Case Presentation:
A 74 year old gentleman with known end-stage alcoholic liver disease (MELD 22) presented to the emergency room with lethargy. He had been deemed unsuitable for liver transplantation due to his age and co-morbidities – which included well controlled diabetes mellitus type 2, hypertension, diastolic heart failure, chronic obstructive lung disease and chronic kidney disease stage III.
He had been admitted about 8 times within 2 months, and his last admission was on the day after the prior discharge.
Physical exam showed obtunded patient who was just responding to painful stimuli. He was vitally stable and was not in distress. His abdominal exam showed no tenderness, no masses, and no evidence of ascites. His neurologic exam showed asterixis, but the rest of his exam was normal. His blood work was stable compared to the most recent one; computerized tomography of the head was normal.
Several investigations done to identify the precipitating factor for recurrent hepatic encephalopathy – electrolytes, esophagogastroduodenoscopy to rule out bleeding, ultrasound (US) of the abdomen for diagnosis of ascites, alpha Fetoprotein, and US abdomen with Doppler – were normal. He was compliant with his medications and diet; he had been instructed to eat non-animal protein by a dietitian. He was receiving optimal therapy for hepatic encephalopathy. A zinc level was checked and it was found to be 28 (low; normal level is 60-130). The patient was started on oral zinc supplementation, 220 mg daily. He was followed over a year and he did not develop any further episodes of hepatic encephalopathy.
Discussion:
Hepatic encephalopathy (HE) is an important complication of cirrhosis with significant morbidity and mortality. The most common precipitating factors of HE include GI bleeding and infections as well as electrolyte abnormalities like hypokalemia.
Patients with liver disease may be at risk of zinc depletion. Zinc supplementation has been shown to contribute to inhibition of liver fibrosis and improvement in HE
Zinc is an essential trace element required for normal cell growth and development. It is contained in vesicles in the presynaptic terminals of certain classes of neurons, the majority of which are a subclass of the glutamatergic neurons that were shown to be involved in pathogenesis of HE. Zinc may also enhance the hepatic conversion of amino acids into urea.
Zinc deficiency has been observed in cirrhotic patients with Child-Pugh score B or C, and with MELD score ≥15; it correlates with disease severity, infection, and a worse transplant-free survival. Its supplementation in patients with chronic liver disease has been associated with improvements in liver function, hepatic encephalopathy and overall nutritional status, but management guidelines do not address screening for zinc deficiency.
Conclusions:
Zinc deficiency should be considered as a precipitant of hepatic encephalopathy. Considering this rare cause after excluding other common precipitating factors will allow for early intervention which will enhance patient care. This case highlights an opportunity to reduce hospitalization for hepatic encephalopathy via zinc therapy in selected patients. Guideline development in this area may improve patient care and reduce healthcare costs.