Etiologies and Outcomes of Acute Liver Failure in HIV + Adults: Results from the ALFSG Registry
Heather N. Simpson1, Timothy J. Davern2, K. Rajender Reddy3, Adrian Reuben4, Valerie Durkalski4, William M. Lee5, Robert J. Fontana1
1Divison of Gastroenterology, Department of Internal Medicine, University of Michigan Hospital, Ann Arbor, MI; 2Hepatology California Pacific Medical Center, San Francisco, CA; 3Gastroenterology, University of Pennsylvania, Philadelphia, PA; 4Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, SC; 5Internal Medicine, Southwestern Medical Center, Dallas, TX
The etiologies and outcomes of acute liver failure (ALF) in HIV + pts are largely unknown. In addition, the long term outcomes of HIV + pts with ALF undergoing transplantation have not been described. The aim of this study is to describe the presenting features, risk factors, and outcomes of adult HIV + pts with ALF enrolled in the ALFSG. METHODS: Clinical outcomes at 3 weeks of consecutive adult ALF HIV + pts enrolled between 1998 and January 2013 were reviewed and a subgroup returned for a study visit at 1 or 2 years after enrollment. RESULTS: Thirty three of the 2264 ALF pts (1.3%) were HIV +, enrolled at 16 sites. Etiologies of ALF included DILI in 11(33%), acetaminophen (APAP) overdose in 9 (27%), and the remaining 13 (39%) were due to HBV (4), AIH (4), indeterminate (3), HAV (1), and ischemia (1). The age, gender, and racial distribution of our cohort was similar to that of HIV+ pts in the general US population (2010 CDC HIV Surveillance Report). Twenty two (67%) were male and their mean age was 39.3 +/- 12.8 yrs; 18 (54%) were Caucasian, 13 (39%) African-American, and 2 (6%) were of other ethnicities. Seven (21%) had HBV co-infection, 2 (6 %) had HCV co-infection, 6 % reported a recent history of alcohol abuse. None had a recent history of IDU; 19/33 (57%) were receiving an antiretroviral agent at study enrollment. RUCAM scores were performed on 14 suspect drugs in the 11 DILI cases that were categorized into: highly probable (1), probable (5), possible (4), and unlikely (4). Implicated agents in the DILI cases included 7 combination antiretroviral agents given for 5-30 days, 2 trimethoprim-sulfamethoxazole cases, and 5 due to other drugs including voriconazole (1), sulfadiazine (2), duloxetine (1), and clarithromycin (1). Twenty four (73%) were alive at 3 weeks including 6 (18%) who had undergone transplantation (2 APAP, 1 DILI, 1 AIH, 1 HBV, 1 HAV). Six of 9 pts that died at 3 weeks were due to DILI. The APAP pts had a 3-week spontaneous survival rate of 78% compared to only 36% in the DILI group. Nine pts were seen at a mean of 26 months after enrollment which included 5 LT recipients (1 APAP, 1 DILI, 3 Other) and 4 spontaneous survivors (2 APAP, 1 DILI, 1 Other). At follow-up,7 (78%) had normal liver biochemistries and none of the LT recipients had experienced rejection or alloimmune hepatitis. CONCLUSIONS: DILI is over-represented in HIV+ ALF patients in comparison to the overall ALFsg cohort (33% vs 10%), but is not limited to anti-retrovirals. The small number of ALF HIV + LT recipients have generally done well, indicating that LT can be offered to selected HIV+ ALF patients.
K. Rajender Reddy - Advisory Committees or Review Panels: Genentech-Roche, Merck, Janssen, Vertex, Gilead, BMS, Novartis, Idenix; Grant/Research Support: Genentech-Roche, Merck, BMS, Ikaria, Gilead, Hyperion, Janssen, AbbVie
William M. Lee - Consulting: Eli Lilly, Novartis; Grant/Research Support: Gilead, Roche, Vertex, BI, Anadys, BMS, merck; Speaking and Teaching: Merck
Robert J. Fontana - Consulting: GlaxoSmithKline, tibotec; Grant/Research Support: Gilead, vertex, Ocera
The following people have nothing to disclose: Heather N. Simpson, Timothy J. Davern, Adrian Reuben, Valerie Durkalski