KARACHI - ON MEETING WE WHO EASTERN MEDITERRANEAN REGIONAL SCIENTIFIC

MEETING OF W E WHO EASTERN MEDITERRANEAN REGIONAL SCIENTIFIC GROUP ON LIVER DISEASES

17

-

19 December 1979 KARACHI

WHO EMRO

TABLE OF CONTENTS

I OPENING OF THE MEETING AND ELECTION OF OFFICERS I1 REVIEW OF LIVER DISEASES IN THE COUNTRIES OF EASTERN

MEDITERRANEAN REGION A. EGYPT

B. IRAN

C , IRAQ

D. LEBANON E. PAKISTAN F. SUDAN

G. INTERNATIONAL AGENCY FOR RESEARCH IN CANCER 111 AN OVERVIEW OF THE COUNTRY REPORTS

IV IDENTIFICATION AND ASSESSMENT OF THE RESEARCH NEEDS IN RELATION TO LIVER DISEASE

V FORMULATION OF A REGIONAL PLAN OF ACTION TO MEET RESEARCH NEEDS

VI SUMMARY AND RECOMMENDATIONS ANNEX I LIST OF PAKTICLYANTS

ANNEX I1 MESSAGE FROM DR A.H. TABA, REGIONAL DIRECTOR ANNEX I11 AGENDA

ANNEX IV PROGRAMME

ANNEX V LIST OF BASIC DOCUMENTS

I OPENING OF THE MEETING AND ELECTION OF OFFICERS

A meeting of t h e WHO E a s t e r n Mediterranean Regional S c i e n t i f i c Group on L i v e r Diseases was held from 17

-

19 December 1979 i n t h e C o l l e g e of P h y s i c i a n s and Surgeons, Karachi, P a k i s t a n . I t was a t t e n d e d by t h e members of t h e

s c i e n t i f i c group, r e s o u r c e e x p e r t s , WHO s t a f f from t h e Regional O i i i c e , and o b s e r v e r s from t h e h o s t c o u n t r y . A l i s t of p a r t i c i p a n t s i s g i v e n i n Annex I .

On behalf of t h e WHO Regional O f f i c e f o r t h e E a s t e r n M e d i t e r r a n e a n , D r J. Hashmi, Regional Adviser f o r Research P l a n n i n g and Development, welcomed t h e p a r t i c i p a n t s i n t h i s meeting, and read a message from D r A.H. Taba, D i r e c t o r , WHO E a s t e r n Mediterranean Region (Annex 11). D r Taba, i n h i s message, thanked t h e M i n i s t r y of Health. Government of P a k i s t a n , and t h e P a k i ~ L a ~ l Medical Research Council f o r h o s t i n g t h i s meeting. He t h e n reviewed t h e medical r e s e a r c h a c t i v i -

t l e a b e i n g sponsored by t h e WHO E a s t e r n Mediterranean Regional O f f i c e , i n c l u d i n g t h e p e r i o d i c meetings of t h e Regional Advisory Committee on Biomedical Research.

This Committee, a t one of i t s m e e t i n g s , had recommended t h a t r e s e a r c h s t u d i e s be promoted and s u p p o r t e d w i t h r e s p e c t t o d i s e a s e s which a r e of concern t o s e v e r a l c o u n t r i e s 1 x 1 L l ~ r R r g i v u , dlld u n w h i c h surne w o r k h a s a l r e a d y been c n r r i c d o u t i n t h e c o u n t r i e s w i t h t h e i r own r e s o u r c e s . L i v e r d i s e a s e was i d e n t i f i e d a s one such a r e a f o r concern.

T h e r e f o r e , t h i s S c i e n t i f i c Group on L i v e r D i s e a s e s was convened i n o r d e r t o a s s e s s t h e magnitude of l i v e r d i s e a s e , t h e e x t e n t of r e l a t e d r e s e a r c h s t u d i e s i n t h e Region and t o l a y down a programme of work f o r f u r t h e r i n g knowledge about liver diseases, w i t h a view t o c n s u r c t h e i r c o n t r o l and p r e v e n t i o n .

D r Taba suggested t h a t t h e Group a l s o d e a l w i t h systems f o r s t a n d a r d i z a t i o n , l a y i n g down of d i a g n o s t i c c r i t e r i a , and o t h e r r e l e v a n t m a t t e r s t o e n s u r e u l t i - mately t h a t t h e d a t a g e n e r a t e d through t h e s e m u l t i c e n t r e s t u d i e s be comparable.

B r i g . M.A.Z. Mohydin, Chairman, P a k i s t a n Medical Research Council, welcomed t h e members of t h e s c i e n t i f i c group t o K a r a c h i , and a s s u r e d them of a l l a s s i s t a n c e

t o e n s u r e t h e s u c c e s s of t h i s meeting. He b r i e f l y d e s c r i b e d how t h e P a k i s t a n Medical Research Council was o r g a n i z e d and t h e p r o g r e s s of r e s e a r c h i n l i v e r d i s e a s e s c a r r i e d o u t under i t s a e g i s .

The following o f f i c e r s were e l e c t e d by t h e p a r t i c i p a n t s : Chairman Dr F. Ala, National D i r e c t o r

I r a n i a n National Blood T r a n s f u s i o n S e r v i c e Teheran, I r a n

Rapporteur Dr S. J. Zuberi, Research D i r e c t o r

Pakistan Medical Research Council Research C e n t r e Jinnah Post-graduate Medical Centre

Karachi, P a k i s t a n

The p r o v i s i o n a l agenda (Annex I11 and t h e programme of work (Annex IV) were adopted by t h e p a r t i c i p a n t s .

I1 REVIEW OF LIVER DISEASES I N THE COUNTRIES OF EASTERN MEDITERRANEAN REGION

The m a t e r i a l p r e s e n t e d was drawn from t h e Ain Shams t e a c h i n g h o s p i t a l i n Cairo. Out of 730 canes, 20% were found t o be s u f f e r i n g from a c c i v e c h r o n i c h e p a t i t i s w i t h no a p p r e c i a b l e c i r r h o s i s and 50% from v a r i o u s forms of c i r r h o s i s . Schistosomiasis and l i v e r turnours accounted for 9.5% and 4.9% c a s e s , r e s p e c t i v e l y .

I Most of t h e c h r o n i c l i v e r d i s e a s e i n Egypt wae considered t o be caused by h e p a t i t i s v i r u s . Of a l l r u r a l p a t i e n t s s u f f e r i n g from l i v e r d i s e a s e s , 65

-

^{96% showed}

evidence of s c h i s t o s o m i a s i s . The prevalence of h e p a t i s B s u r f a c e a n t i g e n (HBsAg) i n a l l forms of c h r o n i c l i v e r d i s e a s e was 28% ( r e v e r s e d haemagglutination t e s t ) .

=~ =,

-~ -~

B Data were a l s o p r e s e n t e d on t h e prevalence of HBsAg i n v a r i o u s p o p u l a t i o n

1

g r o ~ ~ p c . The prevalence of HBsAg amongst p r e p a r a t o r y and secondary school p u p i l s

3

& was 4.1%; i n d u s t r i a l workers, 3.5%; blood donors, 3.2%; t h e r u r a l p o p u l a t i o n ,

.I

1

^3.6%; and army r e c r u i t s , 5.2%. A s t u d y of 1 674 c a s e s of a c u t e v i r a l h e p a t i t i s

4

admitted t o a f e v e r h o s p i t a l i n C a i r o showed t h a t 51.2% were KBsAg p o s i t i v e on

- -

- - - admission, u s i n g R I A . The a n t i g e n p o s i t i v i t y i n t h i s s e r i e s of p a t i e n t s was

-* =-

= found K O be higher in young ddults, a8 c o m p a r e d t o c h i l d r c n less than n i n e y e a r s

- - - - -

- -

--

-

^- - _- of age and a d u l t s over t h e age of 50 y e a r s . The HBsAg found t o p e r s i s t f o r

.- -=

-

- - - - - - - - more than s i x months i n 11% of t h e HBsAg p o s i t i v e c a s e s s t u d i e d (Radioimuno-

The results of screening over 220 000 healthy voluntary blood donors in Teheran (RIA) demonstrated HBs antigenaamia In 3.5%; 31% of the population examined were anti-HBs positive, whereas 42% carried anti HBc. Anti-hepatitis A was found in 91% of all age groups in Teheran, and the prevalence of this

antibody increased with age.

In 483 cases suffering from clinical jaundice, 40% were found to be HBsAg positive. A number of special groups at risk, i.e., hemodialysis patients and staff, haemophiliacs and laboratory staff, were also investigated and the pre- valence was found to vary from 0.8% to 6%. During a two-year follow-up period, only 8.5% of asymptomatic HBsAg carriers cleared the antigen. Forty-two per cent of 134 cases of cirrhosis and

46%

of 29 cases of hepatocellular carcinoma (HCC) were found to be HBsAg positive; 84% of the former, and 74% of the latter, patient group were anti-HBc positive. A significant increase in HLA-B

12 Was found in HBsAg positive cirrhotics, whereas this tissue type was decreased in carriers of HBsAg. Whereas HLA-B5 ahowed a high degree of association with HBsAg carrier state, it was strikingly diminished amongst HBsAg positive cir- rhotics. Special groups peculiar to the Region, such as barber-surgeons and traditional midwives, have been suspected to transmit HBV and therefore should be screened for HBs antigenaemia. Perinatal transmission of HBV was not observed when the offspring of 14 nBsAg posiclve HbeAg negaclve pregnant women were studied for 18 months postpartum.

In the material presented from Shiraz, the severity of hepatitis in southern Iran was stressed, particularly in pregnant women. The frequency of HBs anti- genaemia amongst cases of acute hepatitis was 38%, as compared to 1.5% in a control rural population (Counter immuno-electrophoresis; CIEP).

Cirrhosis in Iran was mainly of macronodular variety and was apparently more frequent in lower socio-economic groups. Patients usually presented wlth gross ascites and splenomegaly. Half of the 169 male, and one-fourth of 58 female, patients with macronodular cirrhosis were HBsAg positive (CIEP). The underlying etiology of cirrhosis was thought to be virus infections.

C .

IRAQ

DaLa from Lhr Leaching h o s p i t a l i n Baghdad showed t h a t 2 . 1 % n f a l l c a s e s admitted during 1978 had l i v e r d i s e a s e , o f which a l i t t l e l e s s than h a l f had c i r r h o s i s of l i v e r , and one f i f t h , h y d a t i d d i s e a s e . Only a t e n t h of t h i s s e l e c t e d group of p a t i e n t s was found t o s u f f e r from h e p a t i t i s . Data from a medical u n i t i n t h e same h o s p i t a l d u r i n g t h e same p e r i o d showed t h a t 8 . 5 % of a l l admissions had l i v e r d i s e a s e s . O f t h e s r cases 55% had cirrhosis, 13%

a c u t e v i r a l h e p a t i t i s and 11% c h r o n i c a c t i v e h e p a t i t i s . HCC accounted f o r 3% and hydatid d i s e a s e f o r 1% ( t h e v a s t m a j o r i t y of c a s e s w i t h t h e l a t t e r d i s e a s e may be going t o t h e s u r g i c a l u n i t of t h e h o s p i t a l ) . I t was pointed o u t t h a t a l c o h o l i c l i v e r d i s e a s e i s being seen with an i n c r e a e i n g frequency now, though i t has n o t y e t acquired t h e magnitude observed i n t h e west.

Chronic a c t i v e h e p a t i t i s and macronodular c i r r h o s i s accounted f o r 70% o f p a t i e n t a w i t h chronic l i v e r d i s e a s e .

The prevalence o f HBsAg i n 1 000 a p p a r e n t l y normal I r a q i s was 3.3%;

amongst 200 Kurds, 5.5%; i n non-professional blood donors, 3.5%; i n h o s p i t a l personnel, 5.3%; and 9.1% i n t h e s t a f f , and 2 7 . 8 % i n t h e p a t i e n t s , of t h e r e n a l d i a l y s i s u n i t (CIEI'). Ihe HEsAg was found i n 40% of cave8 u t acuLe

v i r a l h e p a t i t i s : 7 5 % w i t h c h r o n i c a g g r e s s i v e h e p a t i t i s ; 62%, c i r r h o t i c s ; and 78%, with HCC. HCC was always a s s o c i a t e d w i t h macronodular c i r r h o s i s .

D. _.- LEBANON

Due t o t h e p r e v a i l i n g s i t u a t i o n i n Lebanon, i t has n o t been p o s s i b l e t o add s u b s t a n t i a l l y t o t h e d a t a presented from Lebanon two y e a r s ago a t t h e Inter-Regional Seminar on V i r a l H e p a t i t i s , h e l d i n Kuala Lampur, Malaysia.

H e p a t i t i s ranks f i f t h amongst t h e r e p o r t e d c o m u n i c a b l e d i s e a s e s i n Lebanon. HBsAg was d e t e c t e d i n 3 . 2 % of t h e g e n e r a l p o p u l a t i o n , 5.8% i n profcooionol blood d o n o r s and i n one-third o f jaundica c a s e s a d m i t t e d t o h o s p i t a l .

During 1978-1979, 73 patients were admitted to the AUB Hospital with liver disease. Included in these cases were 27 suffering from unspecified cirrhosis,

6 wlLh alcol~ulli h e p a t i t i s and 12 with hydatid discnac,

During the period 1964

-

1974, 30 cases of biopsy proven HCC (males 19;

females 11) and 200 cases of cirrhosis (males 97; females 103) were seen.

Data for liver disease from Pakistan included clinical, biochemical and immunological studies in acute and chronic liver diseases and certain high risk groups.

Twelve hundred asymptomatic individuals were screened for biochemical and clinical evidence of liver disease. Liver biopsy was carried out in 65 indivi- duals with normal liver function, Twenty-seven cases (2.2%) showed morpholo- gical lesions within the spectrum ascribed to viral hepatitis. This included the presence of councilman-like bodies as well as inflammatory infiltrate. A study of autopsies on individuals dying from accidents has frequently shown Lnf1armaator.y lesions, as well as sirrhosis. It appears that a large reservoir of anicteric disease exists in the population. This could be an important link in the epidemiology of acute hepatitis as well as chronic liver disease.

The HBsAg positivity in the apparently healthy population ranged between 1.4 to 4% (CLEP). HBs antigenaemia was observed in 3.1% of blood donors, 2.8% of health care personnel and 1.3% of pregnant women. Anti-HBs was de-

tcctcd in 35.5% of hcalthy zubjcctz ( P H A ) . Tranoplaccntal tranomiooion of the antigen was demonstrated in two out of four pregnant women with HBs antigenaemia

(RIA). Studies on intra-familial spread suggested sexual spread of the virus.

Thirty-eight per cent of patients with acute viral hepatitis had HBs anti- genaemia and the duration of antigenaemia varied from 3 to 5Y weeks.

Alltnirnrnam~ l i v e r C l i ~ e ~ s e W R Q r n n q i d e r e r l t o h e i n f r e q s ~ c n t i n P a k i q t a n a n d

cirrhosis was mainly of macronodular variety. Twenty-one per cent of cirrhotics were HBsAg positive.

WHO EMRO

Two hundred twency-~wu Gas=* o f llCC werc oeen o v e r a p e r i n d n f t e n y e a r s . The h i g h e s t frequency was observed between t h e ages of 50

-

59 y e a r s . Alpha- f e t o p r o t e i n was p o s i t i v e i n 63.4% of 82 c a s e s and HBsAg i n 21% of 103 p a t i e n t s

(CIEP)

.

SUDAN

F -

-

Data from Sudan was based on a n a n a l y s i s of 410 c a s e s w i t h l i v e r d i s e a s e admitted i n t h e medical wards of Omdurman H o s p i t a l , Khartoum, from January 1975 t o J u l y 1979. These c a s e s c o n s t i t u t e d 7 , 5 % of t o t a l a d m i s s i o n s d u r i n g t h e same p e r i o d . ^Viral h e p a t i t i s c o n s t i t u t e d t h e largest s i n g l e group (148) and was a s s o c i a t e d w i t h high f a t a l i t y . There were 66 c a s e s w i t h macronodular c i r r h o s i s and 50 w i t h h e p a t i c s c h i s t o s o m i a s i s . C l i n i c a l l y , m a l a r i a l i n f e c t i o n o f t e n posed a problem i n t h e d i f f e r e n t i a l d i a g n o s i s of j a u n d i c e . L i v e r c i r r h o s i s and HCC were r e p o r t e d more f r e q u e n t l y from Western Sudan. S e r o l o g i c a l markers of HBV could n o t be determined because o f absence of f a c i l i r l e s .

C. INTERNATTONAL AGENCY FOR RESEARCH I N CANCER

P o p u l a t i o n c o r r e l a t i o n s , c a s e c o n t r o l s t u d i e s and c l i n i c a l i n v e s t i g a t i o n s have shown t h a t t h e r e is a s t r o n g and s p e c i f i c a s s o c i a t i o n between HBV and HCC.

I t i s l i k e l y t h a t t h e a s s o c i a t i o n i s c a s u a l , although t h e e x a c t pathogenic mechanlsma have n o t been clarified. S i n c e s e u b e t a n t i a l p a r t of the p n p u l a - t i o n of t h e EM Region a r e HBV c a r r i e r s , i t a p p e a r s t h a t l a r g e p r o p o r t i o n o f HCC c a s e s i n t h e Region a r e due t o t h i s v i r u s ; t h i s , however, r e q u i r e s con- f i r m a t i o n .

The r o l e of a f l a t o x i n i n t h e e t i o l o g y o i HCC h a s n o t been e s t a b l i s h e d , a l t h o u g h t h e r e a r e i m p r e s s i v e g e o g r a p h i c a l c o r r e l a t i o n s between them. The credibility o f t h e a f l a r n x i n h y p n r h e s i s 1 4 s t r e n g t h e n e d by t h e f a c t t h a t s e v e r a l c a s e s i n t h e EM Region, i n A f r i c a and e l s e w h e r e , a r e n e g a t i v e f o r HBV. A f l a t o x i n s a r e p r e s e n t i n some p a r t s of t h e Region, and t h e i r r o l e i n t h e e t i o l o g y of HCC should be e x p l o r e d . I t h a s r e c e n t l y been s u g g e s t e d t h a t some c a s e s of HCC n e g a t i v e f o r HBV markers may he a s s o c i a t e d w i t h tobacco smoking. s l n c e smuk111g i s d u u i v r ~ s d l phenomenon, and tobacco c o n t a i n i n g

substances with drmo~~sLrable experimental hepatocarcinogenicity (WHO Bull.

54:597-604, 1976) are frequently used in the EM Region, there should be both a scope and an opportunity to evaluate this hypotl~esis epidemiologically in the Region.

111 AN OVERVIEW OF THE COUNTRY REPORTS

The country reports give a fairly consistant picture of the knowledge about liver disease in the EM Region. The knowledge is incomplete, but this is true of almost all knowledge about the epidemiology of liver diseases, due to protean clinical manifesrarlons and the lack or syrciLic d n d sensitive

diagnostic methods.

Most data presented concerns the prevalence of HBsAg. Unfortunately,

methods for determining this marker of hepatitis are not available in all centres in this Region; this is particularly so for the more sensitive diagnostic

techniques. Hepatitis B may be the dominating type of hepatitis in this Region.

Due to its associaLion with chronic hepatitis (CA11) and HCC, it conatitutcs o

major health problem.

The prevalence of HBs antigenaemia has varied little from one report to another, and the final conclusion is likely to be that 4% of the population carries the antigen, higher and lower values being found in certain areas of the Region. The significance of HBsAg 'carriers' as a pool for transmissible virus - end for future cases of chronic liver disease

-

is unknown, but should be investigated. Acute viral hepatitis seems to be HBsAg positive in about 40% of cases, leaving the majority to other types provided that sufficiently early sampling and application of sensitive methods has been assured in all cases. Acute hepatitis carries a higher fatality rate in pregnant women throughout the Region, and by itselt, perhaps, in some populations of the Region. One study suggests that antigenaemia is cleared in 95% of the cases

o f a c u t e hepatitis after s i x months, leaving n proportion of persistent posi-

tivity hardly significantly different from that of the population as a whole.

EM/RSR/U

EM/SCF.GR.MTG.LIV.DIS./lZ page 0

However, further studies (clinical, serological and histological) of cases with persistent HBs antigenaemia, following acute HBV infection, may provide a better understanding of the nature of C ~ I U L L ~ L : liver disease in the Region. provided t h ~ t long-term follow-up studies are feasible.

HBs antigenaemia appears to be more closely associated with chronic liver disease in some areas than in others (e.g,, Iraq as compared with Egypt). Direct comparison of these materials, after appropriate stsndardleaLlun of mcthodologiea, may provide interesting clues to the same question. Other infections and infes- tations common in the Region may be of relevance to elucidation of etiology of chronic liver diseases, the incidence of which, though not exactly known, appears to be high. Thus, contrary to common belief, workers with extensive local ex- perience had the impression that hepatic schistosomiasis may be associated with hepatic cirrhosis and malaria with acute and chronic liver disease. This should stimulate a rranarasment of the question, since it may reveal another group of

preventable chronic liver diseases.

Since both schistosomiasis and malaria can affect the liver and, therefore,' an interaction between either or both of them and viral hepatitis ahould be likely.

However, almoot all studies treating t h i n iasue are based on uncontrolled clinical mrterial, and it is well-known that selection bias can easily produce positive or negative aseociations between two or more disseaes. The frequency of these diaeasem is so high in some area8 of the Region that the iaaua of potential intrr- action batwean them in the causation of liver pathology aesumea urgent priority.

Though HBV, mycotoxina, parasitic infestatione, and, in some parts of the Region, alcohol, may account for a high proportion of chronic liver disease, it is felt that many cases may have other causes. The search for such causes should be continued, and careful registration of cases of chronic liver disease in this Region may help to identify unknown etiological factors.

HCC in most reports constitutes a relatively lesser problem, perhaps less than could be expected from the prevalence of HBsAg. This may be because the populations are less ~usceptiblc to the postulated oncogenic effects of the virus

or, more likely, that cases of HCC are under-represented in the quoted materials for a number of reasons, such as selection bias in admission to hospitals. In most parts of Khe Region, particularly in rural areas, shortnge of hospital beds

presumably leads to many different kinds of selection bias, and estimates of incidence of diseases based on hospital materials in general should be taken with great reservation. Many important questions cannot be answered without field studies.

From existing information, it is clear that liver disease represents a acrious hcnlth problem for the population o f the Region. Viral hepatitis is probably the most important etiological factor for

a

wide range of conditions, apparently similar to those observed in other areas of the world, but there are alao special problems associated with schistosomiasis, malaria and hydatid disease. However, the magnitude and peculiarities of the hepatitis-related problems have not been sufficiently characcrriurd, i l l ~ d Lllr inteldftion between viral hepatitis and parasitic disease have not been explored.

Data concerning hydatid disease, which frequently invades the liver, are equally inadequate. Therefore, there is a need to fill this gap, especially with a view to prevention.

Data on hcpntitia B scrology concerning crucial age groups like newborns, young children and expectant mothers are inadequate, or completely missing, in most cases. The existing information is based on samples, inadequate in size and biased in nature, utilising laboratory procedure of various sensitivity.

The importance of the various ways of transmission of the HBV by age and sex has not been evaluated. Thereiore, even it eiiective procedures of active and/or passive immunization were available it would be impossible to make a

ratinnal a l l n r a t i o n n f prinritiec.

Clinical information cannot be fully utilised, mainly because of the operation of selection factors of different nature and strength in various countries, and because of confusion in terminology. Very few population-

Lased drscriplive and cuntrvlled analytic epidemiologic studies havc been

undertaken in the area of liver diseases. In virtually all instances. "selection bias" and "confusion in terminology" were credible alternative explanations of observed differences and associations.

IV IDENTIFTCATTON AND ASSESSMENT OF THE RESEARCH NEEDS IN RELATION TO

LIVER DISEASE

A. There was a concensus of opinion that attempts should be made to continue generation of reliable information on common forms of liver disease in the Ragion, ualng standard terminology and techniques. This information, from t h e Member

States of the Region, should be periodically collected at a central place,collated, reviewed and disseminated.

B. Suitably designed clinical and epidemiological studies should be carried out to identify the etiology of chronic liver disease,

C. Asymptomatic carriers of HBsAg, particularly in the younger age groups.

ahould be followed up to determine the extent to which the carrier state is aasoclated with emergence of chronic liver disease.

D. Studies should be carried out to determine the role of genetic differences in the development of the carrier scare of HBeAg and chronic liver disease.

E. The susceptibility of pregnant women to hepatitis and the prognostic featurar of the disease amongst them should be evaluated.

F. The possible interactions between HBV and schistosomiasis, and between HBV and malaria in the causation of acute and chronic liver disease should be studied.

It was emphasized t h a t , due Lo Llle ~ou~plex rlsrturr of t h i s i n t e r a c t i o n , special efforts will be needed to design and implement such studies, so that the results are scientifically valid.

G. The infectivity of HBsAg carriers in the family environment and in other settings must be evaluated.

page 11

H. The importance of traditional (scarification and tattooing) and modern (vaccination) medical practices in the spread of HBV should be evaluated.

I. Prospective studies should be undertaken of post-transfusion hepatitis.

J. Studies to determine the frequency of perinatal transmission, and its long-term effects on infected infants with regard to the development of chronic liver disease. should be undertaken.

K. The incidence of HCC should be estimated and the import an^^ n f t h ~ suggested aetiological factors should be evaluated.

L. Properly randomised clinical trials for evaluating prophylactic and therapeutic interventions and for monitoring side effects of such therapeutic I L I L ~ ~ V ~ I I L ~ U I I S sl~uuld be performed.

The group felt that the standardization of laboratory techniques and criteria for diagnostic, clinical and histological diagnosis of various forms of liver disease was essential to ensure the implementation of studies on the above-mentioned topics along scientific lines and for generating comparable information from the different countries of the Region.

V FORMULATION OF A REGIONAL PLAN OF ACTION TO MEET RESEARCH NEEDS

WHO EMRO should continue to foster and promote research in liver diseases within the Region.

The Ministries of Health in the Member States should be encouraged to establish multidisciplinary national cormnittccs for liver diseases, and to plan and to implement national programmes for research in liver diseases with a view to further define all aspects of these diseases and to monitor changes in infectivity, attack rate, and in results of passive and active prophylactic measures.

EM/RSR/I~

EM/SCF.GR.MTG.LIV.DIS./~~

page 12

WHO EMRO

Collection of an adequate data base should be supported with special attention to the following three aspects:

A. Data collecting procedures, including:

(i) characterization of the population from which samples are drawn;

(11) sampll~ip prucedure e random o r s p e c i f i e d oritsria):

(iii)use of proformas;

(iv) quality control (e.g., observer variation); and (v) data analyeis,

B. Standardization of laboratory technique, particularly concerning serological markers of hepatitis.

This implies:

(i) provision of apparatus, reagents and reference material;

(ii) training of doctors and technicians; and

(iii)establishing reference centres for standardization of reagents and procedures, in collaboration wlrh lncernacional cencres

(e.g., American Red Cross and Centre for Disease Contro1,Atlanta).

C. Standardization of nomenclature and diagnostic criteria concerning evaluation of liver biopsy material. This may be achieved by establishing regional panels of pathologists in close collaboration with interested clinicians.

HO EMRO E M / R S R / ~ ~

EM/scF.GR.MTG.LIV.DIS./~~

page 13

WHO EMRO may assist in this development through use of existing reference centres, programming experts to visit each other, and by organization of national and regional workshops.

The Group felt that, at this point in time, it was not feasible and desirable to lay down a timetable of activities for implementing the regional research programme in liver diseases.

However, it was suggested that, by the end of 1980, the following activities

s h o u l d have taken place at the national level:

(a) Formation of a multidisciplinary national committee on liver disease as suggested above;

(L) Enunciation of the priority areas for research;

(c) Identification of research workers at all levels to participate in the research studies;

(d) Formulation of training requirements for which collaboration with WHO EMRO could be sought; and

(e) Assessment of the requirements for equipment, reagents and other supplies of proper quality.

Hopefully, by late 1980 or early in 1981, the material from Member States, along the above given l i ~ ~ e s , cuuld be discussed w i L l l WnO rtnru wiLlr L l ~ r ubJect ul implementing assistance, as mentioned above. It is considered realistic to expect that actual projects may be initiated before the end of 1981.

VI S W Y AND RECOMMENDATIONS

A. The group was highly appreciative of the step taken by the Regional Director, EMR, in eetoblishing the Regional Scientific Group on Liver Diseases.

EM/RSR/Il

EN/sCF.GR.MTG.LIV.DIS ,112 pane 14

B. It was strongly recommended that WHO tKRO should continue to foster, promote, and coordinate research in liver disease in the Region.

C . The Scientific Group agreed that this meeting had achieved its 0bjective.i.e.:

b

(i) to summarise the current knowledge concerning liver disease as a health problem in the Region;

(if) to identify areas where additional knowledge was most urgently needed;

and

(iii)Co consider means by which this knowledge could be acquired.

D. After reviewing national data, the Group concluded that the major fofms of Liver disease constituting a health problem were infectious hepatitis, chronic liver disease, HCC and liver involvement with the parasitic diseases prevalent in the Region.

E. The Group recommended that the Member States in the Region be encouraged to establlsh national gruupa fur the atudy of liver dioeneee, and allocate resources to meet the research needs in this discipline. The national groups, once constituted, could identify research priorities, interested investigators, and could formulate training requirements for collaboration with WHO EMRO and with countries within the Region.

F. It was felt that, as early as possible, regional, followed by national, workohope be planned and organiveA hy WHO EMRO for standardization of histological criteria for diagnosis and standardization of recent serological techniques.

G. Necessary steps should be taken to ensure that the needed reference material for serological and immunological studies are provided to research workers in the Kegion.

EM/RSR/11

EM/SCF.GR.MTG.LIV.DIS./~~

page 1 5

H. Appropriate t e c h n i c a l c o l l a b o r a t i o n , through p r o v i s i o n o i c o n s u l t a n t s e r v i c e s , should be provided by WHO EMRO t o r e s e a r c h workers s o t h a t r e s e a r c h s t u d i e s i n t h e a r e a s i d e n t i f i e d by t h e Group may be designed.

I. I n o r d e r t o provide continued and s u s t a i n e d s u p p o r t t o t h e development of t h e r e g i o n a l r e s e a r c h programme i n l i v e r d i s e a s e s , exchange of s c i e n t i s t s between v a r i o u s c o u n t r i e s of t h e Region was considered h i g h l y d e s i r a b l e ,

EGYPT

IRAN

IRAQ

LEBANON

E M / R S R / ~ ~

EM/scF.GR.~G.LIV.DIS,/~~

Annex I

p a w 1

ANNEX I

LIST OF PARTICIPANTS

Dr Imam Zaghloul Imam President

Egyptian Organization for Biological Production and Vaccine

Agouza

-

^Cairo

Dr Yamean Abdul Ghafiar Profearnor of Medicine Ain Shame Univarrity

Cairo

Dr Freydoun Ala National Director Iranian National Blood

Transfusion Service Teheran

Dr F. Borhanmanesh Professor of Medicine

Department of Internal Medicine Medical School

University of Shiraz

Shiraz

Dr Z.A. Kassir Medical Unlt No.1 Medical City Hospital Baghdad

Dr J. Hatem Director

Cenizral Public Health Laboratory

Beirut

E M / R S R / ~ ~

EM/SCF.GR.MTG.LIV.DIS./12 Annex I

page ii

PAKISTAN

SUDAN

Dr S . J . Zuberi D i r e c t o r

P a k i s t a n Medical Research Council

PECH S o c i e t y Karachi

Col. Manzoor Ahmed

Anned Forces I n s t i t u t e of Pathology

Rawalpindi

Dr M. Abdel Mahmoud Arabi P h y s i c i a n

Omdurmsn C i v i l H o a p i t a l cmdumm

OBSERVERS OF THE HOST COUNTRY

B r i g a d i e r M . A . Z . Mahydin Chairman

P a k i s t a n Medical Research Council Karachi

M r Hasan Nawab

*

J o i n t S e c r e t a r y

M i n i s t r y of S c i e n c e and Technology Islamabad

Professor S a l e h Memon

P r o f e s s o r of Medicine Dow Medical C o l l e g e K a r a c h i

P r o f e s s o r N a s s i r u d d i n Azam Khan

P ~ n f e s q o r of Medicine Khyber Medical C o l l e g e Peshawar

P r o f e s s o r N.A. J a f a r e y P r o f e s s o r of Pathology

J i n n a h P o s t g r a d u a t e Medical Centre Karachi

*

d i d n o t a t t e n d

EM/RSR/ll

EM/SCF.GR.MTG.LIV.DIS./12 Annex I

page iii

Professor M. Yunus W a n P r o f e s s o r of Anatomy

Jinnah P o s t g r a d u a t e Medical C e n t r e Karachi

P r o f e s s o r S.H.M. Z a i d i P r o f e e s o r of Radiotherapy

Jinnah P o s t g r a d u a t e Medical Centre Karachi

Dr Munir Ahmed S i d d i q u i D i r e c t o r

Atomic Energy Medical C e n t r e L i a q u a t Medical College Junshoro

Dr Z u l f i q a r Haidor Rpaaarch D i r a c t o r

P a k i a t a n Medical Raaaarch Council Ranaarch Cantra

Fatima J i n n a h Madical C o l l a g e Lahore

-

D r Taslim Akhtar

*

S e n i o r Research O f f i c e r

P a k i s t a n Medical Research Council Research C e n t r e

Khyber Medical C o l l e g e Poshawar

D r Zahid Husain Khan Chief Research O f f i c e r

P a k i s t a n Medical Research Council Karachi

WHO CONSULTANT

D r N. Tygstrup

P r o f e s s o r of Medicine F a c u l t y of Medicine u n i v e r s i t y of copennagen Copenhagen

*

d i d n o t a t t e n d

E M / R S R / ~ ~

EM/SCF.GR.MTG.LIV.DIS./~~

Annex I page i v

WHO TEMPORARY ADVISER

Maj. Gen. M . I . Burney D i r e c t o r

N a t i o n a l Health Laboratory Islamabad

CONSULTANT OF IARC

Dr D. Trichopoulos

P r o f e s s o r Of EpldemlOlOgY U n i v e r s i t y of Athens Department of Hygiene and

Epidemiolopy School of Medicine Athens

-

WHO EMRO STAFF

--

D r J. Hashmi

S e c r e t a r y of t h e Meeting Regional Adviser, RPD WHO EMRO

Alexaudria

NATIONAL PREPARATORY

COMMITTEE

D r S a w a r J. Zuberi Research D i r e c t o r

P a k i a t a n Medical Research Council Research Centre

Jinnah P o s t g r a d u a t e Medical Centre Karachi

P r o f e s s o r N.A. Jafnrey P r o f e s s o r of Pathology

J i n n a h P o s t g r a d u a t e Medical Centre Karachi

Mr Mazhar Amjad A s s i s t a n t S e c r e t a r y

P a k l a t a ~ i Medical Research COUnCll Karachi

WHO EMRO

Mr Riaz Nohamad Chaudlirl A d m i n i s t r a t i v e O f f i c e r

P a k i s t a n Medical Research Council Karachi

ANNEX I1

MESSAGE FROM DR A.H.

TABA

DIRECTOR

WHO, EASTERN MEDITERRANEAN REGION to _thr

OPENfNO BEl8ION

OI

THE

UPEETZNO OF

TtiE

REQZONAL ICXENTXFIC OROUP

ON L Z V E i BllEAllg

I r*$tut that, on account of pressing comirmenra, IE wae r~uL ponalblo for me to be with

you

on thia a r c a r r i e ~ , Hawevet, it givee

me

great pleabure

to arnd

thid meeaupe of welcome to the dietinstliehod participantd in the Meeting of the Regional 8cientific Oroup on Liver Diseaeee.

f am thankful to the Ministry of Health, Government of Pakidtan, and to the Pakistan Medical Research Council, for hosting thie Maeting,

Though the Regional Office for the Eastern Mediterranean has been involved in medical research activities since its inception, however, these activities have gained fresh impetus by the assumption of responsibility for medical research by the Regional Offices.

In 1976, 'Iestablished a Regional Advisory Committee on Biomedical Research

t o advise me on regional rescarch p o l i c y and p r i o r i t i e s , and on tho means o f

coordinating research on the national, regional and global levels. The Com- mittee also advises on the establishment and strengthening of research capabi- lities in the Member States, and on other related scientific matters. The EMIACMR, as this Committee is called, has met four times so far, and its deliberations have made a valuable contribution to the development of our Regional Programme for Medical Research.

EM/RSR/11

EM/SCF.GR.MTG.LIV.DIS./~~

Annex I1 page ii

~t one of its meetings, the EMIACMR recommended that research studies be promoted and supported on disaases which are of concern to savaral countriaa in the Region, and on which soma work has already bean carried out in the countries with their own resourcas. Liver direarar has bean idantifiad a8

one of such diseoees.

Therefore, I decidad to establish a Scientific Group on Livar Disaases with the following objectives:

-

to assess the magnitude o f liver diaenae. in our Region;

-

to review research studies on liver diaaa~es carried out in the countrirr of the Region; and

-

to discuss end lay down a pragrama of work for furthering the knowlrdgr about liver disease#, with a viaw to anaure thair control and pravantion, In view of the importance of viral hrpstitis a8 a major public health

problem, WHO har, in thr recent past, rponaorrd

a

number

of

activitisr, including a large inter-regional aeminar, held in Malaymia

2

yaara ago, Within thim

Region, viral hepatitis was the rubjsct far a technical discusrion at our Ragionrl Committae meeting in 1976. A Werknhop an Viral Hapatitin

wan

conducted in Cairo in Wovembar 1978 Por training in different aarelaglaal taohndquao, and, this manth, another training couree is being held there on rapid technipuar for idsmtification of viruses. National Collabarating Centre8 far Viral Hepatitis hava bran

ds-

signated in Egypt, Iran, Lebanon and Pakistan, and

I

am pleased to note that tha Directors from these national Centres are participating in this Meeting.

While I am sure that, during your discussions, you would undoubtedly give viral hepatitis the attention it deserves. however. I would also ask this Group to review the status of chronic liver diseases, liver cancer and liver disorders associated with various parasitic diseases prevalent in our Region, and to propose appropriate research studies.

EM/RSR/U

EM/SCF.GR.MTG.LIV.DIS./12 Annex I1

page iii

Following this Meeting, and based on your recommendations, EMRO would be glad to consider financing multicentre studies on topics considered as priority items by you. With this in view, I would suggest that you also deal with systems for standardization, laying down of diagnostic criteria, and other relevant matters, to ensure ultimately that the data generated through these multicentral studies will be comparable.

Finally, I would like to thank all the participants in this Meeting for sparing their valuable time. I sincerely hope that you have a fruitful Meeting and I look forward to receiving your report.

ANNEX I11

AGEMlA

1. Opening of the Meeting

2. Election of Officers

3. Adoption of Agenda and Programme of Work

4 . Review of Liver Diseases in the countries of the EM Region

5. Identification and assessmenL of the r e s e a r c h ~ l e e d s in relation to Liver Diseases

6. Formulation of a Regional Plan of Action to meet research needs

7. Summary Reporr and Rrcommrr~daLlu~~s.

ANNEX IV PROGRAMME

Monday, 17 December 1979 COLLEGE OF PHYSICIANS AND SURGEONS

9.30 a.m.

-

10.30 a.m.

-

Registration and opening of the Meeting 10.30 a.m.

-

11.00 a.m.

-

^Recess

11.00 a.m.

-

^{2.00 p.m.}

-

Election of Officers

-

^{Adoption of Agenda}

-

Review of Liver Diseases in EM Region

-

^Egypt

-

^Iran

-

^Iraq

-

^Lebanon

Tuesday, 18 December 1979

Y.UU a.m.

-

10.30 a.m.

-

Review of Livcr Dieeases in EM Region ( r n n t ' d )

-

^Pakistan

-

^Sudan

-

^IARC, Lyon

Wednesday, 19 December1979 9.00 a.m.

-

10.30 a.m.

-

^Recess

-

Discussion on the research needs in relation to Liver Diseases

-

Pormulation of n Regional Plan of A c t i o n

to meet the identified research needs

-

Formulation of a Regional Plan of Action to meet the identified research needs (cont'd)

-

Recess

-

Summary Report and Recommendations.

Annex V

ANNEX V

LIST OF BASIC DOCUMENTS PROVISIOllAL AGENDA

PROVISIONAL PROGRAMME

PROVISIONAL LIST OF PARTICIPANTS

EPIDEMIOLOGY OF VIRAL HEPATITIS

B

IN EGYPT by Dr Imam Zaghloul Imam

THE PATTERN OF CHRONIC LIVER DISEASE IN EGYPT by Dr Yaseen Abdul Ghaffar

A REVIEW OF INFORMATION PRESENTLY AVAILABLE REGARDING HEPATITIS IN IRAN

-

RECOMMENDATIONS FOR THE FUTURE

by Dr F.A. Ala

LIVER DISEASES IN IRAN by Dr P . Borhanmanesh LIVER DISEASES IN IRAQ by Dr Z.A. Kassir

LIVER DISEASES IN LEBANON by Dr .I. Hatem

LIVER DISEASES IN PAKISTAN by Dr S.J. Zuberi

THE CLINICAL SPECTRUM OF LIVER DISEASE IN THE SUDAN

by Dr M. Abdel Mahmoud Arabi PROGRAMME OF LIVER DISEASE

by the International Agency for Research on Cancer (IARC)

BACKGROUND MATERIAL WHO INTER-REGIONAL SEMINAR ON VIRAL HEPATITIS Kuala Lumpur, November-December 1977

CHRONIC LIVER DISEASE: GLOBAL ASPECTS, EPIDEMIOLOGY AND INTERVENTION

Report of a WHO Meeting Geneva, 21-25 November 1977