Haemolytic jaundice
The increased breakdown of red cells leads to an increase in production of bilirubin. The resulting jaundice is usually mild as normal liver function can easily handle the increased bilirubin.
Lab:
- Unconjugated bilirubin: increased
- ALP: normal
- Transferases: normal
Congenital hyperbilirubinaemias
I. Gilbert's syndrome is most common familial hyperbilirubinaemia and affects 2-7% of population. It is asymptomatic and is usually detected as an incidental finding of a slightly raised bilirubin on a routine check. Mutation occur in the gene HUG-Br1 encoding UDP-glucuronosyl transferase.
II. Criggler-Najjar syndrome also mutation in the gene HUG-Br1 but more severe. Transplantation is the only effective treatment.
III. Dubin-Johnson (autosomal recessive) and Rotor syndromes are due to defects in hepatic bilirubin handling. In the Dubin-Johnson syndrome there are mutations in both MRP2 and transporter genes.
Cholestatic jaundice
I. Intrahepatic cholestasis occurs owing to failure of bile secretion can be caused by viral hepatitis, drugs, alcoholic hepatitis and cirrhosis.
II. Extrahepatic cholestasis is due to large duct obstruction of bile flow at any point in the biliary tract distal to the bile canaculi caused by common duct stones, sclerosing cholangitis, pancreatic pseudocyst etc.
Clinically in both types there is jaundice with pale stools and dark urine and the serum bilirubin is conjugated.
VIRAL HEPATITIS
Hepatitis A
Epidemiology
Hepatitis A is the most common viral hepatitis occuring worldwide, often in epidemics. Spread of infection is mainly by the faeco-oral route and arises from the ingestion of contaminated food or water. Overcrowding and poor sanitation facilitate spread.
Hepatitis A virus (HAV)
Hepatitis A is the most common viral hepatitis occuring worldwide, often in epidemics. Spread of infection is mainly by the faeco-oral route and arises from the ingestion of contaminated food or water. Overcrowding and poor sanitation facilitate spread.
Hepatitis A virus (HAV)
HAV is a picornavirus. It replicates in the liver, is excreted in bile and then excreted in the faeces for about 2 weeks before the onset of clinical illness and for up to 7 days after.
Clinical features
- Non-specific symptoms: unwell, nausea, anorexia, distaste for cigarettes
- Jaundice
- Dark stool/urine
- (Rare) extrahepatic complications: arthritis, vasculitis, myocarditis, acute kidney injury
- Rarely fulminant hepatitis, liver coma and death.
Investigations
- Prodromal stage: the serum bilirubin is usually normal. A raised serum AST/ALT.
- Prodromal stage: the serum bilirubin is usually normal. A raised serum AST/ALT.
- Icteric stage: the serum bilirubin reflects the level of jaundice.
Anti-HAV IgM means an acute infection!
Course and prognosis
The prognosis is excellent, with most patients making a complete recovery. Mortality rate around 0.1%+, death is due to fulminant hepatic necrosis. HAV hepatitis never progresses to chronic liver disease.
Prevention and prophylaxis
- Active immunization: HAV vaccine
- Passive immunization: normal human immunoglobulin is used if exposure to HAV is <2 weeks.
Hepatitis B
Epidemiology
The hepatitis B virus (HBV) is present worldwide with an estimated 360 mil carriers.
- Vertical transmission: mother to child
- Horizontal transmission
HBV spread also occurs by intravenous route, or by close personal conracr e.g. sexual intercourse.
Hepatitis B virus
Hepatitis B virus DNA is surrounded by an outer envelope of surface protein (HVsAg). HBsAg contains a major antigentic determinant as well as several subtypes. Combinations of these subdeterminanrs are used to classify HBV genotypes. These genotypes have bearing on for example
- the time to HBeAg seroconversion
- response to interferon treatment
- development of chronic liver disease
Clinical features of acute hepatitis
The clinical picture is the same as that found in HAV infection, although the illness maybe more severe. In addition, a serum sickness-like immunological syndrome may be seen. This consists of rashes (e.g. urticaria or maculopapular rash) and polyarthritis affecting small joins occuring in up to 25% of cases in the prodromal period. Fever is usual. Extrahepatic immune complex-mediated conditions such as an arteritis or glomerulonephritis are occasionally seen.
Investigations
Same as for hepatitis A.
Significance of viral markers in hepatitis B:
- HBsAg: acute or chronic infection
- HBeAg: acute hepatitis B (persistance implies, continued infectious state/development of chronicity)
- HBV DNA: Implies viral replication
- Anti-HBs: immunity to HBV, previous exposure, vaccination
- Anti-HBe: seroconversion
Course
The majority of patients recover completely, fulminant hepatitis occuring in up to 1%. Some patients go on to develop chronic hepatitis, cirrhosis and hepatocellular carcinoma or have inactive chronic HBV infection.
Chronic HBV infection
Following an acute HBV infection, which maybe subclinical, approximately 1-10% of patients will not clear the virus and will develop a chronic HBV infection. Patients are asymptomatic and HBsAg and HBeAg positive with very high levels of serum HBV DNA. Investigations show a moderate rise in aminotransferases and a slightly raised ALB.
Treatment for chronic hepatitis B
Indications for therapy are similar for HBeAg positive or negative patients with chronic hepatitis. Three criteria are used: serum HBV DNA levels, serum ALT levels and histological grade and stage. The aim of treatment is the seroconversion of HBeAg when present to anti-HBe and the reduction of HBV DNA to 400iu/L or less. Interferon, enteclavir and tenofovir are the most commonly used drugs.
Hepatitis D
Hepatitis D is caused by the hepatitis D virus (HDV or delta virus) which is an incomplete RNA particle enclosed in a shell of HbsAg and belongs to deltaviridae family. It is unable to replicate on its own but is activated by the presence of HBV.
- Co-infections of HDV and HBV which is clinically indistinguishable from an acute icteric HBV infection.
- Superinfection which results in an acute flare-up of previously quiescent chronic HBV infection.
Hepatitis C
Epidemiology
The virus is transmitted by blood and blood products. Vertical transmission from a healthy mother to child can occur, but is very rare. In 20% of cases the exact mode of transmission is unknown.
Clinical features
Most acute infections are asymptomatic, with about 10% of patients having a mild flu-like ilness with jaundice and a rise in serum aminotransferases. Most patients will not be diagnosed until they present, years later, with evidence of abnormal transaminase values at health checks or with chronic liver disease. Extrahepatic manifestation (arthritits, glomerulonephritis etc) are seen.
Diagnosis
This is frequently by exclusion in a high-risk individual with negative markers for HAV, HBV and other viruses. HCV RNA can be detected from 1-8 weeks after infection.
Course
Some 85-90% of asymptomatic patients develop chronic liver disease. A higher percentage of symptomatic patients clear the virus with only 48-75% going on to chronic liver disease. Cirrhosis develops in about 20-30% within 10-30 years and of these patients between 7-15% will develop hepatocellular carcinoma. The course is adversely affected by co-infection with HBV and HIV and by alcohol consumption.
Chronic hepatitis C infection
Clinical features
Patients with chronic hepatitis C infection are usually asymptomatic, the disease being discovered only following a routine biochemical test with mild elevations in the aminotransferases.
Treatment
Treatment is appropriate for patients with chronic hepatitis on liver histology and/or who have HCV RNA in their serum whether or not serum aminotransferases are raised. The presence of cirrhosis is not a contraindication but therapeutic responses are less likely. Patients with decompensated cirrhosis should be considered for transplantation. The aim if treatment is to eliminate the HCV RNA from the serum in order to:
- stop the progression of active liver disease
- prevent the development of hepatocellular carcinoma
Hepatitis E
Hepatitis E virus (HEV) is an RNA virus causing a hepatitis clinically very similar to hepatitis A. It is enterally transmitted, usually by contaminated water, with 30% of dogs, pigs and rodents carrying the virus. Epidemic have been seen in many developing countries. It has a mortality from fulminant hepatic failure of 1-2% which rises to 20% in pregnant women. There is no carrier state and it does not progress to chronic liver disease except in some immunosuppressed patients. HEV RNA can be detected in the serum or stools by PCR.
FULMINANT HEPATIC FAILURE
This is defined as severe hepatic failure in which encephalopathy develops in under 2 weeks in a patient with a previously normal liver. Cases that evolve at a slower pace are called subacute or subfulminant hepatic failure. FHF is a rare but often life-threatening syndrome that is due to acute hepatitis from many causes. Histologically there is multiacinar necrosis involving a substantial part of the liver.
Clinical features
Examination shows a jaundiced patient with a small liver and signs of hepatic encephalopathy. The mental state varies from slight drowsiness, confusion and disorientation to unresponsive coma with convulsion. Fetor hepaticus is common. fever, vomiting, hypotension and hypoglycaemia occur. cerebral oedema develops in 80% of patients with FHF but is far less common with subacute failure and its consequences of intracranial hypertension and brain herniation account of for about 25% of the causes of death.
Investigations
- Hyperbilirubinaemia
- High serum aminotransferases
- Low levels of coagulation factors
Treatment
There is no specific treatment but patients should be managed in a specialized unit. Supportive therapy for hepatic encephalopathy is necessary.
CIRRHOSIS
Cirrhosis results from the necrosis of liver cells followed by fibrosis and nodule formation. The liver architecture is diffusely abnormal and this interferes with liver blood flow and function. This derangement produces the clinical features of portal hypertension and impaired liver cell function.
- Horizontal transmission
HBV spread also occurs by intravenous route, or by close personal conracr e.g. sexual intercourse.
 |
| Hepatitis B Virus |
Hepatitis B virus DNA is surrounded by an outer envelope of surface protein (HVsAg). HBsAg contains a major antigentic determinant as well as several subtypes. Combinations of these subdeterminanrs are used to classify HBV genotypes. These genotypes have bearing on for example
- the time to HBeAg seroconversion
- response to interferon treatment
- development of chronic liver disease
Clinical features of acute hepatitis
The clinical picture is the same as that found in HAV infection, although the illness maybe more severe. In addition, a serum sickness-like immunological syndrome may be seen. This consists of rashes (e.g. urticaria or maculopapular rash) and polyarthritis affecting small joins occuring in up to 25% of cases in the prodromal period. Fever is usual. Extrahepatic immune complex-mediated conditions such as an arteritis or glomerulonephritis are occasionally seen.
Investigations
Same as for hepatitis A.
Significance of viral markers in hepatitis B:
- HBsAg: acute or chronic infection
- HBeAg: acute hepatitis B (persistance implies, continued infectious state/development of chronicity)
- HBV DNA: Implies viral replication
- Anti-HBs: immunity to HBV, previous exposure, vaccination
- Anti-HBe: seroconversion
Course
The majority of patients recover completely, fulminant hepatitis occuring in up to 1%. Some patients go on to develop chronic hepatitis, cirrhosis and hepatocellular carcinoma or have inactive chronic HBV infection.
Chronic HBV infection
Following an acute HBV infection, which maybe subclinical, approximately 1-10% of patients will not clear the virus and will develop a chronic HBV infection. Patients are asymptomatic and HBsAg and HBeAg positive with very high levels of serum HBV DNA. Investigations show a moderate rise in aminotransferases and a slightly raised ALB.
Treatment for chronic hepatitis B
Indications for therapy are similar for HBeAg positive or negative patients with chronic hepatitis. Three criteria are used: serum HBV DNA levels, serum ALT levels and histological grade and stage. The aim of treatment is the seroconversion of HBeAg when present to anti-HBe and the reduction of HBV DNA to 400iu/L or less. Interferon, enteclavir and tenofovir are the most commonly used drugs.
Hepatitis D
Hepatitis D is caused by the hepatitis D virus (HDV or delta virus) which is an incomplete RNA particle enclosed in a shell of HbsAg and belongs to deltaviridae family. It is unable to replicate on its own but is activated by the presence of HBV.
- Co-infections of HDV and HBV which is clinically indistinguishable from an acute icteric HBV infection.
- Superinfection which results in an acute flare-up of previously quiescent chronic HBV infection.
Hepatitis C
Epidemiology
The virus is transmitted by blood and blood products. Vertical transmission from a healthy mother to child can occur, but is very rare. In 20% of cases the exact mode of transmission is unknown.
Clinical features
Most acute infections are asymptomatic, with about 10% of patients having a mild flu-like ilness with jaundice and a rise in serum aminotransferases. Most patients will not be diagnosed until they present, years later, with evidence of abnormal transaminase values at health checks or with chronic liver disease. Extrahepatic manifestation (arthritits, glomerulonephritis etc) are seen.
Diagnosis
This is frequently by exclusion in a high-risk individual with negative markers for HAV, HBV and other viruses. HCV RNA can be detected from 1-8 weeks after infection.
Course
Some 85-90% of asymptomatic patients develop chronic liver disease. A higher percentage of symptomatic patients clear the virus with only 48-75% going on to chronic liver disease. Cirrhosis develops in about 20-30% within 10-30 years and of these patients between 7-15% will develop hepatocellular carcinoma. The course is adversely affected by co-infection with HBV and HIV and by alcohol consumption.
Chronic hepatitis C infection
Clinical features
Patients with chronic hepatitis C infection are usually asymptomatic, the disease being discovered only following a routine biochemical test with mild elevations in the aminotransferases.
Treatment
Treatment is appropriate for patients with chronic hepatitis on liver histology and/or who have HCV RNA in their serum whether or not serum aminotransferases are raised. The presence of cirrhosis is not a contraindication but therapeutic responses are less likely. Patients with decompensated cirrhosis should be considered for transplantation. The aim if treatment is to eliminate the HCV RNA from the serum in order to:
- stop the progression of active liver disease
- prevent the development of hepatocellular carcinoma
Hepatitis E
Hepatitis E virus (HEV) is an RNA virus causing a hepatitis clinically very similar to hepatitis A. It is enterally transmitted, usually by contaminated water, with 30% of dogs, pigs and rodents carrying the virus. Epidemic have been seen in many developing countries. It has a mortality from fulminant hepatic failure of 1-2% which rises to 20% in pregnant women. There is no carrier state and it does not progress to chronic liver disease except in some immunosuppressed patients. HEV RNA can be detected in the serum or stools by PCR.
FULMINANT HEPATIC FAILURE
This is defined as severe hepatic failure in which encephalopathy develops in under 2 weeks in a patient with a previously normal liver. Cases that evolve at a slower pace are called subacute or subfulminant hepatic failure. FHF is a rare but often life-threatening syndrome that is due to acute hepatitis from many causes. Histologically there is multiacinar necrosis involving a substantial part of the liver.
Clinical features
Examination shows a jaundiced patient with a small liver and signs of hepatic encephalopathy. The mental state varies from slight drowsiness, confusion and disorientation to unresponsive coma with convulsion. Fetor hepaticus is common. fever, vomiting, hypotension and hypoglycaemia occur. cerebral oedema develops in 80% of patients with FHF but is far less common with subacute failure and its consequences of intracranial hypertension and brain herniation account of for about 25% of the causes of death.
Investigations
- Hyperbilirubinaemia
- High serum aminotransferases
- Low levels of coagulation factors
Treatment
There is no specific treatment but patients should be managed in a specialized unit. Supportive therapy for hepatic encephalopathy is necessary.
CIRRHOSIS
Cirrhosis results from the necrosis of liver cells followed by fibrosis and nodule formation. The liver architecture is diffusely abnormal and this interferes with liver blood flow and function. This derangement produces the clinical features of portal hypertension and impaired liver cell function.
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