Acute Liver Failure (ALF)

Definition

ALF = jaundice + hepatic encephalopathy within 4 weeks + INR >1.5 in the absence of pre-existing chronic liver disease (CLD) or alcohol use. High mortality; principal cause of death: cerebral oedema, infections, multi-organ failure.

Context

• No prior CLD or alcohol (distinguishes from ACLF on top of cirrhosis)
• Treatment options limited; mainly supportive as bridge to liver transplantation
• A reliable early-mortality indicator panel is a major unmet need

Key aetiologies

• HEV (hepatitis E virus) — dominant in India (ILBS cohort)
• DILI (drug-induced liver injury)

Albumin changes in ALF

Albumin undergoes extensive PTMs in ALF, proportional to severity (non-survivors > survivors > HC):

• ↑ HNA2 (irreversible Cys34 oxidation)
• ↑ AOS (HNA/HMA ratio)
• ↑ AGE, AOPP, IMA, IMAr
• ↓ HMA fraction
• ↓ ABiC (albumin binding capacity)

These mirror the changes seen in cirrhosis/ACLF but in an acute (days–weeks) context.

Albuminome signatures (Sharma et al. 2023)

The “albuminome” — albumin-bound proteome, metabolome, lipidome, and microbiome — identifies non-survivors with near-perfect accuracy. See sharma-2023 for full data. Key validated markers: 5-metabolite panel (nicotinic acid, L-acetyl carnitine, L-carnitine, pregnenolone sulfate, N-(3-hydroxybutanoyl)-L-homoserine lactone); AUC 0.98, HR 5.81, outperforms MELD.

Key studies

• sharma-2023 — ILBS (New Delhi); albuminome multi-omics; 200 ALF + 25 HC; 5-metabolite panel; AUC 0.98