395 TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE (1987) 81, 395-397

Viral hepatitis and pregnancy in Kuwait

S. AL-KANDARI’, E. NORDENFELT 2, B. AL-NAKIB~, S. GROVER’ AND W. AL-NAKIB~‘~ ‘Infectious Diseases Hospital, Kuwait; ‘Department of Clinical Virology, Malmo General Hospital, Sweden; ‘Department of Medicine and Microbiology, Faculty of Medicine, University of Kuwait; 4Medical Research

Council Common Cold Unit, Salisbuty, UK

Abstract The frequency and severity of viral hepatitis among pregnant and non-pregnant women in Kuwait

was studied from 1980 to 1984. 542 female hepatitis patients were investigated, of whom 52 (9.6%) were pregnant. 35 of the 52 (67.3%) cases of viral hepatitis in pregnancy were due to hepatitis B virus while 11 of 52 (21.2%) and 6 of 52 (11.5%) had acute hepatitis non-A, non-B (NANB) and hepatitis A virus infections., respectively. The frequency and severity of viral hepatitis among the pregnant women was sinular to that among non-pregnant women. Hepatitis did not have a deleterious effect on pregnancy and no death was recorded. Fuhninant acute NANB hepatitis was seen in only one patient, who recovered completely.

Introduction The severity of viral hepatitis during pregnancy, its

frequency during the various trimesters, and its effect on the foetus and the mother has often been investigated, although findings have not always been consistent (ADAMS & COMBES, 1965; HAEMMERLI, 1966; MAZAUD et al., 1959; BORHANMANESH et al., 1973.; KHUROO et al., 1981). Although some of these stu&es showed that the severity and fatality of viral hepatitis increases during pregnancy, especially in developing countries (GELPI, 1970; CHRISTIE et al., 1976; GEBREEL? 1983; BERNUAU et al., 1984); HAM- MERLI (1966) indicated that the severity of acute hepatitis in pregnancy is restricted to certain geog- raphical areas of the world. This view was regarded by BORHANMANESH et al. (1973) as misleading, because selective admission of patients with severe and complicated disease rendered the mortality figures unusually high. CAHILL (1%2) and ADAMS & COM- BES (1965) reported that viral hepatitis is not more severe in pregnancy. Furthermore, reports from the USA and EuroDe showed that the course of viral hepatitis during pregnancy is not different from that seen among non-pregnant women (HAEMMERLI, 1966; BERNUAN et al., 1984).

The present study attempted to determine the frequency and severity of viral hepatitis during pregnancy in Kuwait, especially in relation to the types of viral hepatitis.

Patients and Methods Jaundiced patients, suspected of having acute viral

hepatitis, were referred to the Infectious Diseases Hospital (IDH), Kuwait, the only hospital in that country responsible for the admission of cases with acute viral hepatitis. During the period 1980-1984, there were 2199 patients with acute viral hepatitis in the age group 15 fo 45 years. Of these, 1657 (75.4%) were males and 542 (24.6%) were females. Of the 542 females, 52 (9.6%) were pregnant at the time of onsef of symptoms.

All the hepatitis cases were thoroughly examined clinically and subjected to complete serological and biochemical investigation. Patients were accepted as having acute viral Type and age of infection Address for Correspondence: S. Al-kandari, P.O. Box 4710, 35 of the pregnant patients (67.3%) had acute HBV Safat, Kuwait. infection, while only 11 (21.2%) and 6 (11.5%) had

hepatitis if the clinical picture was associated with a level of serum glutamic pyruvic transaminase (SGPT) at least twice the nor&l in thi absence of any other cause of hepatitis such as drugs or other infections.

For serological studies, acute and convalescent phase sera were collected and stored af - 20°C. The presence of specific IgM for hepatitis A virus (HAV), detected by radioimmu- noassay (RIA) (HAVAB-IgM, Abbott Laboratories, USA), in the acute phase sample was taken as evidence of recent infection. Various markers of hepatitis B virus (HBV), such as HBsAg, HBeAg and Anti-HBe, were detected using standard commercially available RIA systems (Abbott Laboratories, USA). Specific IgM to HBV core antigen (anti-HBcIgM) was investigated by solid-phase radioimmu- noassay (SPRIA) (WIDELL er al., 1982).

The presence of HBsAg in the acute phase serum sample, together with the presence of anti-HBc IgM antibodies (titre W5) was accepted as evidence of recent infection by HBV. Persons with HBeAg in the acute phase serum sample who sero-converted to anti-HBe were also considered as having had acute HBV infection. Hepatitis non-A, non-B (NANB) was diagnosed by exclusion of recent infection with HBV, HAV, Epstein Barr virus (EBV) or cytomegalovirus (CMV) infection. Recent EBV or CMV infection was detected by demonstrating virus-specific IgM by indirect im- munofluorescence. Clinical chemistry studies were con- du;;ott)using an automatic clinical Analyser (ACA 3,

The criteria for fulminant hepatitis were the development of hepatic failure, prothrombin activity less than 40% of normal, and development of grade III and IV coma within 4 weeks of onset of the svmotoms of acute heuatitis.

The mean peak value;of’SGPT, bilirubin, iotal protein and albumin in the serum, and the duration of illness in days from the onset of symptoms until the time when serum leviIs returned to normal have been used as indices of severity. These values for pregnant patients were compared with those in non-pregnant cases for each type of virus infection.

Results Over the S-year study period, 542 females with

acute viral heoatitis were examined. of whom 52 (9.6%) were pregnant at the tim; of onset of symptoms.

396 VIRAL HEPATITIS AND PREGNANCY IN KUWAIT

acute NANB or HAV infection, respectively. In the non-pregnant group the frequencies of the 3 viruses, HAV, HBV and NANB, were 140(28*6%), 183(37*3%) and 167(34*1%) respectively (Table 2). The mean age of patients with acute HAV infection (26.4 years) was similar to that of those with acute HBV (26.4 years), while the mean age for those with acute NANB infection (28.3 years) was significantly higher than that of the acute HAV group (E-O-05).

The mean age of pregnant patients (26.6 years) was similar to that of the non-pregnant group (27.3 years). Most of the pregnant patients were in two age groups: 20 to 24 years (15 women) and 25 to 29 years (also 15 women). Significantly more acute HAV cases in the pregnant group occurred among those aged 15 to 29 years (83.3%) than in the 30 to 44-year age group (16.7%). A similar significant difference was noticed in those with HBV infection, 71.4% and 28.6% respectively.

Trimester 26 of the 52 pregnant patients (50%) were found to

be affected during the second trimester of pregnancy. 16 (31%) and 10 (19%) of the 52 had acute infections during the third and first trimesters of pregnancy, respectively. All 3 types of viral hepatitis infection were more common during the second trimester.

SeVen’ty Analysis of mean peak serum bilirubin and mean

peak serum SGPT showed that the course of hepatitis, in the pregnant women, was similar to that which

Table l-Vii hepatitis ia pregnant cases by trimester aad lype during 1980-84 in Kuwait

Trimester HAV HBV NANB All types

First 2 7 1 10 Second 3 16 7 26 Third 1 12 3 16

Total cases (No.) 6 35 11 52 w 11.5 67.3 21.2 100

occurred in the non-pregnant women in all 3 types of virus infection (Table 2). The outcome of acute viral hepatitis in 9 of 542 (1.7%) non-pregnant females was fatal, fuhninant viral hepatitis being the cause of death in all cases. 5 of these deaths were due to NANB, and 4 to HBV, infection. In contrast, only one pregnant woman, aged 23 years, had fuhninant viral hepatitis due to acute NANB hepatitis during the third trimester. This patient survived and had a normal delivery. Thus no fatality was recorded among the pregnant group who had viral hepatitis.

Protein and albumin values, in both the pregnant and non-pregnant groups, besides being an index of severity of infection may also be considered as a marker of nutritional status. No striking difference were observed between these values in the different groups. In the one pregnant patient with NANB fuhninant hepatitis, the minimum protein and albu- min values were 5.2 and l-2 g/100 ml respectively, the lowest recorded values in the whole study group.

Discussion There are conflicting reports on the effect and

outcome of viral hepatitis in pregnancy. Some studies indicated that viral hepatitis during pregnancy was no more severe than among non-pregnant women (CAHILL, 1962; SHERLOCK, 1968; HAEMMERLI, 1966; ADAMS & COMBES, 1965), in contrast with reports of higher incidences of mortality and foetal wastage when viral hepatitis occurs during pregnancy in some developing countries (MAZOUD et al., 1959; GELPI, 1970; BORHANMANESH et al., 1973; GEBREEL, 1983; BERNUAU et al., 1984). We found no evidence to suggest that viral hepatitis has a deleterious effect on pregnancy. In addition, despite the fact that there were 9 deaths among the 542 women with hepatitis studied over the S-year period of study, none was recorded among the pregnant women with viral hepatitis. In a review of 29 cases of viral hepatitis over a period of 28 years at the New York lying-in hospital, CAHILL (1962) also reported no deaths and com- mented that the natural history of viral hepatitis remains unaltered by pregnancy and the disease does

Table 7Biochemical findings in pregnant and non-pregnant cases of HAV, HBV and NANB virus infection

HAV HBV NANB

Quantities Pregnant Non-pregnant Pregnant Non-pregnant Pregnant Non-pregnant (means) (N=6) (N= 140) (N=35) (N=183) (N=ll) (N= 167)

Serum bilirubin b.sw 6.9f 2.1 7-3* 1.9 12*4+ 6.2 12*1+ 7.2 11.6+ 7.4 13.4* 12.5 SGPT* (Wlitre) 361 k2.52 403f271 139Of 1067 1580+1288 1013f875 1181+744

Duration of abnormal SGPT elevation (days) 29.4k13.6 26.7f16.9 46.8f24.8 57.9k33.3 28.5k10.5 39.9f23.1

Lowest total protein W1~~) 5.9+ 0.4 6.2+ O-5 6.1+ 0.5 6.3f 0.6 5.9f 0.6

Lowest total albumin (g/1(-m 2.9+ 0.5 3.0f 0.4 3.1+ 0.4 3.2+ 0.5 2.8+ O-9

*Serum glutamic pyruvic tramaminase. Differences between pregnant and non-pregnant groups not significant by Student’s t-test: P>O.O5.

6.3+ 0.8

3.1+ 0.5

S. AL-KANDARI et d. 397

not appear to be more fulminating in pregnant than in non-pregnant women, provided that their nutrition was adequate.

On the other hand, BORHANMANESH et al. (1973) recorded 21 deaths among 61 cases of pregnancy hepatitis cases in Iran (34%). KHUROO et al. (1981) also observed a higher incidence and severity of viral hepatitis during pregnancy in Kashmir, India, with fulminant hepatitis occurring in some 22% of the cases and death in 66%.

This lack of any common pattern of viral hepatitis during pregnancy is highlighted by contradictory reports from the same region. Thus, HAMMOUDA (1962) reported from Mecca in Saudi Arabia that viral hepatitis-was not particularly severe during pregnancy and that. of the 25 cases studied. onlv one died. GELPI (1970) however, also in Saudi Arabia, observed a higher mortality rate (46.3%) among pregnant women with viral hepatitis than among non-pregnant women (11.9%). A more recent studv (MALLIA. 1981). from Tabouk in Saudi Arabia, also recorded a ‘higher frequency of fuhninant viral hepatitis among pregnant women (9 out of 15), but only two deaths. These differing findings from Saudi Arabia, at different times and from different locations, emphasize once again the prevailing controversy that surrounds the effect of hepatitis in pregnancy.

In our study the majority of pregnant patients (67.3%) were found to have had acute HBV. In addition, 21.2% had acute NANB and 11.5% had acute HAV infection. BERNUAU et al. (1984) and CHRISTIE et al. (1976) attributed the increased sever- ity of disease in pregnancy to NANB hepatitis. CHRISTIE et al. (1976) recorded no death among their HBsAg positive patients, while GEBREEL (1983), on the other hand, found similar fatality rates among patients with HBV and NANB infections. The one patient with fuhninant viral hepatitis in this study was infected with NANB hepatitis virus, during the third trimester of pregnancy. It remains to be seen whether NANB virus infection in pregnancy is more severe than HBV infection.

In conclusion, our findings suggest that viral hepatitis during pregnancy among women in Kuwait follows a similar course to that in non-pregnant women.

Acknowledgements This work was supported by a research grant from the

Health Research Department, Ministry of Public Health, Kuwait and the Swedish Medical Research Council Project No. B, 85-16X-02465-16.

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Accepted for publication 8 February 1986