viral hepatities

VIRAL HEPATITIS

الدكتور خلدون ذنون- كلية طب نينوى
المرحلة الرابعة
Objectives
To pay attention on presenting features and suspect the diagnosis.
To know how to investigate liver disease and discover the causative agent.
How to assess severity and complications.
Role of passive and active immunization.

Causes

98% are caused by hepatitis A-B-C-D & E viruses.
2% caused by: non A-E viral hepatitis, CMV, EBV, herpes simplex virus & yellow fever virus.

Clinical features

Prodromal symptoms before jaundice by few days-2weeks : chills , headache , malaise , anorexia , distaste for cigarrette , nausea , vomiting , diarrhea , steady upper abdominal pain which might be severe .
Liver is tender, may be palpable, and enlarged cervical lymph nodes may occur, splenomegaly particularly in children.
HBV infection: prominent arthralgia, occasionally serum sickness syndrome (skin rash, urticaria, polyarithritis).
Jaundice: yellow sclera, dark urine, pale stool & the liver becomes more easily palpable.
Recovery occurs within 3-6 weeks: appetite improves, jaundice improves, and urine & stool regain their normal colour, hepatomegaly regress.
Mild illness may run an anicteric course .


Investigations
Plasma aminotransferases AST, ALT 200-2000 u / L.
( Serum bilirubin: mainly conjugated.
Small ( in ALP.
( Prothrombin time in severe liver damage.
Bilirubinuria is an early finding, mild proteinuria.
WBC count: normal or low, occasional relative lymphocytosis.
Serology to identify HAV, HBV, HEV, CMV, EBV but unreliable in acute HCV.

Complications of acute viral hepatitis

Acute liver failure
Cholestatic hepatitis (hep.A)
Relapsing hepatitis
Aplastic anemia
Chronic hepatitis and cirrhosis (B,C)

General management

Severely affected patients require hospitalization.
Diet: 2000-3000 kcal / day, light diet, fruit drinks & glucose, encourage good protein intake.
I.v glucose is given in case of vomiting.
Drugs: avoid drugs if possible as some are metabolized in the liver especially sedatives & hypnotics, avoid alcohol &oral contraceptives.
Surgery: during acute viral hepatitis is risky & may result in liver failure, only life-saving operations are indicated.
Liver transplantation: for acute liver failure.


ACUTE HEPATITIS A
RNA enterovirus, highly infectious, incubation period 2-4 weeks.
Spread: faecal-oral route, blood & sexual: uncommon.
Infected persons excrete the virus in faeces for 2-3 weeks before the onset of the illness & for up to 2 weeks later.
Children are mostly affected with over crowding & poor sanitation.
Water, milk, shell fish may transmit the disease.
Chronic carrier state & chronic hepatitis do not occur.

Investigations

Only one HAV antigen is present in the blood transiently during the incubation period, virus is excreted in the stool for 7-14 days after the onset of the illness & it is difficult to culture.
Anti-HAV IgM type indicates a primary immune response & is diagnostic, falls to low levels within about 3 months of recovery.
Anti-HAV IgG type is of no diagnostic value, it persists for years after infection & indicates immunity, can be used to measure prevalence of HAV infection.

Prevention

Improving social conditions e.g over crowding & poor sanitation.
Active immunization by inactive virus vaccine (Havrix), given to persons traveling to endemic areas & persons with chronic HBV & HCV.
Passive immunization by immune serum globulin: gives immediate protection soon after exposure to the virus e.g close contacts, elderly, major disease, pregnant women, and outbreak of hepatitis in a school or nursery.
Both active & passive vaccine (in separate sites) can be given for those traveling to endemic areas if time is limited.

Prognosis

Most of the patients will recover.
Acute hepatic failure is rare.
Those with chronic HBV & HCV manifest serious illness when infected with HAV.


HEPATITIS B VIRUS


HEPATITIS B VIRUS
DNA virus, Hepanda, incubation period 4-20 weeks.
Humans are the only source of infection.
HBsAg: protein found in the viral envelope.
HBcAg: core antigen, a protein which makes up the capsid or core part of the virus (found in the liver but not the blood).
HBeAg: can be found in the blood & indicate infectivity.
Patients with chronic infection are most infectious when they carry HBeAg, HBV-DNA or DNA polymerase in the blood (markers of continuing viral replication).
Chronic HB affects 300 million people around the world.
Spread follow transmission of infected blood or blood products or injections with contaminated needles (parenteral drug misusers), now such mode of transmission constitute <10% of all post transfusion hepatitis because donor blood are tested prior to transfusion.
Tattooing or acupuncture can spread the disease.
Virus is also present in the body fluids e.g saliva, urine, semen & vaginal secretions which result in sexual & vertical transmission (from mother to child) during labour (chief source of infection globally).

Investigations

Depend on detection of viral antigens & antibodies against them.
HBsAg: is a reliable marker of HBV infection in acute hepatitis, chronic hepatitis & carrier state. Negative test makes infection very unlikely, after acute infection it lasts for 3-4 weeks and then disappears.
Antibody to HBsAg (Anti-HBs) appears after 3-6 months and persists for many years or permanently, it indicates previous infection or vaccination.
HBcAg: is found in the liver and not the blood.
Anti-HBc appears in the blood early in the illness & persists, initially IgM & later on IgG.
HBeAg: reflects active replication of the virus in the liver appears transiently at the out set of the illness & is followed by production of Anti-HBe. HBeAg indicates high infectivity.
Anti-HBe: indicate a very lower rate of viral replication.
HBV-DNA: detected in the blood by polymerase chain reaction (PCR) it indicates viral replication, rarely needed for diagnosis but for response to therapy.
Viral load: PCR measures HB-DNA in excess of 105 copies/ml with e antigen indicating viral replication, important in monitoring of antiviral therapy.


Management
Treatment of acute HBV infection ●Supportive with close monitoring for acute liver failure.
●No role for antiviral therapy.

Treatment of chronic HBV infection :

1- Interferon-alfa: indicated in patients with high serum transaminase & active hepatitis on biopsy, given for 16 weeks. Longer acting pegylated interferons given once weekly.
It results in 35% of the patients in loss of HBeAg & HBV-DNA with biochemical, clinical& histological remission with improvement in survival.
2- Lamivudine: anti-HBV nucleoside drug inhibits HBV-DNA polymerase, 100mg/day for one year, it causes complete suppression of serum HBV-DNA in 93-100% of patients with improvement in liver histology & fibrosis, however HBV replication recurs when therapy is stopped.
3. Adefovir: reduces viral load with histological improvement. Relapse occurs after stopping the drug. Effective in suppressing lamivudine-induced mutant viruses.

Prevention

A- Active recombinant hepatitis B vaccine: contains HBsAg, effective in 95% of individuals, given to those not immune with negative Anti-HBs in the blood.
Indications:
1. Close contacts of infected individuals e.g newborn of infected mothers, regular sexual partners.
2. Patients on chronic haemodialysis.
3. Medical & nursery personnel e.g dentists, surgeons, endoscopy unit.
4. Laboratory staff handling blood.
5. Parenteral drug users. 6. Homosexuals.

B- Passive immunization: by i.m hyperimmune serum globulin.

It should be given within 24 hour, or at most a week, of exposure to infected blood e.g accidental needle puncture, contamination with infected blood, oral or mucous membrane contamination .It can be combined with active vaccine.


Prognosis
Hepatic failure in less than 1% of cases.
Full recovery in 90-95% of adults with acute HBV infection.
5-10% develops chronic infection.
Following acute infection 10-20% becomes chronic carrier of the virus in Asia, Africa, Middle East & pacific islands, most infections occurring during infancy, in America & Europe it is 2%.
Mother infecting child during infancy leads to chronic infection in 90% of cases & recovery is rare.
Chronic infection is common in immunodeficient e.g Downs syndrome, HIV infection.
Recovery from acute HBV infection occurs within 6 months, antibodies against viral antigens are formed.
Persistence of HBeAg > 6 months indicates chronic infection.
Most patients with chronic HBV infection are asymptomatic & may develop cirrhosis & liver cancer after many years.

HEPATITIS D

Incomplete RNA virus, incubation period 6-9 weeks.
Requires HBV for replication.
Same source & mode of spread as HBV (blood, sexual, vertical).
Can infect those with HBV infection or chronic carrier of HBV.
Simultaneous infection of both viruses gives rise to severe acute hepatitis.
HDV infection of HBV chronic carriers can cause acute hepatitis with spontaneous recovery.
Chronic infection with both HBV & HDV can also occur & frequently causes rapidly progressive chronic hepatitis & cirrhosis.

Investigations

Diagnosis depends on detecting Anti-HDV against a single antigen only.
Early in the illness it is of IgM type, disappears within 2 months & is replaced later by IgG type, which occurs when there is a chronic infection with HDV.
Prevention: prevented by preventing hepatitis B.


HEPATITIS C
RNA flavivirus, i.p 2-26 weeks.
Mode of transmission: blood or blood products, saliva, while sexual & vertical spread is less common than in HBV infection.
It is the main cause of post-transfusion hepatitis especially in patients with hemophilia.
Prevention of infection is done through screening of blood donors & heat treatment of coagulation factor concentrate.
Parenteral drug users are at high risk of infection.
Chronic infection occurs in 75% of patients (life long), often asymptomatic or have mild fatigue.
Most never suffer an acute infection.
Extra hepatic features: cryoglobulinaemia, vasculitis, arithritis,GN.

Investigations

Identifying antibodies to several HCV antigens which appear in the blood during the first 3 months of the illness.
PCR can show HCV-RNA in the blood, used to confirm the diagnosis and monitor therapy.
Liver function: normal or mild increase in liver enzymes. Jaundice is rare. Liver histology for scoring fibrosis (grade1 to grade4).

Management

Treatment of choice is combination of pegylated( interferon & ribavirin.
Ribavirin: synthetic nucleoside analogue (causes haemolytic anaemia, teratogenic & causes abortion in women, so contraception should be used).
Response : elimination of HCV-RNA from the blood 6 months
After completing therapy in 40% of cases.
Liver transplant for cirrhosis, but the virus recurs in all cases.


Prevention
No available active or passive immunisation .
Blood or blood product screen before donation.
Care in dealing with infected blood samples e.g needles &injections. A programme to deal with parenteral drug users .

Prognosis

Those who acquire HCV infection develop chronic infection in 80% which remain asymptomatic for years .
20% of patients chronically infected develop cirrhosis after 20 year and increase to 50% after 30 year .
Those with cirrhosis develop hepatocellular cancer 2-5% per year.

HEPATITIS E

RNA calicivirus, i.p 3-8 weeks, excreted in the stool.
Spread: feacal-oral.
Causes large epidemics of water-borne hepatitis in countries with poor sanitation which resemble acute HAV & recovery is the rule.
Pregnant women with HEV infection are liable to acute hepatic failure with high mortality.
Chronic infection does not occur.

Investigation: detection of Anti-HEV IgM.

Prevention: no available active or passive protection.










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