Epidemiologi

There are no data on the incubation period,

since there is always concomitant infection with hepatitis B Replication of HDV can only take place in people with acitive HBV replication-either as coinfection or superinfection by an HBCcarrier 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

Structure

The

hepatitis virus, formerly known as the -agent, is a disease agent which is dependent in coinfection with 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 the virus-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 are localized in the highly protected region, and the hepatitis delta antigen is coded in the larger portion of the RNA

Diagnostics

Antigen

demonstration : The HDV antigen can be identified by means of a radioimmunoassay Antibodies : Among the specific antibodies, it has recently become possible to identify those of the IgM, thus enabling diagnosis of acute infection HDV-RNA : demonstrated HDV-RNA can be using both spot

Clinical course

Coinfection with the hepatitis D virus often takes the course of fulminant hepatitis; estimates of endemic disease in drug addicts are as high as 30% Chronic active hepatitides are also reported increasingly Apart from concomitant infection with HBV and HDV, there is also occurrence of HDV superinfections with existing active HBV infection Like coinfection, superinfection is also dependent on replication of the hepatitis B virus Superinfection must be suspected when there is acute exacerbation of chronic hepatitis B and with HBsAg carriers Superinfection with HDV frequently results in

Therapy

There is no specific antiviral therapy for HDV Studies with interferon show temporary inhibition of replication during therapy, but this does not affect the clinical course favourably

Prophylaxi s

No passive immunization exists There is no specific active immunization for hepatitis D It would be desirable for HBV-carriers in order to reduce the risk of superinfection Active hepatitis B immunization also prevents HDV infection in persons who have not yet been

Epidemiology

Formerly

enteric hepatitis non-A, transmitted by fecal and oral routes

non-B

is

Large epidemics have been observed in thirdworld countries Enterically transmitted hepatitides are provoked by 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) on average 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

Structure

The hepatitis E virus is an RNA virus of the calicivirus-family The diameter of the complete virus is 2732 nm Electronoptic inspection reveals no differences between the agents from different continents Only fragments of the sequence can be Diagnostics distinguished so far

test

for

demonstrating

specific

Clinical course

Therapy

As with the other hepatitis, a prodromal phase can be observed here too There is a mortality rate of up to 3% with icteric patients; this figure can reach 22% with women in the third trimenon of pregnancy It is not yet clear whether chronic active hepatitides or liver cirrhoses can be caused by HEV, but it would appear improbable.

Prophylaxis

There is no passive immunization So far it could not be shown that immunoglobulin preparations - especially those won from serums of third-world inhabitans - contain specific antibodies, and would thus afford protection. An active immunization is available As with hepatitis A, prophylaxis consists of strict observance of hygiene recommendations in countries where hepatitis E is endemic

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 not infrequent in some high-risk groups It is blood-borne, but no other transmission routes have yet been proven

Structure

The hepatitis G pathogen is a singlestranded 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.

Diagnosis

Antigen detection : It has not yet been possible to detect the antigen, propably because of too low a virus titre Antibodies : To date, no test methods for routine screening exist RNA detection : Reverse transcription with a subsequent polymerase chain reaction allows hepatitis G virus RNA to be detected This method will be available as routine in the neat future

Clinical features

Hepatitis G virus RNA has been observed in patients at all stages of liver disease However, the frequency of transition to

Table.

Prevalence of Clinical Features of Hepatocellular Carcinoma

PREVALENCE PREVALENCE (%) (%) PHYSICAL SIGNS
59 - 95 34 - 71 22 - 53 28 - 43 Hepatomegaly Hepatic bruit Ascites Splenomegaly Jaundice Wasting Fever 54 - 98 6 - 25 35 - 61 27 - 42 4 - 35 25 - 41 11 - 54

SYMPTOMS
Abdominal pain Weight loss Weakness Abdominal swelling Nonspecific

Gastrointestinal symptoms 25 - 28 Jaundice 5 - 26

Table. with

Paraneoplastic Syndromes Associated Hepatocellular Carcinoma

Hypoglycemia Polycythemia (erythrocytosis) Hypercalcemia Sexual changes: Isosexual precocity, gynecomastia, feminization Systemic arterial hypertension Watery diarrhea syndrome Porphyria Carcinoid syndrome Osteoporosis Hypertrophic osteoarthropathy Thyrotoxicosis Thrombophlebitis migrans Polymyositis Neuropathy Cutaneous markers: Pityriasis rotunda, Leser-trelat sign, dermatomyositis, pemphigus foliaceus

Table. Tumor Markers of Hepatocellular Carcinoma*

DISADVANTAGES SENSITIVITY SPECIFICITY (%) (%) ADVANTAGES
Alpha-fetoprotein Inhigh-incidence populations, 80-90; in lowincidence population, 50-70 DES- -carboxy prothrombin 90 Relatively quick and Relatively easy to measure, expensive most extensively studied Easy and quick to measure Easy and quick to measure; relatively inexpensive Relatively easy and Expensive quick to measure

58 - 91

84

-1-fucosidase

75

70 - 90

Far more expensive than -FP

Isoenzymes of -glutamyl transferase

60

96

that sensitivity and specificity vary both with the population under study and absolute level of the marker. Thus, the specificity of a markedly elevated alphaprotein in high-risk patients greatly exceeds the sensitifity of mildly elevated s in cirrhosis-free patients.

Table. Major

Risk Factors for Hepatocellular Carcinoma in Humans

Chronic WBV infection Chronic HCV infection Repeated exposure to aflatoxin Cirrhosis

Minor

Oral contraceptive steroids Cigarette smoking Hereditary hemochromatosis Wilson disease 1- Antitrypsin deficiency Type 1 hereditary tyrosinemia Glycogen storage disease (types 1 and 2) Hypercitrullinemia Ataxia telangiectasia Membranous obstruction of the inferior vena cava

Table.

Treatment Options for Hepatocellular Carcinoma

Surgical resection: Offers best chance for cure, but seldom is possible when disease is symptomatic. May be technically difficult. High recurrence rate after resection. Liver transplantation : May be succesful in selected patients Requires transfer to a transplant center and, postoperatively, lifelong immunosuppression. High recurrence rate. Expensiveeus Alcohol injection : Palliative for small (usually multiple) tumors that cannot be resected. May be difficult to decide 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. Effect is palliative for localized but unresectable tumors. Chemotherapy : Palliative only; can be used as an adjunct to surgical resection or transplantation. Drug toxicity is frequent.

Table.

Factors Influencing Screening for Hepatocellular Carcinoma

RISK Moderate CONSIDER SCREENING ? Low Yes No

FACTORS

High

HBV carriage Early onset Later onset Chronic HCV infection Hereditary hemochromatosis Membranous obstruction of the inferior vena cava (in black Africans and Japanese) Cirrhosis of most other causes

+ + + +

+ + + + +

+ + +