Necrotic cell death and suppression of T-cell immunity characterized acute liver failure due to drug-induced liver injury.

BACKGROUND & AIMS: The aim of this study was to investigate the clinical characteristics and pathophysiology of drug-induced liver injury (DILI) - acute liver failure (ALF).

METHODS

The patients with acute liver injury (ALI) including ALF from 2009 to 2014 were analyzed. The hepatic encephalopathy (HE) development rate was compared with the findings from a national survey in Japan. The serum cytokines levels and the findings of a liver function test were evaluated in the DILI patients.

RESULTS

The HE development rate substantially decreased for autoimmune hepatitis (AIH) - and undetermined cause-induced ALI owing to the early prediction system, but not in DILI-ALI. Among the DILI-ALF and AIH-ALF cases, the CK-18 fragment (1480.1U/L, 3945.4U/L), IL-8 (82.9pg/mL, 207.5pg/mL), IP-10 (1379.6pg/mL, 3731.2pg/mL) and MIP-1β (1017.7pg/mL, 2273.3pg/mL) levels were lower in the DILI-ALF cases. Among the DILI-ALI and DILI-ALF cases, IL-4 (19.8pg/mL, 25.4pg/mL) and RANTES (14028.0pg/mL, 17804.7pg/mL) were higher in DILI-ALI, and HMGB-1 (397.1pg/μL, 326.2pg/μL) and HGF (2.41ng/mL, 0.55ng/mL) were higher in DILI-ALF. We observed that HGF independently associated with DLI-ALF development.

CONCLUSIONS

Despite the low grade apoptosis and inflammation, DILI patients progressed to ALF comparable with that of the AIH patients.