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 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

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 radioimmunoassay by means of

Antibodies : Among the specific

antibodies, it has recently become possible to identify those of the IgM, thus enabling diagnosis of acute infection

HDV-RNA

using both spot hybridizing (Northern Blot) and the polymerase chain reaction.

: HDV-RNA can be demonstrated

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 chronic active hepatitis and transition to liver cirrhosis

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

Prophylaxis

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 infected with hepatitis B.

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 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 water drunk was from different sources.

Structure

The

hepatitis E virus is an RNA virus of the calicivirus-family The diameter of the complete virus is 27-32 nm Electronoptic inspection reveals no differences between the agents from different continents Only fragments of the sequence can be distinguished so far

Diagnostics

test for demonstrating specific antibodies is

HEV antigen cannot be demonstrated routinely

available

Clinical course

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.

Therapy

No specific therapy exists.

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

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 infrequent in some high-risk groups

be

not

It

is blood-borne, but no other transmission routes have yet been proven

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.

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 chronic hepatitis or liver cirrhosis is unclear.

Table.

Prevalence of Clinical Features of Hepatocellular Carcinoma

PREVALENCE (%)
59 - 95 34 - 71

SYMPTOMS
Abdominal pain Weight loss

PREVALENCE (%) PHYSICAL SIGNS

Hepatomegaly Hepatic bruit 54 - 98 6 - 25 35 - 61 27 - 42 4 - 35 25 - 41 11 - 54

Weakness
Abdominal swelling Nonspecific

22 - 53
28 - 43

Ascites
Splenomegaly Jaundice

Gastrointestinal symptoms 25 - 28
Jaundice 5 - 26

Wasting
Fever

Table.

Paraneoplastic Syndromes Associated with 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*

SENSITIVITY (%) DISADVANTAGES SPECIFICITY (%) ADVANTAGES
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 quick to measure Expensive Far more expensive than -FP

Alpha-fetoprotein

Inhigh-incidence populations, 80-90; in lowincidence population, 50-70 58 - 91

DES- -carboxy prothrombin

84

-1-fucosidase
Isoenzymes of -glutamyl transferase

75

70 - 90

60

96

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

Table.

Risk Factors for Hepatocellular Carcinoma in Humans

Major

Chronic WBV infection Chronic HCV infection Repeated exposure to aflatoxin 1. 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

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