This week at morning report we covered an outpatient approach to a new diagnosis of cirrhosis in a patient who presented with abdominal distension and was found to have new ascites. When we determined that the etiology of cirrhosis in our patient’s case was hereditary hemochromatosis, we took the opportunity to review clinical manifestations, diagnostic criteria, and management of hereditary hemochromatosis. 

Approach to New Cirrhosis:

• Determine etiology
  • Viral, EtOH, NASH, autoimmune, metabolic, etc.
  • Send labs to investigate potential etiologies, abdominal ultrasound (including Dopplers), consider liver biopsy if indeterminate cause
• Assess severity 
  • Child’s-Pugh Score:
    1. Predicts the following mortality for open abdominal surgery:
       • Child’s-Pugh A: 10%
       • Child’s-Pugh B: 30%
       • Child’s-Pugh C: 80%
    2. MELD Scorel
       • If score >15, refer for liver transplant assessment
• Assess & manage complications
  • Varices 
    • Perform upper endoscopy at diagnosis
    • Based on results of endoscopy consider role for non selective beta blocker or endoscopic variceal ligation 
  • Ascites/SBP
    • Perform paracentesis at diagnosis
    • Manage ascites:
      1. Treat underlying liver disease
      2. Nonpharmacologic: salt restriction <2g per day
      3. Pharmacologic: lasix and spironolactone 
      4. If failing medical therapy: regular therapeutic paracentesis, can consider TIPs 
      5. Liver transplant
  • Encephalopathy, hepato-renal syndrome, hepato-pulmonary syndrome, porto-pulmonary hypertension
    • Assess based on history, physical, labs 
  • Screen for hepatocellular carcinoma
    • Perform abdominal ultrasound at diagnosis, and every 6 months thereafter 
• Counselling
  • Abstinence from alcohol, adequate nutrition, weight loss for NAFLD
  • Limit acetaminophen to <2g per day
  • Avoid sedatives, NSAIDs, ACEis/ARBs
  • Hepatitis A, Hepatitis B, flu vaccinations

Hereditary Hemochromatosis

About:

• Autosomal recessive disorder causing increased intestinal absorption of iron, resulting in iron overload and resultant iron deposition in organs leading to organ damage 
• More common in individuals of Northern European descent

Clinical Manifestations of Iron Overload:

• Liver: cirrhosis, elevated liver enzymes
• Skin: ‘bronze’ hyperpigmentation
• Endocrine: hypopituitarism (impotence, amennorhea), diabetes (islet cell destruction)
• MSK: arthropathy (2^nd and 3^rd MCP ‘hooked osteophytes’)
• Fatigue

Approach to Investigations:

To make diagnosis:

• Tsat >45% plus ferritin >300 in men or ferritin >200 in women is suggestive of hemochromatosis
• If the patient meets the above Tsat and ferritin criteria, they should have genetic testing for hereditary hemochromatosis. 
  • Homozygous mutation at C282Y = confirms diagnosis of hereditary hemochromatosis 
  • Heterozygous mutation at C282Y/H63D = less likely (but possible) to have iron overload 
  • Mutation at H63D in the absence of mutation at C282Y = not at risk of increased iron overload 

To assess for end organ damage and other complications:
note: if ferritin is >1000, you should suspect end organ damage! 

• TTE
• TSH, T3, T4
• A1c
• Liver enzymes
• Sex hormones
• X-ray hands/wrists to assess 2^nd and 3^rd MCPs 

Management:

• Dietary considerations: 
  • Limit vitamin C and iron supplementation
  • Avoid raw shellfish and uncooked seafood due to heightened infection risk
    • Certain bacteria have a heightened virulence related to iron: Listeria monocytogenes, Yersinia enterocolita, Vibrio vulnificus 
• Manage the iron overload:
  • Phlebotomy 
    • Initially 500mL per session weekly
    • Target ferritin <50; check every 3 months
    • Avoid anemia; slow down frequency of phlebotomy if Hb < 110
• Test first degree relatives for hemochromatosis with genetic testing
• Refer to Hematology for ongoing management