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7/29/2019 infdrJuke Roslia-2

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Epidemiologi

There are no data on the incubation period, sincethere is always concomitant infection withhepatitis B

Replication of HDV can only take place in people

with acitive HBV replication-either as coinfectionor superinfection by an HBC-carrier with HDV.

Approx. 5% of the worlds 300 million HBscarriers are coinfected with HDV.

Infection is via blood, blood products and sexualintercourse

High-risk groups are drug addicts, hemophiliacsand dialysis patients


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Structure

The hepatitis virus, formerly known as the -agent,is a disease agent which is dependent in coinfectionwith other viruses of the hepadna-family

It has a diameter of 36 nm

The surface consists of the hepatitis B antigen, which

surrounds the actual hepatitis D antigen and thevirus-RNA

The sequence of HDV-RNA, which is 1758 bases long,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, and thehepatitis delta antigen is coded in the larger portionof the RNA


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Diagnostics

Antigen demonstration :The HDV antigencan be identified by means of aradioimmunoassay

Antibodies :Among the specific antibodies,it has recently become possible to identifythose of the IgM, thus enabling diagnosis ofacute infection

HDV-RNA : HDV-RNA can be demonstratedusing both spot hybridizing (NorthernBlot) and the polymerase chain reaction.


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Clinical course

Coinfection with the hepatitis D virus often takes thecourse of fulminant hepatitis; estimates of endemicdisease in drug addicts are as high as 30%

Chronic active hepatitides are also reportedincreasingly

Apart from concomitant infection with HBV and HDV,there is also occurrence of HDV superinfections withexisting active HBV infection

Like coinfection, superinfection is also dependent onreplication of the hepatitis B virus

Superinfection must be suspected when there isacute exacerbation of chronic hepatitis B and withHBsAg carriers

Superinfection with HDV frequently results in chronicactive hepatitis and transition to liver cirrhosis


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Therapy

There is no specific antiviral therapy for HDV

Studies with interferon show temporary inhibition ofreplication during therapy, but this does not affect theclinical course favourably

No passive immunization exists

There is no specific active immunization for hepatitis D It would be desirable for HBV-carriers in order toreduce the risk of superinfection

Active hepatitis B immunization also prevents HDVinfection in persons who have not yet been infected

with hepatitis B.

Prophylaxis


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Epidemiology

Formerly enteric hepatitis non-A, non-B is transmitted by

fecal and oral routes

Large epidemics have been observed in third-world

countries

Enterically transmitted hepatitides are provoked by HEVat least as often as by HAV in these countries

Infectivity does not seem particularly high

The incubation period is 40 days (14-60 days) on average

Retrospective analysis of an epidemic in Calcutta showedthat approx.

2% of people using the same water source acquired

hepatitis, compared with 0.3% when the water drunk

was from different sources.


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Structure

The hepatitis E virus is an RNA virus of thecalicivirus-family

The diameter of the complete virus is 27-32 nm

Electronoptic inspection reveals no differencesbetween the agents from different continents

Only fragments of the sequence can bedistinguished so far

A test for demonstrating specific antibodies is

available

HEV antigen cannot be demonstrated routinely

Diagnostics


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Clinical course

As with the other hepatitis, a prodromal phasecan 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 of pregnancy

It is not yet clear whether chronic activehepatitides or liver cirrhoses can be caused byHEV, but it would appear improbable.

No specific therapy exists.

Therapy


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Prophylaxis

There is no passive immunization

So far it could not be shown that immuno-globulin preparations - especially those wonfrom serums of third-world inhabitans - contain

specific antibodies, and would thus affordprotection.

An active immunization is available

As with hepatitis A, prophylaxis consists ofstrict observance of hygiene recommendationsin countries where hepatitis E is endemic


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Epidemiologi

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 not

infrequent 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 been possible todetect the antigen, propably because of too low avirus titre

Antibodies : To date, no test methods for routinescreening 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 the neatfuture

Hepatitis G virus RNA has been observed in patientsat all stages of liver disease

However, the frequency of transition to chronic

hepatitis or liver cirrhosis is unclear.

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 Associated withHepatocellular Carcinoma

HypoglycemiaPolycythemia (erythrocytosis)HypercalcemiaSexual changes: Isosexual precocity, gynecomastia, feminizationSystemic arterial hypertension

Watery diarrhea syndromePorphyriaCarcinoid syndromeOsteoporosisHypertrophic osteoarthropathyThyrotoxicosis

Thrombophlebitis migransPolymyositisNeuropathyCutaneous markers: Pityriasis rotunda, Leser-trelat sign,dermatomyositis, pemphigus foliaceus


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Table. Tumor Markers of Hepatocellular Carcinoma*

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 more

expensive

than -FP

Expensive

SPECIFICITY(%)

DISADVANTAGES

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

levels 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)Hypercitrullinemia

Ataxia telangiectasiaMembranous obstruction of the inferior vena cava


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Table. Treatment Options for HepatocellularCarcinoma

Surgical resection: Offers best chance for cure, but seldom is

possible when disease is symptomatic. May be technicallydifficult. High recurrence rate after resection.

Liver transplantation : May be succesful in selected patients

Requires transfer to a transplant center and, posto-peratively, lifelong immunosuppression. High recurrence

rate. ExpensiveeusAlcohol injection : Palliative for small (usually multiple) tumors

that cannot be resected. May be difficult to decide if all themalignant cells have been destroyed. Procedure mayfacilitate spread of the tumor.

Chemoembolization : May shrink selected large tumors to thepoint where they may become resectable. Effect is palliativefor localized but unresectable tumors.

Chemotherapy : Palliative only; can be used as an adjunct tosurgical resection or transplantation. Drug toxicity isfrequent.


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HBV carriageEarly onsetLater onset

Chronic HCVinfectionHereditary

hemochromatosisMembranous

obstruction of

the inferior venacava (in blackAfricans andJapanese)

Cirrhosis of mostother causes

+

+

+

+

+

+

++

+

+

+

+

Table. Factors Influencing Screening forHepatocellular Carcinoma

FACTORS

RISKCONSIDER

SCREENING ?

High Moderate Low Yes No

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