What is the appropriate workup and management for a patient with established cirrhosis who develops new-onset jaundice?

Management of New-Onset Jaundice in Established Cirrhosis

In a patient with established cirrhosis who develops new-onset jaundice, immediately assess for acute-on-chronic liver failure (ACLF) using the CLIF-C Organ Failure score, investigate for precipitating factors (particularly infections and alcohol), and initiate organ support while determining transplant candidacy, as jaundice represents decompensation with 40-50% mortality within 90 days without intervention. 1

Immediate Clinical Assessment

Recognize the Prognostic Significance

• Jaundice in cirrhosis signals decompensation and is an ominous sign, marking transition from compensated to decompensated disease with accelerated progression toward death or transplantation. 1
• The majority of patients presenting with acute jaundice already have underlying cirrhosis at diagnosis, even when the presentation appears acute. 1
• Without treatment and abstinence from alcohol (in alcohol-related disease), 90-day mortality reaches 40-50%. 1

Grade the Severity Using ACLF Criteria

Calculate the CLIF-C Organ Failure score immediately to determine if the patient has progressed to ACLF, which fundamentally changes prognosis and management. 1

The CLIF-C Organ Failure score assesses six organ systems: 1

• Liver: Bilirubin ≥12 mg/dL = organ failure
• Kidney: Creatinine ≥3.5 mg/dL = organ failure
• Brain: Hepatic encephalopathy grade III-IV = organ failure
• Coagulation: INR ≥2.5 or platelets ≤20,000/mm³ = organ failure
• Circulation: MAP <70 mmHg or requiring vasopressors = organ failure
• Lungs: PaO2/FiO2 ≤200 = organ failure

ACLF grading determines mortality risk: 1

• Grade I (single organ failure): 22% 28-day mortality
• Grade II (two organ failures): 32% 28-day mortality
• Grade III (≥3 organ failures): 78% 28-day mortality

Calculate Prognostic Scores

• MELD and MELD-Na underestimate mortality in ACLF because they capture intrinsic liver disease but miss extrahepatic organ failures. 1
• Use ACLF-specific scores: CLIF-C ACLF score (includes organ failures + age + WBC), NACSELD score (includes organ failure + age + MELD + WBC + albumin), or AARC score (includes bilirubin + creatinine + lactate + INR + encephalopathy). 1

Mandatory Workup for Precipitating Factors

Screen for Infections Aggressively

Obtain cultures of blood, urine, and ascites (if present) regardless of fever presence, as bacterial infections accelerate decompensation and are present in up to 25% of hospitalized cirrhotic patients. 1

• The immune response is impaired in decompensated cirrhosis, placing patients at risk for bacterial and fungal infections that may not present with typical fever. 1
• Infections are a major precipitant of ACLF and must be identified and treated urgently. 1

Investigate Hepatic Precipitants

Assess for: 1

• Heavy alcohol intake: AST >50 but <400 IU/L, AST/ALT ratio >1.5, recent heavy drinking (>40g/day) suggests alcoholic hepatitis 1
• Viral hepatitis reactivation: Check HBV DNA, HCV RNA, HAV IgM, HEV IgM
• Drug-induced liver injury: Detailed medication history including herbals and supplements taken within 6 weeks 2
• Autoimmune hepatitis flare: Check ANA, ASMA, IgG levels

Evaluate for Extrahepatic Precipitants

• Gastrointestinal bleeding: Check hemoglobin, perform upper endoscopy if indicated 1
• Sepsis from any source: Examine for pneumonia, urinary tract infection, skin infections 1
• Recent surgery or procedures: Hemodynamic derangements can precipitate ACLF 1

Note: In 30-40% of ACLF cases, no precipitant is identified despite thorough investigation. 1

Imaging to Exclude Biliary Obstruction

Perform Abdominal Ultrasound

Ultrasound is mandatory to exclude superimposed biliary obstruction, which can mimic or complicate cirrhotic decompensation. 1, 2, 3

Ultrasound will: 1, 3

• Confirm absence of biliary ductal dilatation (71-97% specificity for excluding obstruction)
• Assess liver morphology for cirrhotic features (nodular surface, volume redistribution)
• Detect ascites and portal hypertension
• Identify hepatocellular carcinoma (a complication that accelerates disease progression) 1

Consider Advanced Imaging Selectively

• MRCP is valuable if ultrasound is negative but clinical suspicion remains high for primary sclerosing cholangitis, primary biliary cholangitis, or subtle biliary pathology. 1
• Avoid iodinated contrast CT when possible, as it increases acute kidney injury risk in this population. 1

Immediate Management Interventions

Hospitalize for Severe Disease

Admit patients with severe jaundice (bilirubin >3 mg/dL), ACLF of any grade, or inadequate outpatient support to encourage abstinence, restore nutrition, and exclude serious infections. 1

Provide Aggressive Nutritional Support

Prescribe 1-1.5 g protein and 30-40 kcal/kg body weight daily, as malnutrition worsens outcomes. 1

• If oral intake is inadequate due to anorexia or altered mental status, place a feeding tube for enteral nutrition. 1
• Parenteral nutrition alone is inadequate and should not be used as monotherapy. 1

Treat Identified Precipitants

• Alcohol cessation is the cornerstone for alcohol-related disease—abstinence is non-negotiable. 1
• Broad-spectrum antibiotics immediately if infection is suspected or confirmed (third-generation cephalosporin or piperacillin-tazobactam). 1
• Antiviral therapy for HBV reactivation (tenofovir or entecavir). 1
• Discontinue hepatotoxic medications immediately. 2

Consider Corticosteroids for Severe Alcoholic Hepatitis

If Maddrey Discriminant Function >32 or MELD >20 in the setting of recent heavy alcohol use with AST/ALT >1.5: 1

• Prednisolone 40 mg daily for 28 days may be considered
• Only after excluding active infection, as steroids suppress immune function in already immunocompromised patients 1

Provide Organ Support

There is no specific effective treatment for ACLF itself—management is based on organ support and complication management. 1

• Renal replacement therapy for acute kidney injury/hepatorenal syndrome
• Mechanical ventilation for respiratory failure
• Vasopressors for circulatory failure
• Lactulose/rifaximin for hepatic encephalopathy

Transplant Evaluation

Urgently Refer for Transplant Assessment

All patients with ACLF grade II or III should be evaluated for liver transplantation, as this is the only definitive treatment with potential for recovery. 1

• ACLF grade III has 78% 28-day mortality without transplantation. 1
• Early transplant evaluation is critical, as the window for successful transplantation may be narrow. 1
• Patients who recover from ACLF remain at high risk for recurrent decompensation. 1

Consider Palliative Care

For patients not eligible for transplantation with ACLF grade III or progressive multi-organ failure, early palliative care consultation is appropriate to align care with patient goals. 1

Critical Pitfalls to Avoid

• Don't assume jaundice is simply "expected" in cirrhosis—it represents acute decompensation requiring urgent evaluation for reversible precipitants. 1
• Don't miss occult infections—culture even without fever, as impaired immune response masks typical signs. 1
• Don't use MELD alone for prognostication in ACLF—it underestimates mortality by missing extrahepatic organ failures. 1
• Don't delay transplant referral—patients with ACLF deteriorate rapidly, and the opportunity for successful transplantation may be lost. 1
• Don't overlook medication-induced injury—question about all medications, herbals, and supplements taken within 6 weeks. 2