Comparative analysis of acute on chronic liver failure related to herbs and anti-tubercular drugs

ABSTRACT

Objectives: Liver injury precipitated by drugs and herbal medicines( DHMs) can have variable presentations and outcomes. In Indian subcontinent, drug induced liver injury due to Anti-tubercular drugs( ATDs) and inadvertent herbs induced liver injury (HILI) are common. Comparative natural history and outcome of acute-onchronic liver failure(ACLF) due to common DHMs is largely unknown. Materials and Methods: Consecutive in-patients with ACLF precipitated by herbs or ATDs(year 2010-2021) were compared for baseline clinical profile, disease severity, histological features and organ failures. Treatment outcomes and predictors of in-hospital mortality were also analyzed. Results: 529 patients presented with ACLF related to HILI(ACLF-H, n = 430) and ATDs(ACLF-D, n = 99) [Mean Age-47.6 - 14 years, mean MELD score and HVPG were 29.1 - 5.4 and 15.5 - 3.4 mmHg respectively]. 61.4% patients had underlying histological cirrhosis. 21.2% patients had additional superadded acute insult [severe alcoholic hepatitis(n = 66), acute hepatitis E or A(n = 24/15)]. Twelve percent ACLF-H patients presented with clinical cholestasis, autoimmune hepatitis(n = 18) and hypersensitivity reactions(n = 4). Most common recognizable agent associated with ACLF-H was Tinospora cordifolia (n = 35,8.1%), inadvertently used in Indian households during the COVID-19 pandemics. Patients with ACLF-H as compared to ACLF-D had higher male preponderance (70.9% vs. 54.5%;p-0.002) and peripheral eosinophilia (6.4% vs. 1%;p-0.03), clinical cholestasis (19.6% vs 10.8%;p-0.05) and acute kidney injury (44.4% vs. 28.3%;p-0.003) at presentation. Use of plasma exchange(18.5%) had no impact on outcomes. None of the patients underwent liver transplantation. In-hospital mortality(19.2%) was higher in ACLF-D compared to HILI ACLF-H (31.3% vs. 17.2%;p-0.002). Presence of AKI [HR5.5 (95%CI2.78 to 11.1)], hepatic encephalopathy[HR4.4(95%CI1.76 to 11)] and pneumonia[ HR7.2(95%CI 3.59 to 14.65)] were independent predictors of mortality. Conclusion: Herbs and anti-tubercular drugs are common precipitants of ACLF in India and have high in-hospital mortality resulting from sepsis and organ(s) failure. In the absence of specific treatment options, prevention and early and careful monitoring of liver functions is of utmost importance.