What is the diagnosis and management for a patient with hepatomegaly, splenomegaly, signs of liver dysfunction, and systemic findings suggestive of acute liver failure?

Diagnosis and Management of Acute Liver Failure with Portal Hypertension

Primary Diagnosis

This clinical presentation is most consistent with acute liver failure with portal hypertension and requires immediate evaluation for the underlying etiology and consideration for liver transplantation. 1

The constellation of hepatomegaly with periportal edema, splenomegaly with infarcts, dilated portal venous system, ascites, pleural effusions, and generalized anasarca represents decompensated liver disease with severe portal hypertension and multiorgan involvement. 2

Critical Immediate Actions

Stabilization and Supportive Care

• Provide intensive cardiovascular support rather than pursuing transplantation initially if ischemic hepatic injury is suspected 1
• Stop fluid resuscitation immediately if hepatomegaly or rales develop, as continued fluid administration worsens outcomes 1
• Implement inotropic support rather than additional volume resuscitation 1
• Administer diuretics for ascites and anasarca management 3

Urgent Diagnostic Workup

Obtain comprehensive liver function tests including total bilirubin, AST, ALT, alkaline phosphatase, GGT, platelet count, prothrombin time/INR, and albumin to assess severity of hepatic dysfunction 1, 2

Perform immediate evaluation for specific treatable causes:

• Viral hepatitis serologies (hepatitis B, C, E if immunosuppressed) 2
• Autoimmune markers (ANA, anti-smooth muscle antibody, immunoglobulins) as presentation can mimic autoimmune hepatitis 2
• Wilson disease screening (ceruloplasmin, 24-hour urinary copper, slit-lamp examination for Kayser-Fleischer rings) - critical in patients under 40 years, though can present up to 8th decade 2
• Alpha-1 antitrypsin level and phenotype 2
• Toxicology screen including acetaminophen level 4
• Serum tryptase level to evaluate for systemic mastocytosis, particularly given hepatomegaly, splenomegaly, and ascites 2

Differential Diagnosis Based on Imaging Findings

Vascular Causes (High Priority)

Budd-Chiari syndrome must be excluded given dilated portal/splenic/mesenteric veins with hepatomegaly and ascites 1

• Typical presentation includes abdominal pain, ascites, and striking hepatomegaly 1
• Initiate anticoagulation immediately if Budd-Chiari confirmed and continue indefinitely 1
• Treat underlying prothrombotic disorder concomitantly 1
• Consider liver transplantation for significant liver failure after excluding malignancy 1

Infiltrative Disorders

Systemic mastocytosis should be considered given:

• Hepatomegaly with ascites and portal hypertension (C-finding indicating organ damage) 2
• Splenomegaly with hypersplenism 2
• Lymphadenopathy 2
• Hypoalbuminemia suggesting malabsorption 2

If suspected, obtain bone marrow biopsy with KIT D816V mutation analysis 2

Malignant infiltration requires exclusion:

• Acute myeloid leukemia can present with hepatomegaly, splenomegaly, and rapid progression to multiorgan failure 5
• Monitor closely for malignant infiltration in patients with massive hepatomegaly 1
• Consider liver biopsy if imaging suggests infiltrative process 2

Metabolic/Storage Disorders

Langerhans cell histiocytosis can present with periportal involvement and minimal liver enzyme elevation 6

• MRI screening recommended for liver involvement 6

Advanced Imaging and Tissue Diagnosis

Liver elastography should be performed when available to assess degree of fibrosis 2, 1

Liver biopsy may be necessary when:

• Diagnosis remains unclear after initial workup 2
• Differentiating cirrhosis from non-cirrhotic portal hypertension 2
• Confirming infiltrative disorders 5, 6

Disease-Specific Management

If Wilson Disease Confirmed

• Initiate chelation therapy with penicillamine or trientine 2
• Consider liver transplantation for fulminant hepatic failure 2

If Acetaminophen Toxicity

• Administer N-acetylcysteine 300 mg/kg IV over 20-21 hours 4
• Loading dose 150 mg/kg over 60 minutes (NOT 15 minutes due to higher hypersensitivity reactions) 4
• Maintenance: 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours 4

If Autoimmune Hepatitis Pattern

• Consider corticosteroid therapy, which can be beneficial in severe cases 7

If Systemic Mastocytosis with C-Findings

• Requires cytoreductive therapy 2
• Consider allogeneic hematopoietic cell transplantation for aggressive disease 2

Monitoring and Complications

Monitor for acute complications:

• Hepatic encephalopathy
• Variceal bleeding (given portal hypertension and splenomegaly) 8
• Splenic rupture risk - patient should avoid contact activities 8
• Acute renal failure (particularly with Wilson disease fulminant presentation) 2
• Coagulopathy requiring fresh frozen plasma/cryoprecipitate 2

Serial laboratory monitoring every 6-12 hours initially:

• Liver function tests, INR, lactate, ammonia 1
• Complete blood count for cytopenias 2
• Renal function 2

Transplant Evaluation

Immediate transplant center consultation is warranted for:

• Fulminant hepatic failure with encephalopathy 2
• Progressive coagulopathy despite vitamin K 2
• Budd-Chiari with significant liver failure 1
• Wilson disease with fulminant presentation 2

Critical Pitfalls to Avoid

• Delaying anticoagulation in Budd-Chiari syndrome can be fatal 1
• Continuing aggressive fluid resuscitation worsens hepatomegaly and outcomes 1
• Missing Wilson disease in patients over 40 years due to age bias - cases confirmed into 8th decade 2
• Failing to check acetaminophen level in all acute liver failure cases 4
• Overlooking malignant infiltration in massive hepatomegaly 1, 5
• Not screening for systemic mastocytosis when hepatosplenomegaly with ascites present 2