Alcoholic hepatitis overview

# Overview
Alcoholic hepatitis is caused be excessive consumption of alcohol. In US, 7.2% of adults suffer from alcohol use disorder. Symptoms of Alcoholic hepatitis may vary from mild  to severe; therefore; any suspected patient should undergo liver function test and ultrasound to screen for Alcoholic hepatitis. Alcoholic hepatitis may progress to hepatic steatonecrosis,fibrosis, cirrhosis or hepatocellular carcinoma. Consequently, all patients must be advised for alcohol abstinence. Additionally, nutritional supplements including folic acid, thiamine, vitamin B6, vitamin A and zinc can be provided. If Alcoholic hepatitis progress to cirrhosis, liver transplant will be considered for treatment.

# Historical Perspective
Alcoholic hepatitis was first recognized in 1961 after investigation of 7 cases with excessive alcohol intake . Before the recognition of Alcoholic hepatitis, it was believed that the symptoms are caused by malnutrition not due to toxic effects of alcohol. Charles S. Lieber developed modern research on alcohol-related liver disease.

# Pathophysiology
The pathophysiology of Alcoholic hepatitis is caused by interplay between alcohol metabolism, inflammation and innate immunity. Alcohol metabolism leads to depletion of NAD and subsequent lipogenesis. Additionally, increased endotoxemia causes translocation of lipopolysaccharide from intestine to hepatocytes. In hepatocytes, lipopolysaccharide activates kupffer cells. Therefore, activated cells release inflammatory markers which lead to Alcoholic hepatitis.

# Causes
Alcohol is a significant cause of Alcoholic hepatitis. Other factors that may associate with Alcoholic hepatitis are  hepatitis C and  malnutrition.

# Differentiating Alcoholic Hepatitis from other Diseases
Alcoholic Hepatitis should be differentiated from viral hepatitis, autoimmune hepatitis, non-alcoholic fatty liver disease, drug-induced liver injury, Wilson disease, cholestatic causes of liver disease, and hepatocellular carcinoma.

# Epidemiology and Demographics
In US, 7.2% of adults suffer from alcohol use disorder.The peak incidence of Alcoholic hepatitis is between 20-60 years of age.In 2007, Alcoholic hepatitis was accounted for 0.71% of all hospital admissions in US. Women are at greater risk of developing Alcoholic hepatitis after shorter duration and smaller amount of alcohol intake.

# Risk Factors
The most commonrisk factors of  developing Alcoholic hepatitis include  heavy alcohol intake, High body mass index, Female gender , Malnutrition and hepatitis C.

# Screening
Patients with excessive alcohol intake requires screening for alcohol use with AUDIT questionnaire. If the score is above 8, Alcohol use disorder is diagnosed and patient requires further evaluation by performing liver test and liver ultrasound.

# Natural history, Complications and Prognosis
Alcoholic liver disease may progress to fatty liver, hepaticsteatosis, Alcoholic hepatitis or alcoholic steatonecrosis,fibrosis, cirrhosis and hepatocellular carcinoma. Complications of Alcoholic hepatitis include [[variceal hemorrhage,hepatic encephalopathy,ascites,coagulopathy, thrombocytopenia,spontaneous bacterial peritonitis, and iron overload. Different scoring systems were presented to predict the prognosis and mortality among patients with Alcoholic hepatitis. The most recent and accurate one is called Asymmetric dimethylarginine (ADMA) score.

# Diagnosis

## History and Symptoms
Alcoholic hepatitis is suspected to occur in patients with excessive drinking over the decades.Symptoms of Alcoholic hepatitis can vary from mild  to severe.The symptoms include nausea,malaise, low-grade fever, abdominal Pain, yellow discoloration of skin increased abdominal girth due to ascites, gastrointestinal bleeding due to variceal hemorrhage, lack of appetite, confusion, and lethargy.

## Physical Examination
Physical examination findings include fever, tachycardia, tachypnea,respiratory alkalosis,hepatomegaly,hepatic tenderness
,scleral icterus,splenomegaly, ascites,ssterixis, darkening of the urine, peripheral edema,gynecomastia,palmer erythema,Spider angiomas, altered hair distribution, Proximal muscle wasting.

## Laboratory Findings
The most frequent laboratory findings of Alcoholic hepatitis include neutrophilic leukocytosis with bandemia,anemia ,AST/ALT ratio greater than 2, mild elevation of Alkaline Phosphatase, hypoalbuminemia, hyperbilirubinemia,prolonged prothrombin time, and elevated gamma-glutamyl transpeptidase level.

## X-Ray
There are no x-ray findings associated with Alcoholic hepatitis.

## CT
CT scan  is usually performed among patients with Alcoholic hepatitis to exclude other abnormalities including neoplasm, biliary obstruction or infiltrative liver disease.CT scan can predict severity and outcome of Alcoholic hepatitis by presence of splenomegaly, ascites, varices, liver length to mid clavicular line, decreased liver attenuation, liver to spleen attenuation ratio and increased liver heterogenecity.

## MRI
MRI findings of Alcoholic hepatitis are non-specific is usually done to exclude other etiologies and include hepatic steatosis, increase T2 signal around portal system, and Increased intensity in parenchymal signal.

## Ultrasound
Ultrasound is the first choice of imaging test in Alcoholic hepatitis. The finding are hepatomegaly,irregular outline of liver surface and edge nodularity, diffuse hyper-echoic liver,Atrophy of right lobe. Additionally, splenomegaly, varices and ] are suggestive features of portal hypertension.

## Other Diagnostic Studies
Liver biopsy is indicated in patients whose diagnosis is uncertain and in patients with severe Alcoholic hepatitis who are probable to undergo medical treatment. Liver biopsy in Alcoholic Hepatitis include Polymorphonuclear infiltration, hepatic necrosis, Mallory bodies in hepatocytes, perivenular and perisinusoidal fibrosis, ballooning hepatocytes, and steatosis.

# Treatment

## Medical Therapy
All patients with Alcoholic Hepatitis must be advised to stopped alcohol use. Additionally, nutritional supplements including folic acid, thiamine, vitamin B6, vitamin A and zinc can be provided. Glucocorticoids is the most common pharmacologic treatment in Alcoholic hepatitis .Pentoxifylline can be used in patient with contraindication to steroids.

## Surgery
Liver transplant is considered in case of cirrhosis. Orthotopic liver transplant is the definitive surgical treatment for hepatic failure associated with Alcoholic Hepatitis. Prior to liver transplant, 6 months of abstinence is required.

## Primary Prevention
The primary prevention of Alcoholic hepatitis is alcohol abstinence.Alcohol abstinence improves histological features of hepatic injury and reduces portal hypertension and the risk of cirrhosis. Risk of recidivism is 67% to 81% after alcohol abstinence; therefore, combination psychotherapy with cognitive behavioral therapy, peer driven support counseling, motivational enhancement therapy, and comprehensive medical care.

## Secondary Prevention
Disulfiram, naltrexone, and acamprosate are used to to maintain alcohol abstinence.Additionally, baclofen and gamma hydroxyl butyrate are options to reduce recidivism in patients with advanced chronic liver disease.