Unfavorable prognosis of patients with acute liver injury due to drug‐induced liver injury and acute exacerbation of hepatitis B virus infection

Abstract

Aim Acute liver injury (ALI) has a favorable prognosis, whereas acute liver failure (ALF) leads to organ failure and thus has an unfavorable prognosis. The effect of each etiology on the clinical course of ALI remains unclear. This study aimed to determine how each etiology and glucocorticoid on the unfavorable etiology affects the clinical course of ALI. Methods This prospective observational study enrolled 522 patients with ALI/ALF from 2004 and 2017. To evaluate the influence of etiology on prognosis, decision tree analysis was carried out using age, disease type, etiology, and the presence of hepatic encephalopathy. Results Of 522 patients, 398 patients satisfied the ALI criteria at registration in this study. The ALI etiologies were as follows: viral hepatitis through oral infection (n = 54), acute hepatitis B virus (HBV) infection (n = 24), acute exacerbation of HBV infection (n = 30), de novo hepatitis due to HBV (n = 5), autoimmune hepatitis (n = 59), drug‐induced liver injury (DILI; n = 85), other viruses (n = 12), and undetermined (n = 129). ALI in 46 patients progressed to ALF after registration. Of 11 patients (age >52 years) with ALF due to acute exacerbation of HBV infection or DILI, seven patients (63.6%) died. Whether glucocorticoid affected the clinical course of ALI due to acute exacerbation of HBV infection or DILI was evaluated using propensity score matching (age, sex, alanine aminotransferase, total bilirubin, and prothrombin time‐international normalized ratio). Glucocorticoid did not improve the prognosis of ALI patients due to the two etiologies. Conclusions Progression of ALI due to DILI or acute exacerbation of HBV infection to ALF showed a poor prognosis.

Early identification using the referral system prolonged the time to onset for hepatic encephalopathy after diagnosing severe acute liver injury

“…We implemented the referral system for patients with ALI in 2004. Parts of the results have previously been reported by us 3,7,9,16,25,28 . The present observational prospective cohort study was registered in University hospital Medical Information Network (UMIN) in 2015 (UMIN000016568).…”

“…First, the number of patients was relatively small; therefore, differences between the influence of specific etiologies on the prognosis of SLI remain unclear. We previously reported that the referral system does not decrease the rate of HE development among patients with SLI/ALF due to drug-induced liver disease 16 , nor does it improve the prognosis of patients with exacerbation of hepatitis B 3 ; therefore, the clinical course of each etiology should be carefully observed. Second, the clinical course of the patients in this study does not reflect the natural course of SLI due to the selective population of the study.…”

“…The inclusion criteria of the study were as follows: the absence of chronic hepatitis or liver cirrhosis, a diagnosis of ALI due to hepatitis, sufficient data for analysis, and prolonged PT-INR ≥ 1.5 or PT activity ≤ 40%. Evaluation of etiology was based on previously described criteria 3 . The exclusion criterion was a diagnosis of ALI due to non-hepatitis (malignancy, ischemic hepatitis, congestive liver, or acute fatty liver of pregnancy).…”

“…It is defined as severe acute liver injury (SLI) that includes ALF without HE, resulting in elevated liver enzymes and coagulopathy. Our previous study revealed that the mortality rate among patients who progressed from acute liver injury (ALI) to SLI/ALF is higher than those with ALI 3 ; thus, progression to SLI/ALF is a risk factor of poor prognosis for ALI. Furthermore, previous studies have reported that the mortality rate increases among patients with ALF who develop HE 4 – 7 .…”

“…After introducing our JHEP model, the rate of HE development among patients with SLI decreased drastically 16 , indicating effective prevention of HE development via the referral system. As the mortality rate was previously found to be only 11.6% among patients with ALI who progress to SLI/ALF 3 , a more sensitive parameter was required to identify patients who would require liver transplantation. To understand potential indications for liver transplantation in patients with ALF who are listed on the referral system, the risk factors associated with poor prognosis must be investigated.…”