends in alcoholic hepatitis-related hospitalizations, financial burden, and mortality in the United States. J Clin Gastroenterol 49: 506-511.
10. Liangpunsakul S (2011) Clinical characteristics and mortality of hospitalized alcoholic hepatitis patients in the United States. J Clin Gastroenterol 45: 714-719.
11. Corrao G, Bagnardi V, Zambon A, Torchio P (1998) Meta-analysis of alcohol intake in relation to risk of liver cirrhosis. Alcohol Alcohol 33: 381-392.
12. Becker U, Deis A, Sorensen TI, Grønbaek M, Borch-Johnsen K, et al. (1996) Prediction of risk of liver disease by alcohol intake, sex, and age: a prospective population study. Hepatology 23: 1025-1029.
13. Bellentani S, Saccoccio G, Costa G, Tiribelli C, Manenti F, et al. (1997) The Dionysos Study Group Drinking habits as cofactors of risk for alcohol induced liver damage. Gut 41: 845-850.
14. Strnad P, Zhou Q, Hanada S, Lazzeroni LC, Zhong BH, et al. (2010) Keratin variants predispose to acute liver failure and adverse outcome: race and ethnic associations. Gastroenterology 139: 828-835.
15. Tian C, Stokowski RP, Kershenobich D, Ballinger DG, Hinds DA (2010) Variant in PNPLA3 is associated with alcoholic liver disease. Nat Genet 42: 21-23.
16. Buch S, Stickel F, Trepo E, Way M, Herrmann A, et al. (2015) A genome-wide associationstudy confirms PNPLA3 and identifies TM6SF2 and MBOAT7 as risk loci for alcohol-related cirrhosis. Nat Genet 47: 1443-1448.
17. NIH news release January 12 2018
18. The times of israel ‘Alcohol consumption in Israel among lowest in OECD countries”. May 2015.
19. Schiff M, Rahav G, Teichman M (2005) Israel 2000: immigration and gender differences in alcohol consumption. Am J Addict 14: 243-247.
20. Sznitman SR, Baron-Epel O, Boker-Keinan L (2013) Convergence of drinking patterns of young Russian immigrants and veteran Israelis decades after mass immigration: results from a bidirectional acculturation model. J Stud Alcohol Drugs 74: 437-446.
21. Walsh SD, Dialovski A, Boniel-Nissim M, Harel-Fisch Y (2014) Parental, peer and school experiences as predictors of alcohol drinking among first and second generation immigrant adolescents in Israel. Drug Alcohol Depend 138: 39-47.
22. NIH ON ALCOHOL ABUSE AND ALCOHOLISM: 46 December 1999
23. Ikejima K, Enomoro N, Limuro Y, Brenner DA, Thurman RG (1998) Estrogen increases sensitivity OF Kupffer cells to endotoxin. Alcohol ClinExp Res 22: 768-769.
24. DamgaardSandahl T (2014) Alcoholic hepatitis. Dan Med J 61: 4755.
25. Cohen SM (2009) The diagnosis and management of alcoholic hepatitis. Aliment PharmacolTher 30: 3-13.
26. Imperiale TF, McCullough AJ (1990) Do corticosteroids reduce mortality from alcoholic hepatitis? A meta-analysis of the randomized trials. Ann Intern Med 113: 299-307.
27. Mathurin P, O'Grady J, Carithers RL, Phillips M, Louvet A, et al. (2011) Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis: meta-analysis of individual patient data. Gut 60: 255-260.
28. EASL (2012) clinical practice guidelines management of alcoholic liver disease. J Hepatol 57: 399-420.
29. Belllentani S, Saccocio G, Costa G, Tiribelli C, Manenti F, et al. (1997) Drinking habits as cofactor of risk for alcohol induced liver damage. Gut 41: 845-850.