Browse publications by year: 2005

  1. The impact of immigration on health systems: a legal analysis from a three-country perspective
    Blum J, Carstens P, Talib N
    Med Law, 2005 Jun;24(2):323-36.
    PMID: 16082868
    The focus of this paper will be on how health care systems in three countries, Malaysia, South Africa and the United States, are responding to the health needs of immigrants with a strong focus on the legal aspects of the respective national responses. The Malaysia portion emphasizes legal immigration and analyses as to how the country's Ministry of Health and the delivery system itself is responding to the demands of immigrant's health. In the context of South Africa, the paper explores implications of the South African Constitution, which establishes a right to access health care, and explores whether such a right can be extended to non-citizens, or can be tempered by economic constraints. In the American discussion the focus is on whether publicly supported health care programs can be accessed to provide coverage for undocumented residents, and highlights recent constraints in using government monies in this area.
    MeSH terms: Delivery of Health Care/legislation & jurisprudence; Delivery of Health Care/organization & administration*; Emigration and Immigration*; Health Services Needs and Demand*; Humans; Malaysia; South Africa; United States
  2. Secondary B-cell acute lymphoblastic leukemia following Wilms' tumor: clinical and in vitro chemosensitivity studies
    Ariffin H, Muthukkumaran T, Stanslas J, Sabariah AR, Veerasekaran N, Lin HP
    Leuk Lymphoma, 2005 Aug;46(8):1233-7.
    PMID: 16085568
    We report the clinical features and in vitro chemosensitivity assay findings of a 13-year-old girl who developed secondary B-cell acute lymphoblastic leukemia (ALL) 7 years after a diagnosis of Wilms' tumor. The patient was treated using the Berlin - Frankfurt - Muenster (BFM) ALL chemotherapy protocol with poor response to initial therapy before succumbing to sepsis. An in vitro chemosensitivity assay on her peripheral blood lymphoblasts was performed while she was undergoing induction therapy and showed a high level of resistance to drugs commonly used for ALL therapy, e.g. steroids, anthracyclines, vincristine and L-asparaginase. The mechanism of chemoresistance was not elicited, but was probably not related to P-glycoprotein (P-gp) over-expression. We believe that the in vitro chemosensitivity assay is a good indicator of cellular response to chemotherapy and may provide reliable information for the basis of the selection of drugs to be used for the treatment of similarly rare patients rather than relying on "standard" protocols.
    MeSH terms: Adolescent; Antineoplastic Agents/therapeutic use; Antineoplastic Combined Chemotherapy Protocols/therapeutic use; Burkitt Lymphoma/complications*; Burkitt Lymphoma/diagnosis; Burkitt Lymphoma/drug therapy; Cell Survival/drug effects; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Female; Humans; Kidney Neoplasms/complications*; Kidney Neoplasms/diagnosis; Kidney Neoplasms/drug therapy; Wilms Tumor/complications*; Wilms Tumor/diagnosis; Wilms Tumor/therapy; Neoplasms, Second Primary/complications*; Neoplasms, Second Primary/diagnosis; Neoplasms, Second Primary/drug therapy; Fatal Outcome; Disease Progression; Sepsis/drug therapy; Drug Resistance, Neoplasm; In Vitro Techniques
  3. A phage-displayed cyclic peptide that interacts tightly with the immunodominant region of hepatitis B surface antigen
    Tan WS, Tan GH, Yusoff K, Seow HF
    J Clin Virol, 2005 Sep;34(1):35-41.
    PMID: 16087122
    The surface antigen (HBsAg) of hepatitis B virus (HBV) is highly conformational and generally evokes protective humoral immune response in human. A disulfide constrained random heptapeptide library displayed on the coat protein III of filamentous bacteriophage M13 was employed to select specific ligands that interact with HBsAg subtype ad. Fusion phages carrying the amino acid sequence ETGAKPH and other related sequences were isolated. The binding site of peptide ETGAKPH was located on the immunodominant region of HBsAg. An equilibrium binding assay in solution showed that the phage binds tightly to HBsAg with a relative dissociation constant (KDrel) of 2.9+/-0.9 nM. The phage bearing this peptide has the potential to be used as a diagnostic reagent and two assays for detecting HBsAg in blood samples are described.
    MeSH terms: Amino Acid Sequence; Bacteriophages/genetics; Binding Sites; Enzyme-Linked Immunosorbent Assay; Hepatitis B Surface Antigens/blood; Hepatitis B Surface Antigens/isolation & purification; Hepatitis B Surface Antigens/metabolism*; Hepatitis B Surface Antigens/chemistry; Humans; Peptides, Cyclic/metabolism*; Peptides, Cyclic/chemistry; Peptide Library
  4. Fulltext Estimates of the burden of rotavirus disease in Malaysia
    Hsu VP, Abdul Rahman HB, Wong SL, Ibrahim LH, Yusoff AF, Chan LG, et al.
    J Infect Dis, 2005 Sep 1;192 Suppl 1:S80-6.
    PMID: 16088810
    BACKGROUND: Accurate national estimates of the disease burden associated with rotavirus diarrhea are essential when considering implementation of a rotavirus vaccination program. We sought to estimate rotavirus disease-associated morbidity and mortality in Malaysia, using available sources of information.
    METHODS: We analyzed national data from the Ministry of Health (Kuala Lumpur, Malaysia) to derive rates of hospitalization, clinic visits, and deaths related to acute gastroenteritis (AG) among children <5 years of age. The number of events attributable to rotavirus infection was estimated by multiplying age-stratified rates of detection of rotavirus from 2 hospital surveillance sites by national data.
    RESULTS: In 1999 and 2000, an average of 13,936 children (1 in 187 children) were hospitalized annually for AG. Surveillance of visits to outpatient clinics for AG identified an average of 60,342 such visits/year between 1998 and 2000. The AG-associated mortality rate was 2.5 deaths/100,000 children. On the basis of the finding that 50% of children were hospitalized for rotavirus diarrhea, we estimated that 1 in 61 children will be hospitalized for rotavirus disease and that 1 in 37 children will seek treatment as an outpatient.
    CONCLUSIONS: Among Malaysian children, there is a significant burden associated with AG- and rotavirus disease-related hospitalizations and outpatient visits, and this burden potentially could be prevented by the use of rotavirus vaccines.
    Data source: (1) hospital discharges, (2) clinic visits for AG, and (3) registration of deaths, together with (4) new data from hospital-based rotavirus surveillance studies
    MeSH terms: Ambulatory Care Facilities; Child, Preschool; Diarrhea/mortality; Diarrhea/epidemiology; Diarrhea/virology; Female; Hospitals; Humans; Infant; Infant, Newborn; Malaysia/epidemiology; Male; Outpatient Clinics, Hospital; Outpatients; Retrospective Studies; Rotavirus Infections/mortality; Rotavirus Infections/epidemiology*; Sentinel Surveillance
  5. Community-acquired vancomycin-resistant Enterococcus faecium: a case report from Malaysia
    Raja NS, Karunakaran R, Ngeow YF, Awang R
    J Med Microbiol, 2005 Sep;54(Pt 9):901-903.
    PMID: 16091445 DOI: 10.1099/jmm.0.46169-0
    Vancomycin-resistant enterococci (VRE) are formidable organisms renowned for their ability to cause infections with limited treatment options and their potential for transferring resistance genes to other Gram-positive bacteria. Usually associated with nosocomial infections, VRE are rarely reported as a cause of community-acquired infection. Presented here is a case of community-acquired infection due to vancomycin-resistant Enterococcus faecium. The patient had been applying herbal leaves topically to his cheek to treat a buccal space abscess, resulting in a burn of the overlying skin. From pus aspirated via the skin a pure culture of E. faecium was grown that was resistant to vancomycin with a MIC of >256 microg ml-1 by the E test and resistant to teicoplanin by disc diffusion, consistent with the VanA phenotype. The organism was suspected of contaminating the leaf and infecting the patient via the burnt skin. This case highlights the need for further studies on the community prevalence of VRE among humans and animals to define unrecognized silent reservoirs for VRE, which may pose a threat to public health.
    MeSH terms: Abscess/microbiology; Adult; Anti-Bacterial Agents/pharmacology; Humans; Malaysia; Male; Microbial Sensitivity Tests; Mouth Mucosa/microbiology; Gram-Positive Bacterial Infections/microbiology*; Enterococcus faecium/drug effects*; Enterococcus faecium/isolation & purification*; Community-Acquired Infections/microbiology*; Vancomycin Resistance*
  6. Effect of various antagonists on the Channa striatus fillet extract antinociception in mice
    Zakaria ZA, Sulaiman MR, Mat Jais AM, Somchit MN
    Can J Physiol Pharmacol, 2005 Jul;83(7):635-42.
    PMID: 16091789
    The effects of an aqueous supernatant of haruan (ASH) (Channa striatus) fillet extract on various antinociception receptor system activities were examined using a mouse abdominal-constriction model. Mice that were pretreated with distilled water, s.c., followed 10 min later by administration of 25%, 50%, and 100% concentration ASH, s.c., produced a significant concentration-dependent antinociceptive activity (p < 0.001). Pretreatment with naloxone (0.3, 1.0, and 3.0 mg/kg body mass), 10 min before ASH administration, failed to block the extract antinociception. Pretreatment of the 100% concentration ASH with mecamylamine (5 mg/kg), pindolol (10 mg/kg), and haloperidol (1 mg/kg) also did not cause any significant change in its antinociception. However, pretreatment with atropine (5 mg/kg), bicuculline (10 mg/kg), phenoxybenzamine (10 mg/kg), and methysergide (5 mg/kg) were found to reverse ASH antinociception. Based on the above findings, the ASH is suggested to contain different types of bioactive compounds that act synergistically on muscarinic, GABAA, alpha-adrenergic, and serotonergic receptor systems to produce the observed antinociception.
    MeSH terms: Analgesics*; Animals; Anti-Inflammatory Agents, Non-Steroidal/pharmacology; Aspirin/pharmacology; Dose-Response Relationship, Drug; Male; Mice, Inbred BALB C; Muscle Contraction/drug effects; Naloxone/pharmacology; Narcotic Antagonists/pharmacology; Pain Measurement/drug effects; Perciformes/physiology*; Reaction Time/drug effects; Receptors, Cell Surface/antagonists & inhibitors; Tissue Extracts/antagonists & inhibitors*; Tissue Extracts/physiology*; Muscle, Skeletal/physiology*; Mice
  7. Tale of two tigers
    Nature, 2005 Aug 11;436(7052):754.
    PMID: 16094324
    MeSH terms: Ethnic Groups; Humans; Investments/trends; Malaysia; Personnel Selection; Research/economics*; Research/manpower; Research/standards; Research/trends*; Singapore
  8. SDS-PAGE electrophoretic property of human chorionic gonadotropin (hCG) and its beta-subunit
    Gam LH, Latiff A
    Int J Biol Sci, 2005;1(3):103-9.
    PMID: 16094462
    The microheterogeneity property of hCG with regards to its sialic acid contents resulted in variable mobility of the glycoprotein in SDS-PAGE. The intact hCG molecule is composed of two dissimilar subunits, namely alpha- and beta-subunits. The identification of hCG bands in SDS-PAGE was accomplished by the immunoblotting experiment, whereby the antibody directed toward the specific region of beta-subunit of hCG was used. The data shows that the different mobility of intact hCG was attributed to the different degree of desialylation of the glycoprotein. Nevertheless, unlike the intact hCG, the mobility of its beta-subunit was not affected by its variety sialic acid content. This characteristic of beta-hCG is beneficial when semi-quantification of total hCG is required. Quantification of hCG using the HPLC-reversed phase C18 analytical column is not possible as the glycoprotein was eluted in multiple fractions at different retention times. The identification of denatured hCG (HPLC eluted fractions) was carried out by immunoblotting experiment whilst immunoassay technique failed to detect its presence in any fraction.
    MeSH terms: Chromatography, High Pressure Liquid; Electrophoresis, Polyacrylamide Gel/methods*; Chorionic Gonadotropin/isolation & purification*; Humans; Blotting, Western
  9. Simultaneous quantification of free fatty acids, free sterols, squalene, and acylglycerol molecular species in palm oil by high-temperature gas chromatography--flame ionization detection
    Lau HL, Puah CW, Choo YM, Ma AN, Chuah CH
    Lipids, 2005 May;40(5):523-8.
    PMID: 16094863
    This paper discusses a rapid GC-FID technique for the simultaneous quantitative analysis of FFA, MAG, DAG, TAG, sterols, and squalene in vegetable oils, with special reference to palm oil. The FFA content determined had a lower SE compared with a conventional titrimetric method. Squalene and individual sterols, consisting of beta-sitosterol, stigmasterol, campesterol, and cholesterol, were accurately quantified without any losses. This was achieved through elimination of tedious conventional sample pretreatments, such as saponification and preparative TLC. With this technique, the separation of individual MAG, consisting of 16:0, 18:0, and 18:1 FA, and the DAG species, consisting of the 1,2(2,3)- and 1,3-positions, was sufficient to enable their quantification. This technique enabled the TAG to be determined according to their carbon numbers in the range of C44 to C56. Comparisons were made with conventional methods, and the results were in good agreement with those reported in the literature.
    MeSH terms: Chromatography, Gas/methods*; Diglycerides/analysis; Fatty Acids, Nonesterified/analysis*; Flame Ionization/methods; Glycerides/analysis*; Hot Temperature; Phytosterols/analysis*; Plant Oils/chemistry*; Squalene/analysis*; Reproducibility of Results
  10. A population-based study of birth defects in Malaysia
    Thong MK, Ho JJ, Khatijah NN
    Ann Hum Biol, 2005 Mar-Apr;32(2):180-7.
    PMID: 16096215 DOI: 10.1080/03014460500075332
    Birth defects are one of the leading causes of paediatric disability and mortality in developed and developing countries. Data on birth defects from population-based studies originating from developing countries are lacking. One of the objectives of this study was to determine the epidemiology of major birth defects in births during the perinatal period in Kinta district, Perak, Malaysia over a 14-month period, using a population-based birth defect register. There were 253 babies with major birth defects in 17,720 births, giving an incidence of 14.3/1000 births, a birth prevalence of 1 in 70. There were 80 babies with multiple birth defects and 173 with isolated birth defects. The exact syndromic diagnosis of the babies with multiple birth defects could not be identified in 18 (22.5%) babies. The main organ systems involved in the isolated birth defects were cardiovascular (13.8%), cleft lip and palate (11.9%), clubfeet (9.1%), central nervous system (CNS) (including neural tube defects) (7.9%), musculoskeletal (5.5%) and gastrointestinal systems (4.7%), and hydrops fetalis (4.3%). The babies with major birth defects were associated with lower birth weights, premature deliveries, higher Caesarean section rates, prolonged hospitalization and increased specialist care. Among the cohort of babies with major birth defects, the mortality rate was 25.2% during the perinatal period. Mothers with affected babies were associated with advanced maternal age, birth defects themselves or their relatives but not in their other offspring, and significantly higher rates of previous abortions. The consanguinity rate of 2.4% was twice that of the control population. It is concluded that a birth defects register is needed to monitor these developments and future interventional trials are needed to reduce birth defects in Malaysia.
    MeSH terms: Congenital Abnormalities/epidemiology*; Cesarean Section/statistics & numerical data; Female; Humans; Infant Mortality; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Length of Stay; Malaysia/epidemiology; Maternal Age; Population Surveillance*; Pregnancy; Registries; Case-Control Studies
  11. A clinical and economic study of community-acquired pneumonia between single versus combination therapy
    Hasali MA, Ibrahim MI, Sulaiman SA, Ahmad Z, Hasali JB
    Pharm World Sci, 2005 Jun;27(3):249-53.
    PMID: 16096896
    BACKGROUND: Pneumonia is one of the leading causes of morbidity and mortality among children in many developing countries. It is reported that 12.9 million children under 5 years of age died world-wide in 1990 and one-third of these deaths or 4.3 million annually were attributed to acute respiratory infection with pneumonia.

    OBJECTIVES: On this basis, a study was conducted in a district hospital to study the therapy outcomes of antibiotic regimens used in pediatric community-acquired pneumonia (CAP) management and to conduct a cost-effectiveness analysis (CE) between IV ampicillin versus combination therapy of IV ampicillin and IV gentamicin.

    METHOD: A prospective, randomized, controlled, single blind study was conducted in a pediatric ward in a 80-bed district hospital. Pediatric patients diagnosed with CAP aged 2 months to 5 years old were randomly and equally divided into two treatment arms: ampicillin versus ampicillin plus gentamicin. The dose of IV ampicillin used in this study was 100 mg/kg/day divided every 6 h and 5 mg/kg of IV gentamicin as a single daily dose. Both clinical and economic evaluations were carried out to compare both treatment arms.

    RESULTS: With the inclusion and exclusion criteria, only 40 patients diagnosed with CAP were included in the study. The results showed that the two treatment arms were significantly different (P < 0.05) in terms of duration of patients on ampicillin, number of days of hospitalization and time to switch to oral therapy. A significant difference was noted between the two treatment modalities in terms of effectiveness and cost (P < 0.05).

    CONCLUSION: Overall, the endpoint of this study showed that the total cost per patient of ampicillin-treated group is cheaper than the total cost with the combination therapy (ampicillin plus gentamicin) and reduced unnecessary exposure to adverse effects or toxicities. Besides that, addition of gentamicin in the treatment modalities will only increase the cost of treatment without introducing any changes in the treatment outcome.

    MeSH terms: Adult; Ampicillin/economics; Ampicillin/therapeutic use; Anti-Bacterial Agents/economics*; Anti-Bacterial Agents/therapeutic use*; Cost-Benefit Analysis; Data Collection; Data Interpretation, Statistical; Double-Blind Method; Female; Gentamicins/economics; Gentamicins/therapeutic use; Humans; Malaysia; Male; Pneumonia/drug therapy*; Pneumonia/economics*; Prospective Studies; Treatment Outcome; Community-Acquired Infections/drug therapy*; Community-Acquired Infections/economics*
  12. Survey of Staphylococcus isolates among hospital personnel, environment and their antibiogram with special emphasis on methicillin resistance
    Shobha KL, Rao PS, Thomas J
    Indian J Med Microbiol, 2005 Jul;23(3):186-8.
    PMID: 16100427
    The objective of this study was to find the prevalence of Staphylococcus spp. carriage among hospital personnel and hospital environment and their antibiogram with special emphasis on methicillin resistance. A total of 205 samples from hospital personnel and environment were collected from casualty, oncology and multidisciplinary cardiac unit ward of Kasturba Medical College Hospital, Manipal. Samples were collected using sterile cotton wool swabs and inoculated into brain heart infusion broth. Subcultures were done onto blood agar and MacConkey's agar. Isolates were identified by standard methods up to species level. Antimicrobial susceptibility test was performed according to standardized disc diffusion Kirby-Bauer method. Each of the isolates was screened for methicillin resistance using oxacillin disc on Mueller Hinton agar plate followed by MIC for methicillin and cefoxitin susceptibility test by disc diffusion method. Sixty five out of 205 strains (31.7%) were Staphylococcus spp. and all of them were coagulase negative. Most of the strains belonged to S.epidermidis 49.23% (32/65) followed by S. saprophyticus 26.15% (17/65). Maximum isolates of S.epidermidis were from anterior nares 28.12% (9/32 strains of S.epidermidis). Highest number of methicillin resistant coagulase negative strains (3/9, 33.33%) were isolated from stethoscope of multidisciplinary cardiac unit ward followed by carriers in the anterior nares (2/9, 22.22%). Methicillin resistant coagulase negative staphylococci are prevalent in anterior nares of hospital personnel and in the hospital environment thereby providing a definite source for hospital acquired infection. All isolates were sensitive to vancomycin, ciprofloxacin and amikacin.
    MeSH terms: Anti-Bacterial Agents/pharmacology*; Humans; India; Microbial Sensitivity Tests; Personnel, Hospital; Staphylococcal Infections/drug therapy; Staphylococcal Infections/microbiology*; Staphylococcus/drug effects; Staphylococcus/growth & development; Staphylococcus/isolation & purification*; Methicillin Resistance*
  13. Package plant of extended aeration membrane bioreactors: a study on aeration intensity and biofouling control
    Ujang Z, Ng SS, Nagaoka H
    Water Sci Technol, 2005;51(10):335-42.
    PMID: 16104438
    Biofouling control is important for effective process of membrane bioreactor (MBR). In this study, phenomena of biofouling for immersed type extended aeration MBR with two different anti-fouling aeration intensities were studied through a laboratory set up. The objectives of this study were (a) to observe biofouling phenomena of MBR that operates under different anti-fouling bubbling intensity, and simultaneously monitors performance of the MBR in organic carbon and nutrients removal; (b) to compare effectiveness of detergent and detergent-enzyme cleaning solutions in recovering biofouled membranes that operated in the extended aeration MBR. For MBR, which operated under continuous anti-fouling aeration, deposition and accumulation of suspended biomass on membrane surface were prohibited. However, flux loss was inescapable that biofilm layer was the main problem. Membrane cleaning was successfully carried out with detergent-enzyme mixture solutions and its effectiveness was compared with result from cleaning with just detergent solution.
    MeSH terms: Detergents; Enzymes/metabolism; Equipment Design; Equipment Failure; Membranes, Artificial*; Waste Disposal, Fluid/methods*; Biofilms/growth & development*; Biomass; Bioreactors*
  14. Liver transplantation in the Asia Pacific region--trials and tribulations
    Fan ST
    Med J Malaysia, 2005 Jul;60 Suppl B:1-4.
    PMID: 16108164
    MeSH terms: Asia; Hepatitis B/pathology; Hepatitis B/prevention & control; Hepatitis B/surgery; Humans; Pacific Islands; Liver Transplantation/methods; Liver Transplantation/trends*; Living Donors*; Secondary Prevention
  15. Advances in portal hypertension
    McCormick A, Qasim A
    Med J Malaysia, 2005 Jul;60 Suppl B:6-11.
    PMID: 16108165
    MeSH terms: Acute Disease; Esophageal and Gastric Varices/physiopathology*; Gastrointestinal Hemorrhage/therapy*; Budd-Chiari Syndrome; Humans; Hypertension, Portal/physiopathology*; Hypertension, Portal/therapy; Liver Cirrhosis/physiopathology; Prognosis
  16. Spontaneous bacterial peritonitis [SBP]
    Chutaputti A
    Med J Malaysia, 2005 Jul;60 Suppl B:12-4.
    PMID: 16108166
    MeSH terms: Ascites/complications; Bacterial Infections/diagnosis; Bacterial Infections/etiology; Bacterial Infections/prevention & control*; Hospitalization; Humans; Liver Cirrhosis/complications*; Peritonitis/diagnosis; Peritonitis/microbiology*; Peritonitis/prevention & control*; Time Factors; Antibiotic Prophylaxis/methods*
  17. Infections in patient with decompensated cirrhosis
    Suresh RL
    Med J Malaysia, 2005 Jul;60 Suppl B:16.
    PMID: 16108167
    MeSH terms: Bacterial Infections/etiology*; Humans; Kupffer Cells/immunology; Liver Cirrhosis/complications*; Liver Cirrhosis/physiopathology; Peritonitis/microbiology*; Risk Factors; Time Factors
  18. Hepatorenal syndrome
    McCormick A, Sultan J
    Med J Malaysia, 2005 Jul;60 Suppl B:17-21.
    PMID: 16108168
    MeSH terms: Hepatorenal Syndrome/diagnosis; Hepatorenal Syndrome/drug therapy; Hepatorenal Syndrome/physiopathology*; Humans; Liver Transplantation; Disease Progression; Renal Insufficiency/diagnosis; Renal Insufficiency/drug therapy; Renal Insufficiency/physiopathology*
  19. Chronic hepatitis B--treatment with nucleoside analogues
    Leung N
    Med J Malaysia, 2005 Jul;60 Suppl B:22-7.
    PMID: 16108169
    Nucleot(s)ide analogues are making milestones in the treatment of chronic hepatitis B (CHB) as safe oral therapy. FDA approved lamivudine in adult patients in 1998, adefovir dipivoxil in 2002, and entecavir in March 2005. Lamivudine is effective in viral suppression, ALT normalization, and improvement in histology in both HBeAg positive and HBeAg negative / HBV DNA positive patients. HBeAg seroconversion rates correlate directly with pretreatment ALT levels at 18-30% after one year of therapy. Hepatitis flares may occur if lamivudine is stopped before HBeAg seroconversion. Lamivudine resistant YMDD mutants emerge at a rate of 15-20% per year of therapy; often associated with the rebound viraemia, relapse of hepatitis or even hepatic decompensation. Durability of response off lamivudine therapy is not satisfactory and may be dependent on duration of therapy post-seroconversion. Lamivudine is well tolerated with few serious adverse events, even in patients with decompensated cirrhosis. Long term therapy in viraemic patients with advanced fibrosis or cirrhosis delays clinical progression. Adefovir dipivoxil is an oral prodrug of adefovir. 10 mg daily is effective in suppressing both wild-type HBV and YMDD mutants, normalising ALT and improving histology. Adefovir dipivoxil has been shown to be well tolerated in longterm therapy. Renal toxicity reported in higher dosages is rarely seen except among patients with creatinine clearance less than 50 ml/min. Adefovir resistance may emerge and the overall rate is much lower than lamivudine, reaching 18% after 4 years of therapy. Adefovir-resistant mutants (rt N236T) are susceptible to lamivudine and entecavir. Little data is available for durability of response off therapy. Entecavir is an oral nucleoside analogue with a recommended dosage of 0.5 mg daily for nucleoside-naive patients, and 1 mg daily for lamivudine-refractory patients. It is a potent antiviral and may also reduced intrahepatitic cccDNA. Entecavir resistance so far has only been detected in lamivudine resistant patients in the one-year studies. Patient counseling is very important to decide on the choice among available therapeutic options. The assessment of the risks/benefits of each option should be carefully explained to individual patient.
    MeSH terms: Adenine/analogs & derivatives*; Adenine/therapeutic use; Drug Resistance; Drug Therapy, Combination; Guanine/analogs & derivatives*; Guanine/therapeutic use; Humans; Nucleosides*; Time Factors; Liver Transplantation; Reverse Transcriptase Inhibitors/therapeutic use*; Lamivudine/therapeutic use*; Hepatitis B, Chronic/drug therapy*; Organophosphonates/therapeutic use*
  20. 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.
    MeSH terms: Antiviral Agents/therapeutic use*; Chronic Disease; Drug Therapy, Combination; Hepatitis B/drug therapy*; Hepatitis B/immunology; Humans; Polyethylene Glycols/therapeutic use*; Recombinant Proteins; Time Factors; Interferon-alpha/therapeutic use*
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