Which of the following statements are correct for a 19‑year‑old patient with jaundice and disorientation, total bilirubin 5 mg/dL, direct bilirubin 3 mg/dL, AST 2000 IU/L, markedly elevated ALT, alkaline phosphatase 1.5 × upper limit of normal, gamma‑glutamyl transferase 2 × upper limit of normal, INR 2.0, albumin 3.0 g/dL, HBsAg positive, IgM anti‑HBc positive, anti‑HCV positive, and HCV RNA negative?

Acute Liver Failure Due to Acute Hepatitis B Requiring Urgent Transplant Evaluation and Antiviral Therapy

This 19-year-old patient has acute liver failure (ALF) secondary to acute hepatitis B and requires immediate listing for urgent liver transplantation while initiating antiviral therapy with tenofovir or entecavir. The combination of hepatic encephalopathy (disorientation), coagulopathy (INR 2.0), severe hyperbilirubinemia (total bilirubin 5 mg/dL), and markedly elevated transaminases (AST 2000 IU/L) with HBsAg and IgM anti-HBc positivity defines acute hepatitis B with progression to ALF 1.

Diagnostic Confirmation of Acute Liver Failure

The patient meets criteria for acute liver failure based on:

• Hepatic encephalopathy: Disorientation in space and time indicates at least grade II encephalopathy, which combined with coagulopathy defines ALF 1, 2
• Coagulopathy: INR 2.0 with albumin 3.0 g/dL indicates impaired synthetic function consistent with decompensated cirrhosis (Child-Pugh score ≥7: INR ≥1.7, albumin <3.5 g/dL) 1
• Severe hyperbilirubinemia: Total bilirubin 5 mg/dL (≥5× upper limit of normal) is an independent predictor of ALF development in acute hepatitis B with 84.6% sensitivity and 85.7% specificity 2
• Hepatocellular injury pattern: AST 2000 IU/L with markedly elevated ALT indicates severe hepatocellular necrosis 1, 2

The serological profile (HBsAg positive, IgM anti-HBc positive) confirms acute hepatitis B infection rather than chronic hepatitis B exacerbation, as IgM anti-HBc is present in 98% of acute HBsAg-positive hepatitis B cases 3.

Acute Hepatitis B vs. Chronic Hepatitis B Exacerbation

This is acute hepatitis B, not chronic hepatitis B with severe exacerbation, based on:

• IgM anti-HBc positivity: This marker is highly specific for acute infection, present in 98% of acute cases but only 17% of chronic persistent hepatitis and 63% of chronic aggressive hepatitis 3
• Absence of cirrhosis indicators: While albumin is borderline low (3.0 g/dL), there is no mention of preexisting cirrhosis, which is the strongest predictor of adverse outcome in chronic hepatitis B exacerbation (60.9% mortality when present) 4
• Age and presentation: A 19-year-old presenting with fulminant hepatic failure is more consistent with acute infection than chronic disease exacerbation 2, 4

Approximately 4% of acute hepatitis B cases progress to ALF, and this patient falls within that subset 2.

HCV Co-infection Assessment

The patient does NOT have active HCV infection requiring DAA therapy:

• HCV RNA negative: This definitively excludes active HCV replication despite positive anti-HCV antibody 1
• Anti-HCV positive likely represents: Either false-positive serology (cross-reactivity with acute hepatitis B), resolved prior HCV infection, or passive antibody transfer 1
• No indication for DAA therapy: HCV guidance explicitly states that treatment is only for patients with detectable HCV RNA, and this patient is HCV RNA negative 1

The acute liver failure is attributable solely to acute hepatitis B, not HCV co-infection 1, 2.

Urgent Liver Transplantation Listing

This patient requires immediate evaluation and listing for urgent liver transplantation:

• Decompensated cirrhosis criteria met: Child-Pugh score ≥7 based on total bilirubin >2.0 mg/dL (5 mg/dL), albumin <3.5 g/dL (3.0 g/dL), INR ≥1.7 (2.0), and encephalopathy present 1
• Poor prognostic indicators: Total bilirubin ≥5× ULN combined with hepatic encephalopathy predicts 92.3% adverse outcome (death or transplantation) in severe hepatitis B exacerbation 4
• Guideline recommendation: Patients with decompensated cirrhosis require urgent antiviral treatment and should be considered for liver transplantation 1
• ALF-specific criteria: The presence of encephalopathy with INR 2.0 indicates significant risk of progression to irreversible liver failure 2, 4

The EASL guidelines state that patients with decompensated cirrhosis may not always benefit if treated at a very late stage and should be considered for liver transplantation 1.

Antiviral Therapy with Tenofovir or Entecavir

Immediate initiation of antiviral therapy with tenofovir or entecavir is mandatory:

• Guideline recommendation: Oral antiviral therapy with tenofovir or entecavir monotherapy is preferred for decompensated liver cirrhosis with detectable HBV DNA regardless of ALT levels (A1 recommendation) 1
• Contraindication to peginterferon: The use of peginterferon-α is absolutely contraindicated in decompensated cirrhosis due to risk of serious complications such as hepatic failure (A1 recommendation) 1
• Rationale for nucleos(t)ide analogues: Rapid and profound viral suppression with efficacious prevention of resistance is particularly needed in decompensated cirrhosis 1
• Expected benefit: Significant clinical improvement can be associated with control of viral replication, though patients with very advanced disease may not always benefit 1

Both tenofovir and entecavir are first-line therapies with high genetic barriers to resistance, making them ideal for this critically ill patient 1.

Management Algorithm

Immediate actions (within hours):

1. List for urgent liver transplantation based on decompensated cirrhosis with encephalopathy and INR 2.0 1
2. Initiate tenofovir or entecavir immediately without waiting for HBV DNA results 1
3. Monitor for hepatic decompensation progression: Assess for worsening encephalopathy, ascites, and coagulopathy 1
4. Supportive care: Manage encephalopathy, correct coagulopathy if bleeding occurs, and monitor for infections 1

Monitoring parameters:

• Liver function tests every 1-3 months including bilirubin, albumin, and INR 1
• HBV DNA by real-time PCR every 2-6 months to assess virologic response 1
• Clinical assessment for complications: Encephalopathy grade, ascites, variceal bleeding risk 1

Critical Prognostic Factors

Factors predicting high mortality risk in this patient:

• Total bilirubin ≥5× ULN: Independent predictor of ALF with 84.6% sensitivity and 85.7% specificity 2
• INR 2.0: Prothrombin time activity likely <50%, and if it drops below 20%, mortality risk increases dramatically 2, 4
• Hepatic encephalopathy present: Peak hepatic encephalopathy grade III-IV is an independent predictor of death or need for transplantation 2
• Young age (19 years): While not inherently poor prognosis, the severity of presentation at this age suggests aggressive disease 2

If prothrombin time activity falls below 20% or encephalopathy progresses to grade III-IV, the probability of death or need for transplantation approaches 90% without liver transplantation 2, 4.

Common Pitfalls to Avoid

• Do not delay transplant evaluation: Waiting for "further deterioration" may result in the patient becoming too unstable for transplantation 1, 4
• Do not use peginterferon: This is absolutely contraindicated in decompensated cirrhosis and will worsen hepatic failure 1
• Do not withhold antivirals pending HBV DNA results: Treatment should be initiated immediately in decompensated cirrhosis with detectable HBsAg 1
• Do not treat HCV: The patient is HCV RNA negative and does not require DAA therapy 1
• Do not assume chronic hepatitis B: IgM anti-HBc positivity indicates acute infection, which has different management implications 3

Correct Statements Summary

Statement a (CORRECT): Acute liver failure due to acute hepatitis B—confirmed by HBsAg positive, IgM anti-HBc positive, hepatic encephalopathy, INR 2.0, and bilirubin 5 mg/dL 2, 3

Statement b (INCORRECT): This is NOT acute hepatitis B without liver failure—the patient has clear evidence of liver failure with encephalopathy and coagulopathy 1, 2

Statement c (CORRECT): The patient needs urgent liver transplant listing—decompensated cirrhosis with encephalopathy and poor prognostic factors mandate transplant evaluation 1, 4

Statement d (INCORRECT): No DAA therapy needed—HCV RNA is negative, excluding active HCV infection 1

Statement e (CORRECT): Needs treatment with tenofovir or entecavir—guideline-recommended first-line therapy for decompensated cirrhosis due to HBV 1