What is the next step in managing a patient with alcoholic hepatitis and worsening hyperbilirubinemia despite being on prednisolone (corticosteroid)?

Management of Worsening Alcoholic Hepatitis Despite Prednisolone

Calculate the Lille score immediately at day 7 to determine if prednisolone should be continued or stopped, as worsening bilirubin (11.0 to 11.8 mg/dL) suggests treatment failure and requires urgent reassessment. 1, 2, 3

Immediate Assessment Required

Calculate the Lille score now (at day 7 of treatment) using: age, albumin at day 0, change in bilirubin from day 0 to day 7, renal function (creatinine), bilirubin at day 0, and prothrombin time. 1, 2

The rising bilirubin from 11.0 to 11.8 mg/dL indicates lack of early improvement, which is a critical prognostic marker. 4

Treatment Decision Based on Lille Score

If Lille Score ≥0.56 (Null Responder):

• Stop prednisolone immediately - these patients have 53.3% 28-day survival and derive no benefit from continued steroids, only increased infection risk. 1, 2, 3, 5
• Continuing steroids beyond day 7 in null responders exposes patients to infection without survival benefit. 3

If Lille Score 0.45-0.56 (Partial Responder):

• Consider stopping prednisolone on a case-by-case basis - these patients have intermediate outcomes (79.4% 28-day survival). 1, 5
• The decision to continue requires careful weighing of infection risk versus potential marginal benefit. 1

If Lille Score <0.45 (Responder):

• Continue prednisolone 40 mg daily to complete the full 28-day course despite the modest bilirubin rise - these patients have 85% 6-month survival. 2, 3, 5
• Complete responders (Lille ≤0.16) have 91.1% 28-day survival. 2, 5

Critical Concurrent Actions

Screen extensively for infection immediately - perform blood cultures, urine cultures, chest radiograph, and ascites fluid culture if ascites present. 1, 3

• Infection develops in 25% of patients during the first month of corticosteroid treatment. 1
• Infection under corticosteroids is associated with increased short-term mortality. 1
• Clinical deterioration during hospitalization indicates very high infection risk requiring repeated screening. 1

Optimize nutritional support aggressively - ensure 30-40 kcal/kg/day and 1.2-1.5 g protein/kg/day via enteral route. 3

Avoid nephrotoxic medications including diuretics, as renal function deterioration worsens prognosis. 3

Supplement vitamins - thiamine, vitamin B12, folic acid, pyridoxine, vitamin D, and zinc. 3

Alternative Therapies NOT Recommended

Do not switch to pentoxifylline - multiple large trials show no survival benefit when added to or substituted for corticosteroids, and no reduction in hepatorenal syndrome. 3, 6

• The 2013 STOPAH trial (270 patients) showed no difference in 6-month survival between pentoxifylline-prednisolone (69.9%) versus placebo-prednisolone (69.2%). 6

Do not add N-acetylcysteine - insufficient evidence for routine recommendation despite some early data. 2

Prognosis Assessment

Combine MELD and Lille scores for optimal mortality risk prediction integrating both baseline severity and early treatment response. 1

The therapeutic window for corticosteroid benefit is MELD 21-51, with maximum benefit at MELD 25-39 (21-30% survival improvement). 7

• No benefit is seen with MELD >51. 7

Critical Pitfall to Avoid

The most common error is continuing steroids in non-responders (Lille ≥0.56) - this exposes patients to infection risk without any survival benefit and delays consideration of other interventions including early liver transplantation evaluation. 1, 3

Patients without early change in bilirubin level (ECBL) at day 7 have only 23% 6-month survival compared to 82.8% in those with ECBL. 4

If Patient is a Non-Responder

Consider early liver transplantation evaluation after careful selection in patients with Lille score ≥0.45 who are null responders. 1

Novel therapies are urgently needed for this population, as switching to pentoxifylline or MARS does not modify outcomes. 1