PMID- 27142208
OWN - NLM
STAT- MEDLINE
DCOM- 20171214
LR  - 20220801
IS  - 1179-1942 (Electronic)
IS  - 0114-5916 (Linking)
VI  - 39
IP  - 9
DP  - 2016 Sep
TI  - Drug-Induced Liver Injury: Highlights from a Review of the 2015 Literature.
PG  - 801-21
LID - 10.1007/s40264-016-0427-8 [doi]
AB  - Numerous publications contributed to the expanding knowledge base about 
      drug-induced liver injury (DILI) in 2015. New findings from the US Drug Induced 
      Liver Injury Network (DILIN) in their most recently updated registry include a 1- 
      to 3-week delay in the appearance of acute DILI from short-course antibiotics 
      such as cefazolin. They corroborated the finding that acute DILI in patients with 
      underlying liver disease was far more severe and potentially fatal than in 
      patients without liver disease. The only drug that seemed to have an increased 
      risk of hepatotoxicity in these patients was azithromycin. While nearly one in 
      six patients with acute DILI had persistently elevated liver tests at 6 months, 
      and results for 75 % of these patients continued to be abnormal at 12 months, 
      most of these "chronic" injury cases were relatively minor and the result of 
      cholestatic hepatotoxins. Newly described DILI agents include tolvaptan, as well 
      as some new direct-acting antiviral protease inhibitors for chronic hepatitis C. 
      The latter have been associated with serious acute hepatitis, hyperbilirubinemia, 
      and decompensation. Herbal hepatotoxicity continues to be increasingly reported, 
      although applying causality assessment to these cases can, in fact, be more 
      challenging than with prescription drugs. As important as cases with DILI, the 
      class of PCSK9 inhibitors used to lower low-density lipoprotein (LDL) cholesterol 
      have not been associated with significant liver injury, in contrast with other 
      lipid-lowering agents. With respect to pharmacologic DILI risk factors, new data 
      show that drugs metabolized by cytochrome P450 enzymes had a nearly four times 
      higher likelihood of causing DILI. Interestingly, high lipophilicity, which was 
      previously felt to be a risk factor for DILI, was not found to be associated, 
      although more study is needed to confirm this observation. While human leukocyte 
      antigen (HLA) genotypes have been linked to several specific agents, the role of 
      such testing in the general population remains undefined due to the currently low 
      positive and negative predictive values of the available tests. New DILI 
      biomarkers, specifically microRNA-122 and keratin-18, among others, appear to 
      have the necessary predictive value to determine the prognosis and outcome of 
      patients with paracetamol (acetaminophen [AAP])-induced acute liver failure 
      (ALF), and may be of great benefit in deciding who requires N-acetylcysteine 
      (NAC), and for what duration. Treatment options for other forms of DILI remain 
      limited; no firm conclusions can currently be drawn for the use of NAC in non-AAP 
      ALF.
FAU - Sarges, Philip
AU  - Sarges P
AD  - Department of Medicine, Division of Gastroenterology, Hepatology Section, 
      Georgetown University Hospital, 3800 Reservoir Road, NW, Washington, DC, 20007, 
      USA. psarges@gmail.com.
FAU - Steinberg, Joshua M
AU  - Steinberg JM
AD  - Department of Medicine, Division of Gastroenterology, Hepatology Section, 
      Georgetown University Hospital, 3800 Reservoir Road, NW, Washington, DC, 20007, 
      USA.
FAU - Lewis, James H
AU  - Lewis JH
AD  - Department of Medicine, Division of Gastroenterology, Hepatology Section, 
      Georgetown University Hospital, 3800 Reservoir Road, NW, Washington, DC, 20007, 
      USA. LewisJH@gunet.georgetown.edu.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - New Zealand
TA  - Drug Saf
JT  - Drug safety
JID - 9002928
SB  - IM
MH  - Animals
MH  - Chemical and Drug Induced Liver Injury/*epidemiology
MH  - Humans
MH  - Liver Diseases/*complications
MH  - Liver Function Tests
MH  - Predictive Value of Tests
MH  - Prognosis
MH  - Risk Factors
MH  - Severity of Illness Index
MH  - Time Factors
EDAT- 2016/05/05 06:00
MHDA- 2017/12/15 06:00
CRDT- 2016/05/05 06:00
PHST- 2016/05/05 06:00 [entrez]
PHST- 2016/05/05 06:00 [pubmed]
PHST- 2017/12/15 06:00 [medline]
AID - 10.1007/s40264-016-0427-8 [pii]
AID - 10.1007/s40264-016-0427-8 [doi]
PST - ppublish
SO  - Drug Saf. 2016 Sep;39(9):801-21. doi: 10.1007/s40264-016-0427-8.