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 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 : HDV-RNA can be demonstrated

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

A test for demonstrating specific antibodies is

available
HEV antigen cannot be demonstrated routinely
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 immuno-
globulin 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 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 single-stranded
RNA virus, which shares features in common
with the hepatitis C virus, although the nucleic
acid sequence homology is only approx. 30%
Ithas 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
Table. Prevalence of Clinical Features of
Hepatocellular Carcinoma

PREVALENCE PREVALENCE
SYMPTOMS (%) PHYSICAL SIGNS (%)

Abdominal pain 59 - 95 Hepatomegaly 54 - 98

Weight loss 34 - 71 Hepatic bruit 6 - 25

Weakness 22 - 53 Ascites 35 - 61

Abdominal swelling 28 - 43 Splenomegaly 27 - 42

Nonspecific Jaundice 4 - 35

Gastrointestinal symptoms 25 - 28 Wasting 25 - 41

Jaundice 5 - 26 Fever 11 - 54
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 SPECIFICITY DISADVANTAGES
(%) (%) ADVANTAGES
Inhigh-incidence 90
Alpha-fetoprotein Relatively quick and Relatively
populations, easy to measure, expensive
80-90; in low- most extensively
incidence studied
population, 50-70

DES- -carboxy 58 - 91
84
Easy and quick to Far more
prothrombin measure expensive
70 - 90 than -FP
-1-fucosidase 75 Easy and quick to
measure; relatively
inexpensive
96
60 Relatively easy and Expensive
Isoenzymes

of -glutamyl quick to measure
transferase

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 alpha-
fetoprotein 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
- Antitrypsin deficiency
1
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, posto-
peratively, 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
CONSIDER
RISK SCREENING ?
FACTORS High Moderate Low Yes No

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