P2906 - A Fragile Liver: Coexisting Hemochromatosis and Alpha-1-Antitrypsin Deficiency in a Patient With Alcoholic Hepatitis

Mustafeez Ur Rahman, MD, Yasir Ahmad, MD, Ronald S. Jordan, MD, Pallavi Patil, MD, Phillip Henderson, DO
University of South Alabama Health Systems, Mobile, AL

Introduction: Hereditary hemochromatosis (HH) and Alpha-1 Antitrypsin (A1AT) deficiency are autosomal recessive conditions causing liver disease. Alcohol use has been shown to compound the effect of hemochromatosis on the liver and causes rapid progression of A1AT associated liver fibrosis. An association between A1AT deficiency and HH was described in some reports. However, later studies refuted this association. We describe a case of coexistent Homozygous A1AT deficiency and HH in a patient with alcoholic hepatitis.

Case Description/Methods: A 26-year-old female with a history of smoking, significant alcohol use resulting in alcoholic hepatitis was referred for transplant evaluation. The patient was found to have an elevated ferritin level of 1337 ng/ml (normal: 13-114 ng/ml). Genetic testing revealed homozygous H63D mutation. Lab work ruled out viral hepatitis, autoimmune hepatitis, or Wilson's disease. However, serum A1AT was low34 mg/dl (normal: 90-2000 mg/dl). Genetic testing confirmed that the patient was homozygous for PiZZ mutation. The patient underwent a liver biopsy and was found to have cirrhosis with moderate macro-vesicular steatosis (40%) and mild steatohepatitis. Periodic acid–Schiff–diastase (PAS) positive intracytoplasmic hyaline globules were noted and Iron stain showed mild siderosis predominantly in hepatocytes and Kupffer cells (Figure. 1). The patient is currently on the transplant list.

Discussion: HH is an autosomal recessive condition that leads to excess iron in tissues and multiorgan damage. Two variants of the HFE (C282Y and H63D) gene responsible for most cases of HH. Iron overload is reported to be less common in homozygous H63D variants than homozygous C282Y and heterozygous C282Y/H63D variants.

A1AT deficiency is an autosomal recessive condition characterized by augmented accumulation of the mutant A1AT molecule in the endoplasmic reticulum (ER) of hepatocytes resulting in increased ER stress. Patients with A1AT are at increased risk for chronic hepatitis, cirrhosis, and hepatocellular carcinoma.

The coexistence of A1AT deficiency and hemochromatosis has been reported in case studies. Data on the association and the effect of the two conditions on each other is limited to case reports and animal studies. The treatment, however, is mostly targeted at managing the complication of cirrhosis and liver transplant.


Figure: Figure 1: Liver biopsy light microscopy. A, hematoxylin and eosin, 100x: The liver biopsy shows regenerative nodules of hepatocytes with moderate macrovesicular steatosis and mild steatohepatitis. B, trichrome, 100x: Bridging fibrosis and patchy sinusoidal fibrosis is identified by the green stain taken up by collagen. C, periodic acid–Schiff–diastase (left and right), 600x: Periodic acid-Schiff positive diastase resistant globules are highlighted by pink stain, represent polymers of abnormal protein in the rough endoplasmic reticulum. D, Prussian blue stain for Iron, 400x: Siderosis is highlighted by blue stain in hepatocytes and Kupffer cells


Disclosures:
Mustafeez Ur Rahman indicated no relevant financial relationships.
Yasir Ahmad indicated no relevant financial relationships.
Ronald Jordan indicated no relevant financial relationships.
Pallavi Patil indicated no relevant financial relationships.
Phillip Henderson indicated no relevant financial relationships.


Mustafeez Ur Rahman, MD, Yasir Ahmad, MD, Ronald S. Jordan, MD, Pallavi Patil, MD, Phillip Henderson, DO. P2906 - A Fragile Liver: Coexisting Hemochromatosis and Alpha-1-Antitrypsin Deficiency in a Patient With Alcoholic Hepatitis, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.