Infective hepatitis and cirrhosis


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Infective hepatitis and cirrhosis

  1. 1. Infective hepatitis and cirrhosis Dr. S. Parasuraman Faculty of Pharmacy, AIMST.
  2. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 17. Aetiology of Cirrhosis • • • • • • • • • • 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. 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: – – – – – – – – Ascites Portosystemic encephalopathy Cerebral oedema Hypoglycaemia, hyperglycaemia Electrolyte imbalance Respiratory failure Anaemia, coagulation disorders Hepatocellular necrosis
  19. 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. 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. 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. 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. 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. 24. Thank you