What is the diagnosis and recommended treatment for a patient with elevated liver enzymes, anemia, and hormonal imbalances?

Diagnostic Assessment: Primary Biliary Cholangitis with Iron Deficiency Anemia

This patient has Primary Biliary Cholangitis (PBC) based on the positive anti-mitochondrial antibody with cholestatic liver enzyme pattern, and requires treatment with ursodeoxycholic acid along with iron supplementation for concurrent iron deficiency anemia. 1

Key Diagnostic Features

Cholestatic Liver Disease Pattern

• The markedly elevated alkaline phosphatase (298-302 U/L) and gamma-GT (622-642 U/L) with only mildly elevated transaminases (ALT 58-64, AST 40-41) defines a cholestatic pattern where alkaline phosphatase is elevated >2.5-fold above normal while transaminases are <5× upper limit of normal 1
• The positive anti-mitochondrial antibody with this cholestatic pattern is diagnostic of PBC, even without liver biopsy 1
• Normal bilirubin (6 umol/L) and albumin (41-43 g/L) indicate early-stage disease without synthetic dysfunction 1

Iron Deficiency Anemia

• The microcytic anemia (hemoglobin 96 g/L, MCV 73 fL, MCH 20.8 pg) with severely low iron (4.0 umol/L), low ferritin (12 ug/L), and markedly reduced iron saturation (0.04) confirms iron deficiency anemia 2, 3
• The elevated reticulocyte immature fraction (32.3%) and low reticulocyte hemoglobin content (22.9 pg) indicate active but ineffective erythropoiesis due to iron deficiency 2
• This pattern is inconsistent with hemochromatosis, which would show elevated transferrin saturation (≥45%) and ferritin >200-300 μg/L 2, 4

Hormonal Findings

• The elevated FSH (35.5 IU/L) and LH (17.2 IU/L) with low-normal estradiol (144 pmol/L) suggest perimenopausal or early menopausal state, which is common in women with chronic liver disease 1
• Low testosterone levels (1.0 nmol/L) and SHBG within normal range (34.8 nmol/L) are consistent with chronic liver disease affecting sex hormone metabolism 1

Immediate Management Priorities

Treatment of Primary Biliary Cholangitis

• Initiate ursodeoxycholic acid (UDCA) 13-15 mg/kg/day as first-line therapy for PBC 1
• Monitor liver enzymes (alkaline phosphatase, gamma-GT, ALT, AST) and bilirubin every 3 months initially, then every 6 months once stable 1
• Assess response to UDCA at 12 months using alkaline phosphatase normalization or reduction to <1.67× upper limit of normal 1

Iron Replacement Therapy

• Begin oral ferrous sulfate 325 mg (65 mg elemental iron) once or twice daily with meals to minimize gastrointestinal side effects 5
• Recheck complete blood count, iron studies (serum iron, ferritin, transferrin saturation) in 8-12 weeks to assess response 2
• Continue iron supplementation until ferritin reaches 50-100 μg/L and hemoglobin normalizes 4

Investigation for Source of Iron Loss

• Evaluate for gastrointestinal blood loss with fecal occult blood testing and consider upper and lower endoscopy if positive or if anemia persists despite supplementation 1
• Assess menstrual history for heavy menstrual bleeding as a potential source of iron loss 1
• Screen for celiac disease with tissue transglutaminase antibodies, as it can cause both iron deficiency and elevated liver enzymes 6

Hepatocellular Carcinoma Surveillance

• Begin ultrasound surveillance for hepatocellular carcinoma every 6 months starting now, as PBC patients have increased HCC risk even without cirrhosis 1
• Alpha-fetoprotein has limited utility in PBC-related HCC surveillance 1

Monitoring for Disease Progression

Annual Assessments Required

• Liver enzymes (alkaline phosphatase, gamma-GT, ALT, AST, bilirubin) every 6 months 1
• Complete blood count and iron studies annually or more frequently if anemia persists 2
• Assess for symptoms of advanced liver disease (pruritus, fatigue, jaundice, ascites) at each visit 1
• Monitor platelet count as thrombocytopenia <200 × 10⁹/L suggests portal hypertension 1

Liver Biopsy Considerations

• Liver biopsy is NOT required for diagnosis given positive anti-mitochondrial antibody with cholestatic pattern 1
• Consider biopsy only if: (1) atypical features develop, (2) concern for overlap syndrome with autoimmune hepatitis, or (3) inadequate response to UDCA after 12 months 1

Common Pitfalls to Avoid

• Do not attribute elevated liver enzymes solely to "alcohol use" without investigating the cholestatic pattern and obtaining autoimmune markers 1
• Do not delay iron supplementation waiting for complete gastrointestinal workup, as symptomatic anemia requires immediate treatment 5
• Do not assume normal bilirubin excludes significant liver disease—PBC can have normal bilirubin for years before progression 1
• Do not screen for hemochromatosis with genetic testing when transferrin saturation is severely LOW (0.04), as this indicates iron deficiency, not overload 2, 4
• Do not repeat liver enzymes without initiating specific therapy—the cholestatic pattern with positive AMA requires treatment, not observation 1

Prognosis and Long-term Considerations

• Patients with PBC who achieve biochemical response to UDCA (alkaline phosphatase <1.67× ULN at 12 months) have near-normal life expectancy 1
• The normal platelet count (347 × 10⁹/L) and albumin (41-43 g/L) indicate absence of cirrhosis and portal hypertension 1
• Liver transplantation should be considered if bilirubin rises >100 μmol/L, albumin falls <35 g/L, or complications of portal hypertension develop 1