Chapter 24: Other Indications of Liver Transplantation

OTHER CAUSES OF LIVER FAILURE

Hemochromatosis

• Etiologies:

  • Hereditary hemochromatosis (HH)

  • Non-HFE-related hemochromatosis: juvenile HH, other forms

  • Secondary hemochromatosis

• Most commonly identified genetic disorder in Caucasians

• Prevalence: 1 per 220 to 250 individuals with Nordic or Celtic ancestry

• Gender ratio: Men:women: 10:1

• Gene mutation:

  • Mutation in the HFE gene, C282Y homozygotes, C282Y/H63D, or C282Y/S65C, most frequent mutations

  • Phenotypic expressions only occur in 70% of C282Y homozygotes, and <10% of these subjects will develop severe organ iron overload

  • Juvenile HH: mutations in 2 different genes (hemojuvelin and hepcidin)

  • Other: mutations in the gene for the iron transporter ferroportin

• Pathophysiology:

  • Increased absorption of dietary iron in the upper intestine

  • Decreased expression of the iron-regulatory hormone hepcidin

  • Altered function of HFE protein

  • Tissue injury and fibrogenesis induced by iron

• Clinical features

  • Symptoms (Table 24-1)

  • Physical findings (Table 24-2)

• Diagnosis (see Fig. 24-1)

  • A combination of transferrin saturation and serum ferritin should be the initial approach

  • Screening: transferrin saturation cutoff >45%

  • Serum ferritin: false-positive rates (inflammatory marker)

  • HFE mutation analysis, including C282Y, H63D, and S65C.

  • A serum ferritin level >1000 ng/L: accurate predictor of liver cirrhosis independent of the duration of the disease

  • Liver biopsy: recommended to stage the degree of disease if liver enzymes are elevated or if ferritin is >1000 ng/mL

• Management

  • Family screening

  • Average-risk population screening for HH is not recommended

  • Patients with HH and liver cirrhosis should be screened regularly for hepatocellular carcinoma (HCC) via ultrasound every 6 months

  • Vitamin C supplements and iron supplements should be avoided

  • In HH:

    • Early identification and preemptive treatment with phlebotomy

    • Target levels of phlebotomy should be a ferritin level of 50 to 100 µg/L

    • Liver transplantation for decompensated cirrhosis, caution with phlebotomies

  • Secondary hemochromatosis

    • Iron chelation with deferoxamine mesylate or deferasirox

    • Consider follow up with liver biopsy

Wilson Disease

• First described by Kinnear Wilson in 1912 as “progressive lenticular degeneration”

• Autosomal recessive ...