Hepatitis B : eradicable? / by Wolfgang Jilg and Friedrich Deinhardt

Hepatiti~ B ; eradicaBle ? by Wolfgang Jilg and Friedrich Deinhardt Drs Wolfgang Jilg and Friedrich OeiQhardt are with)the Max van Pettenkofer Institute, University of Munich R ecent progress in developing hepatitis B vaccines has brought much closer the ul- timate goal of controlling and elimi- nating this disease- much as that other viral disease, smallpox, was eradicated. Hepatitis B today remains one of the most important global infec- tious diseases ; every year, around 40 million people die from the con- sequences of chronic hepatitis. About six million people develop hepatocellular carcinoma, a disease which is also associated with hepati- tis B virus (HBV). Between 200 and 300 million people carry HBV chronically, and they constitute the major reservoir of this infectious agent. Hepatitis B is highly endemic in South-East Asia and in Central and Southern Africa. Some 70 to 80 per cent of people living in these re- gions have had contact with the vi- rus, of whom five to ten per cent (in certain areas even 20 per cent or more) are chronic virus carriers. In industrialised countries, such as the United States and the western and northern parts of Europe , the hepa- titis B prevalence is rather low, not exceeding five or ten per cent, with a chronic carrier rate well below one per cent. In these countries, 10 it is a disease of particular risk groups, such as medical personnel , patients needing frequent blood products (for instance , haemophi- liacs and chronic haemodialysis pa- tients) , persons with close contacts to HBV carriers , drug abusers who share contaminated needles, male homosexuals and prostitutes. The prevalence of HBV infection ranges from about 20 per cent in medical personnel to more than 90 per cent in haemophiliacs who have received frequent treatments with non-inactivated clotting factors pre- pared from unscreened human blood. The acute disease caused by HBV does not differ from hepatitis due to other viral agents, such as hepatitis A virus or the hepatitis non-A, non-B viruses. In a typical case, the disease starts after an in- cubation period of two to six months. For several days , there are only vague symptoms similar to those of other viral infections. They include fever, anorexia, weakness and headache ; a more specific symptom is right upper quadrant pain with local tenderness. This so- called "prodromal" phase is fol- lowed typically by jaundice (yellow- ing of the skin and mucous membranes) lasting for about two to four weeks. This typical course of acute hepatitis B has several variations. In about one per cent of cases , acute fulminant hepatitis de- velops with an often lethal out- come; by constrast, many infec- tions cause a mild illness without jaundice ("anicteric hepatitis ") or may even occur without any symp- toms at all. Two characteristics make infec- tion with HBV so important: the development of chronicity (persis- tence over a long period of time) , and the association of HBV with a type of cancer called hepatocellular carcinoma. Most patients recover from acute hepatitis, but five to ten per cent continue to carry the virus in their livers for a long time , even for a lifetime. And even patients without any signs of acute hepatitis may develop chronic infections. These chronic HBV carriers may remain asymptomatic or they may develop chronic hepatitis, of which there are two forms : chronic persis- tent hepatitis , which may eventual- ly resolve itself; and chronic active hepatitis, which usually proceeds to cirrhosis , chronic liver failure and death. Irrespective of the clinical condi- tion , all chronic carriers are a po- tential source of infection to others, WORLD HEALTH , July 1988 and all are at a considerable risk of developing hepatocellular carcino- ma. This malignancy is one of the most common tumours in such ar- eas of high hepatitis B endemicity as South-East Asia and Central Africa. Although at a molecular level the relationship between HBV and the development of hepa- tocellular carcinoma is still unex- plained, epidemiological data have shown that this tumour is indeed associated with chronic hepatitis B infection. The hepatitis B virus (HBV) is a spherical particle measuring 42 nano- meters ( 42 thousand-millionth of a meter) in diameter. A protein en- velope called hepatitis B surface antigen (HBs antigen or HBsAg) surrounds the virus core, which contains deoxyribonucleic acid (DNA) as carrier of the viral genet- ic information. HBV has a very narrow host range ; only man and the great apes are susceptible to this virus. But in recent years simi- lar viruses have been detected, in- fecting woodchucks, ground squir- rels and peking ducks ; and all these viruses together with HBV are clas- sified as "hepadna" (for hepatitis- DNA) viruses. Hepatitis B virus is present in the blood of chronic carriers, and can WORLD HEALTH, July 1988 also be present but in considerably lower concentrations in other body fluids such as saliva, tears or se- men. Faeces and urine, as long as they are not contaminated by blood, can be assumed not to con- tain HBV. Transmission is only possible when infectious virus en- ters the bloodstream. This may take place by direct percutaneous inoculation, through skin cuts or scratches, or through mucous mem- branes which sometimes have small breaks allowing the virus to enter. Intact skin, however, cannot be penetrated by HBV. Before the screening for HBs antigen was introduc:ed, transfusion of HEY-contaminated blood was a common mode of transmission. This is still a frequent means of trans- mitting the disease in areas where donor screening is not customary. In medical surroundings, one of the most important ways of trans- mission is through inadvertent inju- ry, for example, by a contaminated needle, scalpel or similar instru- ment, but it may also be passed from patient to patient by inade- quately cleaned and sterilised in- struments used in -dentistry, cardiac catheterisation and endoscopic pro- cedures. Transmission is also common in Port~ait i of the hepatitis B virus. HBV has iJ very narrOJY host rqnge ," Only man and the great apes are susceptible tq this virus. Left: A visiting Chinese scientist carry- ing out radio-irrimuno assays to detect hepatitis.B infection atFairfield Hospi- tal, Melbourne, Australia. paramedical situations where poor hygiene is prevalent, such as the use of insufficiently or non-steri- lised instruments for acupuncture, tattooing or ear and nose piercing. In the household setting, too, there are possibilities for percutaneous inoculation and transmission of HBV; there is a considerable risk of contracting hepatitis by sharing razors, toothbrushes, nail brushes, nail files or scissors or similar in- struments of personal hygiene with acutely infected persons or chronic virus carriers; contaminated work surfaces which may come in contact with injured mucous membranes or skin are also a danger. This danger is increased by the persistence of in- fectivity of dried serum for at least a week. The most important routes by far, however, are the infection of new-born babies by infectious mothers, transmission by close per- sonal contact (especially between mother and child and between chil- dren), and transmission by sexual contact. Infections during the neo- natal period or during early infancy are particularly frequent in regions where HBV endemicity is high. In- fected new-born babies almost in- variably become chronic carriers, and infections in young infants fre- 11 Hepatitis B: eradicable? quently progress to chronicity ; this explains the high rate of chronic carriers in certain countries . We have no specific therapy , so prevention of hepatitis B by hygien- ic measures, passive immunization and active vaccination is vitally im- portant. In the medical field , hy- gienic measures include wearing gloves while taking blood , care- fully cleaning and sterilising instru- ments , and using disposable sy- ringes , needles and other instru- ments whenever possible. Similar measures must be adopted in para- medical situations , for instance , the strict use of sterile instruments for ear piercing or tattooing. Passive immunization with hepa- titis B immunoglobulin (HBig) is a specific means of preventing the disease . HBig is an immunoglobu- lin preparation which contains anti- bodies in high concentrations against HBsAg, the envelope com- ponent of HBV; these antibodies neutralise the virus : that is they in- hibit its infectivity. The main disad- vantages of this method are the lim- ited period of protection (only about three months) and its very high cost; so such passive immuni- zations against hepatitis B are only used, for example , after an injury with a contaminated needle or for the new-born children of HBV-car- rier mothers. Today, in both of these instances , passive immuniza- tion should be combined with ac- tive vaccination. Active vaccination avoids the dis- advantages of HBig; it produces a long-lasting immunity and is cheap- Drug abusers who share needles are at particular risk of contracting hepatitis B. Photo WHO/P. Laurie er. The first hepatitis B vaccine , prepared from the plasma of chron- ic HBV carriers , is highly immuno- genic, very effective and safe . Its use is indicated in areas where there is a low prevalence of hepati- tis B in high-risk groups such as health care personnel, haemodia- lysis patients , intravenous drug abusers , male homosexuals and babies newly born to HBV-positive mothers. In high prevalence areas , this vaccine should be given to all children or at least to all children of carrier mothers. But it is expensive because both the starting material , human plasma, and the extensive purification procedures are costly. Whereas industrialised countries can afford to vaccinate the relative- ly few members of high-risk groups , it is impossible for other countries to immunize large numbers of people. A new vaccine produced by re- combinant gene technology was the first step towards reducing these costs. First licensed in 1986 in the United States and the Federal Republic of Germany, it is made from HBsAg-producing recombi- nant yeast cells . At present , it is only slightly cheaper than the plas- ma vaccine , but the production costs can undoubtedly be reduced in the future . Other techniques such as the use of synthetic peptides-small parts of the surface protein of HBsAg-are currently being investigated in the hope of producing alternative vac- cines. And transfer of technology to countries of the Third World, without lowering the standards set by WHO for hepatitis B vaccines , will enable those countries to pro- duce their own vaccines from local- ly obtained plasma, thus reducing the costs considerably. WHO's Expanded Programme on Immunization (EPI) has included the elimination of hepatitis B among its goals, and even though it will be long before we can vaccinate everyone at risk, plans for mass vaccination programmes are not utopian . We could begin to put these plans into practice in the near future. And as the costs of vaccines drop further, it will become possi- ble to vaccinate all people at risk , so preventing disease and death among millions of people and lead- ing- ultimately- to the eradication of hepatitis B. • W ORLD HEALTH , July 1988