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Alcoholic Hepatitis

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Information about Alcoholic Hepatitis

Published on April 3, 2008

Author: hanash

Source: slideshare.net

Description

overview of alcoholic hepatitis
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Alcoholic Hepatitis Dr E M Said Gastroenterology Ward 11

Background Spectrum of ALD Alcoholic Hepatitis Presentation Investigation Prognosis management

Background

Spectrum of ALD

Alcoholic Hepatitis

Presentation

Investigation

Prognosis

management

background major cause of morbidity and mortality in the West Per capita consumption has doubled between 1980-1995 Even though per capita consumption has plateaued in 1990s, recent surveys suggest drinking among females and the young continues to rise Alcohol consumption in the UK accounts for: 40,000 premature deaths per year 1.3% of GP consultations 12.5% of A&E attendances 25% of ICU admissions 30% of male and 15% of female admissions to general medical and surgical wards

major cause of morbidity and mortality in the West

Per capita consumption has doubled between 1980-1995

Even though per capita consumption has plateaued in 1990s, recent surveys suggest drinking among females and the young continues to rise

Alcohol consumption in the UK accounts for:

40,000 premature deaths per year

1.3% of GP consultations

12.5% of A&E attendances

25% of ICU admissions

30% of male and 15% of female admissions to general medical and surgical wards

background CMO's report 2001 stated a significant increase in liver cirrhosis and mortality rate in England and Wales (four- to eight-fold increase in males, three- to seven-fold increase females) Alcoholic cirrhosis mortality rate: 11/100,000 males 6/100,000 females Alcohol accounts for 50% of chronic liver disease Economic cost: £10 billion per year

CMO's report 2001 stated a significant increase in liver cirrhosis and mortality rate in England and Wales (four- to eight-fold increase in males, three- to seven-fold increase females)

Alcoholic cirrhosis mortality rate:

11/100,000 males

6/100,000 females

Alcohol accounts for 50% of chronic liver disease

Economic cost: £10 billion per year

Metabolism of Alcohol Alcohol metabolism by the liver result in increase in the NADH/NAD ratio & change in the oxidation-reduction status with reduced intracelluar state.this lead to: 1-Increase hepatic fatty acid production 2-Impaired carbohydrate and protein metabolism 3-Centrilobular necrosis of the hepatic acinus The exact mechanism of alcohol hepatitis and cirrhosis is unknown.

Alcohol metabolism by the liver result in increase in the NADH/NAD ratio & change in the oxidation-reduction status with reduced intracelluar state.this lead to:

1-Increase hepatic fatty acid production

2-Impaired carbohydrate and protein metabolism

3-Centrilobular necrosis of the hepatic acinus

The exact mechanism of alcohol hepatitis and cirrhosis is unknown.

 

Spectrum of alcoholic liver disease The three most widely recognised forms of ALD are : alcoholic fatty liver (steatosis). acute alcoholic hepatitis. alcoholic cirrhosis.

The three most widely recognised forms of ALD are :

alcoholic fatty liver (steatosis).

acute alcoholic hepatitis.

alcoholic cirrhosis.

 

alcoholic fatty liver (steatosis ) appears to be the initial change and is the most common response to alcohol ingestion The increased liver fat is derived from the diet, from free fatty acids mobilized from adipose tissue, and from lipid synthesized in the liver and inadequately degraded or excreted may cause mild abnormalities of liver function tests, including elevated ALT patients have an excellent prognosis if they abstain from alcohol.

appears to be the initial change and is the most common response to alcohol ingestion

The increased liver fat is derived from the diet, from free fatty acids mobilized from adipose tissue, and from lipid synthesized in the liver and inadequately degraded or excreted

may cause mild abnormalities of liver function tests, including elevated ALT

patients have an excellent prognosis if they abstain from alcohol.

 

alcoholic hepatitis It is characterized by necrosis of hepatocytes, and deposition of Mallory hyaline bodies. A polymorphonuclear reaction develops locally in response to the Mallory-containing and necrotic liver cells. typically presents with jaundice, low grade fever, and tender hepatomegaly Alcoholic hepatitis is often viewed as the intermediary step between fatty liver and cirrhosis

It is characterized by necrosis of hepatocytes, and deposition of Mallory hyaline bodies.

A polymorphonuclear reaction develops locally in response to the Mallory-containing and necrotic liver cells.

typically presents with jaundice, low grade fever, and tender hepatomegaly

Alcoholic hepatitis is often viewed as the intermediary step between fatty liver and cirrhosis

alcoholic cirrhosis represents end-stage disease Classically of micronodular type develop in 10 to 20% of those who are chronically heavy drinkers. Although irreversible, patients may live many years with few obvious effects particularly with cessation of drinking Decompensation of cirrhosis triggered by sepsis, bleeding, continued excessive drinking

represents end-stage disease

Classically of micronodular type

develop in 10 to 20% of those who are chronically heavy drinkers.

Although irreversible, patients may live many years with few obvious effects particularly with cessation of drinking

Decompensation of cirrhosis triggered by sepsis, bleeding, continued excessive drinking

 

It is estimated ,that although 90-100% of heavy drinkers show evidence of fatty liver, only 10-35% develop alcoholic hepatitis and 8-20% develop cirrhosis

It is estimated ,that although 90-100% of heavy drinkers show evidence of fatty liver, only 10-35% develop alcoholic hepatitis and 8-20% develop cirrhosis

Mechanisms of liver injury in Alcoholic hepatitis Genetic factors Malnutrition Toxic effects on cell membranes Hypermetabolic state of the hepatocyte Generation of free radicals and oxidative injury Formation of acetaldehyde adducts Role of the immune system Cytokines Role of concomitant viral disease

Genetic factors

Malnutrition

Toxic effects on cell membranes

Hypermetabolic state of the hepatocyte

Generation of free radicals and oxidative injury

Formation of acetaldehyde adducts

Role of the immune system

Cytokines

Role of concomitant viral disease

presentation

INVESTIGATIONS Laboratory findings Ultrasonography Liver biopsy

Laboratory findings

Ultrasonography

Liver biopsy

laboratory findings in alcoholic hepatitis Liver Function tests Increased AST to ALT ratio (2 to 1) (below 400IU/L) ALT usually < 100 IU/L Increased Gamma-GT (variable) Increased alkaline phosphatase (variable) Note: AST has 50% sensitivity, 82% specificity for alcohol-induced liver injury. ALT has 35% sensitivity, 86% specificity for alcohol-induced liver injury. Liver synthetic function (decrease after significant liver injury) INR Albumin

Liver Function tests

Increased AST to ALT ratio (2 to 1) (below 400IU/L)

ALT usually < 100 IU/L

Increased Gamma-GT (variable)

Increased alkaline phosphatase (variable)

Note: AST has 50% sensitivity, 82% specificity for alcohol-induced liver injury. ALT has 35% sensitivity, 86% specificity for alcohol-induced liver injury.

Liver synthetic function (decrease after significant liver injury)

INR

Albumin

laboratory findings in alcoholic hepatitis Renal function (impaired in advanced ALD) Urea/ creatinine Haematological Mild anaemia (usually macrocytic) Thrombocytopenia Other abnormalities Hyperuricaemia Hypertriglyceridaemia Raised IgA Hyperglycaemia

Renal function (impaired in advanced ALD)

Urea/ creatinine

Haematological

Mild anaemia (usually macrocytic)

Thrombocytopenia

Other abnormalities

Hyperuricaemia

Hypertriglyceridaemia

Raised IgA

Hyperglycaemia

Exclusion of other causes of liver disease: Alpha-1 antitrypsin genotype Serum caeruloplasmin/ serum copper Iron studies Autoantibodies (including LKM (Liver kidney microsomal)/ AMA (anti-mitochondrial)/ ANCA (anti-nuclear)) Immunoglobulins/ complement Hepatitis serology (HBsAg/HbCAb/HCVAb)

Alpha-1 antitrypsin genotype

Serum caeruloplasmin/ serum copper

Iron studies

Autoantibodies (including LKM (Liver kidney microsomal)/ AMA (anti-mitochondrial)/ ANCA (anti-nuclear))

Immunoglobulins/ complement

Hepatitis serology (HBsAg/HbCAb/HCVAb)

Ultrasonography Preferred study as inexpensive ,noninvasive and widely available The liver appears enlarged and diffusely hyperechoic. Helpful in excluding gallstones ,bile duct obstruction and hepatic or biliary neoplasm.

Preferred study as inexpensive ,noninvasive and widely available

The liver appears enlarged and diffusely hyperechoic.

Helpful in excluding gallstones ,bile duct obstruction and hepatic or biliary neoplasm.

Liver biopsy Accurate assessment of severity of liver damage Consider in patients in whom diagnosis is uncertain A stestosis B black arrows Mallory bodies C pericellular fibrosis D satellitosis Degeneration of hepatocytes

Accurate assessment of severity of liver damage

Consider in patients in whom diagnosis is uncertain

A stestosis

B black arrows

Mallory bodies

C pericellular fibrosis

D satellitosis

Degeneration of hepatocytes

PROGNOSIS Alcoholic hepatitis carries a significant mortality The most established tool for predicting survival in alcoholic hepatitis is Maddrey's discriminant function (MDF) An MDF ≥32 indicates a poor prognosis with a risk of mortality around 35%.

Alcoholic hepatitis carries a significant mortality

The most established tool for predicting survival in alcoholic hepatitis is Maddrey's discriminant function (MDF)

An MDF ≥32 indicates a poor prognosis with a risk of mortality around 35%.

PROGNOSIS Others factors that correlate with poor prognosis include : older age, impaired renal function, encephalopathy, rise in the white blood cell count in the first 2 weeks of hospitalization Nearly 2/3 of patients with severe alcoholic hepatitis will die in the hospital

Others factors that correlate with poor prognosis include :

older age,

impaired renal function,

encephalopathy,

rise in the white blood cell count in the first 2 weeks of hospitalization

Nearly 2/3 of patients with severe alcoholic hepatitis will die in the hospital

management General measures: Stop drinking Treat withdrawal symptoms Thiamine/multivitamins Bed rest High protein diet Treat decompansaton

General measures:

Stop drinking

Treat withdrawal symptoms

Thiamine/multivitamins

Bed rest

High protein diet

Treat decompansaton

THERAPY Evidence support use of: 1-corticosteroids 2-pentoxifylline 3-nutritional support Insufficient evidence: 1-Anabolic steroids 2-Malotilate 3-Etanercept 4-Infliximab Therapeutic agents for alcoholic hepatitis: Evidence not supporting use: 1-Propylthiouracil 2-Insulin and glucagon 3-Colchicine

Evidence

support use of:

1-corticosteroids

2-pentoxifylline

3-nutritional support

Insufficient

evidence:

1-Anabolic steroids

2-Malotilate

3-Etanercept

4-Infliximab

Therapeutic agents for alcoholic hepatitis:

Corticosteroids Steroid effects are mediated through a decrease in immune mediated injury, inhibition of cytokine production and activation, as well as suppression of extracellular matrix protein expression. should not be started until a sepsis screen has excluded infection Meta-analysis of three randomised trials showed an improvement in 28 day survival, but benefit was not seen at later time points The side effects of corticosteroids are justified only in patients with severe alcoholic hepatitis (MDF >32).

Steroid effects are mediated through a decrease in immune mediated injury, inhibition of cytokine production and activation, as well as suppression of extracellular matrix protein expression.

should not be started until a sepsis screen has excluded infection

Meta-analysis of three randomised trials showed an improvement in 28 day survival, but benefit was not seen at later time points

The side effects of corticosteroids are justified only in patients with severe alcoholic hepatitis (MDF >32).

Randomized, controlled trials using prednisolone 40 mg/d (or an equivalent) for 28 days have shown an increase in both short-term (30 and 60 day) and long-term (1 year) survival in a subgroup of patients with severe alcoholic hepatitis

Randomized, controlled trials using prednisolone 40 mg/d (or an equivalent) for 28 days have shown an increase in both short-term (30 and 60 day) and long-term (1 year) survival in a subgroup of patients with severe alcoholic hepatitis

Pentoxifylline Pentoxifylline inhibits tumor necrosis factor (TNF)- production. showed promise in one randomised controlled trial of patients with an MDF ≥32 who were not treated by steroids associated with a marked reduction in the incidence of hepatorenal syndrome and improved 28 day mortality with no significant side effects No trial has assessed combination therapy with steroids and pentoxifylline

Pentoxifylline inhibits tumor necrosis factor (TNF)- production.

showed promise in one randomised controlled trial of patients with an MDF ≥32 who were not treated by steroids

associated with a marked reduction in the incidence of hepatorenal syndrome and improved 28 day mortality with no significant side effects

No trial has assessed combination therapy with steroids and pentoxifylline

A recent randomized, controlled study in severe alcoholic hepatitis used pentoxifylline 400mg thrice daily (mean duration, 21 days), to show a short-term survival benefit of 22% (absolute risk reduction)

A recent randomized, controlled study in severe alcoholic hepatitis used pentoxifylline 400mg thrice daily (mean duration, 21 days), to show a short-term survival benefit of 22% (absolute risk reduction)

Nutritional support Energy expenditure increased up to 60% in AH Severe negative nitrogen balance occurs in AH Nutritional status correlates with survival in moderate and severe AH 1-1.5g/Kg/day protein is required to achieve neutral balance in cirrhotics. This requirement increases significantly in AH Total enteral nutrition is recommended in patients admitted with AH. Studies have shown a decreased mortality rate in patients receiving enteral feeding. Oral supplementation is ineffective due to anorexia and poor compliance due to encephalopathy and insufficient protein-calorie content to meet metabolic demands

Energy expenditure increased up to 60% in AH

Severe negative nitrogen balance occurs in AH

Nutritional status correlates with survival in moderate and severe AH

1-1.5g/Kg/day protein is required to achieve neutral balance in cirrhotics. This requirement increases significantly in AH

Total enteral nutrition is recommended in patients admitted with AH. Studies have shown a decreased mortality rate in patients receiving enteral feeding.

Oral supplementation is ineffective due to anorexia and poor compliance due to encephalopathy and insufficient protein-calorie content to meet metabolic demands

In summary… Common condition, high mortality Diagnosis :history of alcohol intake, physical finings,imaging,lab results and exclusion of other conditions Treatment:steroids,after exclusion of sepsis,pentoxifylline and nutrition support.

Common condition, high mortality

Diagnosis :history of alcohol intake, physical finings,imaging,lab results and exclusion of other conditions

Treatment:steroids,after exclusion of sepsis,pentoxifylline and nutrition support.

 

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