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Vol. 19 No. 2, June 2004Tanzania Medical Journal

SERO – PREVALENCE OF HEPATITIS B SURFACE ANTIGEN AMONG INDIVIDUALS WITH HIV – RELATED CUTANEOUS DISORDERS AT A TERTIARY REFERRAL DERMATOLOGY CLINIC IN DAR ES SALAAM.

YM Mgonda

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Vol. 19 No. 2, June 2004Tanzania Medical Journal

Summary

Background: HIV and hepatitis B virus (HBV) infections are common in sub Saharan Africa. HIV/AIDS is associated with a wide variety of cutaneous disorders which herald the onset of severe immunosuppression. In sub Saharan Africa, HBV is transmitted mainly horizontally through skin contact. Few studies if any have determined the prevalence of HBV infection among HIV sero-positive individuals with HIV – related cutaneous disorders.

Objective: To determine the sero – prevalence of hepatitis B surface antigen among HIV – seropositive individuals with HIV- related cutaneous disorders.

Setting: Tertiary referral Dermatology clinic, MuhimbiliNationalHospital, Dar es Salaam.

Design and methods: Hospital based controlled study whereby consecutive patients with HIV – related cutaneous disorders were enrolled. After filling in a questionnaire and undergoing dermatological examination blood was drawn for HBsAg and HIV antibody screening. Adult and secondary school student blood donors were used as controls.

Results: 384 patients with HIV-related skin lesions were enrolled into the study. 354 (92%) were HIV sero positive while 30 (8%) were sero- negative. The majority, 204/354 (58%) had PPE alone or co existing with other cutaneous lesions. Thirty of the 354 (8%) HIV - positive patients were co infected with hepatitis B virus. Of the adult voluntary blood donors, 28/333 (8%) were HIV sero positive, 32/333 (10%) were HBsAg positive while 4/333 (1.2%) had HIV and HBV co infection. For student blood donors, 2/120 (2%) were HIV positive while 10/120 (8%) were HBsAg positive and none of them had HIV and HBV co infection. The sero prevalence of HBsAg did not differ significantly between patients with HIV – related skin disorders, adult and secondary school student blood donors (p= 0.64)

Conclusion: Although the prevalence of HBsAg among HIV positive individuals with HIV related cutaneous disorders was apparently similar to that of adult and student blood donors, the HBV and HIV co infection rate of 8% among individuals with HIV related cutaneous disorders may pose a significant challenge in terms of the implicated liver - related mortality and rational choice of anti- retroviral drugs especially in this era of HAART.

Key words: HBsAg, HIV, HIV – related skin diseases.

Introduction

Hepatitis B virus (HBV) infection is endemic throughout sub Saharan Africa where it is associated with significant morbidity and mortality.(1) On average, 10 - 11% of the general population has chronic HBV infection (HBsAg carriers).(2) Horizontal transmission by skin contact is the most important transmission route in sub Saharan Africa.(3) The prevalence of HIV infection is highest in the same areas where hepatitis B virus infection is very common.(4) HIV and HBV are transmitted by similar mechanisms but differ in their infectivity and the predominance of the modes of transmission. HBV, whose transmission in sub Saharan Africa is mostly horizontal, is about 100 times more infective than HIV which on the

Correspondence to: Mgonda YM, Box 65001, MuhimbiliUniversityCollege of Health Sciences

Department of Internal Medicine

contrary, is mainly transmitted heterosexually.(3) Studies have shown that the onset of some of the HIV – related skin diseases predicts the occurrence of an advanced stage of immunosuppression with an increased risk of acquiring opportunistic infections.(5) Hepatitis B virus is a well-documented opportunistic pathogen among HIV infected individuals. The presence of HIV – related skin lesions, may make horizontal transmission of HBV more likely.(3) Furthermore, HIV disease causes multidimensional immunosuppression, which could compromise one’s ability to recover spontaneously from an acute HBV infection thus leading to a chronic disease.(6)

The prevalence of HBV infection among individuals with HIV related cutaneous disorders is largely unknown, particularly in sub Saharan Africa although the prevalence of both infections in the general population is alarmingly high. The effect of HIV infection on those infected with HBV is not clearly understood. Some studies suggest that the progression of liver disease is diminished, which might be expected since the pathogenesis of hepatitis B is immunologically mediated and the immunity is compromised in the presence of HIV infection.(7) However, other studies suggest that the progression of liver destruction is increased leading to early chronic active hepatitis, liver cirrhosis and finally hepatocellular carcinoma the mechanism of which is not very clear.(6, 12) The effect of HIV infection on the natural course of hepatitis B could also be modified by the highly active antiretroviral therapy (HAART).(7) The HAART associated liver toxicity and immune restoration could both accelerate liver damage leading to increased of early liver related death.(7)

There is therefore a need to determine the disease burden of HBV co infection among different categories of HIV positive individuals, like those with HIV- related cutaneous lesions many of which are potentially ulcerative and markers of severe immunosuppression. This knowledge would challenge clinicians to take appropriate preventive and therapeutic interventions including rational choice of anti retro viral drugs. It was on this background that this study was conducted with the main objective of determining the prevalence of HBV co infection among HIV – seropositive individuals with HIV- related cutaneous disorders.

Materials and methods

The study was conducted at the tertiary referral dermatology unit of MuhimbiliNationalHospital in Dar es Salaam, between June 2002 and July 2003. During this period, consecutive patients with HIV - related cutaneous disorders were recruited into the study after obtaining their fully informed verbal consent. Each patient underwent a full physical and dermatological examination. Diagnoses of HIV related - skin diseases were made clinically in most cases except for doubtful dermatoses as well as cases of cutaneous Kaposi’s sarcoma where skin biopsies were performed for histological confirmation. A structured questionnaire was used for data recording.

After a pre – test counseling, whole blood for HIV and HBsAg screening was collected in empty sterile vacutainer tubes from which plasma was separated. A qualitative immunoassay for the detection of antibodies to HIV 1&2 was done using Determine TM kit (Abbot Japan Co Ltd. Minato – Ku Tokyo, Japan). Screening for HBsAg was performed with Virotect – HBsAg kit (Omega diagnostics Ltd, Omega House, Scotland, UK). Post – test counseling was offered to all subjects.

Samples of blood from all adult and student voluntary blood donors who came to the hospital over a randomly selected period of three months within the study period were anonymously collected and screened for HIV and HBV using the same techniques as for the study subjects. These were used as controls.

Data were entered into a computer and validated to ensure that all entries were accurate. Analysis was done using Epi info version 6 software and p – value was considered to be significant if it was less than 0.05.

Results

A total of 384 patients with skin disorders suggestive of HIV infection were enrolled into the study. Of these, 354 (92%) tested HIV sero positive while 30 (8%) were sero negative. Out of 354 - sero positive individuals, 171(48%) were males while183 (52%) females. The age (table 1) ranged from 2 to 57 years with a mean of 35 years. The 25th and 75th centiles were 30 and 42 years of age respectively. Overall, the age group that was mostly affected was 31 – 40 years (43%) followed by 41 – 50 (22%) and 21 – 30 years (17%).

Table 1: Age and sex distribution of patients with HIV

related skin disorders (n=354)

Age / Sex
Male (%) / Female (%) / Total (%)
0 - 10 / 12 (3) / 3 (1) / 15 (4)
11 – 20 / 12 (3) / 12 (3) / 24 (7)
21 – 30 / 18 (5) / 42(12) / 60 (17)
31 – 40 / 63 (18) / 87 (25) / 150 (43)
41 – 50 / 54 (15) / 24 (7) / 78 (22)
51 – 60+ / 12 (3) / 15 (4) / 27 (7)
Total / 171 (48) / 183 (52) / 54 3 (100)

Table 2 shows the different HIV – related skin diseases among the 354 HIV – positive patients. The majority, 204/354 (58%) had PPE either alone or co existing with other cutaneous lesions. PPE presented alone in 168 (47%) patients. Cutaneous epidemic Kaposi’s sarcoma (CEKS) was seen in 60/354 (17%) of whom, 48 (80%) had this lesion alone. All patients with CEKS alone or in combination with other skin diseases were HIV sero - positive. Psoriasis alone or in combination with seborrhoeic eczema (sebo – psoriasis) was seen in 36/354 (10%). Herpes zoster with or without other skin conditions was seen in 27 (8%) patients. Eighteen patients (5%) had genital herpes simplex in addition to other cutaneous lesions. The other skin conditions encountered with numbers in brackets included; superficial mycosis including onychomycosis (18), plane warts (12), molluscum contagiosum (9), genital warts (9) and lichen planus subtropicus (3).

Table 2: HIV related skin disorders among HIV positive

patients (n=354)

Skin disorder / No. (%)
PPE alone / 168 (47.5)
PPE +other cutaneous disorders / 36 (10)
Cutaneous KS (with or without other skin diseases) / 60 (17)
Psoriasis + seborrhoeic eczema / 36 (10)
Herpes zoster / 27 (8)
Genital herpes simplex / 18 (5)
Superficial mycosis (+onychomycosis) / 18 (5)
Plane warts / 12 (3)
Genital warts / 9 (2.5)
Molluscum contagiosum / 9 (2.5)
Lichen planus subtropicus / 3 (1)

Thirty of the 354 (8%) HIV - positive patients were co infected with hepatitis B virus. Of these only three subjects (10%) had received blood transfusion in the past. Twenty-four HBV positive individuals (80%) were males while 6 (20%) were females. The age among the HIV and HBV co infected patients ranged from 11 to 50 years. None of the 30 HIV – negative individuals had HBV infection.

There were 333 adult voluntary and 120 secondary school student voluntary blood donors respectively who were included in the study as controls. Of the adult voluntary blood donors, 28/333 (8%) were HIV sero positive, 32/333 (10%) were HBsAg sero positive while 4/333 (1.2%) had HIV and HBV co infection. For the student blood donors, 2/120 (2%) were HIV positive, 10/120 (8%) were HBsAg sero positive while none had HBV and HIV co infection. The sero prevalence of HBsAg infection did not differ significantly among patients with HIV – related skin diseases, adult and student voluntary blood donors (p= 0.64).

Discussion

Certain skin diseases predict fairly accurately the presence of HIV infection even before testing and more importantly, they correlate well with the severity of the underlying immunosuppression.(5, 8) Studies have shown for example, that the presence of PPE in an individual is associated with 99% chances of being HIV – 1 positive and 70% chances of having CD 4+ T – lymphocyte count of 200cells/ml or less, i.e. having AIDS by CDC criteria . In this study, 92% of all individuals who presented with skin lesions suggestive of HIV infection turned out to be HIV positive and the majority (58%) had PPE.

HIV and HBV co infection has been shown by many studies to be common due to shared modes of transmission 7. Chloe et al found that among 326 HBsAg positive men having sex with men, 213 (65%) were co infected with HIV – 1.(7) This study has determined the sero prevalence of HBsAg among individuals with HIV related skin diseases and compared it with that in adult and student blood donors as controls. The prevalence of HBsAg did not differ significantly between the three groups which were 8%, 10% and 8% respectively for HIV infected individuals with cutaneous manifestations, adult blood donors and student blood donors.

The HBsAg sero prevalence of 8% among the HIV positive patients with HIV – related cutaneous disorders, is almost the same as what has been observed in the general population. This may have several explanations. Firstly, the level of HBsAg in the general population could have stabilized during the ‘teenager’ period when the majority of HBV infections in sub Saharan Africa occur, and that HIV infection occurs much later during youth hood and adulthood when individuals have already acquired HBV infection. Secondly, the low prevalence of HBsAg positive may be due to HBsAg false negative results among HIV infected individuals with compromised immunity. Studies have shown that false negative HBsAg is possible among immunocompromised patients.(9) In order to detect all true HBsAg positives, other sero markers like serum HBV DNA and HBeAg should have been performed but this was not logistically feasible in this study.

The HIV and HBV co infection rate of 8% in individuals with HIV related skin diseases in this study, although seemingly low, (possibly also due to presence of HBsAg false negatives) has significant repercussions. Studies have shown an increased risk of death from liver disease in persons infected with either HIV – 1 or HBV, but the risk is highest in individuals who are co infected with both viruses.(7) Furthermore, rates of liver – related deaths are higher in individuals with the lowest CD4+ T - cell nadir.(7) It has already been established that the majority of HIV positive patients with some HIV – related skin disorders like PPE have very low CD4+ T – cell counts(8,10) who could therefore be at a higher risk of liver related death if they happen to be co infected with HBV. The increased risk of liver – related mortality among HBsAg positive individuals co infected with HIV – 1 although notable has got no clear explanation. HIV – 1 may destroy CD 4+ lymphocytes which are normally activated to combat HBV infection and stop disease initiation and progression. However, it is not clear how depletion of CD 4+ T – lymphocytes would directly enhance liver damage, which has been linked with a more vigorous cytotoxic T – cell response.(7) The increased risk of liver – related deaths among individuals co infected with HIV and HBV has also been noted since the introduction of HAART in 1996.(11, 12)This has been attributed to several factors including direct hepatotoxicity from individual drugs, as well as the immune restoration induced by HAART which might reactivate HBV infection leading to disease progression as has been noted with other infections like tuberculosis and cytomegalovirus infection.(6, 7)

This study therefore, implicitly emphasizes the importance of considering comprehensive measures to accurately define the HBV disease burden among individuals infected with HIV – 1 who present with cutaneous lesions thatmay increase the risk of HBV infection leading to early liver – related death particularly in this era of HAART. More logistically sound studies need to be conducted which will have to include detection of all markers of HBV infection such as HBeAg and HBV DNA in order to offset the problem of HBsAg false negativity in HIV infected immunocompromised individuals. The liver injury in co infected individuals should also be comprehensively ascertained using both indirect measures like serum liver enzymes and directly by liver biopsy and histology.

Conclusion

Although the prevalence of HBsAg among HIV sero positive individuals with HIV related cutaneous disorders in this study was apparently the same as that of adult and student blood donors who were used as controls, the HBV and HIV co infection rate of 8% among individuals with HIV related cutaneous disorders may pose significant challenges in terms of the implicated liver - related mortality and the rational choice of anti- retroviral drugs especially in this era of HAART.

Acknowledgement

The author would like to thank Sister Mary Nkaina for smoothly organizing the clinic at the time of this study. She also helped with collection of all blood samples for screening. Mrs. Mlalasi of the clinical research laboratory performed all the HIV and HBsAg screening tests and is being highly acknowledged. The other costs including stationeries and the purchase of reagents were met by the author.

References

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Vol. 19 No. 2, June 2004Tanzania Medical Journal