JAUNDICE & HEPATITIS

- Dr. Bipin Maharjan

- Dept.of Pathology, NMCTH
 What is Jaundice?

❑Jaundice: (French, jaune-yellow)

➢Jaundice may be defined as yellow discoloration of the skin, sclera and
mucous membranes due to an elevated bilirubin concentration in the
body fluid above normal.
• Normal serum bilirubin: 0.2-1 mg/dl (5.1-17 μmol/L).
• Clinical jaundice: When bilirubin in plasma exceeds 2-2.5 mg/dl (50
µmol/L).
• Latent jaundice: Clinically there is no jaundice but serum bilirubin is
more than normal and <3mg/dl.
 Causes and Clinico-pathological classification
of Jaundice
1.Haemolytic/pre-hepatic jaundice:
✓Congenital defect in RBC: Sickle cell anaemia, thalassaemia,
haemoglobinopathies
✓Certain infection: Malaria.
✓Certain drugs: Quinine.
✓Snake venom.
✓Incompatible blood transfusion
✓Erythroblastosis foetalis
2.Hepatocellular/ hepatic jaundice:
✓Viral hepatitis.
✓Chronic alcoholic hepatitis.
✓Liver cirrhosis.
✓Infections: Yellow fever, septicaemia.
✓Poisons: Arsenic, chloride.
3.Obstructive/post-hepatic jaundice:
➢Intrahepatic cholestasis: Due to drugs, alcohol, primary biliary cirrhosis, viral
hepatitis etc.
➢Extrahepatic cholestasis:
✓Impaction of gall stone in common bile duct.
✓Carcinoma of head of pancreas.
✓Metastatic carcinoma of common bile duct.
✓Stricture of common bile duct.
✓Ascaris impaction in common bile duct.
✓Pressure from outside by enlarged coeliac lymph nodes.
Pathophysiology of Jaundice
 Pathophysiology of Jaundice

Jaundice becomes evident when the serum bilirubin levels rise above 2 to
2.5 mg/dL.
↓
The elevation can predominantly involve unconjugated (indirect) or
conjugated (direct) bilirubin.
↓
Excess bilirubin production (e.g., due to hemolytic anemia or ineffective
erythropoiesis) or defective conjugation (due to immaturity or hereditary
causes) leads to the accumulation of unconjugated bilirubin.
↓
 ↓
Although most unconjugated bilirubin is tightly bound to albumin in the
blood, at excessive levels the unbound fraction rises and may diffuse into
tissues and elevated bilirubin becomes clinically evident as yellow
discoloration of the skin (jaundice) and sclera (icterus).

❑Conjugated hyperbilirubinemia most often results from hepatocellular

disease, bile duct injury, and biliary obstruction. Since this form is
water-soluble and loosely bound to serum albumin, it can be excreted
in the urine.
 Complications of Jaundice

✓Acute bilirubin encephalopathy

✓Kernicterus – cerebral palsy and hearing loss
✓Electrolyte abnormalities - hyponatremia, hypokalemia, hypouricemia, normal
gap metabolic acidosis
✓Anemia
✓Infection/sepsis
✓Chronic hepatitis
✓Liver failure
✓Bleeding and coagulopathy
✓Kidney failure
 Hepatotrophic viruses

➢Hepatitis A virus:It is transmitted through the fecal-oral route, causes

acute (infectious) hepatitis, and does not lead to chronic liver disease.
➢Hepatitis B virus:It is transmitted parenterally with most infections
being subclinical, but can cause acute hepatitis, chronic hepatitis, and
cirrhosis.
➢Hepatitis C virus:It causes hepatitis which is most often associated
with progression to chronic liver disease (80% or more), while acute
infections are almost always subclinical. It is common cause of post-
transfusion hepatitis.
 Hepatotrophic viruses

➢Hepatitis D virus:is a defective virus, requiring hepatitis B co-

infection for replication and infection.
➢Hepatitis E virus: is endemic in equatorial regions and
frequently epidemic; it causes acute disease, which can be
severe in pregnancy and can lead to chronic hepatitis in
immunocompromised individuals.
Hepatotrophic viruses
Hepatitis B Virus
 Modes of spread of Hepatitis B virus
❑Parenteral route:
➢In developing countries, the most common mode of transmission is
via blood and blood products transfusion and needle prick injuries
➢Transmission also occurs by inoculation during surgical or dental
procedures or percutaneous inoculation via shared razors and tooth
brushes
➢HBV is more infectious than HIV and HCV As little as 0.00001 mL of
blood can be infectious
➢Chance of transmission ofHBV following a contaminated needle prick
injury is nearly 30% as compared to 3% and 0.3% with HCV and HIV
respectively.
 Modes of spread of Hepatitis B virus
❑Sexual transmission: It is found to be the most common route in
most developed countries; particularly homosexual males being at
higher risk
❑Vertical (perinatal) transmission:
The spread of infection from HBV carrier mothers to babies appears to
be an important mode of transmission particularly in China and South
East Asia
Transmission occurs at any stage; in utero, during delivery (maximum
risk) and during breastfeeding
Risk is maximum if the mother is HBeAg positive.
❑Direct skin contact:with infected open skin lesions may trasmit the
virus, e.g. impetigo (especially in children)
Clinical outcomes of Hepatitis B
 Complications of Hepatitis B

❑Pre-icteric phase (predominant gastrointestinal symptoms

such as nausea and vomiting) followed by; Icteric phase or
jaundice.
❑Hepatic complications: Very few cases may proceed to
complications such as:
✓Fulminant hepatitis
✓Cirrhosis
✓Acuteliver failure
✓Hepatocellular carcinoma.
❑Extrahepatic complications:
✓During the prodromal phase, a serum sickness-like syndrome
characterized by arthritis, rash, angioedema.
✓Hematuria, proteinuria and glomerulonephritis may develop in
5-10% of patients. This is due to immune complex deposition.
✓Polyarteritis nodusa
 Serological markers of Hepatitis B
❑Hepatitis B Surface Antigen (HBsAg):
➢HBsAg is the first marker to be elevated following infection; appears
within 1-12 weeks (usually between 8 and 12 weeks of infection).
➢It appears during incubation period; 2-6 weeks before the biochemical and
clinical evidence of hepatitis.
➢Presence of HBsAg indicates onset of infectivity (i.e. patient is capable of
transmission of HBV).
➢It remains elevated in the entire duration of acute hepatitis; becomes
undetectable 1-2 months after the onset of jaundice.
➢However, it persists rarely beyond 6 months if the disease progresses to
chronic hepatitis or in carrier state.
➢HBsAg is used as an epidemiological marker of hepatitis B infection (i.e. to
calculate prevalence of infection).
 Serological markers of Hepatitis B

❑Hepatitis B Precore Antigen (HBeAg) and HBV DNA:

➢HBeAg and HBV DNA appear concurrently with or shortly after
appearance of HBsAg in serum.
➢They are the markers of:
➢• Active viral replication
➢• High viral infectivity (i.e. high transmission rate).
 Serological markers of Hepatitis B

❑Hepatitis B Core Antigen (HBcAg):

➢HBcAg is a hidden antigen due to its surrounding HBsAg coat.
➢It is also non-secretory in nature; hence, it cannot be
detected in blood.
➢ However, HBcAg may be detected in hepatocytes by
immunofluorescence test.
 Serological markers of Hepatitis B

❑Anti-HBc lgM (Hepatitis B Core Antibody):

➢Anti-HBc IgM is the first antibody to be elevated following
infection.
➢It appears within first 1-2 weeks after the appearance of
HBsAg and lasts for 3-6 months.
➢Its presence indicates acute hepatitis B infection.
➢It is probably the only marker ( sometimes anti-HBclgG)
present during the period between appearance of anti HBs
antibody and disappearance of HBsAg.
 Serological markers of Hepatitis B

❑Anti-HBc lgG (Hepatitis B Core Antibody):

➢Anti-HBc IgG appears in late acute stage and remains positive
indefinitely whether the patient proceeds to:
✓Chronic stage ( with persistence of HBsAg, symptomatic and
elevated liver enzymes)
✓Carrier state ( with persistence of HBsAg, but asymptomatic)
✓Recovery (appearance of anti-HBs antibody).
➢It can also be used as epidemiological marker of HBV
infection.
 Serological markers of Hepatitis B

❑Anti-HBe (Hepatitis B Precore antibody):

➢Anti-HBe antibodies appear after the clearance of HBeAg and
remain elevated for variable period.
➢ Its presence signifies diminished viral replication and
decreased infectivity.
 Serological markers of Hepatitis B

❑Anti-HBs (Hepatitis B Surface Antibody):

➢It appears after the clearance of HBsAg and remains elevated
indefinitely.
➢Its presence indicates recovery, immunity and non-infectivity
(i.e. stoppage of transmission).
➢It is also the only marker of hepatitis B vaccination.
 Serological markers of Hepatitis B

❑HBsAg – Indicates hepatitis B infection ( Earliest marker)

❑Anti HBs – Immunity to hepatitis B (After vaccination)
❑Anti HBc –IgM – Acute infection (Detects recent infction)- Most reliable
marker, Detects even in window period
- IgG – Chronic infection (Prior exposure)
❑HBeAg- Active viral replication (Indicates high transmit rate)
❑Anti HBe – Low transmit rate
 Clinico-pathological syndromes of Viral
Hepatitis
❑Acute asymptomatic infection with recovery: Here,
infection is identified due to minimally elevated serum
transaminases or, after recovery, by the presence of antiviral
antibodies like anti-HAV or anti-HBV antibodies.
❑Acute symptomatic infection with recovery: Symptomatic
disease can be divided into four phases: (1) incubation period,
(2) symptomatic preicteric phase, (3) symptomatic icteric
phase, and (4) convalescence.
➢Peak infectivity occurs during the last asymptomatic days of
the incubation period and the early days of acute symptoms.
 Clinico-pathological syndromes of Viral
Hepatitis
❑Acute liver failure: Viral hepatitis accounts for approximately 10%
of cases of acute hepatic failure.
➢Liver transplantation is the only option if the disease does not
resolve before secondary infection and failure of other organs
develops.
❑Chronic hepatitis: This is defined as symptomatic, biochemical, or
serologic evidence of continuing or relapsing hepatic disease for
more than 6 months.
➢Clinical findings are prolongation of the prothrombin time,
hyperglobulinemia, hyperbilirubinemia, mild elevations in alkaline
phosphatase, fatigue, malaise, loss of appetite, mild jaundice,
vasculitis, glomerulonephritis, and cryoglobulinemia.
 Clinico-pathological syndromes of Viral
Hepatitis
❑Carrier state: A “carrier” is an individual who harbors and can transmit
an organism, but has no symptoms.
➢For hepatotropic viruses, carrier state has been used to describe two
separate scenarios: (1) individuals who harbor the virus but have no
liver disease; and (2) individuals who harbor the virus and have
asymptomatic non progressive liver damage.
➢For example, in HBV infection, the term “healthy carrier” has been
used for an individual with HBsAg and anti-HBe, but without HBeAg.
➢These patients have normal aminotransferases, low or undetectable
serum HBV DNA, and lack of significant inflammation or liver injury on
biopsy