1. Infective hepatitis and cirrhosis
Dr. S. Parasuraman
Faculty of Pharmacy,
AIMST.

2. Infective hepatitis and cirrhosis
• Hepatitis - inflammation and injury of the liver
• Hepatitis may be caused by
– Viruses
– Alcohol
– toxins and drugs
• Liver is inflamed/ injured because of viral infection it is
termed a viral hepatitis (three main virus are hepatitis A, B
and C and other hepatitis D, E and G).

3. Acute Hepatitis
• Acute hepatitis is an inflammatory process
• It cause liver cell death either by:
– necrosis or
– triggering apoptosis (programmed cell death)
• Acute hepatitis is also caused by exposure to:
– drugs (isoniazid) or poisons (e.g. ethanol)
• Manifestations
– relatively asymptomatic
– symptoms and signs, including anorexia, fatigue, weight
loss, nausea, vomiting, right upper quadrant abdominal
pain, jaundice, fever, splenomegaly and ascites
– hepatic dysfunction can also vary tremendously

4. Infective hepatitis
• Primary hepatocyte injury by stimulating host inflammatory
immune reactions
• Secondary hepatocyte injury by viral hepatitis
• The inflammatory reactions involve in
– Mast-cell degranulation
– Histamine release
– Cytokine production
– Complement activation
– Lysis of infected and neighboring cells
– Edema and swelling of the interstitium
• Later immune response supports the inflammatory responses
and

5. Aetiology of Infective hepatitis
• Hepatitis A
– non-enveloped, single-stranded RNA viruses
– transmitted via the fecal/oral route (fecal-contaminated
food, water or shellfish
– highest incidence occurs in children and adolescent
– HAV infection is endemic
– Onset: abrupt
– incubation period: 15–50 days
– Chronic hepatitis: rare

6. Aetiology of Infective hepatitis
• Hepatitis B
– enveloped, polyhedral, double stranded DNA virus
– blood-borne pathogen
– major routes of transmission include intravenous drug use,
unprotected sexual contact and exposure to contaminated
blood products

7. Aetiology of Infective hepatitis
• Hepatitis B:
– approx. 300 million people suffering from chronic infection
– in Southeast Asia, China and Africa, HBV is endemic. More than
8% of the infected population being chronic carriers
Transmission usually occurs by:
– mother to infant before or during birth (or)
– one child to another in early childhood
• Diagnostic method:
– Identification of the core antigen (HBcAg) or the hepatitis DNA
– Blood donations are routinely screened for HBV antigens
– Onset: insidious
– incubation period: 30–180 days
– Chronic hepatitis: possible

8. Aetiology of Infective hepatitis
• Hepatitis C (post-transfusion hepatitis):
• Is an enveloped, polyhedral, single stranded RNA virus
• The virus is present in semen and vaginal secretions.
• Multiple sexual (high risk behavior) partners become infected
• At least 30% of HIV-positive individuals are infected with HCV.
• Transmission: blood and body
fluids
• Onset: insidious
• incubation period: 15–160
days
• Chronic hepatitis: possible

9. Aetiology of Infective hepatitis
• Hepatitis D:
– unusual circular RNA, incomplete virus; delta hepatitis
agent
– Blood-borne pathogen.
– Can only infect individuals with active hepatitis B infection.
– Transmitted through contaminated blood and body fluids.
– The HDV virus is passed similarly to HBV virus.
– Onset: insidious
– incubation period: 30–180 days
– Chronic hepatitis: possible

10. Aetiology of Infective hepatitis
• Hepatitis E: Fecal/oral route of transmission. Outbreaks are
more common in developing nations and refugee camps due
to poor sanitation and fecal contamination of water supplies.
Young children are most frequently affected. The effects of
hepatitis E infection are particularly severe in pregnant
women.
– Onset: abrupt
– incubation period: 10–60 days
– Chronic hepatitis: unlikely

11. Manifestations of viral hepatitis
• Initially a prodromal anicteric phase, i.e. no jaundice, with
nausea, vomiting, headache, malaise, and a varying degree of
fever.
• In moderate to severe disease this is followed by the icteric
phase, with jaundice, dark urine and pale faeces (caused by
intrahepatic cholestasis), abdominal discomfort, hepatomegaly
and enlargement, sometimes splenomegaly and tenderness.

12. Manifestations of viral hepatitis
• Range from asymptomatic to severe
• Fatigue, malaise, anorexia, nausea
• Jaundice
• Liver inflammation and abdominal pain
• Abnormal liver function and enzyme levels

13. Complications of hepatitis
• Chronic active or persistent hepatitis can lead to progressive
liver injury, liver failure and death.
• The chronic form of hepatitis is most common with hepatitis B,
C, D, but rare with hepatitis A and E.
• Chronic active hepatitis is also associated with an increased
incidence of hepatocellular carcinoma.

14. Treatment of hepatitis
• Many hepatitis infections will resolve within 4 to 8 weeks
without treatment.
• Hepatitis A rarely becomes chronic and rarely requires
treatment. The long-term course of hepatitis B and C is less
predictable.
• Alpha interferon is currently approved for treatment of chronic
hepatitis B and C in US.
• Effective vaccines are currently available against hepatitis A, B
and C.

15. Drug induced &Toxic Hepatitis
• The relationship between the liver and drugs is important for
three reasons:
• The liver is the principal site for drug metabolisms
– lipophilic drugs, which are normally metabolized to
hydrophilic compounds for urinary excretion.
• Liver impairment has other physiological effects, which affect
drug handling and disposition.
– Reduced
biliary
excretion
(cholestasis)
causes
hyperbilirubinaemia and reduced excretion, e.g. of
rifampicin and fusidic acid.
• Drugs may cause liver damage
e.g. paracetamol (acetaminophen) and antidepressants.

16. Cirrhosis
• Cirrhosis - destruction or chronic, irreversible degeneration of
the normal liver cells
• characterized by diffuse scarring and fibrosis of the liver in
response to chronic inflammation and injury
• One of the major features of cirrhosis is the replacement of
functional liver tissue by scar tissue
• The most prevalent cause of liver cirrhosis is alcohol abuse.
Alcoholic liver disease presents in three progressive stages.

17. Aetiology of Cirrhosis
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Common causes : prolonged alcoholism and viral hepatitis
Primary biliary cirrhosis (young female)
Autoimmune hepatitis
haemochromatosis (iron overload caused by repeated blood
transfusions)
Genetic mutations
Haemorrhagic conditions
Impaired erythropoiesis, excessive oral iron intake
Wilson’s disease
Schistosomiasis
Drugs and toxins

18. Clinical features of Cirrhosis
• Clinical features of cirrhosis are numerous and varied, and
depend on both liver failure and past patient history.
• Generalized pruritus may precede jaundice by some years
• Ascites and encephalopathy occur inevitably in the later
stages
• Problems associated with liver cirrhosis:
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Ascites
Portosystemic encephalopathy
Cerebral oedema
Hypoglycaemia, hyperglycaemia
Electrolyte imbalance
Respiratory failure
Anaemia, coagulation disorders
Hepatocellular necrosis

19. Stages of alcoholic liver disease
• Alcoholic steatosis — “Fatty liver.” Accumulation of fat in the
hepatocytes, may results altered fat metabolism in the liver
and increase synthesis of fatty acids and triglycerides.
Enlargement of the liver is accompanied by symptoms that
may include anorexia, nausea and jaundice. At this point the
fatty changes are generally reversible if alcohol consumption
ceases.

20. Stages of alcoholic liver disease
• Alcoholic hepatitis — Inflammation, degeneration and
necrosis of hepatocytes with continued alcohol intake.
Symptoms can range from mild to severe and can include
anorexia and weight loss. Structural changes in alcoholic
hepatitis are also reversible to a large extent if alcohol
consumption ceases.
• Alcoholic cirrhosis — Diffuse scarring and fibrosis of the liver
that occurs after many years of alcohol abuse.

21. Manifestations of alcoholic cirrhosis
• Hepatosplenomegaly
• Ascites - Accumulation of fluid in the peritoneal cavity; results
from portal hypertension and decreased plasma protein
production by the liver; presents with massive distention of
the abdomen
• Portal hypertension
• Hepatorenal syndrome - Renal failure that can accompany
advanced liver disease
• Edema
• Jaundice

22. Manifestations of alcoholic cirrhosis
• Hepatic encephalopathy — Neurologic dysfunction
(accumulation of ammonia and other toxins in the circulation)
• Reduced metabolism of circulating sex hormones can result in
gynecomastia, menstrual irregularities, abnormal sexual
function
• Liver failure

23. Treatment of cirrhosis
• Nutritional and vitamin supplementation. A reduced-protein
diet is useful to decrease ammonia production.
• Diuretics to relieve fluid accumulation.
• Intubation or shunting to relieve bleeding from accessory
blood vessels.
• Management of symptoms of liver failure.

24. Thank you