1) Alcoholic hepatitis is caused by chronic excessive alcohol ingestion and can lead to fatty liver, alcoholic hepatitis, or alcoholic cirrhosis. Risk increases with more than 60-80 g of alcohol per day for 10 years in men or 20-40 g per day for 10 years in women. 2) Alcoholic hepatitis presents with fever, jaundice, abdominal pain, and muscle wasting. Liver tests show elevated AST and ALT levels and AST:ALT ratio over 2. Treatment involves alcohol abstinence, nutrition support, corticosteroids or pentoxifylline, and liver transplantation may be considered. 3) Drug-induced hepatitis can occur through direct toxicity or idiosyncratic reactions.

1. ALCOHOLIC HEPATITIS
NUR IZZATUL NAJWA - 36

2. OBJECTIVES
• Know the brief components of alcoholic liver
disease
• Know the threshold developing ALD
• Know the pathophysiology
• Know the clinical syndrome specifically on
alcoholic hepatitis
• Know the investigation
• Describe the prognosis
• Describe the management of alcoholic hepatitis

3. INTRODUCTION
According to the WHO, alcohol consumption accounts for 3.8% of
the global mortality and 4.6% of DALYs. Liver disease represents
9.5% of alcohol-related DALY’s worldwide, while individual rates
vary in different regions. Alcohol is the main cause of liver-related
death in Europe with highest mortality rates reported from France
and Spain (approximately 30 deaths per 100,000 per year). There is
a possibility of underestimation of mortality due to legal issues of
documenting alcohol as primary cause of death. The lack of
specificity of the national survey questionnaires also fails to allow
accurate classification of liver diseases. Today, even in Asian
countries like India, alcohol is emerging as the commonest cause of
chronic liver disease 11.

4. INTRODUCTION
• Chronic and excessive ingestion of alcohol can
cause liver disease :
– Fatty liver
– Alcoholic hepatitis
– Alcoholic cirrhosis

6. THRESHOLD FOR DEVELOPING ALD
• THE VALUE MIGHT VARIES, BECAUSE THERE’S NO LINEAR
RELATIONSHIP BETWEEN DOSE AND LIVER DAMAGE
INTAKE OF >60-80 G/DAY
FOR 10 YEARS IN MEN
INTAKE OF >20-40
G/DAY FOR 10 YEARS IN
WOMEN

7. RISK FACTOR
• Drinking pattern – continous drinkers
• Gender - women
• Genetics
• Nutrition

8. PATHOPHYSIOLOGY

9. CLINICAL FEATURES

11. 2) ALCOHOLIC HEPATITIS
( STEATOHEPATITIS )
• Most asymptomatic
• Fever, rapid onset of jaundice, abdominal discomfort and proximal muscle
wasting
• Hepatomegaly
• Features of CLD ; spider angiomata, palmar erythema, chapped lips,
gynaecomastia
• Severe cases ; portal hypertension, ascites and variceal bleeding occur
without cirrhosis
• Non hepatic manifestation ; polyneuropathy, cardiomyopathy
• AST and ALT elevated two to seven fold, but usually <400 IU
• AST : ALT ratio > 2
• Elevated bilirubin
• Mild increase in alkaline phosphatase
• Reduced albumin
• Leucocytosis, elevated c-reactive protein
• POTENTIALLY REVERSIBLE BUT MANY PROGRESS TO CIRRHOSIS!

12. PATHOLOGICAL FEATURES
• Lipogranuloma
• Neutrophil infiltration
• Mallory’s hyaline
• Pericellular fibrosis

14. INVESTIGATION
• LAB FINDINGS
• LIVER BIOPSY

15. PROGNOSIS
• High mortality in severe hepatitis
• Poor prognostic factors include :
– Prothrombin time > 5 sec of control
– Anaemia
– Albumin < 2.5g/dL
– Bilirubin > 8mg/dL
– Renal failure
– Presence of ascites

17. MANAGEMENT
• Complete abstinence from alcohol
• Treatment for complication such as ; variceal
bleeding, encephalopathy and ascites
• Good nutrition
• Drugs :
– Corticosteroids
– Pentoxifylline
• Liver transplantation (poorer outcome if
patients still not abstinent)

18. • If Glasgow score > 9
• Side effect of sepsis
• Contraindicated in sepsis and variceal hemorrhage
• If bilirubin has not fallen in 7 days, then it should be stopped

19. DRUG AND TOXIN
INDUCED HEPATITIS

20. OBJECTIVES
• KNOW THE RISK FACTORS FOR DRUG
INDUCED HEPATITIS
• KNOW THE BRIEF PATHOPHYSIOLOGIC
MECHANISM
• KNOW THE DRUGS AND ITS PATTERN OF
ACTION
• KNOW HOW TO DIAGNOSE
• KNOW THE TREATMENT

21. INTRODUCTION
• Liver is the primary site of drug metabolism
• Liver disease may affect the capacity of liver to
metabolise drugs, thus unexpected toxicity
may occur

22. RISK FACTOR
• AGE
• SEX
• ALCOHOL INGESTION
• LIVER DISEASE
• GENETIC FACTORS
• OTHER COMORBIDITIES
• DRUG FORMULATION

23. PATHOPHYSIOLOGIC MECHANISM
• DISRUPTION OF
THE HEPATOCYTE
• DISRUPTION OF
TRANSPORT
PROTEIN
• CYTOLYTIC T-CELL
ACTIVATION
• APOPTOSIS OF
HEPATOCYTE
• BILE DUCT INJURY

24. MECHANISM
• Two major mechanism of chemical
hepatotoxicity :
DIRECT TOXIC
• PREDICTABLE
•DOSE RELATED TOXICITY
•SHORT LATENT PERIOD
•ABSENCE OF EXTRA-HEPATIC
MANIFESTATION
IDIOSYNCRATIC
•UNPREDICTABLE
•MOSTLY DOSE-
INDEPENDENT TOXICITY
•VARIABLE LATENT PERIOD
•PRESENCE OF EXTRA-
HEPATIC MANIFESTATION ;
FEVER, RASHES, ARTHRALGIA,
EOSINOPHILIA

25. CLINICAL MANIFESTATION
• The manifestations of drug-induced
hepatotoxicity are highly variable :
– ranging from asymptomatic elevation of liver
enzymes to fulminant hepatic failure.

26. DRUGS

27. 1) CHOLESTASIS
– Condition where bile cannot flow from the liver
to the duodenum
– Pure cholestasis ( high concentrations of
estrogen, 50mcg/day)
– Cholestatic hepatitis due to inflammation and
canalicular injury
2) HEPATOCYTE NECROSIS
– Inflammation does not always happen but does
accompany necrosis in liver injury

28. 3) STEATOSIS
– Microvesicular hepatocyte fat deposition, due to
direct effects on mitochondrial beta- oxidation
– Macrovesicular hepatocyte fat deposition
4) VASCULAR/ SINUSOIDAL LESION
– Damage the vascular endothelium and lead to
hepatic venous outflow obstruction
– Damage of sinusoids can trigger local fibrosis and
result in portal hypertension ( overdose of vit A)
5)HEPATIC FIBROSIS

31. TREATMENT
• Withdrawal of the suspected agent
• Supportive therapy as in viral hepatitis

32. SUMMARY

33. REFERENCES