Managing Acute-on-Chronic Liver Failure: A Clinical Perspective from Mumbai

Acute-on-chronic liver failure (ACLF) remains one of the most challenging emergencies in hepatology. It is characterised by acute decompensation of previously stable chronic liver disease, multi-organ failure, and a 28-day mortality that can exceed 50% without timely intervention. Having managed hundreds of ACLF patients — first at the Institute of Liver and Biliary Sciences (ILBS), New Delhi, under Prof S. K. Sarin, and now at Gleneagles Hospital, Mumbai — I want to share what the data, and bedside experience, actually teach you about this condition.

What ACLF Is — and What It Is Not

A common pitfall I see in referral patients is confusion between simple decompensated cirrhosis (ascites, variceal bleeding, encephalopathy) and true ACLF. The difference matters enormously for prognosis and management.

ACLF, as defined by the Asian Pacific Association for the Study of the Liver (APASL), requires an acute hepatic insult leading to jaundice (bilirubin ≥5 mg/dL) and coagulopathy (INR ≥1.5), complicated by clinical ascites and/or encephalopathy, in a patient with previously diagnosed or undiagnosed chronic liver disease — all within four weeks of onset. The APASL AARC score, developed from a large Asian cohort that includes data our team at ILBS contributed to, predicts 28-day mortality with strong discrimination and should be calculated for every ACLF patient on admission.

Simple decompensation does not carry the same short-term mortality risk. Calling it ACLF without meeting criteria leads to over-intervention; missing ACLF in a patient who meets criteria leads to under-preparation and delayed transplant evaluation.

A Typical Presentation

A 48-year-old man was referred to my clinic with a two-week history of progressive jaundice, abdominal distension, and confusion. He had known alcohol-related cirrhosis, compensated for three years, and had resumed heavy drinking six weeks prior. On examination: deeply icteric, gross ascites, grade II hepatic encephalopathy, no active gastrointestinal bleeding.

Investigations: bilirubin 18.4 mg/dL, INR 2.8, creatinine 1.9 mg/dL, sodium 126 mmol/L. APASL AARC score: 11 — predicted 28-day mortality approximately 65%. No evidence of bacterial infection on initial workup, though we treated with prophylactic antibiotics empirically while cultures were pending, given how consistently infection precipitates and worsens ACLF in our experience.

What Changes Outcomes

Three things, in my clinical experience, consistently shift the needle in ACLF:

1. Identify and eliminate the precipitant

In alcohol-related ACLF, the precipitant is often reintroduction of alcohol after a period of abstinence — a pattern that generates a particularly severe acute-on-chronic insult. In non-alcoholic patients, we aggressively screen for hepatitis B reactivation (always check HBV DNA regardless of HBsAg status), drug-induced liver injury including herbal and Ayurvedic medications (Tinospora cordifolia / Giloy is an underrecognised cause — our group published a nationwide multicentre case series in Hepatology Communications, 2022 [PMID 35037744]), and bacterial infections including spontaneous bacterial peritonitis.

2. Aggressive nutritional support from day one

Malnutrition is near-universal in ACLF and independently worsens outcomes. Our group demonstrated in a randomised controlled trial (Indian Journal of Gastroenterology, 2022 [PMID 35235198]) that long-term aggressive nutrition therapy significantly improves survival in alcohol-related cirrhosis. In ACLF, we target ≥35 kcal/kg/day and ≥1.5 g protein/kg/day, with enteral feeding preferred whenever feasible. Late-night snacks and branched-chain amino acids are incorporated per ESPEN guidelines.

3. Early, honest transplant evaluation

This is the conversation that gets delayed too long. If the AARC score is ≥10, if there is renal failure (creatinine >1.5 mg/dL), or if the patient is not improving at 72 hours, a liver transplant evaluation should begin — not as a last resort, but as a parallel pathway. Every day of delay without improvement is a day the patient’s fitness for surgery deteriorates. In Mumbai, we are fortunate to have access to living-donor liver transplantation, which removes the constraint of organ availability.

When to Refer

If a patient with cirrhosis develops jaundice (bilirubin ≥5 mg/dL) and coagulopathy (INR ≥1.5) together, refer immediately — do not wait for encephalopathy or ascites to develop before escalating. ACLF is a time-sensitive emergency. Early specialist involvement changes outcomes.

At Gleneagles Hospital, Mumbai, I see ACLF referrals from across India and internationally. If you are managing a patient you suspect has ACLF, I am available for urgent teleconsultation.

Key References

• Sarin SK, Choudhury A, et al. APASL ACLF consensus 2019. Hepatol Int. 2019. PMID 31172417
• Choudhury A, et al. Kyoto Consensus on ACLF 2025. Hepatol Int. 2025. PMID 39961976
• Kalal CR, et al. MAHAL RCT — mannitol vs hypertonic saline in acute liver failure. Dig Dis. 2021. PMID 34763338
• Kalal C, et al. Nutrition RCT in alcohol-related cirrhosis. Indian J Gastroenterol. 2022. PMID 35235198
• Kulkarni AV, et al. Giloy (Tinospora cordifolia) liver injury. Hepatol Commun. 2022. PMID 35037744