infdrJuke Roslia-2
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Transcript of 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
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Table. Factors Influencing Screening forHepatocellular Carcinoma
FACTORS
RISKCONSIDER
SCREENING ?
High Moderate Low Yes No