Corticosteroids can be used to treat alcoholic hepatitis after a recent upper gastrointestinal bleed
Authors: Timothy R. Morgan
Journal: Journal of Hepatology (2014)

Prognosis of treated severe alcoholic hepatitis in patients with gastrointestinal bleedingJournal of HepatologyVol. 62Issue 4PreviewAll trials on severe alcoholic hepatitis (AH) have included patients with “pure” AH, i.e., without concomitant gastrointestinal bleeding (GIB). Severe AH is often suspected in cirrhotic patients with GIB. We aimed at (1) assessing the prevalence of AH in patients with GIB and Maddrey discriminant function (DF) ⩾32; (2) comparing the outcome in AH patients with or without GIB (AH-GIB+, AH-GIB−); and (3) assessing the performance of the Lille model for survival in AH-GIB+ patients. Full-Text PDF Alcoholic hepatitis (AH) is a disease that is diagnosed clinically by a constellation of findings, including a long and recent history of heavy alcohol use, onset of jaundice within the prior 3 months, and AST>ALT (and AST usually <500 IU/ml). Patients with severe AH usually have ascites and are malnourished, and not uncommonly have hepatic encephalopathy. Other causes of liver disease need to be excluded based on blood tests (e.g., autoimmune hepatitis) or tested for (e.g., hepatitis C, hepatitis B). Imaging of the abdomen and liver is recommended to evaluate for ascites, masses in the liver, biliary duct obstruction, and vascular structures. Infections in the urine, ascites, blood and, if indicated, lungs should be routinely assessed. Liver biopsy is helpful to make the diagnosis of AH and to differentiate from alcoholic cirrhosis without features of AH. However, in practice, most clinicians do not perform liver biopsy. Studies in which patients with clinical AH were biopsied found that most patients with histologic AH have underlying alcoholic cirrhosis [[1]Hardy T. et al.White cell count and platelet count associate with histological alcoholic hepatitis in jaundiced harmful drinkers.BMC Gastroenterol. 2013; 13: 55Crossref PubMed Scopus (31) Google Scholar]. EASL and AASLD guidelines recommend patients with AH and a Maddrey’s Discriminant Function score (DF) >32 receive prednisolone 40 mg/day for 4 weeks [2European Association for the Study of L EASL clinical practical guidelines: management of alcoholic liver disease.J Hepatol. 2012; 57: 399-420Abstract Full Text Full Text PDF PubMed Scopus (548) Google Scholar, 3O’Shea R.S. et al.Alcoholic liver disease.Hepatology. 2010; 51: 307-328Crossref PubMed Scopus (952) Google Scholar]. However, both EASL and AASLD guidelines specify that patients with recent upper gastrointestinal (UGI) bleed or with renal failure are not ideal candidates for prednisolone treatment. The reason for excluding patients with recent UGI bleeding is a carryover from clinical trials performed in the 1970’s and 1980’s in which patients with UGI bleeding were excluded. Although the justification for excluding patients with recent UGI bleeding from older studies is speculative, I believe there were two major reasons. First, there was widespread belief in the 1970s and 1980s that corticosteroids caused duodenal ulcers. Second, there was no effective treatment for UGI bleeding. Many cirrhotic patients with UGI bleeding died from repeat bleeding (or its complications: infection and renal failure) within a week or two, thereby limiting the efficacy of a drug that required several weeks to provide efficacy. Much has changed in the past 30–40 years. First, corticosteroids mildly increase the risk of UGI bleeding, especially in patients with liver disease [[4]Narum S. Westergren T. Klemp M. Corticosteroids and risk of gastrointestinal bleeding: a systematic review and meta-analysis.BMJ Open. 2014; 4: e004587Crossref Scopus (158) Google Scholar]. If one is concerned about corticosteroids causing ulcers one can add an H2 blocker or proton pump inhibitor (although there is reason to avoid proton pump inhibitors in patients with advanced cirrhosis [[5]O’Leary J.G. et al.Long-term use of antibiotics and proton pump inhibitors predict development of infections in patients with cirrhosis.Clin Gastroenterol Hepatol. 2014; ([Epub ahead of print])https://doi.org/10.1016/j.cgh.2014.07.060Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar]). Second, we now have treatments for most causes of UGI bleeding in AH. Endoscopic variceal band ligation plus beta blockers reduce esophageal variceal rebleeding risk and may improve survival [6O’Brien J. Triantos C. Burroughs A.K. Management of varices in patients with cirrhosis.Nat Rev Gastroenterol Hepatol. 2013; 10: 402-412Crossref PubMed Scopus (40) Google Scholar, 7Garcia-Tsao G. Bosch J. Management of varices and variceal hemorrhage in cirrhosis.N Engl J Med. 2010; 362: 823-832Crossref PubMed Scopus (656) Google Scholar]. Various endoscopic techniques, including injection and clips, can be used to reduce rebleeding from bleeding non-variceal sources in the stomach and duodenum [[8]Laine L. Jensen D.M. Management of patients with ulcer bleeding.Am J Gastroenterol. 2012; 107 (quiz 361): 345-360Crossref PubMed Scopus (500) Google Scholar]. Transjugular intrahepatic portosystemic shunts can reduce UGI bleeding in cirrhotic patients who fail endoscopic methods [[9]Garcia-Pagan J.C. et al.Early use of TIPS in patients with cirrhosis and variceal bleeding.N Engl J Med. 2010; 362: 2370-2379Crossref PubMed Scopus (845) Google Scholar]. Finally, antibiotics, given for 7 days after gastrointestinal bleeding in a cirrhotic patient, reduce infections and increase survival [[10]Chavez-Tapia N.C. et al.Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding.Cochrane Database Syst Rev. 2010; 9: CD002907PubMed Google Scholar]. Taken together, these treatments reduce the likelihood that a cirrhotic patient with UGI bleeding will die in the short-term. Thus, it seems reasonable to ask whether recent UGI bleeding should remain an exclusion to prednisolone treatment in AH. Rudler and colleagues from Hôpital Pitié-Salpêtrière in Paris have conducted a retrospective analysis of survival among patients with biopsy-proven AH who presented to hospital between 2005 and 2011 with recent UGI bleed as compared with patients with AH who were admitted without UGI bleeding [[11]Rudler M. Mouri S. Charlotte F. Lebray P. Capocci R. Benosman H. et al.Prognosis of treated severe alcoholic hepatitis in patients with gastrointestinal bleeding.J Hepatol. 2015; 62: 816-821Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar]. A total of 58 patients with UGI bleed and 47 patients without UGI bleed were analyzed. The two groups did not differ in presence of AH on biopsy (approximately 80%), DF or MELD score. 6-month survival was similar in both groups (74% vs. 70%). The probability of developing an infection after starting steroids was lower among subjects with UGI bleed (24%) as compared with subjects without an UGI bleed (45%). How do we incorporate these data into our current thinking about treatment of AH? Although this is a retrospective study, I believe the data are sufficiently strong that we should not exclude patients with AH and recent UGI bleeding from receiving prednisolone treatment. My reasoning is largely based on data, cited above, that UGI bleeding is no longer a major deterrent for short-term survival (especially if one waits 48 h or longer after the acute bleeding before starting corticosteroids) and that prednisolone minimally increases UGI bleeding risk. The reduction in infections among subjects with UGI bleeding is provocative. The authors speculate that prophylactic antibiotics, routinely given for 7 days after an UGI bleed, reduced the risk of infection. This explanation seems plausible. However, despite the reduction in infections, 1-month and 6-month survival was similar in the GIB and the non-GIB groups. The reason for the lack of reduction in mortality is not directly addressed by the authors. In my opinion, the data are not sufficiently strong to suggest that antibiotics be routinely prescribed to patients with AH to prevent infections. The position that prednisolone can be safely administered to subjects with recent UGI bleeding would be strengthened if other investigators would retrospectively analyze their database of AH, either individually, or collective (as a type of meta-analysis of primary data) for survival according to recent UGI bleeding. I don’t believe there will ever be a randomized control trial of prednisolone treatment (vs. no treatment) among AH patients with recent UGI bleeding. Until additional data are available, I will aggressively manage UGI bleeding in AH endoscopically, administer antibiotics for 7 days, and, if the patient has not re-bled for 48 h or longer, recommend prednisolone 40 mg/day for 28 days. The author declared that he does not have anything to disclose regarding funding or conflict of interest with respect to this manuscript. The underlying research reported in the study was funded by the NIH Institutes of Health. This manuscript was supported in part by the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health under award number U01AA021886.