A Predisposing Condition of Hemochromatosis Complicated by Alcoholic Liver Disease

Abstract

Cirrhosis and chronic liver failure are common causes of morbidity and mortality in the United States. The majority of preventable cases of these are attributed to alcohol (ETOH) consumption, viral hepatitis, or nonalcoholic fatty liver disease. End-stage cirrhosis without hereditary hemochromatosis (HH) is often associated with a significant amount of hepatic iron overload especially in those with ETOH abuse and/or hepatitis C. We present a case of a 78 year old male admitted for cirrhosis secondary to alcoholic liver disease (ALD) but was found to have a preexisting condition that may have precipitated his symptoms. A 78 year—old male with history of ETOH abuse (12 beers/day) was admitted for altered mental status with fevers, hematuria, and disorientation for 1 week. On exam, he was altered and jaundiced with a distended abdomen. Initial lab results: Creatinine (3.18), Bilirubin (1.58), Albumin (2.14), AST (35), ALT (18.6), Ammonia (141), PT (16), INR (1.46), PTT (36), Iron Saturation (89%), negative viral hepatitis panel. His MELD score was calculated at 21. Abdominal imaging showed liver cirrhosis, esophageal/gastric varices, ascites, bilateral anasarca and pleural effusions. EGD revealed severe portal gastropathy, erosive antral gastritis, and gastric varices. He was found to be a carrier of a single mutation in the S65C gene. Diuretics, albumin and fluid hydration were administered prior to discharge. HH and ALD are known risk factors for the development of cirrhosis. S65C substitution has been associated with mild HH. Studies looking at the heterozygous genotype of S65C with C282Y or H63D show a similar risk to developing HH as with homozygous carriers of these genes. Both diseases have shown links between hepatic iron deposition and developing cirrhosis. However, together, these diseases increase the risk of cirrhosis by 9 fold. This is due to oxidative stress, stellate cell activation, and fibrosis caused by iron deposition and ETOH. In addition, up to 50% of patients with HH drink above the average amounts of ETOH. This can increase iron accumulation and phenotypic expression of HH. By contrast, other studies propose that heavy deposition of iron, regardless of ETOH intake, is an indication of HH. For this reason, it is important to assess for other causes when there are persistently elevated ALT levels. Workup should include viral/autoimmune hepatitis assays and transferrin saturation to guide treatment and prevent end stage liver disease.