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Treatment of chronic hepatitis B in HIV co-infected patients

Guan R

Med J Malaysia, 2005 Jul;60 Suppl B:52-6.
PMID: 16108174

In the Asia Pacific region Human Immunodeficiency virus (HIV) is often acquired in individuals already infected with hepatitis B virus (HBV). The immune suppression caused by HIV infection reduces cellular immune response against HBV and liver inflammation may improve, but the risk of developing cirrhosis is not. HBV infection does not affect the progression of HIV disease. Anti-retroviral agents may be directly hepatotoxic and cause ALT elevations in patients with chronic hepatitis. Highly active anti-retroviral therapy (HAART) improves immunity and as cytotoxic lymphocyte responses improve, hepatitis flares can occur, usually r within 3 months of initiation of HAART. These hepatitis flares may be followed by normalization of ALT and clearance of HBVDNA. If lamivudine is included in the HAART regime, hepatitis flares may not occur till late and these late flares signal the development of lamivudine resistant HBV strains (90% of HBV/HIV co-infection). Treatment options for chronic HBV infection include interferon (IFN), and nucleoside analogues. Lamivudine, adefovir dipivoxil, tenofovir disoproxil fumarate (DF) are nucleoside analogues with activity against both HBVDNA polymerase and HIV reverse transcriptase. The latter two compounds have added activity against lamivudine resistant HBVDNA. Lamivudine should be avoided in the initial treatment of both hepatitis B as well as HIV because of the high incidence of resistance. Interferon should be considered first for treatment of HBV in HIV co-infected individuals and is usually unsuccessful in the later stages of HIV infection when immune suppression is extreme. As new and improved agents in HAART continue to prolong survival, the use of liver transplantation for cirrhotic patients co-infected with HIV and HBV may increase.

Matched MeSH terms: Hepatitis B, Chronic/complications; Hepatitis B, Chronic/drug therapy*; Hepatitis B, Chronic/physiopathology
Treatment of chronic hepatitis B virus infection in special groups of patients: decompensated cirrhosis, immunosuppressed and paediatric patients

Merican I

J Gastroenterol Hepatol, 2000 May;15 Suppl:E71-8.
PMID: 10921386
Matched MeSH terms: Hepatitis B, Chronic/complications; Hepatitis B, Chronic/immunology; Hepatitis B, Chronic/therapy*
Cloning, expression and display of the PreS domain of hepatitis B virus on filamentous bacteriophage M13

Kok WL, Yusoff K, Nathan S, Tan WS

J. Biochem. Mol. Biol. Biophys., 2002 Feb;6(1):55-8.
PMID: 12186783

The PreS domain of hepatitis B virus (HBV) is believed to be involved in virion assembly and attachment to a hepatocyte receptor during infection. In order to study the functions of this region, we fused it to the g3p protein of bacteriophage M13 that allows the fusion protein to be displayed at the tip of the filament. The fusion protein was detected by the anti-E tag antibody on a Western blot. The polypeptide in a soluble form was produced by transfecting a non-suppressor E. coli host cell with the recombinant phagemid. The soluble protein was detected in cytoplasm, in the periplasmic space and also in the medium. The functional display of the PreS domain would provide an alternative means to study its interactions with the nuleocapsid and hepatocytes.

Matched MeSH terms: Hepatitis B Surface Antigens/genetics*; Hepatitis B Surface Antigens/metabolism; Hepatitis B Surface Antigens/chemistry*
Fulltext Viral hepatitis

Yasmin AM

Med J Malaysia, 1997 Jun;52(2):188-92; quiz 193.
PMID: 10968083
Matched MeSH terms: Hepatitis B/complications; Hepatitis B/drug therapy; Hepatitis B/prevention & control
The full-length clone of cucumber green mottle mosaic virus and its application as an expression system for Hepatitis B surface antigen

Ooi A, Tan S, Mohamed R, Rahman NA, Othman RY

J Biotechnol, 2006 Feb 24;121(4):471-81.
PMID: 16271415

A cucumber green mosaic mottle virus (CGMMV) full-length clone was developed for the expression of Hepatitis B surface antigen (HBsAg). The expression of the surface displayed HBsAg by the chimeric virus was confirmed through a double antibody sandwich ELISA. Assessment of the coat protein composition of the chimeric virus particles by SDS-PAGE analysis showed that 50% of the coat proteins were fused to the HBsAg. Biological activity of the expressed HBsAg was assessed through the stimulation of in vitro antibody production by cultured peripheral blood mononuclear cells (PBMC). PBMC that were cultured in the presence of the chimeric virus showed up to an approximately three-fold increase in the level of anti HBsAg immunoglobulin thus suggesting the possible use of this new chimeric virus as an effective Hepatitis B vaccine.

Matched MeSH terms: Hepatitis B Surface Antigens/biosynthesis*; Hepatitis B Surface Antigens/genetics; Hepatitis B Surface Antigens/immunology
Fulltext Hepatitis in Malaysia: Past, Present, and Future

Raihan R

Euroasian J Hepatogastroenterol, 2016 Jan-Jun;6(1):52-55.
PMID: 29201726 DOI: 10.5005/jp-journals-10018-1167

Malaysia is multiethnic, with a population of 31,127,247 comprising a mixture of Malays (50.1%), Chinese (22.6%), Indians (6.7%), Aborigines (11.8%), others (0.7%), and noncitizens (8.2%). Like other countries in the region, viral hepatitis is an important public health problem in Malaysia. The 3 most common causes for hepatitis in Malaysia are hepatitis A, B, and C. Hepatitis A has been a reportable disease in Malaysia since 1988. Due to the introduction of government control programs, the national incidence rate has dropped steadily. It is now estimated that 50% of Malaysians less than 30 years of age do not have antibodies to hepatitis A and are therefore susceptible to the disease, which can be prevented by reinforcing the hygiene status of the general population. Malaysia is a country of medium seroprevalence for the hepatitis B virus (HBV) surface antigen (HBsAg) in the general population (1.5-9.8%). The major route of transmission is from infected mother to fetus. There are an estimated 1 million people chronically infected with hepatitis B in Malaysia. Approximately 75% of all viral hepatitis cases are due to hepatitis B infection, with a male-to-female ratio of 2:1. Chronic hepatitis B (CHB) accounts for more than 80% of the hepatocellular carcinoma (HCC) cases seen in Malaysia and HCC is the 3rd most common malignant neoplasm and among the 10 leading causes of death. Most common genotypes are B and C. Incidence rates among Chinese, Malays, and Indians are 36, 26, and 15% respectively. The hepatitis B vaccination program for children was introduced in 1989, which successfully managed to reduce the seroprevalence of infection among Malaysians to 0.01% (graph 4, 2014). But the disease burden will still remain high for some time as the infected people are getting older and living longer. Hepatitis C virus (HCV) infection is a growing problem in Malaysia. An estimated 453,700 people were living with HCV infection in Malaysia in 2009 (2.5% of the population aged 15-64 years), of whom 59% acquired their infection through injection and the most common genotypes found are genotype 3 and 1. The HCV-related disease burden is already high and is forecast to rise steeply over the coming decades under current levels of antiviral treatment. Increased governmental resources to improve HCV screening and treatment rates and to reduce transmission are essential to address the high projected HCV disease burden in Malaysia.

How to cite this article: Raihan R. Hepatitis in Malaysia: Past, Present, and Future. Euroasian J Hepato-Gastroenterol 2016;6(1):52-55.

Matched MeSH terms: Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic
Fulltext Enhanced cell disruption strategy in the release of recombinant hepatitis B surface antigen from Pichia pastoris using response surface methodology

Tam YJ, Allaudin ZN, Lila MA, Bahaman AR, Tan JS, Rezaei MA

BMC Biotechnol, 2012 Oct 05;12:70.
PMID: 23039947 DOI: 10.1186/1472-6750-12-70

BACKGROUND: Cell disruption strategies by high pressure homogenizer for the release of recombinant Hepatitis B surface antigen (HBsAg) from Pichia pastoris expression cells were optimized using response surface methodology (RSM) based on the central composite design (CCD). The factors studied include number of passes, biomass concentration and pulse pressure. Polynomial models were used to correlate the above mentioned factors to project the cell disruption capability and specific protein release of HBsAg from P. pastoris cells.
RESULTS: The proposed cell disruption strategy consisted of a number of passes set at 20 times, biomass concentration of 7.70 g/L of dry cell weight (DCW) and pulse pressure at 1,029 bar. The optimized cell disruption strategy was shown to increase cell disruption efficiency by 2-fold and 4-fold for specific protein release of HBsAg when compared to glass bead method yielding 75.68% cell disruption rate (CDR) and HBsAg concentration of 29.20 mg/L respectively.
CONCLUSIONS: The model equation generated from RSM on cell disruption of P. pastoris was found adequate to determine the significant factors and its interactions among the process variables and the optimum conditions in releasing HBsAg when validated against a glass bead cell disruption method. The findings from the study can open up a promising strategy for better recovery of HBsAg recombinant protein during downstream processing.

Matched MeSH terms: Hepatitis B Surface Antigens/genetics*; Hepatitis B Surface Antigens/isolation & purification; Hepatitis B Surface Antigens/metabolism
Organization of a blood transfusion service in tropical areas

Lopez CG

Southeast Asian J Trop Med Public Health, 1979 Jun;10(2):177-83.
PMID: 524138
Matched MeSH terms: Hepatitis B Core Antigens/analysis; Hepatitis B Surface Antigens/analysis
N-terminally His-tagged hepatitis B core antigens: construction, expression, purification and antigenicity

Yap WB, Tey BT, Ng MY, Ong ST, Tan WS

J Virol Methods, 2009 Sep;160(1-2):125-31.
PMID: 19433111 DOI: 10.1016/j.jviromet.2009.04.038

The core antigen of the hepatitis B virus (HBcAg) has been used widely as a diagnostic reagent for the identification of the viral infection. However, purification using the conventional sucrose density gradient ultracentrifugation is time consuming and costly. To overcome this, HBcAg particles displaying His-tag on their surface were constructed and produced in Escherichia coli. The recombinant His-tagged HBcAgs were purified using immobilized metal affinity chromatography. Transmission electron microscopy and enzyme-linked immunosorbent assay (ELISA) revealed that the displayed His-tag did not impair the formation of the core particles and the antigenicity of HBcAg.

Matched MeSH terms: Hepatitis B Core Antigens/genetics; Hepatitis B Core Antigens/immunology*; Hepatitis B Core Antigens/isolation & purification*
Novel hepatitis B virus strain developing due to recombination between genotypes H and B strains isolated from a Japanese patient

Uchida Y, Kouyama JI, Naiki K, Sugawara K, Inao M, Nakayama N, et al.

Hepatology research : the official journal of the Japan Society of Hepatology, 2014 Oct;44(11):1130-1141.
PMID: 24020990 DOI: 10.1111/hepr.12238

AIM: In Japan, genotypes B and C are the predominant genotypes isolated from patients with chronic hepatitis B, while genotype A predominates in patients with acute hepatitis B. Globalization, however, appears to have changed the distribution of the hepatitis B virus (HBV) genotypes. Thus, the viral characteristics of HBV genotypes other than genotypes A, B and C were examined.
METHODS: Screening of genotypes was performed by enzyme immunoassay and/or polymerase chain reaction INVADER method in 222 patients with HBV. The full-length nucleotide sequences of unusual strains were compared to those in the database, followed by construction of a phylogenetic tree.
RESULTS: Unusual HBV strains were isolated from two patients: a 27-year-old Japanese bisexual man with acute hepatitis B with HIV co-infection and a 52-year-old Japanese man with chronic hepatitis B. The former strain was classified as genotype H, showing an overall identity of 99.8% to the Thailand strain (EU498228), while the nucleotide sequence of the latter strain showed similarity to the genotype B strains isolated in Malaysia (JQ027316) and Indonesia (JQ429079) between DR2 and DR1 in the X region, with identities of 96.9%. However, this strain was classified as genotype H by full-length sequence analysis, and the sequence between nt2023 and nt2262 showed no similarity to that in any previously reported strains.
CONCLUSION: HBV strains showing recombination between genotype B and H strains were found even in chronic hepatitis patients in Japan. Globalization may yield HBV strains of possible novel genotypes containing novel nucleotide sequences in the precore/core region.

Matched MeSH terms: Hepatitis B; Hepatitis B virus; Hepatitis B, Chronic
Fulltext Knowledge, attitudes and practices among people with chronic hepatitis B attending a hepatology clinic in Malaysia: a cross sectional study

Mohamed R, Ng CJ, Tong WT, Abidin SZ, Wong LP, Low WY

BMC Public Health, 2012;12:601.
PMID: 22856889 DOI: 10.1186/1471-2458-12-601

BACKGROUND: Hepatitis B (HBV) is the leading cause of cirrhosis and hepatocellular carcinoma worldwide. This study assessed the knowledge, attitudes and practices of people with chronic HBV and the associated factors.
METHODS: This cross-sectional study was conducted at an outpatient adult hepatology clinic at a tertiary hospital in Kuala Lumpur. A self-administered questionnaire was administered on a one-to-one basis to assess knowledge, attitudes, and lifestyle practices of people with chronic HBV.
RESULTS: The response rate was 89% (n = 483/543). Participants had a mean age of 46.3 (±14.7) years and the mean duration of HBV from time of diagnosis was 12.2 (±8.8) years. The mean knowledge score was 12.57/20 (standard deviation: ±4.4, range: 0-19). Participants aged 30-39 years, with higher educational attainment, employed in professional jobs, longer duration of diagnosis and those without cirrhosis had significantly higher knowledge scores. Age, education level and duration of diagnosis were significant predictors of the knowledge score on standard multiple regression analysis. More than half of the participants were worried of spreading HBV infection to family and friends and worried since the diagnosis. A third of the participants (33.5%) were embarrassed to reveal their diagnosis to the public but most of them (93.6%) would inform their family. Those who reported feeling worried since their diagnosis were more likely to be middle-aged, of Malay ethnicity, have shorter duration of diagnosis of less than 10 years and have received therapy. About half of the participants (50.6%) did not share dining utensils and the majority (93.2%) believed that HBV can be transmitted by sharing of eating and drinking utensils. Older patients were significantly less likely to share utensils. Those who felt worried since diagnosis had significant higher knowledge of HBV.
CONCLUSION: The findings highlight the stigma and misconceptions that still exist among the HBV patients. More patient and public education about HBV and its prevention are essential to increase awareness and to demystify the disease.
Study site: Hepatology clinic, University of Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia

Matched MeSH terms: Hepatitis B, Chronic/psychology*; Hepatitis B, Chronic/therapy*
Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update

Liaw YF, Kao JH, Piratvisuth T, Chan HL, Chien RN, Liu CJ, et al.

Hepatol Int, 2012 Jun;6(3):531-61.
PMID: 26201469 DOI: 10.1007/s12072-012-9365-4

Large volume of new data on the natural history and treatment of chronic hepatitis B virus (HBV) infection have become available since 2008. These include further studies in asymptomatic subjects with chronic HBV infection and community-based cohorts, the role of HBV genotype/naturally occurring HBV mutations, the application of non-invasive assessment of hepatic fibrosis and quantitation of HBV surface antigen and new drug or new strategies towards more effective therapy. To update HBV management guidelines, relevant new data were reviewed and assessed by experts from the region, and the significance of the reported findings was discussed and debated. The earlier "Asian-Pacific consensus statement on the management of chronic hepatitis B" was revised accordingly. The key terms used in the statement were also defined. The new guidelines include general management, indications for fibrosis assessment, time to start or stop drug therapy, choice of drug to initiate therapy, when and how to monitor the patients during and after stopping drug therapy. Recommendations on the therapy of patients in special circumstances, including women in childbearing age, patients with antiviral drug resistance, concurrent viral infection, hepatic decompensation, patients receiving immune suppression or chemotherapy and patients in the setting of liver transplantation and hepatocellular carcinoma, are also included.

Matched MeSH terms: Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic
Fulltext Delivery of chimeric hepatitis B core particles into liver cells

Lee KW, Tey BT, Ho KL, Tan WS

J Appl Microbiol, 2012 Jan;112(1):119-31.
PMID: 21992228 DOI: 10.1111/j.1365-2672.2011.05176.x

To display a liver-specific ligand on the hepatitis B virus core particles for cell-targeting delivery.

Matched MeSH terms: Hepatitis B Core Antigens/genetics*; Hepatitis B Core Antigens/metabolism*
Fulltext Risk of blood-borne infection among health care workers in two Kuala Lumpur hospitals

Hesham R, Tajunisah ME, Ilina I

Med J Malaysia, 2008 Aug;63(3):222-3.
PMID: 19248694

Health care workers (HCW) are at high risk of acquiring blood-borne diseases. This study compared the risk of infection among HCW in different hospital units and also between HCW and students in medical fields. This cross-sectional study involved pre-tested questionnaires that were completed by 625 HCW and undergraduate students undergoing clinical attachments from February to August 2001. The respondents were separated into two groups: i) HCW from Hospital Kuala Lumpur, HKL (n=241) and Hospital Universiti Kebangsaan Malaysia, HUKM (n=153) ii) Medical students from Universiti Kebangsaan Malaysia, UKM (n=171) and HUKM student nurses (n=60). The results obtained showed that the risk of transmission of blood-borne infections varied significantly according to professional ranks (p<0.05) and to hospital units (p<0.05). The medical intensive care (ICU), haemodialysis, and nephrology and urology units had the highest scores for the risk of infection while the diagnostic laboratory had the lowest risk of infection (p<0.05). Preventive measures taken by the subjects in this study were not satisfactory especially with reference to the use of personal protective equipment and the practice of universal precautions.

Matched MeSH terms: Hepatitis B/prevention & control; Hepatitis B/transmission*
Interactions of hepatitis B core antigen and peptide inhibitors

Tang KF, Abdullah MP, Yusoff K, Tan WS

J Med Chem, 2007 Nov 15;50(23):5620-6.
PMID: 17918821

The core protein (HBcAg) of hepatitis B virus (HBV) has been shown to interact with the large surface antigen during HBV morphogenesis, and these interactions can be blocked by small peptides selected from either linear or constrained phage display peptide libraries. The association of HBcAg with peptide inhibitors was quantitatively evaluated by isothermal titration calorimetry. The thermodynamic data show that the interaction between HBcAg and peptide MHRSLLGRMKGA is enthalpy-driven and occurs at a 3:1 stoichiometry and dissociation constant (Kd) value of 79.4 muM. However, peptide WSFFSNI displays a higher binding affinity for HBcAg with a Kd value of 18.5 muM when compared to peptide MHRSLLGRMKGA. A combinatorial approach using chemical cross-linking and surface-enhanced laser desorption/ionization-time-of-flight-mass spectrometry shows that the Lys of peptide MHRSLLGRMKGA interacted either with D64, E77, or D78 of HBcAg.

Matched MeSH terms: Hepatitis B Core Antigens/isolation & purification; Hepatitis B Core Antigens/chemistry*
Treatment of chronic hepatitis B infection using interferon

Guan R

Med J Malaysia, 2005 Jul;60 Suppl B:28-33.
PMID: 16108170

Four to 6 months of conventional interferon alpha (IFN-alpha) (5MU daily or 10MU three times weekly) resulted in HBeAg loss in approximately 33% of HBeAg positive patients (controls: 12%). Longer treatment duration improved HBeAg seroconversion. Children with chronic HBV infection and high ALT respond to IFN-a at similar rates. Good end-of-treatment (ET) biochemical and virological response were also achieved with IFN-alpha in HBeAg negative, HBV-DNA positive hepatitis patients. Sustained response (SR) however, was disappointing, but improved with longer duration of treatment: (10-15% SR with 4/6 months treatment: 30% SR with 24 months treatment). Weekly pegylated IFN-alpha2a (PegIFN-alpha2a) for 24 weeks gave a significantly higher HBeAg conversion rate (33%) than conventional IFN-alpha2a (25%). Fifty-two weeks of PegIFN-alpha2b gave a sustained HBeAg loss in 35% patients and HBeAg seroconversion in 29% patients. Similar results were obtained with 48 weeks of weekly PegIFN-alpha2a. PegIFN-alpha2a monotherapy was found to be superior to lamivudine monotherapy in affecting a 6-month SR (normal ALTs and HBV DNA < 20,000 copies/mL) in HBeAg negative/anti-HBe positive chronic hepatitis B patients. There is a tendency for IFN-a and lamivudine combination to result in better sustained response than lamivudine monotherapy. This tendency is also observed with PegIFN-a and lamivudine combination although the combination did not appear to be better than PegIFN-alpha monotherapy. IFN induced HBeAg seroconversion is durable, could increase over time and resulted in better overall survival and survival free of hepatic decompensation or hepatocellular cancer. The main advantage of IFN-a therapy is that a course of finite duration may achieve sustained off-therapy response in a proportion of both HBeAg positive and HBeAg negative chronic hepatitis B patients. However, IFN treatment is usually associated with side-effects, especially flu-like symptoms, fatigue, neutropenia, thrombocytopenia and depression. These are usually tolerable but may require dose modification and premature cessation of treatment (5%). Interferon therapy induced hepatitis flares may lead to decompensation in patients with cirrhosis and can be dangerous in patients with decompensated liver function despite dose reduction.

Matched MeSH terms: Hepatitis B/drug therapy*; Hepatitis B/immunology
Treatment of immunosuppressed chronic hepatitis B patients

Lau GK

Med J Malaysia, 2005 Jul;60 Suppl B:57-62.
PMID: 16108175
Matched MeSH terms: Hepatitis B, Chronic/drug therapy*; Hepatitis B, Chronic/immunology
Awareness and acceptance of the hepatitis B vaccine by dental practitioners in Malaysia

Yaacob HB, Samaranayake LP

J Oral Pathol Med, 1989 Apr;18(4):236-9.
PMID: 2769596

A postal survey of 730 Malaysian dental practitioners was undertaken to assess their awareness and acceptance of the plasma derived hepatitis B vaccine. Only 32% of the 325 practitioners who responded had been vaccinated, 41% intended to be and 15% categorically refused vaccination. The main reservations about vaccine acceptance were fear of side effects including AIDS, cost of the vaccine and lack of information. Vaccine efficacy was not confirmed by serology in two-thirds of the vaccinees and two-fifths of the respondents were unaware that 5% of the vaccinees do not develop a successful antibody response after vaccination. Seventy-eight percent of dentists believed that their risk of contracting hepatitis B was high or very high while 71% recalled having received needle stick injuries in the 3 yr prior to the survey. Only 13% of respondents were aware of delta hepatitis while 63% were aware of non-A non-B hepatitis. The survey has highlighted the need for dissemination of information on hepatitis B vaccine among dentists in Malayasia.

Matched MeSH terms: Hepatitis B/prevention & control*; Hepatitis B/transmission
Fulltext The use of several markers of hepatitis B infection to monitor risks of infection in a haemodialysis unit and in laboratories

Ton SH, Lopez CG

Med J Malaysia, 1981 Dec;36(4):209-11.
PMID: 7334954
Matched MeSH terms: Hepatitis B/diagnosis; Hepatitis B/epidemiology*
Awareness and attitudes toward hepatitis B among Malaysian dentists

Razak IA, Latifah RJ, Nasruddin J, Esa R

Clin Prev Dent, 1991 Jul-Aug;13(4):22-4.
PMID: 1884572

A questionnaire was mailed to 1217 dentists whose names appear in the Dentist Register of 1987 in order to assess their awareness and acceptance of hepatitis B vaccine and their pattern of glove usage. Almost all the respondents (99.6%) were aware of the availability of the hepatitis B vaccine yet only 44.8% have received the vaccine. This is in spite of the fact that the majority (61.2%) of the vaccine non-acceptors have no reservations concerning the vaccine. About 71% and 63% of the vaccine-acceptors and non-acceptors respectively believed that the risk of their contracting hepatitis B was high or very high. About 22% of the vaccine non-acceptors never used gloves when treating patients as compared to 9% among vaccine acceptors. Overall, about 78% of the respondents have experienced needleprick injuries in the 3 years preceding the survey.

Matched MeSH terms: Hepatitis B/prevention & control*; Hepatitis B/transmission

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