The sequence of events following acute HBV infection are shown in Fig. 5.15. Clinical features are the same as those found in HAV infection. In addition, a serum sicknesso like immunological syndrome may be seen. This consists of rashes, e.g. urticaria or a maculopapular rash and polyarthritis affecting small joints occurring in up to 25% of cases in the prodromal period. Fever is usual. The illness may be more severe than hepatitis A. Extrahepatic immune complex-mediated conditions such as an arteritis or glomerulonephritis are occasionally seen.
This is generally the same as for hepatitis A.
The markers for HBV are shown . HBsAg is looked for initially; if it is found, a full viral profile is then performed. In acute infection HBsAg may be cleared rapidly and in such cases IgM anti-core antibodies are helpful. HBV DNA is the most sensitive index of viral replication; it is tested by the Southern blot technique or by the polymerase chain reaction (peR).
The majority of patients recover completely, fulminant hepatitis occurring in up to 1%. Some patients go on to develop chronic hepatitis and hepatocellular carcinoma or become asymptomatic carriers. The outcome depends upon several factors, including the virulence of the virus and the immunocompetence and age of the patient.
There is no specific treatment apart from symptomatic therapy.
PREVENTION AND PROPHYLAXIS
Prevention depends on avoiding risk factors, e.g. shared needles, multiple male homosexual partners and prostitutes. Infectivity is highest in those with the e antigen and HBV DNA in their blood. These patients should be counselled about their infection. In developing countries, blood and blood products are still a hazard. Standard safety precautions in laboratories and hospitals must be strictly enforced to avoid accidental needle punctures and contact with infected body fluids.
Passive and active immunization Vaccination should be given to:
• All health-care personnel in the UK
• Members of emergency and rescue teams
• Morticians and embalmers
• Long-term travellers, e.g. airline travellers
• Homosexual and bisexual men and prostitutes
• Children in high-risk areas
• Intravenous drug abusers
• Patients and staff of some psychiatric units.
Combined prophylaxis, i.e, vaccination and immunoglobulin, should be given to:
• Staff with accidental needlestick injury
• All newborn babies of HBsAg-positive mothers
• Regular sexual partners of HBsAg-positive patients, who have been found to be HBV negative
Give 500 IU to adults (200 IU to newborn) of specific hepatitis B immunoglobulin (HBIG) and the vaccine i.m. at another site.
This is with a recombinant yeast vaccine produced by insertion of a plasmid containing the gene of HBsAg into a yeast.
DOSAGE REGIMEN. Three (0, 1, 6 months) injections are given into the deltoid muscle and this gives shortterm protection in over 90% of patients. Persons over 50 years or clinically ill and/or immunocompromised (including those with HIV infection or AIDS) have a poor antibody response; more frequent and larger doses are required. Antibody levels should be measured at 7-9 months after the initial dose in all at-risk groups. Antibody levels fall steadily after vaccination and booster doses may be required after approximately 3-5 years. It is not cost-effective to check antibody levels prior to active immunization. There are few side effects from the vaccine soreness at the site of injection and very occasionally a fever, rash or a ‘flu-like’ illness.
CHRONIC ASYMPTOMATIC CARRIERS
Following an acute HBV infection which may be subclinical, approximately 5-10% of patients will not clear the virus and will become carriers of HbsAg. Children are more likely to remain carriers than adults. There is a vast geographical variation in the incidence of carriers. In the UK, carriers are usually discovered incidentally on blood tests, e.g. when they are screened for donating blood for transfusion or when attending genital medicine clinics. Carriers with HBeAg or viral DNA in the serum (and thus having active viral replication) are highly infectious. The progression of the disease in carriers is uncertain but most remain HBsAg positive. Some may seroconvert, i.e. develop HBe antibodies, and therefore are a lower infective risk to others. However, mutant strains occur . Some patients may carry the virus for many years without developing chronic liver disease, whereas others, particularly those with the e antigen, may go on to develop chronic hepatitis and cirrhosis and there is an increased risk of hepatocellular carcinoma. Treatment of chronic HBV carriers Patients who are HBeAg positive or have HBV DNA in their serum should be treated with interferon-a . The aim of the treatment is to seroconvert and clear HBeAg and HBV DNA from the serum.
This is caused by the hepatitis D virus (HDV or delta virus). It is an incomplete RNA particle enclosed in a shell of HBsAg. It is unable to replicate on its own but is activated by the presence of HBV. It is particularly seen in intravenous drug abusers but can affect all risk groups for HBV infection. Active HBV synthesis is reduced by delta infection and patients are usually HBeAg and HBV DNA negative.
HDV infection can occur either as a coinfection with HBV or as a superinfection in an HBsAg-positive patient. Coinfection of HDV and HBV is clinically indistinguishable from an acute icteric HBV infection but a biphasic rise of serum AST may be seen. Diagnosis is confirmed by finding serum IgM anti-S in the presence of IgM anti-
HBc. IgM anti-S appears at 1 week and disappears by 5- 6 weeks (occasionally 12 weeks) when serum IgG anti-S is seen. The infection may be transient but the clinical course is variable. Superinfection results in an acute flare-up of previously quiescent chronic HBV infection. A rise in serum AST may be the only indication of infection. Diagnosis is by finding serum IgM anti-S at the same time as IgG HBc; patients are usually negative for IgM anti-HBc. Fulminant hepatitis can follow both types of infection but is more common after coinfection.
HDV RNA in the serum and liver can be measured and is found in acute and chronic HDV infection. Chronic HDV is a severe form of liver disease. Spontaneous resolution is rare and 60-70% of patients will develop cirrhosis in the long term. In 15% the disease is rapidly progressive with the development of cirrhosis in a few years. 0′ Interferon produces remission but relapse is common.
Hev was identified in 1988 and was responsible for 70- 90% of post-transfusion hepatitis in all countries where blood was tested for HBV markers. Since the screening of HCv in donor blood was introduced, this incidence has fallen to 4%. In the UK, 1 : 1800 samples of donated blood are positive for Hev antibodies; the prevalence may well be higher than this figure. H’CV is much more common in southern Europe and Japan than in the UK, and in Egyptian blood donors the prevalence is as high as 19%. It is transmitted by blood and blood products and it is postulated that 76% of haemophiliacs in the UK may have been infected. The incidence in intravenous drug abusers is very high. A high prevalence amongst homosexual men (2.2% vs. 0.4% in heterosexuals) suggests sexual transmission and it may be transmitted from mother to child. Other routes of community-acquired infection, e.g. close contact, are unlikely. In many cases the exact mode of transmission is unknown.