Hepatitis Research Program

 
Remigio M. Olveda, MD
Research Program Leader

TECHNICAL
GROUP MEMBERS

Gemiliano Aligui, MD, MPH,  PhD
Albert Anduyon
Florencio C. Dizon, MD
Cynthia Miguel, MSc
Rebecca Notorio, B.Sc.
Fe Amor Vinculado, B.Sc.


In 1983, the Hepatitis Study Group at RITM, in collaboration with the Liver Study Group at the UP-PGH was established with the main thrust of conducting research on hepatotrophic viruses, especially the hepatitis B and C viruses. Utilizing tools in molecular biology, molecular epidemiology, immunology and socio-behavioral sciences, the program’s objectives are directed towards better understanding of the extent of hepatitis problem in the Philippines and the development of cost-effective measures for the control of viral hepatitis as well as the containment of many chronic liver disease sequelae associated with the infection.

Hepatitis B virus infection continues to be a public health problem in the Philippines. The need to suppress the spread of this highly contagious disease is one of the primary concerns of the Department of Health. Since 1980, the DOH has been promoting Hepatitis B surveillance and control programs, which include mass immunization, health education and information, and screening of blood and blood products for transfusion. Due to the rising cost of imported diagnostic kits to screen blood for the different hepatitis B markers, the need to produce the reagent was conceptualized. 

acute respiratory infections

Hepatitis


Acute Respiratory Infections
Dengue
Diarrheal Diseases
Filariasis
Filovirus
HIV/AIDS
Malaria
Rabies
Schistosomiasis
Tuberculosis
Leprosy


Through the joint effort of the UP-PGH Liver Study Group, RITM and the Philippine National Red Cross (PNRC) for constant supply of hepatitis contaminated human plasma for research and development, the production of local reagents for Hepatitis B diagnosis was initiated. The transfer and establishment of the technology for the purification of native HBs antigens from human blood was made possible through the cooperation of the Japan International Cooperation Agency (JICA), the Philippine Council for Health Research and Development (PCHRD) and the World Health Organization (WHO).

The hepatitis laboratory at RITM has been successful in developing diagnostic kits from purified HBs antigens and antibodies. These were used in detecting HBsAg using RPHA (reverse passive hemagglutination assay), anti-HBs using PHA (passive hemagglutination assay) and anti-HBc using HI (hemagglutination inhibition) tests. However, enzymeimmunoassays (EIAs) have been shown to surpass these diagnostic methods in terms of sensitivity and specificity. Recently, under a PCHRD grant the group embarked on developing a ‘dip-stick’-based enzyme immunoassay that will meet the need for simple, rapid and sensitive method for detecting HBsAg and anti-HBs in serum or plasma. While there is considerable benefit in purifying native HBsAg from rejected blood donors, the same is not true for the core antigen (HBc) because of the latter’s very small yield. The program now attempts to generate sufficient amount of recombinant core antigen from HBV DNA isolate to develop the test kit for anti-HBc.

Community-based studies on Hepatitis B were started in 1987. In a double-blind randomized controlled trial, the protective effect against the hepatitis B surface antigen carrier-state of a one-dose HBV immunization was compared with the standard three-dose regimen. This study on the immunogenicity and efficacy of the Hepatitis B vaccine among Filipino infants was done to assess possible implication, for optimal use, of the vaccine in the expanded program for immunization (EPI). Several studies were also initiated, namely: 1) The detection and direct sequencing of Hepatitis B virus (HBV) genome in human sera by DNA amplification techniques; 2) Distribution of HBV subtypes and genotypes and identification of vaccine and immunodiagnostic escape variants; and 3) The molecular virological aspects and clinical spectrum of Hepatitis C in the Philippines.

The program will thus continue to support the production and development of improved immuno-diagnostic kits for Hepatitis B. Future directions of the program will include: 1) Sero-epidemiology of Hepatitis E virus and other hepatothropic viruses; 2) production of structural and non-structural HCV protein by recombinant DNA technology; 3) In-situ hybridization technique of HBsAg among hepatocellular carcinoma cases; 4) purification of HBsAg for use in the immuno-histochemistry to detect antigen in tissues; and 5) characterization of HBV vaccine escape mutants and their incorporation in vaccines.