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  1. 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.
  2. Raihan R, Akbar SMF
    Euroasian J Hepatogastroenterol, 2023;13(2):152-158.
    PMID: 38222956 DOI: 10.5005/jp-journals-10018-1412
    BACKGROUND AND AIMS: Bangladesh's unique epidemiological landscape presents an intriguing puzzle. This South Asian nation, with its complex sociodemographic and environmental factors, is home to a diverse array of hepatitis-B virus (HBV) genotypes, identified as Genotype C, with Genotypes D and A also making a significant contribution to the viral landscape. Reviewing such insights is necessary not only to underscore the country's regional diversity in HBV strains but also to bring into focus the clinical implications these genetic variations may have on disease progression and management.

    METHODS: A thorough database search covered various sources using relevant keywords like "Hepatitis B virus genotypes", "HBV genotypes in Bangladesh", and "HBV clinical implications". The review synthesized findings and analyzed HBV genotype prevalence and clinical implications in Bangladesh.

    RESULTS: Genotypes C and D collectively represent 82% of chronic hepatitis-B infection (CHB) cases in Bangladesh, underscoring their regional prevalence. The geographic context is pivotal in understanding HBV infection dynamics and disease progression in this area. Notably, genotype C and the presence of A1762T/G1764A mutations appear to have a distinct impact on disease development, potentially affecting the immune response in CHB patients. This highlights the need for tailored management approaches in this specific region. Further research is vital to confirm and elaborate on these findings, particularly in relation to how these mutations influence the host's immune response.

    CONCLUSION AND CLINICAL SIGNIFICANCE: In summary, studies on HBV genotypes in Bangladesh stress the need for genotype-specific clinical considerations and more research to improve diagnostics and therapies.

    HOW TO CITE THIS ARTICLE: Raihan R, Akbar SMF. A Narrative Review on the Specific Pattern of HBV Genotype in Bangladesh: Clinical Implications for Management. Euroasian J Hepato-Gastroenterol 2023;13(2):152-158.

  3. Raihan R, Azzeri A, H Shabaruddin F, Mohamed R
    Euroasian J Hepatogastroenterol, 2018 05 01;8(1):54-56.
    PMID: 29963463 DOI: 10.5005/jp-journals-10018-1259
    Hepatocellular carcinoma (HCC) is one of the leading causes of death globally. In Malaysia liver cancer is the eighth most common cause of cancer for both gender and fifth most common cause of cancer for males. Liver cancer is a cause of premature death in Malaysia: The trend from 1990 to 2010 was observed upward. Since 1990, the annual years of life lost (YLLs) from liver cancer have increased by 31.5%. Older persons are at higher risk and there is male predominance observed. Curative surgical resection, liver transplantation, and supportive symptomatic care, including percutaneous ethanol injection and radiofrequency ablation (RFA), and noncurative transarterial chemoembolization (TACE) are among available treatment facilities. Yet the survival rate is very poor as majority of patients present at very advanced stage. Hepatitis B virus (HBV) remained the leading cause of HCC in Malaysia. Several studies showed cryptogenic causes, which are mainly nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) among the predominant causes of HCC in Malaysia than hepatitis C virus (HCV), alcohol, or any other reason. This mainly correlates with the increasing incidence of diabetes and obesity in Malaysia. How to cite this article: Raihan R, Azzeri A, Shabaruddin FH, Mohamed R. Hepatocellular Carcinoma in Malaysia and Its Changing Trend. Euroasian J Hepato-Gastroenterol 2018;8(1):54-56.
  4. Raihan R, Mohamed R, Radzi Abu Hassan M, Md Said R
    Euroasian J Hepatogastroenterol, 2017 Jan-Jun;7(1):65-67.
    PMID: 29201775 DOI: 10.5005/jp-journals-10018-1214
    Malaysia is a country where an estimated 1 million people are chronically infected with hepatitis B virus (HBV) and an estimated 2.5% of the adult population are positive for antibody to hepatitis C virus (HCV). Effective nationwide vaccine coverage seems to be a highly effective measure to prevent new HBV infection. Treatment of HCV infection is also a regular practice in Malaysia. These measures highlight the possibility to reach the World Health Organization elimination target by 2030. To achieve this target, the Health Ministry and other nongovernmental organizations, such as My Commitment to Cure (MyC2C) are working together to develop a strategic road map to reach the global elimination target in Malaysia by 2030. How to cite this article: Raihan R, Mohamed R, Hasan MRA, Rosaida MS. Chronic Viral Hepatitis in Malaysia: "Where are we now?" Euroasian J Hepato-Gastroenterol 2017;7(1):65-67.
  5. Raihan R, Akbar SMF, Al Mahtab M, Khan MSI, Tabassum S, Tee KK, et al.
    Viral Immunol, 2020 09;33(7):530-534.
    PMID: 32513066 DOI: 10.1089/vim.2019.0198
    Hepatitis B virus (HBV) is a noncytopathic virus and billions of HBV-infected patients live uneventful lives and do not suffer from notable liver damage. However, HBV also causes progressive liver diseases characterized by hepatic inflammation, hepatic fibrosis, and liver cancer in millions of HBV-infected patients. The goal of this study was to evaluate the role of mutant HBV in HBV pathogenesis. In a cohort of 360 chronic HBV-infected patients, mutations at T1762/A1764 of HBV genome were detected in most of the patients with HBV-induced liver cirrhosis and hepatocellular carcinoma. To explore if mutations at T1762/A1764 of HBV genome has any role in progressive liver disease, peripheral blood mononuclear cells (PBMCs) and antigen-presenting dendritic cells (DCs) were isolated from five chronic hepatitis B (CHB) patients with mutations at T1762/A1764 and five comparable patients of CHB without mutations at T1762/A1764. DCs were pulsed with hepatitis B surface antigen (HBsAg). The levels of cytokines produced by PBMCs and DCs as well as nitrite production by DCs were evaluated. Significantly higher levels of interleukin-12, tumor necrosis factor-alpha, interferon-gamma, and transforming growth factor-beta were detected in cultures of PBMCs, DCs, and HBsAg-pulsed DCs from CHB patients with mutations at T1762/A1764 compared with those without mutations (p 
  6. Akbar SM, Al-Mahtab M, Khan MS, Raihan R, Shrestha A
    Ann Transl Med, 2016 Sep;4(18):335.
    PMID: 27761439
    Although several antiviral drugs are now available for treatment of patients with chronic hepatitis B (CHB), sustained off-treatment clinical responses and containment of CHB-related complications are not achieved in majority of CHB patients by antiviral therapy. In addition, use of these drugs is endowed with substantial long term risk of viral resistance and drug toxicity. The infinite treatment regimens of antiviral drugs for CHB patients are also costly and usually unbearable by most patients of developing and resource-constrained countries. Taken together, there is a pressing need to develop new and innovative therapeutic approaches for CHB patients. Immune therapy seems to be an alternate therapeutic approach for CHB patients because impaired or distorted or diminished immune responses have been detected in most of these patients. Also, investigators have shown that restoration or induction of proper types of immune responses may have therapeutic implications in CHB. Various immunomodulatory agents have been used to treat patients with CHB around the world and the outcomes of these clinical trials show that the properties of immune modulators and nature and designing of immune therapeutic regimens seem to be highly relevant in the context of treatment of CHB patients. In this review, the general properties and specific features of immune therapy for CHB have been discussed for developing the guidelines of effective regimens of immune therapy for CHB.
  7. Chakraborty S, Chakravorty R, Alam S, Kabir Y, Mahtab M, Islam MA, et al.
    Euroasian J Hepatogastroenterol, 2020 3 3;9(2):84-90.
    PMID: 32117696 DOI: 10.5005/jp-journals-10018-1303
    Aim: Attainment of sustainable development goal (SDG) targets requires reducing the rate of new hepatitis B virus (HBV)-induced infection and mortality rate to 90% and 65%, respectively, by 2030. Therefore, it is important to investigate the feasibility of reducing the required rates of HBV-induced infection and death incidents at the current rate of vaccination coverage in Bangladesh. Moreover, factors influencing vaccination coverage like negative bias toward girls during immunization can affect the current vaccination program and ultimately hinder the efforts to reduce HBV-induced infection and death rates. To investigate the possibility of reducing HBV-induced infection and death rates with current vaccination coverage, we adopted mathematical molding-based approach.

    Materials and methods: We developed a mathematical model based on the susceptible-infectious-recovered model to simulate the HBV-induced infection in children under the age of five at three different vaccination rates: 80, 90, and 95%. Additionally the impact of current vaccination coverage was assessed on HBV-induced death rates in the future. Moreover, we took advantage of the mathematical model to investigate the impact of negative bias toward girls in vaccination program on HBV-induced infection and death rates.

    Results: The model simulations revealed that 10% increase in the vaccination rate from 80 to 90% can potentially contribute to the significant lowering (around 40%) of HBV-induced infection rate among children. When increased by 5% of vaccination rate from 90 to 95%, the HBV-infection rate is likely to be decreased by another 22%. Likewise, 44% reduction in HBV-induced death rate in the future (2050 onward) can potentially be achieved by 10% increase in the current vaccination rate from 80 to 90%, whereas 5% increase in the current vaccination rate (90-95%) may lead to 24% further reduction of death rate. These results underscored the significant impact of vaccination in reducing HBV-induced infection among children and future death rates in adults. Moreover, at 90% vaccination coverage, the negative bias of vaccination toward girls contributes to an increase of 15 and 12% of HBV-induced infection and death rates, respectively, in female subjects compared to their male counterparts.

    Conclusion: The current vaccination coverage (80-90%) is further aggravated by untimely vaccination, dropouts from vaccination program, and negative bias toward girls in vaccination program. Therefore, if the current situation persists, it will not be possible to accomplish the required reduction in HBV-induced infection and death rates by 2030, according to the SDG guidelines. Moreover negative bias in the vaccination program may intensify the HBV-induced infection and death rates in the future.

    Clinical significance: In light of the mathematical model, we suggest that the vaccination coverage should be increased to 95% without any negative bias toward girls. To accomplish this, the concerning authorities must ensure timely and full completion of the HBV vaccine schedules, reducing dropouts from vaccination program, and lastly preventing negative bias toward girls to uplift vaccination coverage to more than 95% with gender equality. Without these strategies, the necessary reduction in the HBV-induced infection and death rates in Bangladesh may not be attained per SDG directives.

    How to cite this article: Chakraborty S, Chakravorty R, Alam S, et al. A Dynamic Mathematical Modeling Revelation about the Impact of Vaccination on Hepatitis B Virus-induced Infection and Death Rate in Bangladesh. Euroasian J Hepato-Gastroenterol 2019;9(2):84-90.

  8. Raihan R, Akbar SMF, Al Mahtab M, Takahashi K, Masumoto J, Tabassum S, et al.
    PLoS One, 2019;14(6):e0218744.
    PMID: 31251754 DOI: 10.1371/journal.pone.0218744
    The direct cytopathic effects of the hepatitis B virus (HBV) on subsequent liver damage are not fully understood in HBV-infected patients. However, associations between the prevalence of various HBV genotypes and the extent of liver damage have been reported from different parts of the world. The purpose of this study was to determine the distribution of HBV genotypes in patients with chronic HBV infection in Bangladesh, a country of 160 million people, of which approximately 3-6 million are chronically infected HBV patients. In addition, whole and partial genome sequencing of HBV was performed to evaluate the relationship between HBV mutations and genotypes. We found that 42% of the patients with low HBV DNA and normal levels of alanine aminotransferase (ALT) had HBV genotype D. In contrast, the HBV genotype C was dominant among patients with high HBV DNA levels (>2000 IU/ml) and elevated ALT and in patients with liver cirrhosis (LC) and hepatocellular carcinomas (HCC). Whole and partial genome sequences of HBV revealed that most patients with LC and HCC had HBV genotype C with mutations at the T1762/A1764 positions. It seems that Bangladesh represents a borderline country, situated within East Asia, which mainly consists of individuals with HBV genotypes B and C, whereas in the western parts of Asia, HBV genotypes A and D are prevalent. Bangladesh is, therefore, an excellent model for the comparison of the pathophysiology of three major HBV genotypes in a single population. The findings of this study suggest a possible association between HBV viral factors and the extent of liver damage in chronic HBV-infected patients.
  9. Raihan R, Tabassum S, Al-Mahtab M, Nessa A, Jahan M, Shamim Kabir CM, et al.
    Euroasian J Hepatogastroenterol, 2015 Jan-Jun;5(1):7-10.
    PMID: 29201677 DOI: 10.5005/jp-journals-10018-1120
    Background: Hepatitis B virus (HBV) infection has many faces. Precore and core promoter mutants resemble inactive carrier status. The identification of hepatitis B core antigen (HBcAg) in hepatocytes may have variable clinical significance. The present study was undertaken to detect HBcAg in chronic hepatitis B (CHB) patients and to assess the efficacy of detection system by indirect immunofluorescence (IIF) and indirect immunoperoxidase (IIP).

    Materials and methods: The study was done in 70 chronic HBV-infected patients. Out of 70 patients, eight (11.4%) were hepatitis B e antigen (HBeAg) positive and 62 (88.57%) were HBeAg negative. Hepatitis B core antigen was detected by indirect immunofluorescence (IIF) and indirect immunoperoxidase (IIP) methods in liver tissue.

    Results: All HBeAg positive patients expressed HBcAg by both IIF and IIP methods. Out of 62 patients with HBeAg-negative CHB, HBcAg was detected by IIF in 55 (88.7%) patients and by IIP in 51 (82.26%) patients. A positive relation among viral load and HBcAg detection was also found. This was more evident in the case of HBeAg negative patients and showed a positive relation with HBV DNA levels.

    Conclusion: Hepatitis B core antigen can be detected using the IIF from formalin fixed paraffin block preparation and also by IIP method. This seems to reflect the magnitudes of HBV replication in CHB.

    How to cite this article: Raihan R, Tabassum S, Al-Mahtab M, Nessa A, Jahan M, Kabir CMS, Kamal M, Aguilar JC. Hepatitis B Core Antigen in Hepatocytes of Chronic Hepatitis B: Comparison between Indirect Immunofluorescence and Immunoperoxidase Method. Euroasian J Hepato-Gastroenterol 2015;5(1):7-10.
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