Metabolic Etiologies of Liver Disease

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🌱 來自: Huppert’s Notes

Metabolic Etiologies of Liver Disease🚧 施工中

Metabolic Etiologies of Liver Disease

Nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH)

•   Risk factors: Associated with obesity, HLD, DM2

•   Clinical features: Patients are usually asymptomatic but 10–20% of patients progress and develop cirrhosis (especially patients with NASH, which is an advanced form of NAFLD)

•   Diagnosis: Can make presumptive diagnosis but need liver biopsy for definitive diagnosis. Histology appears similar to cirrhosis due to alcohol use, but patient reports no/minimal alcohol use.

•   Treatment: Control risk factors for insulin resistance, weight loss, consider bariatric surgery. OK to use statins. Vitamin E is sometimes used for nondiabetic NASH.

Wilson’s disease

•   Pathophysiology: Autosomal recessive mutation of the ATP7B gene that encodes for ceruloplasmin (copper-binding protein needed for excretion); therefore, copper accumulates in the liver and blood. Typical age of onset is 5–35 yr.

•   Clinical features:

-   Liver: Acute hepatitis, cirrhosis, liver failure

-   Eyes: Kayser-Fleischer rings, yellow rings in cornea

-   CNS: Copper deposits in the basal ganglia which can cause extrapyramidal signs (parkinsonism), depression, paranoia

-   Renal: Aminoaciduria, nephrocalcinosis

-   Hemolytic anemia: Caused by sudden release of copper from liver cells

•   Diagnosis: Low serum ceruloplasmin, high urine copper, molecular test for mutation in ATP7B gene

•   Treatment: Penicillamine or trientine (chelator), zinc (prevents dietary copper uptake), liver transplantation

Hemochromatosis

•   Pathophysiology: Autosomal recessive disease of iron absorption; excess iron is absorbed in the gut and accumulates as ferritin and hemosiderin in organs, causing fibrosis

•   Clinical features: Bronze diabetes (deposits in the pancreas), arthralgias, hepatomegaly, impotence, restrictive cardiomyopathy, arrhythmias

•   Diagnosis: Ratio of iron to TIBC ≥45%, ferritin >150 ng/mL (women) and >200 ng/mL (men). Definitive diagnosis = HFE gene testing with C282Y polymorphism

•   Treatment: Repeat phlebotomy for patients with ferritin >500 ng/mL, evidence of tissue injury, or increased tissue iron by imaging/biopsy. Target ferritin to normal range. Counsel patients to avoid raw seafood (increased risk of Vibrio infection). Liver transplantation may be necessary.

Alpha-1 antitrypsin deficiency

•   Pathophysiology: Autosomal recessive disease that causes deficiency in alpha-1 antitrypsin production

•   Clinical features: Lung (emphysema) and liver disease (cirrhosis, HCC, hepatitis)

•   Diagnosis: Low serum alpha-1 antitrypsin

•   Treatment: Liver transplantation