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Time trends of chronic HBV infection over prior decades - A global analysis

Ott JJ, Horn J, Krause G, Mikolajczyk RT

J Hepatol, 2017 Jan;66(1):48-54.
PMID: 27592304 DOI: 10.1016/j.jhep.2016.08.013

BACKGROUND & AIMS: Information on trends in chronic hepatitis B virus (HBV) prevalence across countries is lacking. We studied changes in chronic HBV infection over previous decades by country, and assessed patterns of change between and within WHO-defined regions.
METHODS: Based on data from a published systematic review on chronic HBV, we applied a linear model on the logit scale to assess time trends in country-specific prevalence. Estimated HBsAg prevalence in 2000 and relative changes in prevalence over time were evaluated by country and region.
RESULTS: Sufficient data were available for 50 countries, mostly showing reductions in prevalence over time. Various degrees of heterogeneity were observed within regions, with a relatively homogenous pattern in the Eastern Mediterranean region with strong decreases in HBsAg prevalence. Europe showed a mixed pattern: higher and stable chronic HBsAg prevalence in Eastern, and constantly low prevalence in Western Europe. In Africa, some countries demonstrated no change in prevalence; increases were seen in Uganda (odds ratio 1.05 per year; 95% confidence interval 1.04-1.06), Nigeria (1.02; 1.02-1.02), Senegal (1.01; 1.01-1.02), and South Africa (1.02; 1.01-1.02). With some exceptions, country-patterns overlapped among countries of South East Asian and Western Pacific regions, characterized by low-medium HBsAg decreases, most prominent in China and Malaysia.
CONCLUSIONS: Most countries experienced decreases in HBsAg prevalence. Dynamics varied, even within regions; decreases occurred mostly before the direct effects of childhood vaccination may have manifested. These findings together with stable and increasing HBsAg prevalence in some countries of Africa and Eastern Europe indicate the need for further tailored country-specific prevention.
LAY SUMMARY: This study investigated time trends in prevalence of chronic HBV infection in 50 countries worldwide over the last decade, by estimating relative changes in prevalence. Results show decreases in chronic HBV infection in most countries; no changes or increases in prevalence are noted in some African countries. Reasons for time changes need to be investigated further; based on the results, various prevention measures have contributed to reductions, and further tailored HBV prevention is required to combat the disease on a global level.

Matched MeSH terms: Hepatitis B Surface Antigens/analysis
Tissue microarray immunohistochemical profiles of p53 and pRB in hepatocellular carcinoma and hepatoblastoma

Azlin AH, Looi LM, Cheah PL

Asian Pac J Cancer Prev, 2014;15(9):3959-63.
PMID: 24935581

The tumour suppressor genes, p53 and pRb, are known to play important roles in neoplastic transformation. While molecular routes to the uncontrolled growth of hepatocytes, leading to primary liver cancer have generated considerable interest, the roles of p53 and pRb mutations in hepatocellular carcinoma (HCC) and hepatoblastoma (HB) remain to be clarified. We examined the immunohistochemical expression of p53 and pRb gene products in 26 HCC and 9 HB, sampled into tissue microarray blocks. 10 (38%) of 26 HCC showed > 10% tumour nuclear staining for p53 protein, 3 of these also being HbsAg positive. Conversely, none of 9 HB expressed nuclear p53 immunopositivity. Some 24 (92%) HCC and 8 (89%) HB showed loss of pRb nuclear expression. Two of the 26 HCC and one of the 9 HB showed >10% tumour nuclear staining for pRb protein. Our results suggest that p53 does not have an important role in the development of HB but may contribute in HCC. There is also loss of pRb expression in the majority of HCC and HB, supporting loss of pRb gene function in the hepatocarcinogenesis pathway. However, a comparison of the staining profiles of p53 and pRb proteins in HCC and HB did not reveal a consistent pattern to differentiate between the two types of tumours immunohistochemically. Hence the use of p53 and pRB protein expression has no contribution in the situation where there is a diagnostic difficulty in deciding between HCC and HB.

Matched MeSH terms: Hepatitis B Surface Antigens/analysis
Antigenicity and immunogenicity of the immunodominant region of hepatitis B surface antigen displayed on bacteriophage T7

Tan GH, Yusoff K, Seow HF, Tan WS

J Med Virol, 2005 Dec;77(4):475-80.
PMID: 16254965

The immunodominant region of hepatitis B virus (HBV) located in the viral small surface antigen (S-HBsAg) elicits virus-neutralizing and protective antibodies. In order to develop an easy and inexpensive method to produce this region without the need for extensive purification, amino acid residues 111-156 of S-HBsAg were fused to the C-terminal end of the 10B capsid protein of T7 phage. Western blotting and ELISA confirmed the expression of the recombinant protein on the surface of the phage particles. The recombinant phage exhibited the antigenic and immunogenic characteristics of HBsAg, illustrating its potential as an immunological reagent and vaccine.

Matched MeSH terms: Hepatitis B Surface Antigens/analysis
Fulltext Hepatitis B surface antigen subtypes in hepatitis B seropositive subjects in University Hospital, Kuala Lumpur

Ng KP, Saw TL

Med J Malaysia, 1999 Sep;54(3):352-7.
PMID: 11045062

Hepatitis B surface antigen can be serologically defined as ayw1, ayw2, ayw3, ayw4, ayr, adw2, adw4 and adrq+ or adrq-. A study of common HBsAg subtypes in 44 HBsAg reactive sera in University Hospital was conducted using a solid-phase sandwich EIA. Eleven samples were found not typable and among the 33 typable HBsAg reactive sera, 3 HBsAg subtypes: adw, adr and ayw were identified. Subtype adw was found in 66.7% (22/33) of the typable HBsAg reactive sera; 24.2% (8/33) was of subtype adr and 6.0% (2/33) of subtype ayw. One sample was found to be reactive to both adw and adr. HBsAg subtype adw was found more commonly in Chinese but among the Malays, HBsAg subtype adr appeared to predominate. However, the small sample size precludes firm conclusions on the predominant subtype among the Malays.

Matched MeSH terms: Hepatitis B Surface Antigens/analysis*
Fulltext The prevalence of hepatitis B surface antigen and anti-HCV antibody in paediatric oncology patients in Hospital Universiti Sains Malaysia

Menon BS, Aiyar S

Med J Malaysia, 1997 Dec;52(4):331-4.
PMID: 10968109

This study examined the prevalence of hepatitis B and C markers in 55 paediatric oncology patients who had completed treatment at the Hospital Universiti Sains Malaysia in Kota Baru. All these children had received blood products and had been treated between 1985-1996. Forty seven per cent of patients were positive for hepatitis B or C. Twenty nine per cent were positive for hepatitis C and twenty two per cent were HBsAg positive. Two children were positive for both and none were HIV positive. Four children had an elevated ALT level and one child had jaundice and hepatomegaly. Some children were marker-positive despite immunization and screening of blood.

Matched MeSH terms: Hepatitis B Surface Antigens/analysis*
The cellular immune status of HBsAg-positive carriers in Malaysia

Choong ML, Ton SH, Cheong SK

Asian Pac J Allergy Immunol, 1996 Jun;14(1):19-24.
PMID: 8980796

The percentage of lymphocyte subsets from the peripheral blood of healthy adults and hepatitis B surface antigen (HBsAg) carriers were analyzed by flow cytometry. The five lymphocyte subsets studied were:- T (CD3) cells, B (CD19) cells, CD4 cells, CD8 cells, Natural Killer (CD3- CD16+/CD56+) cells (NK cells) and the CD4/CD8 ratio. The percentage (mean +/- SD) for the five lymphocyte subsets from the healthy adults were (67.5 +/- 8.5)%, (12.4 +/- 4.5)%, (35.5 +/- 7.8)%, (36.8 +/- 8.5)%, (17.9 +/- 8.1)% and 1.1 +/- 0.6, respectively. HBsAg carriers positive for HBV-DNA had a lower CD4/CD8 ratio than the healthy population (P = 0.030). The percentage of CD8 cells in HBsAg carriers increased significantly (r = 0.28; P = 0.019) with an increase in ALT levels but the values remained within normal range. The percentage of NK cells and CD4/CD8 ratio in HBsAg carriers positive for anti-HBe were higher than HBsAg carriers negative for anti-HBe (92% of which are HBeAg positive) (P = 0.045 and P = 0.035, respectively). The CD4/CD8 ratio in HBsAg carriers negative for anti-HBe (92% positive for HBeAg) was also lower than in the healthy population (P = 0.042). HBsAg carriers positive for HBV-DNA, HBeAg and raised ALT levels had a lower CD4/ CD8 ratio than did the healthy population. The lower ratio was due to an increase in the percentage of CD8 cells. This suggests an activated immune response triggered by the infection in an attempt to clear the virus. HBsAg carriers with normal ALT levels and who are negative for HBV-DNA may be in a state of tolerance.

Matched MeSH terms: Hepatitis B Surface Antigens/analysis*
Fulltext Hepatitis C--the Malaysian story

Sinniah M, Ooi BG

Singapore Med J, 1993 Apr;34(2):132-4.
PMID: 8266152

We studied the presence of Hepatitis C Virus (HCV) antibodies in a defined Malaysian population and examined the association, if any, between HCV and the Hepatitis B Virus (HBV), using sensitive recombinant DNA second generation Enzyme Immunoassay (EIA) test kits. This sero-prevalence study comprised 1,434 sera from eleven distinct groups comprising intravenous drug users (IVDU), haemophiliacs, male homosexuals, female prostitutes, healthy blood donors, staff of dialysis unit and laboratory personnel, chronic renal failure patients undergoing dialysis (CRFD), patients with liver cirrhosis, chronic active hepatitis, chronic persistent hepatitis and primary liver cancer. Except in laboratory personnel and dialysis staff, HCV antibodies were detected in each group of patients ranging from 3% in blood donors to 85% in IVDU. The main modes of HCV transmission identified were parenteral drug use, transfusion and/or dialysis related. The HBV was found to be the major viral etiological agent in 75% of chronic liver disease (CLD); while in 10% of cases both HCV and HBV were detected. HCV was implicated as the sole viral agent in only a small proportion (1.5%) of patients with chronic liver disease.

Matched MeSH terms: Hepatitis B Surface Antigens/analysis
Fulltext Sero-prevalence of hepatitis B infection among dental professionals

Vadivale M, Tan TC, Ong CN

Singapore Med J, 1992 Aug;33(4):367-9.
PMID: 1411666

Dental employees in government institutions in a State in Peninsular Malaysia were screened for exposure to hepatitis B virus (HBV) in 1989. Almost all (96.8%) of the 217 employees responded. One quarter (24.8%) was positive for at least one serological markers to HBV; 2.4% had hepatitis B surface antigen (HBsAg) and 22.4% had anti-body to HBsAg (anti-HBs). The presence of HBsAg was unrelated to age, sex, ethnicity, geographical locality and occupations of the subjects. The prevalence of anti-HBs increased with age and was highest for ethnic Chinese (53.6%), followed by Indians (25%), compared to Malays (14.9%) (p less than 0.001) and were increased among dentists (53.1%) and assistant nurses (33.3%). The overall prevalence of HBsAg and anti-HBs were similar to the situation in the community. However, dentists and their chairside assistant nurses, with a higher proportion of Chinese, had higher anti-HBs prevalences compared with that of the general population.

Matched MeSH terms: Hepatitis B Surface Antigens/analysis*
Incidence of hepatitis B infection in Brunei Darussalam--analysis of racial distribution

Alexander MJ, Sinnatamby AS, Rohaimah MJ, Harun AH, Ng JS

Ann Acad Med Singap, 1990 May;19(3):344-6.
PMID: 2393233

Brunei Darussalam has a mixed population with entirely different cultures and religions. The overall incidence of Hepatitis B virus (HBV) infection is 6%. A racial analysis of the incidence of HBV infection in Brunei shows a significantly higher incidence in Chinese compared to the other races. This is consistent with the incidence in the neighbouring countries.

Matched MeSH terms: Hepatitis B Surface Antigens/analysis
Preimmunisation hepatitis B screening in Singapore--a viewpoint from private sector clinics

Mah GK, Yeo A

Ann Acad Med Singap, 1990 May;19(3):339-43.
PMID: 2144101

Blood samples from 1,600 persons who sought immunisation against hepatitis B in private clinics in Singapore in 1988-1989 were screened for two viral markers. Of that total, 4.81% were positive for HBsAg and 17.31% had anti-HBs levels greater than 10 mIU/ml, indicating that about 22.12% of the general population would not benefit from immunisation. Preimmunisation screening will identify persons not requiring the hepatitis B vaccine and thus, avoid wastage. When immunisation has already been performed without screening, recall for post-immunisation screening should be considered in order to detect the infectious hepatitis B carriers. Data in this study indicates that at this point in time, it is important to immunise adolescents and adults, in addition to neonates and children.

Matched MeSH terms: Hepatitis B Surface Antigens/analysis
Childhood primary hepatocellular carcinoma and hepatitis B virus infection

Cheah PL, Looi LM, Lin HP, Yap SF

Cancer, 1990 Jan 1;65(1):174-6.
PMID: 2152851

In the 7-year period between 1980 and 1987, six cases of childhood primary hepatocellular carcinoma (PHC) were confirmed histologically in our institution. Hepatitis B surface antigen (HBsAg) seropositivity was confirmed in five of the cases, and tissue HBsAg was shown in four of these using the Shikata's orcein stain. An associated maternal HBsAg seropositivity was shown in two of the seropositive children. The youngest seropositive patient who developed PHC was 7 years old. The mother of this patient was also seropositive. These observations support a causal relation between childhood Hepatitis B virus infection and PHC. The importance of vertical or perinatal transmission of HBV in the causation of childhood PHC and the prophylactic role of childhood vaccination is emphasized. Attention is also drawn to the relative short malignant transformation time seen in some of these patients.

Matched MeSH terms: Hepatitis B Surface Antigens/analysis
Hepatitis in renal transplant recipients with and without donor-specific blood transfusion

Morad Z, Suleiman AB, Kong CT

Transplant Proc, 1989 Feb;21(1 Pt 2):1825-6.
PMID: 2652593
Matched MeSH terms: Hepatitis B Surface Antigens/analysis*
Fulltext Hepatitis B in jaundiced neonates admitted to a special care nursery

Nem-Yun B, Isahak I

Med J Malaysia, 1988 Jun;43(2):162-5.
PMID: 3237132
Matched MeSH terms: Hepatitis B Surface Antigens/analysis
Hepatitis B markers in non-icteric medical patients in Malaysia

Tan DS, Zaini Rahman M, Fang R, Collett D, Ooi BG

Southeast Asian J. Trop. Med. Public Health, 1986 Jun;17(2):214-8.
PMID: 3538435

Sera were obtained from 494 non-icteric patients admitted with illnesses other than overt hepatitis into the medical wards of the rural and urban hospitals in Malaysia. They were tested for HBsAg, HBeAg, and anti-HBs by enzyme immunoassay. The overall HBsAg carrier rate was 18.0% ranging from 9.6% in children, (10 years and under), to a maximum of 23.5% in the adolescents (11 to 20 years), the rates decreasing subsequently to 16.5% and 20.8% in the adult and middle-age groups, respectively. The Chinese (18.6%) and Malays (19.9%) had similar HBsAg carrier rates but the rate in the Indians (9.0%) was distinctly lower. Similar rates were observed in the males (16.5%) and the females (19.8%). The carrier rate was 17.1% in rural patients compared with 21.4% in the urban ones. The 'e' antigen was found in 14 of the 89 HBsAg carriers (15.7%). The overall prevalence was 14/494 (2.8%) rising sharply from childhood (2.9%) to adolescence (5.3%), subsequently declining with advancing age. The Chinese had the highest rate (6.2%) followed by the Indians (1.5%) and the Malays (1.1%). Males had a rate of 3.3% compared to the females with 2.3%. Anti-HBs was found in 33.8% of the patients, increasing steadily from childhood (18.3%) to middle-age (46.4%). The Chinese had a higher prevalence rate (41.6%) than the Indians (32.8%) and the Malays (29.3%). The rates were similar for the males (35.6%) and the females (31.5%). Rural patients (46.1%) had a higher rate than urban patients (35.7%). Both areas showed rising prevalence with increasing age.(ABSTRACT TRUNCATED AT 250 WORDS)

Matched MeSH terms: Hepatitis B Surface Antigens/analysis*
Delta hepatitis in Malaysia

Sinniah M, Dimitrakakis M, Tan DS

Southeast Asian J. Trop. Med. Public Health, 1986 Jun;17(2):229-33.
PMID: 3787309

Sera from one hundred and fifty nine Malaysian individuals were screened for the prevalence of delta markers. These included 15 HBsAg positive homosexuals, 16 acute hepatitis B cases, 9 chronic hepatitis B patients, 13 healthy HBsAg carriers and 106 intravenous (i.v.) drug abusers, of whom 27 were positive for HBsAg only and the rest were anti-HBc IgG positive but HBsAg negative. The prevalence of delta markers in the homosexuals was found to be 6.7%, in the HBsAg positive drug abusers 17.8%, in acute hepatitis B cases 12.5%. No evidence of delta infection was detected in healthy HBsAg carriers, chronic hepatitis B cases and HBsAg negative i.v. drug abusers. With reference to i.v. drug abusers, the prevalence of delta markers was higher in Malays (23%) than in Chinese (7%) although the latter had a higher HBsAg carrier rate. Although the HBsAg carrier rate in the homosexuals was high, their delta prevalence rate was low as compared to drug abusers. In Malaysia, as in other non-endemic regions, hepatitis delta virus transmission appeared to occur mainly via the parenteral and sexual routes. This is the first time in Malaysia that a reservoir of delta infection has been demonstrated in certain groups of the population at high risk for hepatitis B.

Matched MeSH terms: Hepatitis B Surface Antigens/analysis
Markers of hepatitis B virus infection in asymptomatic drug abusers in Malaysia

Mangalam S, Tan DS, Vijayamalar B, Collett D, Fang R

Southeast Asian J. Trop. Med. Public Health, 1986 Jun;17(2):209-13.
PMID: 3787308

Sera from 200 Malaysian male drug abusers were tested for markers of Hepatitis B virus (HBV) infection, viz. HBsAg, HBeAg, anti-HBs and anti-HBc using commercially available enzyme immunoassay (EIA) kits supplied by Abbot Laboratories, Chicago. Of these, 103 (51.5%) were positive for at least one HBV marker, 11 (5.5%) were positive for HBsAg; 4 (2%) for HBeAg, 74 (37%) for anti-HBs and 85 (42.5%) for anti-HBc. The HBsAg carrier rate was roughly the same as the carrier rate in the general population of Malaysia. The majority of drug abusers (95%) have had subclinical, asymptomatic HBV infection. Racially the Malay drug abusers had the highest exposure rate (54.2%). The HBsAg carrier rate was highest in the Chinese drug abusers (15.3%) and lowest in the Indians (0%). The mean age for the HBsAg carriers was found to be 26 years with a mean duration of drug abuse of 72 months. The Malaysian Anti-Narcotics Task Force of the National Security Council reported in the Malay Mail (July 13, 1985) that there were about 106,000 identified drug abusers in Malaysia and that 63% of these were in the 20-29 age groups. It appears from our study that this age group also coincides with the period of high HBsAg carrier rate. Age wise, those less than 21 years old had the highest HBsAg (11%) and HBeAg (5.6%) prevalence rates indicating high infectivity. After the age of 30 years, nearly 50% of the drug abusers appear to be immune with the HBe prevalence of 0%.(ABSTRACT TRUNCATED AT 250 WORDS)

Matched MeSH terms: Hepatitis B Surface Antigens/analysis*
Hepatitis B virus markers in prostitutes in Singapore

Goh CL, Kamarudin A, Chan SH, Rajan VS

Genitourin Med, 1985 Apr;61(2):127-9.
PMID: 3980022

The prevalence of hepatitis B virus markers in 121 men and 239 women prostitutes was studied. Of 33 (9.7%) with hepatitis B surface antigen (HBsAg), nine (27.3%) also had hepatitis Be antigen, which was more prevalent in men than women. Antibodies to HBsAg (anti-HBs) and to hepatitis B core antigen (anti-HBc) were found in about 71% of men and women prostitutes. Hepatitis B virus markers were more prevalent in men than in women prostitutes. Compared with other people, prostitutes had a significantly greater prevalence of hepatitis B virus markers. This study strongly suggested the importance of sexual transmission of infection with hepatitis B virus in a country where infection is endemic.

Matched MeSH terms: Hepatitis B Surface Antigens/analysis
Fulltext Hepatitis B markers in heterosexuals involved in promiscuous sexual activity

Rajakumar MK, Ton SH, Lim KF, Oorloff KH

Med J Malaysia, 1984 Mar;39(1):65-8.
PMID: 6513842

179 heterosexuals, selected for VDRL testing on the basis of a history of involvement in promiscuous sexual activity, mainly prostitution, had their serum also tested for hepatitis B infection markers, HBsAg, HBeAg and anti-HBe. 51 samples (29%) were found to be positive for at least one of the three markers, at levels higher than the already high levels in voluntary random blood donors in Malaysia.

Matched MeSH terms: Hepatitis B Surface Antigens/analysis*
HBeAG and anti-HBe in the Malaysian population and in Malaysian prisoners

Ton SH, Lopez CG, Noriah R

Southeast Asian J. Trop. Med. Public Health, 1983 Jun;14(2):252-4.
PMID: 6635764

The incidence of HBsAg in random blood donors was found to be twice that of the prisoner population. The anti-HBe however, was about twice that in the prisoners when compared with the random blood donors. Both the random blood donors and the prisoners had similar incidence of HBeAg. The percentage frequency of HBsAg positivity with anti-HBe positivity was also similar in both groups. The 18 normal non-blood donors did not have HBsAg, HBeAg or anti-HBe.

Matched MeSH terms: Hepatitis B Surface Antigens/analysis
Assessment of infectiousness of male Malaysian blood donors

So-Har T, Gladys LC, Ramli N

Vox Sang, 1983;45(5):389-91.
PMID: 6636661

HBeAg and anti-HBe were determined in the blood of 189 male blood donors. The incidence of HBsAg was 6.9% while that for HBeAg and anti-HBe was 1.6 and 18%, respectively. Of the 13 samples positive for HBsAg, two (15.4%) were positive for HBe while six (46.2%) were positive for anti-HBe. One specimen was negative for HBsAg but was positive for HBeAg and anti-HBe. The observations are discussed.

Matched MeSH terms: Hepatitis B Surface Antigens/analysis

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