Symptoms of Liver Amyloidosis
Liver amyloidosis commonly presents with hepatomegaly and elevated alkaline phosphatase, often with minimal symptoms until advanced stages, when patients may develop jaundice, ascites, and portal hypertension. 1
Clinical Presentation
Common Symptoms and Signs
- Hepatomegaly (often massive and disproportionate to symptoms) 2, 1
- Right upper quadrant pain or discomfort 2, 1
- Fatigue and general malaise 2, 1
- Weight loss (can be significant, up to 15kg over months) 3, 4
- Diminished appetite 3
- Nausea 2
Laboratory Findings
- Elevated alkaline phosphatase (most common laboratory abnormality) 2, 5
- Normal or mildly elevated transaminases in early stages 4
- Hypertransaminasemia in advanced disease 5
- Hyperbilirubinemia (cholestatic jaundice) in late stages 3, 5
Advanced Disease Manifestations
- Ascites 6, 5
- Portal hypertension 5
- Gastroesophageal varices 5
- Jaundice (cholestatic) 3
- Hyponatremia 3
- Hepatic encephalopathy 3
Diagnostic Considerations
Key Points in Diagnosis
- Liver involvement occurs in approximately 15-20% of patients with AL amyloidosis 2
- Liver amyloidosis is often part of systemic amyloidosis rather than isolated 2, 1
- Diagnosis requires tissue biopsy with Congo red staining 2, 1
- Hepatomegaly may be present despite normal liver chemistries 4
Associated Findings
- Concurrent cardiac involvement (in up to 50% of AL amyloidosis cases) 2, 1
- Renal involvement with proteinuria or nephrotic syndrome 1, 4
- Soft tissue manifestations:
- Peripheral and autonomic neuropathy (more common in ATTR type) 1
Types of Amyloidosis Affecting the Liver
AL (Primary) Amyloidosis
- Most common type affecting the liver 2
- Associated with plasma cell dyscrasias 4
- Median survival of 13 months (4 months if heart failure present) 2
AA (Secondary) Amyloidosis
- Less frequent liver involvement (<10%) 2
- Associated with chronic inflammatory conditions 6
- Median survival of 25 months 2
ATTR Amyloidosis
- Both hereditary and wild-type forms can affect the liver 2, 1
- Hereditary ATTR has variable liver involvement with median survival of 70 months 2
- Wild-type ATTR (formerly senile) has common cardiac involvement with median survival of 75 months 2
Clinical Pearls and Pitfalls
Important Considerations
- Liver amyloidosis may be misdiagnosed as alcohol-related cirrhosis or other liver diseases 7
- Hepatomegaly can be massive and disproportionate to liver function abnormalities 6, 4
- Early diagnosis is crucial as treatment effectiveness depends on initiating therapy before irreversible organ damage 2, 1
- Prognosis is poor when liver failure develops, with rapid progression in some cases 3, 5
High-Risk Populations for Screening
- Patients with monoclonal gammopathy of undetermined significance (MGUS) 2, 1
- Unexplained hepatomegaly with mildly abnormal liver tests 1, 4
- Unexplained weight loss with GI symptoms 1
- Patients with known cardiac amyloidosis 2
Liver amyloidosis should be considered in any patient with unexplained hepatomegaly, especially when accompanied by elevated alkaline phosphatase, weight loss, and systemic symptoms. Early recognition and diagnosis are essential for improving outcomes in this challenging condition.