Grand Rounds: Alcoholic Hepatitis

Abstract

A 33-year-old Caucasian male was admitted to hospital with recent onset of jaundice of 2-3 weeks duration. He reported heavy use of alcohol for the last 10 years with the last drink a day prior to the onset of symptoms. At admission, he was alert and oriented to time, place, and person, and was deeply jaundiced. His laboratory profile can be summarised as follows: haemoglobin 12.1 g/dl, white blood cell count 18,700 with 81% neutrophils, serum bilirubin 33 (direct 22) mg/dl, aspartate aminotransferase 147 IU/L, alanine aminotransferase 62 IU/L, alkaline phosphatase 117 IU/L, serum albumin 2.8 gm/dl, serum creatinine 0.6 mg/dl, prothrombin time 18.3 (control 14.5) seconds, and international normalized ratio 1.48. He was diagnosed with severe alcoholic hepatitis (Maddrey discriminant function score of 50) and treated with prednisolone for 28 days with symptomatic and biochemical improvement. His Lille score at seven days was 0.4, and his serum bilirubin had decreased to 3.5 mg/dl at the end of treatment. He was also seen by the addiction team during hospitalisation; he agreed to follow through on recommendations. He was dismissed after completing a three-week inpatient rehabilitation programme but relapsed to alcohol use three months later, and was readmitted with alcohol withdrawal. He was readmitted two months later (about six months from the first episode) for a second episode of severe alcoholic hepatitis. At admission, his model for end-stage liver disease score was 32 and he was treated again with corticosteroids. His Lille score at seven days was 0.6 and steroids were discontinued. The hospital course was complicated by spontaneous bacterial peritonitis and pneumonia with development of acute kidney injury. He continued to worsen, developing multiorgan failure. After a course of one month, the family's preference was for him to receive comfort measures. This scenario raises several questions.

Keywords: Alcoholic liver disease; Corticosteroids; Liver biopsy; Liver transplantation.

Fig. 1.. Algorithm for diagnosis of alcoholic hepatitis.

*Clinical criteria: Heavy alcohol use (>2 drinks in females and >3 drinks in males) for >5 years; Active alcohol use until at least 8 weeks prior to presentation; Recent (<1 month) onset or worsening of jaundice; Exclude other liver diseases, biliary obstruction, HCC. *Biochemical criteria: Serum bilirubin >3 mg/dl, AST >50 and <500, AST >ALT by 1.5:1; **Transjugular route preferred for obtaining the liver tissue. **Characteristic histological findings: Cell balooning, neutrophil infiltration, cholestasis, varying degree of steatosis and fibrosis. ***Needed for inclusion in clinical trials and before starting specific pharmacologic therapy. AH, alcoholic hepatitis; ALT, alanine aminotransferase; AST, aspartate aminotransferase; HCC, hepatocellular carcinoma.

Fig. 2.. Pathophysiology of alcoholic hepatitis.

Alcohol-induced liver injury occurs through a convergence of toxic effects of alcohol on the intestine which affect the liver indirectly as well as direct toxic effects of alcohol on hepatocytes. Indirect gut effects occur from alcohol-induced increases in bacterial translocation including LPS that lead to IL-1B production from liver macrophages. Direct effects of alcohol on hepatocytes generate acetaldehyde and oxidative stress, which leads to hepatocyte apoptosis and release of EVs. These EVs together with IL-1B act on other liver cell types including PMN cells, HSCs, and ECs to propagate inflammation and fibrosis that is observed in alcoholic liver disease (slide courtesy of Dr. Vikas Verma). EC, endothelial cell; EV, extracellular vesicle; HSC, hepatic stellate cell; IL-1B, interleukin-1 beta; LPS, lipopolysaccharide; PMN, polymorphonuclear.

Fig. 3.

Algorithm for surveillance of infections in patients with severe alcoholic hepatitis.

Fig. 4.. Algorithm for optimal management of patients with alcoholic hepatitis.

*Using Lille score. **Excellent psychosocial support in a patient with first episode of AH. AH, alcoholic hepatitis; ICU, intensive care unit; LT, liver transplantation; OF, organ failure.