Alcoholic liver disease

You don't need to be Editor-In-Chief to add or edit content to WikiDoc. You can begin to add to or edit text on this WikiDoc page by clicking on the edit button at the top of this page. Next enter or edit the information that you would like to appear here. Once you are done editing, scroll down and click the Save page button at the bottom of the page. Alcoholic liver disease is the major cause of liver disease in Western countries, (in Asian countries, viral hepatitis is the major cause). It arises from the excessive ingestion of alcohol and can present as fatty liver, alcoholic hepatitis, and cirrhosis. Fatty liver and alcoholic hepatitis may be asymptomatic and reversible with abstinence from alcohol. Alcoholic hepatitis involves acute or chronic inflammation of liver parenchyma and is the most common precursor of cirrhosis in the United States. Findings suggestive of alcoholic liver disease are: a history of chronic alcohol intake > 80 g/d in male and 40 g/d in female, findings suggestive of alcoholic hepatitis (fever, right upper quadrant pain, tender hepatomegaly, and jaundice). Among lab findings AST is an important factor and is greater than ALT, usually by a factor of 2 or more.

Pathophysiology
Fatty change and alcoholic hepatitis are probably reversible. The later stages of fibrosis and cirrhosis tend to be irreversible but can usually be quite well managed for long periods of time. The cause of fatty change are:

The excess generation of NAD by the enzymes alcohol dehydrogenase and aldehyde dehydrogenase which cause shunting of normal substrates from catabolism towards lipid biosynthesis. Impaired assembly and secretion of lipoproteins and increased peripheral lipid catabolism may also contribute

The cause of alcoholic hepatitis are:

Acetaldehyde formed from alcohol induces lipid peroxidation and acetaldehyde protein adduct formation which disrupt cytoskeleton Directly affect microtubule organization, mitochondrial function and membrane fluidity Generation of ROS Neutrophil attack at the site of hepatocyte necrosis

Fatty change

Fatty change, or steatosis is the accumulation of fat in liver cells which can be seen as fatty globules under the microscope. Alcoholism causes large fatty globules (macrovesicular steatosis). Other causes of macrovesicular steatosis include diabetes, obesity and starvation. Alcoholic fatty change is probably dose related. Small fatty globules have different causes.

Alcoholic hepatitis

Some people get an acute hepatitis or inflammatory reaction to the cells affected by fatty change. This is not directly related to the dose of alcohol. Some people seem more prone to this reaction than others. This is called alcoholic steatonecrosis and the inflammation probably predisposes to liver fibrosis.

Liver fibrosis

Liver fibrosis, in itself, is largely asymptomatic but as it progresses it can turn into cirrhosis, where the fibrosis alters the architecture and impairs the function of the liver.

Cirrhosis

Cirrhosis is a late stage of liver disease marked by fibrosis and altered liver architecture. It is often progressive and may eventually lead to liver failure. Late complications of cirrhosis or liver failure include portal hypertension, coagulation disorders, ascites and other complications including hepatic encephalopathy and the hepatorenal syndrome. Cirrhosis also has number of other causes, such as hepatitis and toxins. The late stages of cirrhosis (say from viral hepatitis or alcohol) may look similar. This phenomenon is termed a "final common pathway" for a disease.

Differential diagnosis

Cholecystitis Cholelithiasis Drug toxicity Hepatitis (viral, autoimmune) Nonalcoholic fatty liver disease

Diagnosis
History and symptoms
History

Recent history of heavy drinking Chronic alcohol intake i.e. > 80 g/d in men and 40 g/d in women with alcoholic hepatitis or cirrhosis.

Symptoms

Heaviness and pain below right side of chest (hepatomegaly) Abdominal pain

Jaundice Anorexia Nausea/vomiting

Physical examination

Fever Jaundice Abdominal tenderness Hepatosplenomegaly Ascites Confusion, coma (encephalopathy)

Lab diagnosis
Hemogram

Macrocytic Anemia Thrombocytopenia (causes are toxic effect of alcohol on platelet and splenomegaly) Leukocytosis

Liver function test

Raised serum bilirubin Elevated liver enzyme o AST usually elevated more than ALT (commonly by factor of 2 or more) o AST usually elevated but not more than 300 u/L o Elevated alkaline phosphatase (infrequently more than 3 times of normal) Prolonged prothrombin time (> 6 seconds above control) Serum protein o Decreased serum albumin o Increased gamma globulin Iron studies o Increased transferrin saturation, hepatic iron stores, and sideroblastic anemia Folic acid deficiency

Ultrasonography

Used for excluding biliary obstruction Ascites

CT scan

To exclude pancreatic disease To exclude Space occupying lesions Collateral vessels

MRI

To exclude pancreatic disease To exclude space occupying lesions Collateral vessels

Other studies
Liver biopsy

Fatty liver o Macrovesicular fat Alcoholic hepatitis o Polymorphonuclear infiltration o Hepatic necrosis o Mallory bodies in hepatocytes o Perivenular and perisinusoidal fibrosis o Ballooning hepatocytes o Steatosis, Alcoholic cirrhosis o Micronodular cirrhosis

Treatment
Medical therapy
General

Abstinence from alcohol Counseling and family support during alcohol abstinence Naltrexone or acamprosate to reduce relapse Nutritional support - Adequate amounts of carbohydrates and calories as alcoholics are commonly malnourished. This prevents endogenous protein catabolism, and hypoglycemia. Administration of thiamine is important with glucose supplements. This is so because glucose administration increases B1 consumption and B1 deficiency may lead to WernickeKorsakoff syndrome. Folic acid, thiamine, and zinc supplements are recommended.

Drug therapy
Alcoholic hepatitis

Methylprednisolone o Decreases short term mortality o Usually given for 1 month

Serum bilirubin is used as a predictor for treatment success. Failure of the serum bilirubin level to decline after 7 days of treatment predicts poor prognosis o Another predictor of treatment is Lille model comprising, age, serum creatinine, serum albumin, prothrombin time (or INR), serum bilirubin on admission, and serum bilirubin on day 7 Pentoxifylline It is a tumor necrosis factor inhibitor Used in patients with contraindications to steroids Usually given for 1 months Decreases mortality Decreases risk of hepatorenal syndrome

Other less commonly used drugs

Steroids + N-acetylcysteine Propylthiouracil Oxandrolone S-adenosyl-L-methionine Infliximab

Prognosis
In absence of steroid therapy 1 in every three patient dies.

Poor Prognostic factor

Prolonged prothrombin time Serum Bilirubin >10 mg/dL Hepatic encephalopathy Azotemia Leukocytosis Unresponsive to steroid treatment Reversal portal flow on doppler USG

Prognostic scores

MELD score for cirrhosis Glasgow alcoholic hepatitis score (age, white blood cell, blood urea nitrogen, prothrombin time ratio, and bilirubin level) ABIC score - age, serum bilirubin, serum creatinine

Complications
Alcoholic hepatitis

Portal hypertension (ascites, variceal bleeding, hepatorenal syndrome) Coagulopathy Intractable jaundice

Cirrhosis

Hepatocellular carcinoma

Glasgow Alcoholic Hepatitis score (GAHS)

Age ( years)
9

<50+1 >50+2

WBC (10 /L)

<15 +1 >15 +2

Urea (mmol/L)

<5 +1 >5 +2

PT ratio or INR

<1.5 +1 1.5-2.0 +2 >2 +3

Bilirubin (mol/L)

<125 +1 125-250 +2

>250 +3 A score of 9 or more identify patients most at risk of death. A score of 9 or more can be used either on day 1 (admission day) or day 6-9. Patients with severe alcoholic hepatitis mDF > 32 (modified discriminant function) or more specifically GAHS>9 benefit from corticosteroids, and perhaps pentoxifylline. Day 28 survival for patients with GAHS <9 is 87 % whereas if GAHS >9 survival drops to 46% in absence of treatment.

Glasgow Alcoholic Hepatitis Score Day 28 Day 84 survival ( % survival ( % ) )

Day 1 score GAHS <9 GAHS >9 Day 6-9 score GAHS <9 GAHS >9

87 46 93 47

79 40 86 37