Download 02-Hepatitis

LIVER DISEASE
ACUTE HEPATITIS
CAUSES OF ACUTE HEPATITIS
•
Viruses
- hepatotropic viruses A,B,C,D,E,(F,G), “non-A-E.”
- others,eg,Epstein-Barr virus, cytomegalovirus, herpes
simplex virus, yellow fever.
•
Other organisms.
•
Drugs, herbal remedies.
•
Alcohol.
ACUTE VIRAL HEPATITIS
•
•
Incubation period - depends on the particular hepatotropic virus.
Clinical features - malaise, anorexia, nausea.
- +/- pyrexia, upper abdominal pain.
- jaundice, +/- dark urine and pale stool.
- tender hepatomegaly.
Note: can be asymptomatic and/or anicteric.
•
Blood tests - those of “hepatocellular” jaundice.
- viral markers.
MORPHOLOGY OF VIRAL HEPATITIS
•
•
•
•
•
•
•
Alternating ballooning degeneration and necrosis of liver cells. The
latter occuring as lysis with focal loss of hepatocytes (“spotty necrosis”)
or apoptosis evidenced by acidophil bodies.
Lymphocytic infiltrate in the parenchyma and portal tracts. This
infiltrate decreases with time as resolution occurs.
Phagocytic cells (Kupffer cells) increase with time to remove debris.
Cholestasis may be present in zone 3 (perivenular).
Hepatocyte regeneration occurs concurrently.
Variations - confluent liver cell necrosis may occur in different patterns
- bridging hepatic necrosis (portal-venular; venular-venular)
- panacinar
- periportal (interface hepatitis).
The necroinflammatory process centres on the liver parenchyma, is
pan-acinar but maximal in zone 3 (perivenular).
POSSIBLE OUTCOME OF VIRAL HEPATITIS
•
Resolution - +/- relapses
+/- protracted course.
•
Fulminant hepatitis - 1% or less. (HAV & HBV causes about 12 % of
cases of fulminant hepatitis).
Massive liver necrosis (panacinar necrosis).
Death in liver failure.
•
Chronic hepatitis - 5 - 10% but much higher in HCV.
Some types do not progress to chronicity.
•
Cirrhosis - +/- hepatocellular carcinoma.
Hepatitis A virus (HAV)
•
•
•
•
Virus - RNA 27nm. Picornavirus group. Enterovirus.
Pathogenesis - mixed cell mediated and humoral immune response.
Epidemiology - spread by faecal-oral route.
- endemic in some countries.
- epidemics occur.
Course - incubation period 15 - 50 days.
- mild or asymptomatic in children, more severe in adults.
- fulminant in less than 1%.
- no chronicity.
Hepatitis B virus (HBV)
•
•
•
•
Virus - DNA 42nm. Hepadna virus.
Pathogenesis - damage due to the body’s immune reaction,
T-cell cytotoxicity (CD8+/CD4+ lymphocytes)
Antibody-dependent cellular cytotoxicity
Antibody/complement-mediated cytotoxicity
Cytokine cytotoxicity (interferon,interleukin,TNF).
Epidemiology - spread by parenteral route (blood/blood products).
- horizontal and vertical transmission.
- marked geographical variation.
Course - incubation period 50 - 160 days.
- tends to be severe; can be asymptomatic.
- fulminant in less than 1%.
- chronicity in 5 -10% of whom 15 - 20% develop cirrhosis.
- risk of hepatocellular carcinoma.
Hepatitis C virus (HCV)
•
•
•
•
Virus - RNA 30-38nm. Hepacivirus, a sub genus of Flaviviridae.
Pathogenesis - cytopathic and immune mediated damage,
CD4+, CD8+, NK cells.
Epidemiology - parenteral route (blood/blood products) in 60%.
- in 40% the means of infection is uncertain (“sporadic”
or “community acquired”).
Course - incubation period 15 - 160 days.
- usually asymptomatic; mild illness if symptomatic.
- extrahepatic manifestations occur.
- chronicity in 70 - 90% of whom 20% develop cirrhosis.
- risk of hepatocellular carcinoma.
Hepatitis D virus (HDV)
•
•
•
•
Virus - incomplete single stranded RNA.
- requires HBV in order to replicate.
Pathogenesis - directly hepatotoxic.
Epidemiology - parenteral route.
Course - co-infection with HBV = severe but usually self-limiting
hepatitis (fulminant in 4%).
- superinfection on already existing HBV = severe hepatitis
(fulminant in 8%) with chronicity +/- cirrhosis in over
70%.
Hepatitis E virus (HEV)
•
•
•
Virus - RNA 32 - 34nm.
Epidemiology - faecal-oral route.
- epidemics in Asia, Africa, S.America.
Course - usually mild.
- fulminant in 2% but in 10-20% of pregnant women when it
carries a high mortality.
- no chronicity.
Other hepatitis viruses
•
Hepatitis F (HFV). Toga virus-like particles seen in a very few patients
with fulminant hepatitis but also a designation given to othr agents so
not an officially designated virus.
•
Hepatitis G (HGV). RNA virus of Flavivirus group, spread by
parenteral route but not thought to be pathogenic.
•
Other viruses. Some known, but some remain to be identified (there
are cases of hepatitis which cannot be proven to be due to the
presently known viruses).
CHRONIC HEPATITIS
•
•
•
•
•
Chronic hepatitis is an inflammation of the liver continuing without
improvement for at least 6 months.
Is a clinico-pathological syndrome, not a single disease.
Has several causes.
Is characterised by varying degrees of inflammation, necrosis and
usually fibrosis.
It may or may nor be associated with cirrhosis (cirrhosis may already
be established at the time of diagnosis).
CLASSIFICATION ACCORDING TO AETIOLOGY
•
•
•
•
•
Chronic viral hepatitis B, C, B+D.
Chronic viral hepatitis NOS (unknown).
Autoimmune hepatitis.
Chronic drug induced hepatitis.
Chronic hepatitis of unknown cause (cryptogenic).
Conditions to be considered in the differential diagnosis include
- primary biliary cirrhosis.
- primary sclerosing cholangitis.
- Wilson’s disease.
- alpha-1-antitrypsin deficiency.
- alcoholic liver disease.
CLINICAL FEATURES
•
•
•
•
•
•
•
•
Fatigue, anorexia, +/- dyspepsia, malaise.
May present with jaundice.
Can be asymptomatic and be discovered incidentally.
May present with evidence of cirrhosis.
Can directly follow unresolved acute hepatitis.
Signs of chronic liver failure may be present, spider naevi etc.
Worsening liver failure with hepatic encephalopathy may ensue.
Laboratory blood tests show (usually mild) rise in transaminases but
can be normal.
MORPHOLOGY OF CHRONIC HEPATITIS
•
•
•
•
•
•
Lymphocytes +/- plasma cells in portal tracts.
Extension of inflammatory infiltrate into adjacent parenchyma
(periportal or zone 1) with loss of liver cells, a feature known as
interface hepatitis.
Spotty necrosis and inflammation in liver acini. There may be bridging
hepatic necrosis.
Fibrosis of portal tracts with progression to portal to portal and portal to
venular bridging necrosis
The necroinflammatory process centres on portal tracts.
Liver biopsy necessary for diagnosis and used to grade and stage the
disease and monitor response to therapy.
Grading = the degree of interface hepatitis and acinar
necroinflammation. This determines the grade of activity.
Staging = the degree of fibrosis and architectural change from
involvement of a few tracts up to and including cirrhosis.
CHRONIC HEPATITIS B
•
•
•
•
•
•
•
Worldwide 2 billion have been infected, 350 million are carriers.
Prevalence >8% Asia & Africa,2-7% S&E Europe,<2%W.Europe/USA.
Especially likely to occur in men, neonates and adults with impaired
immunity.
Usually mild hepatitis histologically with characteristic “ground glass”
hepatocytes due to HBsAg in proliferated smooth endoplasmic
reticulum.
Diagnosed by detecting HBV markers in blood and in the liver, HBsAg
in hepatocyte cytoplasm and HBcAg in nuclei.
Occasionally immune complex disease develops resulting in vasculitis
or glomerulonephritis.
Risk of hepatocellular carcinoma once cirrhosis develops, but may
occur without cirrhosis in areas of high incidence.
CHRONIC HEPATITIS C
•
•
•
•
•
•
•
Worldwide 400 million are carriers.
The cause of almost 50% of chronic liver disease in the Western world
with the potential to become the most common cause.
Over 50% of patients with unexplained cirrhosis or hepatocellular
carcinoma have anti-C antibodies.
Characterised by a fluctuating clinical, biochemical and histological
course due mainly to development of quasi species of the virus.
Usually histologically mild but 20% develop cirrhosis and therefore risk
of hepatocellular carcinoma. Lymphoid aggregates, bile duct damage
and fatty change are histological pointers to HCV infection.
Diagnosed by detection of viral RNA in blood by PCR.
Can cause immune complex disease. 35% develop cryoglobulinemia.
THE LIVER IN INFECTIOUS DISEASES
•
•
•
•
•
Viruses - viral haemorrhagic fevers, herpes group, HIV with
opportunistic infections in AIDS.
Bacteria - bacterial septicaemia.
- pyogenic organisms - liver abscess.
- organisms causing granulomas, eg tuberculosis,
brucellosis, typhoid fever, Q-fever.
- spirochaetes, eg syphilis and leptospirosis (Weil’s disease).
Fungi - Candida, Aspergillus, Histoplasma.
Parasites - malaria, amoebic “abscess”, ascariasis, hydatid disease,
Schistosoma, Clonorchis, Opisthorchis.
Neonatal hepatitis - characterised by multinucleated giant
hepatocytes. Several causative organisms have been
identified but most are of unknown aetiology.
AUTOIMMUNE HEPATITIS
•
•
•
•
•
•
•
•
•
•
•
More common in females (78%) than in males.
Any age but especially young women and perimenopausal women.
Up to 60% have other forms of autoimmune disease eg rheumatoid
arthritis, thyroiditis, Sjogren’s syndrome, ulcerative colitis.
HLA B8 and HLA DR3 frequent.
High titres of IgG and antibodies to various bacterial and viral antigens.
High titres of antinuclear (ANA), antismooth muscle (SMA), and/or
antiliver/kidney microsomes (anti-LKM1) antibodies.
Reduced number and function of suppressor T lymphocytes.
Is a cytotoxic T-cell attack on hepatocytes.
Severe chronic hepatitis histologically with marked interface hepatitis
and numerous plasma cells in the inflammatory infiltrate.
Responds well to steroids. Liver transplantation may be necessary.
Untreated 40% die of liver failure in 6mo. 40% of survivors -> cirrhosis.