hepatitis fazil
TRANSCRIPT
Submitted By :
Mohammed Fazil.K
Final yr BDS ,Part A
Definition :
Hepatitis is an acute parenchymal disease of liver due to variety of causes in which variable number of hepatocytes undergo necrosis.
Depending on the onset and course of liver cell injury, hepatitis is classified into
i)Acute Hepatitis
ii)Chronic Hepatitis
Viral Hepatitis is a systemic disease with primary inflammation in the liver.
There are 6 hepatitis viruses-
Hepatitis A
Hepatitis B-caused by DNA virus
Hepatitis C
Hepatitis D
Hepatitis E
Hepatitis G
Dentists are 3-4 times more likely to be exposed to Hepatitis than with general population.
Acute parenchymal disease of the liver evolving within hours, days to few weeks is called Acute hepatitis.
PATHOLOGY
Mild liver cells injury –Inflammatory damage or liver cells necrosis
More severe damage –Subacute bridging necrosis
Very severe damage-Massive necrosis , Acute liver cells atrophy
infective
Viral-hepatitis A,B,C,D,E,.EBV.cytomegalo virus
Post viral-reyes syndrome in children
Non viral- leptospira,toxoplasma
Non infective
Drugs-paracetamol,halothane,rifampicin,isoniazid
Poisons-aflatoxin,carbontetrachloride
Metabolic-wilsons disease,pregnancy
Vascular-CHF,shock,budd chiari syndrome
Depending on the type of causative virus,acute hepatitis is classified as
Hepatitis A
HEPATITIS B
Hepatitis C
Hepatitis D
Hepatitis E
Also called as infectious hepatitis
It is endemic and occurs in person ,lives in poor conditions-occur mainly in children and young adults
Mode of transmission is by faeco-oral route.can also spread by blood transfusion and homosexual activity.
Incubation period is 30 days.
Period of infectivity is highest during the week before the onset of clinical symptoms
Once it occurs it gives life long immunity.
HAV is 27 nm non enveloped single stranded rna-virus with an icosahedral symmetry
HAV Belongs to the picornavirus family
CLINICAL FEATURES
2 stages
Prodromal stage/pre icteric and
Icteric stage
Preicteric occur before the development of jaundice.
o Fever,chills,headache.
o Malaise,pains,
o Git symptoms,anorexia,liver tenderness nausea,vomiting,disturbed smell,dark coloured urine,clay coloured stools.
o Lasts for few days to 2 weeks and is called anicteric phase.
o These usually subside with the onset of jaundice
With clinical onset of jaundice,fever usually disappears along with other prodormal symptoms but weight loss persist
Liver is enlarged,tender and associated with right hypochondriac pain .
Associated features of cholestasis[deep jaundice,dark coloured urine,clay colored stools,pruritis]
Splenomegaly usually does not occur in acute viral hepatitis but has reported in 5-10%cases.
It occur in all cases and takes 2-8 weeks.the prodormal symptoms disappear and jaundice starts regressing but liver enlargment and biochemical abnormalities persist.full recovery occurs within 1-2 months.
[1] demonstration of virus [2]detection of antibody [3]biochemical tests1)DEMONSRATION OF VIRUSi)Immunoelectron microscopy[IEM]Virus can be visualised by IEM in faeces.ii)enzyme-linked immunosorbent assay(ELISA)Detected in faeces by ELISAiii)IsolationVirus has been grown in human and simian cultures but it
is not possible to grow them routinely from faeces of patients
2)Detection of antibody Diagnosis depends on demonstration of specific antibody to HAV in the blood. ELISA kits for detecting igM & igG antibodies are available 3)Biochemical tests Liver function test such as alanine aminotransferase (ALT) and bilirubin supplement the diagnosisThe rise in serum transaminases[SGOT andSGPT] starts during prodormal phase and proceeds with rise in bilirubin,the rise is maximum during icteric phase(400-4000IU),and they fall during recovery phase.Rise in enzymes with prodormal symptoms may be the only clue to diagnose hepatitis during anicteric phase,which is otherwise difficult.
Serum albumin levels are normal.
Prothrombin time may be normal in mild disease but gets prolonged in severe cases.
Serum alkaline phosphatase levels are normal except in cholestatic phase.
Urine urobilinogen is increased in early phase of disease,it dissapears if intrahepatic cholestasis develops.
During cholestatic phase ,bile salts and bile pigments appear in urine.
During recovery phase ,urobilinogen reappears and bile salts and bile pigments dissapear.
Ultrasound of the liver shows an enlarged liver with normal echotexture.
As the cases are highly infectious ,hence barrier nursing care should be enforced with proper disposal of urine and faeces.
1)BED REST-enforced in patients with severe hepatitis till the signs and symptoms dissapear and liver functions start returning towards normal.Bed rest is usually adviced to ill patients,pregnant women.
2)DIET-due to anorexia these persons usually do not accept solid diet ,hence light diet in the form of fruit juice,soft drinks and glucose is acceptable,normal diet of 3000kcal should be advised as apetite returns.
Good amount of protiens and high carbohydrate intake should be encouraged.
PROPHYLAXIS
General prophylaxis
Improved sanitary practices. Prevention of fecal contamination of food and
water. Isolation and proper disposal of faeces and urine
Specific passive prophylaxis
Immune serum globulins(anti-HAV) have been employed in close contacts,pregnant women.
Vaccine for hepatitis A is available
HEPATITIS B VIRUS (HBV) (SERUM HEPATITIS)
Caused by hepadna virus,the virus only replicates in liver.
Its route of transmission is mostly through infected blood and blood products,hence also called as TRANSFUSION HEPATITIS
MORPHOLOGY
HBV is a complex 42 nm double shelled Particle.
The outer surface or envelope of virus contains hepatitis B surface antigen (HBs Ag).
It encloses an inner icosahedral 27 nm nucleocapsid (core), which contains hepatitis B core antigen (HBc Ag).
lnside the core is the genome, a circular double stranded DNA and a DNA polymerase
Blumberg and coworkers (1965):described
a protein antigen in serum of an
Australian aborigine, which gave a positive
Precipitation reaction with sera from two
Haemophiliacs who had received multiple
transfusions. This antigen was named
Australia antigen. It was subsequently
established to be the surface component of
hepatitis B virus (HBsAg).
ELECTRON MICROSCOPY of sera of hepatitis B patients shows three types of particles.
The most abundant form is a spherical particle (22nm in diameter
second type is tubular (22 nm in diameter)particle of varying length.
These two types are antigenically identical and are the surface subunits of hepatitis B virus (HBsAg).
The third type is a double shelled spherical structure (42 nm in diameter).
This particle is the complete hepatitis B virus or Dane particle.
ANTIGENIC STRUCTURE
1.HBsAg- Surface antigens (envelope protein)
2. HBcAg- It is the core (nucleocapsid) antigen of the virus. It is not detectable in patients blood.
3. HBeAg- It is the hidden antigenic component of
core.
VIRAL GENES AND ANTIGENS
The viral genome consists of two linear strands of DNA held in a circular configuration.Associated with one strand of DNA is a viral DNA polymerase .
This polymerase can repair the gap in the incomplete (the plus strand) strand and render the genome fully double stranded
MODES OF TRANSMISSION
There are three important modes of transmission of HBV infection:
1. Parenteral
2. Perinatal
3. Sexual
1) Parenteral Transmission
Transmission of infection may result from accidental inoculation of minute amounts of blood, blood products or fluid containing HBV during medical, surgical or dental Procedures.
2) Perinatal transmission -occurs when carrier mother's blood contaminates the mucous membranes of the newborn during birth.That is occurs primarily in infants born to HbsAg carrier mothers or mothers suffering from acute infection.
3) sexual Transmission
HBV is present in body fluids such as semen and vaginal secretions, hence it can be transmitted by sexual contact.
CLINICAL FEATURES
Onset is slow, usually insidious but more severe.
from 6weeks to 6 months.
The course of acute HBV infection can be divided into three phases:
Preicteric phase
Icteric phase
Convalescent phase
1) Preicteric Phase
Patient develops malaise, anorexia, weakness,myalgia, nausea and vomiting.
2) lcteric Phase
Patient develops jaundice, pale stools and dark urine (bilirubinuria).
3) Convalescent Phase
This phase is long and drawn out with malaise and fatigue,
Hepatitis B CarriersThere are two types of hepatitis B carriers
1.super carriers
2.simple carriers
1.Super carriers: They have HBe Ag in blood and are highly infectious. Very minute amount of serum or blood can transmit the infection. These are called super carriers.
2. Simple carriers: They are more common type of carriers who have no HBeAg and a low level of HBs Ag in blood. They transmit the infection only when large volumes of blood or serum are transferred, as in blood transfusion. These are named simple carriers.
L.D--------1)DETECTION OF VIRAL MARKERS
(i) HBsAg
HBsAg is recognised as a specific marker for HBV infection.
It is the first marker to appear in blood after infection.
HBsAg disappears with recovery from clinical disease in most patients, however it persists for years in carriers.
Antibody to HBsAg appears within weeks after the disappearance of HBsAg and persists for very long periods.
Anti-HBs is the protective antibody
(ii) HBeAg
Sera containing HBeAg are believed to be highlyinfectious and those with anti-HBe of little infectivity
The presence of HBeAg is thought to be an adverse prognostic sign.
The disappearance of HBeAg is followed by appearance of anti-HBe.
(iii) HBcAg
It is not detectable in the serum but can be demonstrated in liver cells by immunofluorescence.
Anti-HBc antibody usually appears in serum a week or two after the appearance of HBsAg.
It remains lifelong and thus serves as a useful indicator of prior infection with HBV, even after all the othermarkers become
undetectable.
2) Viral DNA Polymerase
It appears transiently in serum during pre-icteric phase.
3) Polymerase Chain Reaction (PCR)
HBV DNA level can be detected in serum by PCR. It is a highly sensitive test.
Prophylaxis
1. General Preventive Measures
health education,improvement of personal hygiene and strictattention to sterility.
An important preventive measure is the screening for HBsAg and HBeAg in blood donors.
Use of unsterile needles,syringes and other material must be avoided to prevent hepatitis B infection.
2. Immunization
i)Passive immunisation
Passive immunisation may be employed following any accidental exposure to hepatitis B infection.
Hepatitis B immunoglobulin(HBIG) is prepared from donors with high titres of anti-HBs.
It can be given in doses of 300-500 IU intramuscularly
It may not prevent infection but protects against illness and the development of carrier state.
(ii) Active immunisation
Following vaccines are available.
(a) Plasma derived vaccine:
Vaccine is prepared by purifying 22 nm particle of HBs Ag from the plasma of healthy carriers.
The particles are inactivated with formaldehyde.
The vaccine is immunogenic and safe.
(b) Recombinant yeast hepatitis B vaccine:
It is produced by a recombinant DNA in yeasts in which a plasmid containing the gene of HBs Ag has been incorporated.
HBsAg particles produced are extracted and purified for use as vaccine.
The vaccine is as immunogenic as plasma-derived vaccine.
It is safe and free from side effects.
Both vaccines are adsorbed with aluminum hydroxide as adjuvant, stored in cold but not frozen.
Three doses at O, 1 and 6 months are administered intramuscularly into deltoid muscle.
HEPATITIS C VIRUS (HCV)
It is a 50-60 nm virus with a linear single stranded RNA.
Modes of infection
It is transmitted by needle stick injuries, use of contaminated needles and syringes,transfusion of infected blood and blood products, and sexual intercourse.
Maternal-neonatal transmission has also been reported.
Clinical Features
Clinical infection with hepatitis C is generally less
severe, with milder symptoms, absent or less marked
jaundice.
Laboratory Diagnosis
It can be established by
detection of anti-HCV (antibody) by ELISA.
Viral genome(HCV RNA) can be detected by polymerase chain reaction (PCR) and by immunofluorescence
Prophylaxis
general prophylaxis
blood or blood products screening is possible.
HEPATITIS D VIRUS (HDV)(DELTA ANTIGIEN) . The HDV is a defective virus as it is
dependent on the helper function of HBV for its replication and expression.
It belongs to genus Delta virus It is spherical, 36-38 nm diameter RNA
particle surrounded by HBsAg enveIope . The genome is a single stranded small
circular molecule of RNA. It encodes its own nucleoprotein, the delta
antigen or HDAg , but the outer envelope (HBs Ag) of HDV is encoded by the genome of HBV coinfecting the same cell.
HBV is necessary for the production of HDV virions.
clinical features
HDV infection can occur in presence of HBV under two situation :
(i) Simultaneous infection with both HDV and HBV (coinfection)(ii) Super infection of an HBsAg carrier by
HDV.Transmission occurs parenterally
Coinfection with HBV and HDV results in hepatitis of increased severity than the disease caused by HBV alone.
Laboratory Diagnosis
Diagnosis can be made by detecting the IgM anti-delta antibody in serum.
ELISA and RIA kit are commercially available for detection of antibodies to HDV.
HDAg (Delta antigen)is primarily expressed in liver cell nuclei,where it can be detected by immuno-fluorescence.
It is occasionally present in serum.
HDVRNA can be detected by hybridisation using a radiolabelled probe.
Prophylaxis
No specific prophylaxis exists, but immunization with the hepatitis B vaccine is effective because delta antigen cannot infect Persons immune to HBV.
Screening of blood donors for HBsAg will also limit blood borne HDV infection.
HEPATITIS E virus (HEV)
Belongs to family calciviridae
They are spherical,nonenveloped and 27-38 nm in diameter.
They possess single stranded RNA genome, which is surrounded by icosahedral capsid
Pathogenesis
Hepatitis E has been shown to occur in epidemic, endemic and sporadic forms almost exclusively in developing countries.
It isprimarily associated with ingestion of faecally contaminated drinking water.
Clinically the disease resembles that of hepatitis A.
The disease is generally mild and self limited.
Laboratory Diagnosis
1) Exclusion Of hepatitis A and hepatitis B
Hepatitis A can be excluded by lgM serology and hepatitis B by absence of HBs Ag and anti HBc-igM
2) lmmunoelectron microscopy
Faeces is examined by electron microscopy of aggregated calcivirus-like particles using monoclonal antibodies.
3) ELISA test and western blot assay
These are used for detection of lgM and lgG antibodies.
4) Polymerase chain reaction (PCR)
HEV RNA can be detected in faeces or acute phase sera of patients.
Prophylaxis
Hepatitis E can be prevented by
1. improved standards of sanitation
2. chlorinated water
HEPATITIS G VIRUS- (HGV)
In 1996, this virus was first isolated from a patient with chronic hepatitis, this has been called hepatitis G virus.
HGV RNA has been found in patients with acute, chronic and fulminant hepatitis, haemophiliacs, patients with multipletransfusions, blood donors and intravenous drug addicts.
Its role in hepatitis is not clear
The genome of HGV consists of singlestranded RNA.
HGV replicates in peripheral blood cells.
The virus is transmitted parenterally, sexually and from mother to child.
A significant proportion of HIV-infected individuals are also HGV-co infected ,there is no evidence of a relationship between HGV infection and hepatic carcinoma.
HGV infection subsides after several years and anti-hepatitis G envelope antibody develops
PROPHYLAXIS.
HGV infection can be prevented by employing the general prophylactic measures used for HBV and HCV.
NON-A, NON-B (NANB) HEPATITIS
It refers to viral hepatitis resembling type A or type B clinically and epidemiologically but not caused by either of these virus.
Now 4 types (hepatitis C,D,E,G) of NANB virus are known.
The diagnosis is possible with serological test.
CLINICAL MANIFESTATIONS
• HCV virus DNA has been detected in the saliva of patients with chronic Hepatitis C infection and it has been demonstrated that the saliva of HCV carriers is infectious.
• A number of reports suggesting association between HCV
and Sjogren’s syndrome.
• Extrahepatic manifestations including salivary gland enlargement.
• Patients may report xerostomia along with chronic major
salivary gland enlargement.
• Females with chronic HCV infection had greater tendency for sialadenitis.
• HCV infected patients do not commonly experience dry eyes along with xerostomia.
• There is greater prevalence of HCV infection in dialysis patients and are encouraged to undergo periodic testing for HCV infectivity.
• Disease manifestation include jaundice, malaise, fever, anorexia, nausea, abdominal pain, dark “stormy” “foamy” urine, chalky grey stools, rash and arthritis.
• Many chronic hepatitis carriers are also at higher risk of hepatocellular carcinoma
Modes of transmission of HCV in health care settings
• Accidental needlesticks
• Blood splashes into eyes
• Blood transfusion
• Contaminated immunoglobulins
• Organ transplantation
• Infected cardiac surgeons to patients
• Patient to patient via colonoscope
Prolonged course of therapy with interferon-alpha have beneficial effects
A daily regimen of interferon alpha-2b plus ribavirinfor 6 to 12 months provide more promising results than interferon monotherapy
An effective vaccine for hepatitis C is not commercially available
Acute fulminant hepatitis is said to be present when a previously healthy person develops acute hepatitis and goes in to hepatic encepholapathy within 8 weeks of illness .
Cases that evolve at a slower pace are called sub acute or subfulminant hepatitis or hepatic failure.
It is a life threatening syndrome characterised by fever,jaundice and mental features(confusion, precoma and coma)
1)Acute viral hepatitis all types,but rare with hepatitis A.
2)Drugs- all hepatotoxic drugs
3)Pregnancy with hepatitis
4)Wilsons disease
5)Poisons-ccl4,phosphorus.
6)Reyes syndrome(fatty liver with encephalopathy in children).
a)cerebral features-disturbed concentration,poor alertness,disorientation,slurred speech.
b)jaundice
c)fetor hepaticus-ammoniacal odour in breath due to methyl mercaptans.
d)flapping tremors
e)liver dullness
f)Bleeding diathesis
g)cerebral oedema-nuerological manifestations
h)signs of portal hypertension
Bilirubin-it is raised both conjugated and unconjugated
Serum transaminases are raised,they may fall with progression of the disease.
Serum albumin is usually normal to low.
Prothrombin time may be prolonged in severe form of the disease.
Leucocytosis may occur
EEG is done to grade the hepatic encephalopathy
Serum ammonia levels are usually high
Reduced liver size with normal echotexture
No sedation is given unless the patient is violent.if necessary a small dose of phenobarbitone or 5mg of IV Diazepam may be given
Care of comatosed patients .care of back, bowel,bladder,skin,respiration,pulse,BP
Intravenous 5-10% glucose drip to give nutrition and to prevent hypoglycemia
Intravenous vitamin K,10 mg daily for 3 days with IV vitamin C 500 mg daily in the drip to prevent bleeding.
Intravenous H2 blockers,ranitidine 50 mg twice a day,may be given to prevent gastrointestinal bleeding.
It is defined as any hepatitis lasting 6 months or longer
AETIOLOGY
1)infective-hepatitis B,C,D.
2)Toxic-Drugs(alpha methyldopa,isoniazid)
3)Metabolic-Wilsons disease,heamochromatosis.
Unknown-autoimmune hepatitis
This type occurs commonly in men over 30 years
It may also come to physicians attention in a patient who is being treated for viral hepatitis,which fails to resolve within 12 weeks.
In these patients HbcAg and HBV DNA persist with low levels of IgM anti-HBc (HbcAg positive Hepatitis B)
In some cases spontaneous mutation of core promoter region of HBV genome may result in chronic Hepatitis called HbeAg-negative hepatitis B
Non specific features include ill health , fatigue, weakness.
Clinical relapses occur , sometimes super conversion of HbeAg to anti-Hbe and vice versa.
The physical signs include tender hepatomegaly. Jaundice may be mild or absent.Splenomegaly occurs in
25% cases . Some patients may have spider telangiectasia INVESTIGATIONSo Moderate increase in serum bilirubin and serum
transaminaseso Hypoalbuminaemia is present if the disease is advanced.o Viral markers of hepatitis B (HbsAg, Hbv DNA and Hbc
Ag)are present.o Liver Biopsy shows histological changes-GROUND
GLASS appearance inside the cytoplasm of hepatocytes.
INTERFERON-alpha 2a(180microgram per week for 48 weeks)or recombinant human interferon alpha(5 million daily or 10 million units thrice a week IM for 4-6 months.
Nucleoside and analogs are better tolerated and more effective than interferon
Lamivudine100 mg daily suppreses HBV DNA in serum and improves liver histology in 60% cases and normalises enzyme levels in 40% cases after 1 year treatment .
Adefovir is also effective in Hbc-positive and HbcAg negative patients.
Risk to dental professionel-hepatitis B,C and other types can be transmitted to the dentist by blood contaminated needles or instrument stick from an infected patient in acute phase of disease.
Clotting factors assesment- if surgery is necessary , obtain preoperative prothrombin time and bleeding time , as in liver diseases deficiency of clotting factor may be present.
Universal infection precaution-dental personnel may act as a source of infection to patient . Dentists who are carriers of HBV and who do not practice universal infection control precautions can transmit the infection to patient . At the same time it is required to avoid infection from patient to be transmitted to dental personnel.
Strict aseptic procedure-use of masks , gloves for all persons is a must.
Minimize aerosol production-by using a slow speed hand piece and using air syringe.
