New strategies in management of severe alcoholic hepatitis

Aim of investigation. To evaluate efficacy and safety of S-adenosyl-L-methionine for treatment of alcohol-induced hepatitis of high severity.

Material and methods. Overall 40 patients with severe alcoholic hepatitis from two medical centers were selected for the study. Patients were randomly divided in two groups. The first group included 20 patients (16 men, 4 women, mean age 46,85±11,89 years). Median daily alcohol consumption — 71 years, 25-th and 75-th percentiles — 45,5 and 92,0 years respectively, duration of intake — 16,85±13,32 year. The mean score of Maddrey index (MI) was 58,5±26,8. The second group included 20 patients as well (11 men and 9 women, mean age — 46,10±10,47 years). The median of alcohol consumption per day was 73,8 years, 25-th and 75-th percentiles — 64,25 and 80,0 years respectively, duration of use — 16,25±5,18 year. The mean MI was 79,6±18,7. Groups were comparable by basic clinical and laboratory features. Patients of the first group received prednisolone 40 mg/day orally, patients of the second group received combination of prednisolone 40 mg/day orally and S-adenosyl-L-methionine (Adomet) 800 mg/day as intravenous infusions for 7 days, followed by 400 mg tid orally up to the 28 day of treatment. Lille index was utilized as treatment response criterion. During statistical data analysis Wilcoxon, Manna– Whitney and chi-square criteria were used. The survival analysis was done using Kaplan–Meyer curve with Breslow and LogRank significance estimation.

Results. Treatment response was higher in the group of patients receiving prednisolone in combination to Adomet (95 and 65% respectively, р=0,018). In this group the trend to increase survival was marked in comparison to the group receiving prednisolone monotherapy (100 and 90%). The rate of adverse events did not differ (р=0,50) significantly between two groups. Hepatorenal syndrome was significantly more frequent in patients receiving prednisolone (20 and 0%, р=0,03).

Conclusions. Prescription of prednisolone and Adomet combination at severe alcohol-induced hepatitis increases the treatment response rate to corticosteroids, promotes decrease of short-term mortality and results in significantly less frequent development of hepatorenal syndrome as compared to standard therapy.

1. Liver and biliary diseases: Manual for doctors / Ed. V.T. Ivashkin. 2nd ed. M.: LLC «Publishing house M-Vesti», 2005.

2. Ivashkin V.T., Buyeverov A.O. Rational pharmacotherapy in hepatology: Manual for practitioners. M.: Litterra, 2009.

3. Ivashkin V.T., Buyeverov A.O., Mayevskaya M.V. Differential approach to treatment of alcohol-induced liver diseases. Klin perspektivy gastroenterol gepatol 2005; 5:8-13.

4. Ivashkin V.T., Mayevskaya M.V. Alcoholic and viral liver diseases. - M.: Litterra, 2007. P. 85-118.

5. Mayevskaya M.V., Morozova M.A., Ivashkin V.T. Algorithm of management of alcohol-induced liver disease. Ros zhurn gastroenterol gepatol koloproktol 2007; 17(6):1- 10.

6. Khazanov A.I. Alcoholic liver disease. Ros med vesti 2002; 7 (1).

7. Ashwani K. Singal, Patrick S. Kamath, Gregory J. Gores, Vijay H. Shah. Alcoholic hepatitis: Current challenges and future directions. Clin Gastroenterol Hepatol 2014; 12:555-64.

8. Botta F., Giannini E., Romagnoli P., Fasoli A., Malfatti F., Chiarbonello B., Testa E., Risso D., Colla G., Testa R. MELD scoring system is useful for predicting prognosis in patients with liver cirrhosis and is correlated with residual liver function: a European study. Gut 2003; 52(1):134-9.

9. Bradley K.A., Bush K.R., McDonell M.B., Malone T., Fihn S.D. Screening for problem drinking: comparison of CAGE and AUDIT. Ambulatory Care Quality Improvement Project (ACQUIP). Alcohol Use Disorders Identification Test J Gen Intern Med 1998; 13(6):379-88.

10. Cynthia L. Vuittonet, Michael Halse, Lorenzo Leggio, Samuel B. Fricc hione, Michael Brickley, Carolina L. Haass-Koffler, Tonya Tavares, Robert M. Swift, George A. Kenna. Pharmacotherapy for alcoholic patients with alcoholic liver disease Am J Health-Syst Pharm 2014; 71(1).

11. http://gtmarket.ru/ratings/rating-countries-alcohol-consumption/info

12. Ki Tae Suk, Moon Young Kim, Soon Koo Baik. Alcoholic liver disease: Treatment World J Gastroenterol 2014; 20(36):12934-44.

13. Lee T.D., Sadda M.R., Mendler M.H., Bottiglieri T., Kanel G., Mato J.M., et al. Abnormal hepatic methionine and glutathione metabolism in patients with alcoholic hepatitis. Alcohol Clin Exp Res 2004; 28(1):173-81.

14. Louvet A., Naveau S., Abdelnour M., Ramond M.J., Diaz E., Fartoux L., Dharancy S., Texier F., Hollebecque A., Serfaty L., Boleslawski E., Deltenre P., Canva V., Pruvot F.R., Mathurin P. The Lille model: a new tool for therapeutic strategy in patients with severe alcoholic hepatitis treated with steroids. Hepatology 2007; 45(6):1348-54.

15. Maddrey W.C., Boitnott J.K., Bedine M.S., et al. Corticosteroid therapy of alcoholic hepatitis. Gastroenterology 1978; 75:193-9.

16. Mathurin P., O’Grady J., Carithers R.L., et al. Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis: meta-analysis of individual patient data. Gut 2011; 60:255-60.

17. Posey D., Mozayani A. The estimation of blood alcohol concentration: Widmark revisited. Forensic Sci Med Pathol 2007; 3(1):33-9.

18. Quentin M. Anstee, Christopher P. Day. S-adenosylmethionine (SAMe) therapy in liver disease: A review of current evidence and clinical utility. J Hepatol 2012. 57:1097-109.

19. Rajender K. Chawla, Walter H. Watson, Charles E. Eastin, Eun Y. Lee, Jack Schmidt, Craig J. McClain S-adenosylmethionine deficiency and TNF-a in lipopolysaccharide-induced hepatic injury. Am J Physiol 1998; 275 (Gastrointest. Liver Physiol. 38):125-9.