infdrjuke roslia-2.ppt

7/27/2019 infdrJuke Roslia-2.ppt

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Epidemiologi

There are no data on the incubation period,since there is always concomitant infectionwith hepatitis B

Replication of HDV can only take place in

people with acitive HBV replication-eitheras coinfection or superinfection by an HBC-carrier with HDV.

Approx. 5% of the worlds 300 million HBs

carriers are coinfected with HDV. Infection is via blood, blood products and

sexual intercourse

High-risk groups are drug addicts,

hemophiliacs and dialysis patients


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Structure

The hepatitis virus, formerly known as the-agent, is a disease agent which is dependentin coinfection with other viruses of thehepadna-family

It has a diameter of 36 nm

The surface consists of the hepatitis B antigen,which surrounds the actual hepatitis D antigenand the virus-RNA

The sequence of HDV-RNA, which is 1758 baseslong, is not homologous with that of HBV

The RNA consists of circular RNA single-strand It inhibits replication of HBV

Factors which are important for replication arelocalized in the highly protected region, andthe hepatitis delta antigen is coded in thelarger portion of the RNA


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Diagnostics

Antigen demonstration : The HDVantigen can be identified by means of aradioimmunoassay

Antibodies : Among the specificantibodies, it has recently becomepossible to identify those of the IgM,

thus enabling diagnosis of acuteinfection

HDV-RNA : HDV-RNA can be

demonstrated using both spot


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Clinical course

Coinfection with the hepatitis D virus oftentakes the course of fulminant hepatitis;estimates of endemic disease in drug addictsare as high as 30%

Chronic active hepatitides are also reported

increasingly Apart from concomitant infection with HBV and

HDV, there is also occurrence of HDVsuperinfections with existing active HBVinfection

Like coinfection, superinfection is alsodependent on replication of the hepatitis Bvirus

Superinfection must be suspected when thereis acute exacerbation of chronic hepatitis B and

with HBsAg carriersSu erinfection with HDV fre uentl results in


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Therapy

There is no specific antiviral therapy for HDV

Studies with interferon show temporaryinhibition of replication during therapy, but thisdoes not affect the clinical course favourably

No passive immunization exists

There is no specific active immunization forhepatitis D

It would be desirable for HBV-carriers in order toreduce the risk of superinfection

Active hepatitis B immunization also preventsHDV infection in persons who have not yet been

Prophylaxis


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Epidemiology

Formerly enteric hepatitis non-A, non-B istransmitted by fecal and oral routes

Large epidemics have been observed in third-

world countries

Enterically transmitted hepatitides are provokedby HEV at least as often as by HAV in these

countries

Infectivity does not seem particularly high

The incubation period is 40 days (14-60 days) onaverage

Retrospective analysis of an epidemic in Calcutta

showed that approx.

2% of people using the same water source

acquired hepatitis, compared with 0.3% when the


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Structure

The hepatitis E virus is an RNA virus ofthe calicivirus-family

The diameter of the complete virus is 27-32 nm

Electronoptic inspection reveals nodifferences between the agents fromdifferent continents

Only fragments of the sequence can be

distinguished so far

A test for demonstrating specific

Diagnostics


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Clinical course

As with the other hepatitis, a prodromalphase can be observed here too

There is a mortality rate of up to 3% withicteric patients; this figure can reach 22%

with women in the third trimenon ofpregnancy

It is not yet clear whether chronic activehepatitides or liver cirrhoses can be

caused by HEV, but it would appearimprobable.

Therapy


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Prophylaxis

There is no passive immunization

So far it could not be shown that immuno-globulin preparations - especially thosewon from serums of third-world

inhabitans - contain specific antibodies,and would thus afford protection.

An active immunization is available

As with hepatitis A, prophylaxis consistsof strict observance of hygienerecommendations in countries where

hepatitis E is endemic


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Epidemiolog

i To data, no data on the incubation period

exist

According to provisional studies, approx.

10% of the hitherto unexplained cases of

hepatitis non-A-E infections are caused by

the hepatitis G virus

Coinfection with HCV appears to be notinfrequent in some high-risk groups

It is blood-borne, but no other

transmission routes have yet been proven


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Structure

The hepatitis G pathogen is a single-

stranded RNA virus, which shares features

in common with the hepatitis C virus,

although the nucleic acid sequence

homology is only approx. 30%

It has been identified using molecular

biology methods The virus titre is low

The genome structure is similar to that of

HCV.


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Diagnosis

Antigen detection : It has not yet beenpossible to detect the antigen, propablybecause of too low a virus titre

Antibodies : To date, no test methods forroutine screening exist

RNA detection : Reverse transcription with asubsequent polymerase chain reaction allowshepatitis G virus RNA to be detected

This method will be available as routine in theneat future

Hepatitis G virus RNA has been observed inpatients at all stages of liver disease

However, the frequency of transition to

Clinical features


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Table. Prevalence of Clinical Features ofHepatocellular Carcinoma

Abdominal pain

Weight loss

Weakness

Abdominal swelling

Nonspecific

Gastrointestinal symptoms

Jaundice

59 - 95

34 - 71

22 - 53

28 - 43

25 - 28

5 - 26

Hepatomegaly

Hepatic bruit

Ascites

Splenomegaly

Jaundice

Wasting

Fever

54 - 98

6 - 25

35 - 61

27 - 42

4 - 35

25 - 41

11 - 54

SYMPTOMS

PREVALENCE(%) PHYSICAL SIGNS

PREVALENCE(%)


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Table. Paraneoplastic Syndromes Associatedwith Hepatocellular Carcinoma

HypoglycemiaPolycythemia (erythrocytosis)HypercalcemiaSexual changes: Isosexual precocity, gynecomastia,feminizationSystemic arterial hypertensionWatery diarrhea syndromePorphyriaCarcinoid syndromeOsteoporosisHypertrophic osteoarthropathy

ThyrotoxicosisThrombophlebitis migransPolymyositisNeuropathyCutaneous markers: Pityriasis rotunda, Leser-trelat sign,

dermatomyositis, pemphigus foliaceus

T bl T M k f H t ll l


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Table. Tumor Markers of HepatocellularCarcinoma*

Alpha-fetoprotein

DES- -carboxyprothrombin

-1-fucosidase

Isoenzymesof -glutamyltransferase

Inhigh-incidencepopulations,

80-90; in low-incidence

population, 50-70

58 - 91

75

60

Relatively quick andeasy to measure,most extensivelystudied

Easy and quick tomeasure

Easy and quick tomeasure; relativelyinexpensive

Relatively easy andquick to measure

90

84

70 - 90

96

SENSITIVITY(%) ADVANTAGES

Relatively

expensive

Far moreexpensive

than -FP

Expensive

SPECIFICITY(%)

DISADVANTAGES

that sensitivity and specificity vary both with the population under study andbsolute level of the marker. Thus, the specificity of a markedly elevated alpha-rotein in high-risk patients greatly exceeds the sensitifity of mildly elevated

s in cirrhosis-free patients.


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Table. Risk Factors for HepatocellularCarcinoma in Humans

MajorChronic WBV infectionChronic HCV infectionRepeated exposure to aflatoxin 1.

Cirrhosis

MinorOral contraceptive steroidsCigarette smokingHereditary hemochromatosisWilson disease 1- Antitrypsin deficiency

Type 1 hereditary tyrosinemiaGlycogen storage disease (types 1 and 2)HypercitrullinemiaAtaxia telangiectasiaMembranous obstruction of the inferior venacava


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Table. Treatment Options for HepatocellularCarcinoma

Surgical resection: Offers best chance for cure, but

seldom is possible when disease is symptomatic. Maybe technically difficult. High recurrence rate afterresection.

Liver transplantation : May be succesful in selectedpatients

Requires transfer to a transplant center and, posto-peratively, lifelong immunosuppression. Highrecurrence rate. Expensiveeus

Alcohol injection : Palliative for small (usually multiple)tumors that cannot be resected. May be difficult todecide if all the malignant cells have been destroyed.

Procedure may facilitate spread of the tumor.Chemoembolization : May shrink selected large tumors to

the point where they may become resectable. Effectis palliative for localized but unresectable tumors.

Chemotherapy : Palliative only; can be used as an

adjunct to surgical resection or transplantation. Drugtoxicity is frequent.


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HBV carriageEarly onsetLater onset

Chronic HCVinfectionHereditary

hemochromatosisMembranous

obstruction of

the inferior venacava (in blackAfricans and

Japanese)Cirrhosis of most

other causes

+

+

+

+

+

+

++

+

+

+

+

Table. Factors Influencing Screening forHepatocellular Carcinoma

FACTORS

RISKCONSIDER

SCREENING ?

High Moderate Low Yes No

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