Test: Viral Hepatitis- 1 - NEET PG MCQ

• GGTP is not specific to alcohol since it is easily inducible and elevated in all forms of fatty liver.
• AST and ALT are increased 2-7 times with AST/ ALT ratio > 1 in alcoholic hepatitis
• ALP is used for evaluation of obstructive jaundice LDH is elevated in hemolytic anemia and malignancy.

Hepatitis C is an RNA virus and it presents as chronic hepatitis C. It is transmitted by parenteral route.

Essential mixed cryoglobulinemia is characterised by cryoglobulins. They are cold precipitable monoclonal or polyclonal antibodies leading to systemic vasculitis. It is associated with hepatitis C. The features seen are:

1. Cutaneous vasculitis leading to palpable purpura (MC manifestation)
2. Arthralgia
3. Neuropathy leading to weakness
4. Glomerulonephritis

Integration of HBV DNA is seen in >90% of Hepatitis B related HCC. This can lead to truncation of HBx gene which happens to be a potent tumor activator. This explains the difficulty in achieving a cure as the viral inserts itself into host DNA and allows it to persist in the face of drugs that impair its replication. Harrison has used the term insertional mutagenesis.

Serum Hyaluronic acid is a glycosaminoglycan and is a component of ECM that is produced by hepatic stellate cells. The degradation of same occurs in sinusoidal endothelial cells. The serum concentration of Hyaluronic Acid is elevated in patients of hepatic fibrosis and can serve as a non-invasive surrogate for liver biopsy.

1. Fibrosure/ Fibro Test
   1. Incorporates haptoglobin, bilirubin, GGT and Apolipoprotein A-1 and α2 macroglobulin.
   2. High level of positive and negative predicitive values for diagnosing advanced fibrosis.
2. Flbroscan/ Transient Elastography
   Evaulates hepatic stiffness
3. Magnetic resonance Elastography

• The serological status of this patient shows HCV infection since anti-HCV antibody is reactive.
• Hepatitis B surface antigen is negative and IgG Anti- HBcAg is reactive indicating remote infection with hepatitis B.
• Recovery is the rule in hepatitis B. In contrast hepatitis C results in development of cirrhosis. Even if transaminases are normal, hepatitis C results in long term damage to the liver.
• Hence the reason for elevated liver enzymes with development of liver fibrosis points to HCV being the culprit.
• The next step shall be to perform a PCR-HCV RNA and initiate treatment based on prevalent genotype in the area.
• Liver biopsy is ruled out as question says patient is already having fibrosis.

The following characteristics of Hepatitis E virus are enumerated in Table 332-2 of Harrison. Hepatitis E does not have a-

1. Percutaneous spread
2. Perinatal spread
3. Sexual route spread

• HBeAg, appearance coincides with high levels of virus replication and reflects the presence of circulating intact virions and detectable HBV DNA.(with the notable exception of patients with precore mutations who cannot synthesize HBeAg).
• Inself-limited HBV infections.HBeAg becomes undetectable shortly after peak elevations in aminotransferase activity, before the disappearance of HBsAg, and anti-HBe then becomes detectable, coinciding with a period of relatively lower infectivity.

• In Chronic HBV infection, possibilities are:
  1. HBsAg remains detectable beyond six months
  2. Anti-HBc is primarily of the IgG class
  3. Anti-HBs is either undetectable or detectable allow levels
• During early chronic HBV infection, HBV DNA can be detected both in serum and in hepatocyte nuclei, where it is present in free or episomal form.
• HBeAg is a qualitative marker and HBV DNA a quantitative marker of replicative phase
• In chronic hepatitis B is the degree of hepatitis B virus (HBV) replication is more important than histology alone.
• In both HBeAg-reactive and HBeAg negative chronic hepatitis B, the level of HBV DNA correlates with the level of liver injury and risk of progression.
• The level of HBV replication is the most important risk factor for the ultimate development of cirrhosis and HCC in both HBeAg-reactive and HBeAg-negative patients.

Tenofovir is a first-line agent in the treatment of hepatitis B. It prevents the formation of 5' to 3' phosphodiester linkage essential for DNA chain elongation. Hence it causes premature termination of DNA transcription.

• Glomerulonephritis with the nephrotic syndrome is observed occasionally; HBsAg, immuno-globulin, and C3 deposition has been found in the glomerular basement membrane.
• While generalized vasculitis (polyarteritis nodosa) develops in considerably fewer than 1 % of patients with chronic HBV infection, 20-30% of patients with polyarteritis nodosa have HBsAg in serum.
• Due to decreased humoral response and repeated admissions in hospital in childhood patients of Down’s have a higher prevalence of hepatitis B infection.

Transfusion of blood contaminated with HCV was once an important source of transmission. Since 1990, however, the screening of donated blood for HCV antibody has decreased the risk of transfusion-associated HCV infection to less than 1 case in 103,000 transfused units
Persons who inject illegal drugs with non-sterile needles or who snort cocaine with shared straws are at highest risk for HCV infection. In developed countries, most new HCV infections are related to intravenous drug abuse (IVDA).

Incubation period of heoatotrophlc viruses

The fat in the buttock reduces the immunogenicity of the vaccine.

Since patient has voluntarily come for blood transfusion, it implies clinically his hepatitis B status is inactive disease. The patient in question is the first column of these AASLD guidelines and does not require any treatment. PCR DNA report will determine viral load. Serial monitoring of SGPT should be done for 3-6 months.

Retreatment is indicated for Relapsers after a previous course of standard interferon monotherapy or combination standard interferon/ribavirin therapy with a course of PEG IFN plus ribavirin.
A course of PEG IFN plus ribavirin-more likely to achieve a sustained virologic response in white patients without previous ribavirin therapy, with low baseline HCV RNA levels, with a 2-log10 reduction in HCV RNA during previous therapy, with genotypes 2 and 3, and without reduction in ribavirin dose. However in current scenario ledipsavir + sofosbuvir for 12 weeks is indicated for genotype la and lb.

• The proportion of babies that become HBV carriers is about 10-30% for mothers who are HBsAg-positive but HBeAg-negative. Now in this question anti-HBeAg is positive it implies that the viral replication has declined and HBeAg has become negative.
• However, the incidence of perinatal infection is even greater, around 70-90%, when the mother is both HBsAg-positive and HBeAg-positive.
• There are three possible routes of transmission of HBV from infected mothers to infants: transplacental transmission of HBV in utero; natal transmission during delivery; or postnatal transmission during care or through breast milk. Since transplacental transmission occurs antenatally, hepatitis B vaccine and HB1G cannot block this route.

• India has one of the largest pools of hepatitis B-infected patients.
• In a study reported from North India genotype-D was most common in patients suffering from chronic liver disease (CLD).
• The genotype-C was found to be only in one-tenth (10%) of the study population.

Country Wise Serotypes

• Genotype 3 is the most common type of hepatitis C in India.

• Chronic hepatitis is defined as a chronic inflammatory reaction of the liver of more than 3-6 months duration, demonstrated by persistently abnormal serum aminotransferase levels and characteristic histologic findings
• The causes of chronic hepatitis include. HBV- HCV, and HDV, autoimmune hepatitis, chronic hepatitis associated with certain medications (particularly isoniazid), Wilsons disease, and a1-antiprotease deficiency.
• Autoimmune hepatitis responds to steroids.

In detecting a recent hepatitis B infection, the most reliable marker in the blood is the IgM anti-HBc antibody. This marker indicates that the infection is new and shows the body's immediate response to the virus.

• HbsAg (Hepatitis B surface antigen) can indicate an active infection but does not specify if it is recent.
• IgG anti-HBs suggests past infection or immunity, not recent infection.
• IgM anti-Hbe is less commonly used and is not as specific for a recent infection.

Therefore, IgM anti-HBc is the key marker to confirm a recent hepatitis B infection.

• Gastritis is ruled out on account of epigastric pain and pleurisy would present with inspiratory catch in respiration. Since jaundice is not mentioned hence viral hepatitis is less likely.
• Typical symptoms of acute hepatitis are fatigue, anorexia, nausea, and vomiting. Very high aminotransferase values (>1000 U/L) and hyperbilirubinemia are often observed. On examination hepatomegaly is seen with sharp edge of liver.
• The most common presenting symptom of acute cholecystitis is upper abdominal pain. The Signs of peritoneal irritation may be present, and the pain may radiate to the right shoulder or scapula.

• Hepatitis B is the only hepadna virus causing infection in humans.
• It comprises capsule and a core containing DMA and DNA polymerase enzymes. Blood is the main source of infection.
• Chronic HBV infection is marked by the presence of HBS Ag and Anti HBC IgG in the blood.

Hepatitis E is not transmitted by percutaneous perinatal and sexual route.

• Even if HCV RNA is present in breast milk, there is little evidence for its relevance to HCV transmission to children.
  Reasons are:
  • High blood-to-milk gradient ranging from 103 to 107, and low concentrations of viral particles may be inactivated in the gastrointestinal tract. In addition, there may be a neutralizing effect of persisting maternal antibodies in nursed children.
  • Noninfectious viral particles or viral concentrations that were too low to result in transmission.
  • Presence of lactoferrin in mammalian breast milk, which has been described to inhibit the replication of viruses such as cytomegalovirus and HIV-1 in vitro 

The rate of vertical transmission of HCV from infected mothers to their children is 3%-5%.

The correct marker of hepatitis B during the window period is the IgM Anti-HBcAg. This marker indicates recent infection, as it is typically the first antibody produced in response to the virus.

• HBsAg is present during active infection but is not specific to the window period.
• Anti-HBs Ag indicates recovery or vaccination, not infection.
• IgG Anti-HBcAg appears later and indicates past infection.

Therefore, the marker that best signifies the window period of hepatitis B is IgM Anti-HBcAg.

• After a person is infected with HBV, the first virologic marker detectable in serum within 1-12 weeks, usually between 8-12 weeks, is HBsAg
• Circulating HBsAg precedes elevations of serum aminotransferase activity and clinical symptoms by 2-6 weeks and remains detectable during the entire icteric or symptomatic phase of acute hepatitis B and beyond.
• By contrast, anti-HBc is readily demonstrable in serum, beginning within the first 1-2 weeks after the appearance of HBsAg and preceding detectable levels of anti-HBs by weeks to months.

Hepatitis D accounts for maximum number of fulminant cases of viral hepatitis, a sizable proportion of which are associated with HBV infection.

• Chronic infection with hepatitis C is common even in those patients with return of amino-transferases to normal. There is 85% chances of chronic hepatitis C after acute hepatitis C. Amino-transferases continue to fluctuate and can be normal in patients with long-standing disease
• A pretreatment liver biopsy to assess histologic grade and stage provides substantial information about progression of hepatitis C in the past, and has prognostic value for future progression. It can identify such histologic factors such as steatosis and stage of fibrosis, which can influence responsiveness to therapy.
• Therefore final decision for therapy for these patients should be considered and the decision made based on such factors as patient motivation, genotype, stage of fibrosis, age, and comorbid conditions.

The virus that is transmitted non-parenterally is the Hepatitis E virus (HEV). Unlike other types of hepatitis, which are often spread through blood or bodily fluids, HEV is primarily spread through the consumption of contaminated water or food.
Key points about HEV transmission:

• HEV is mainly found in areas with poor sanitation.
• It is often associated with outbreaks linked to contaminated drinking water.
• Prevention involves ensuring access to clean water and proper hygiene practices.

Choice C & D are ruled out as current screening tests are sensitive for detecting surface antigen and HCV testing is routinely done.
Possible reasons for post transfusion hepatitis in spite of screening:

1. CMV can cause asymptomatic infection
2. Transfusion transmitted CMV can cause problems in premature neonates, allograft recipients, splenectomized patients.
3. Leukocytes depleted blood use of frozen deglycerolized RBCs and screening of donors for the absence of antibody to CMV.
4. Inactive hepatitis B carrier does not mean patient is HBsAg negative. It means persistent HBV infection of liver with low or undetectable serum HBV DNA/levels with normal serum aminotransferase.