Prevalence and clinical relevance of serum anti-p53 antibodies in patients with cholangiocarcinoma

Cholangiocarcinoma (CCA) constitutes carcinoma of the bile duct found at a high prevalence in northeastern Thailand. In the present study, we examined the sera of altogether 82 Thai CCA patients for the presence of anti-p53 antibodies in order to investigate a role of the tumor suppressor gene, p53 in the carcinogenesis. Our results revealed anti-p53 antibodies in 7.3% of the cases tested, which conforms to the prevalence rate of p53 gene mutation recently reported at 5% among Thai patients. With limited number of the patients, anti-p53 antibodies were rapidly detected more frequently among patients with peripheral tumors than those with central tumors. However, further studies is required to establish significance and prognostic value of the antibodies in the context of CCA.     

The genome sequence analysis of H5N1 avian influenza A virus isolated from the outbreak among poultry populations in Thailand

In this report, the genome of the Thai avian influenza virus A (H5N1); A/Chicken/Nakorn-Pathom/Thailand/CU-K2/04, isolated from the Thai avian influenza A (AI) epidemic during the early of 2004 was sequenced. Phylogenetic analyses were performed in comparison to AI viruses from Hong Kong 1997 outbreaks and other AI (H5N1) isolates reported during 2001-2004. Molecular characterization of the Thai AI (H5N1) HA gene revealed a common characteristic of a highly pathogenic AI (HPAI), a 20-codon deletion in the neuraminidase gene, a 5-codon deletion in the NS gene and polymorphisms of the M2 and PB2 genes. Moreover, the HA and NA genes of the Thai AI displayed high similarity to those of the AI viruses isolated from human cases during the same epidemic. Finally, our results demonstrated that the Thai AI emerged as a member of 2000's AI lineage with most of the genetic sequences closely related to the Influenza A/Duck/China/E319.2/03 (H5N1).     

Characterization of the hemagglutinin and neuraminidase genes of recent influenza virus isolates from different avian species in Thailand

The hemagglutinin (HA) and neuraminidase (NA) genes of eight influenza A virus (H5N1) isolates obtained from various avian species in Thailand in 2003-2004 have been characterized in comparison with the Thai isolate A/Chicken/Nakorn-Pathom/Thailand/CU-K2/04(H5N1). Phylogenetic analyses of both genes revealed that all the eight avian isolates were closely related to the A/Chicken/Nakorn-Pathom/Thailand/CU-K2/ 04(H5N1). The amino acid sequence of the HA cleavage site revealed a common characteristic of a highly pathogenic virus strain. Moreover, a deletion of 20 amino acids in the NA stalk region was detected in all Thai isolates in contrast to the H5N1 strain that had caused outbreaks in eastern Asia in 1996-1997 and 2000-2001.     

Hepatitis C virus genotype 6:Virology,epidemiology,genetic variation and clinical implication

Hepatitis C virus(HCV)is a serious public health problem affecting 170 million carriers worldwide.It is a leading cause of chronic hepatitis,cirrhosis,and liver cancer and is the primary cause for liver transplantation worldwide.HCV genotype 6(HCV-6)is restricted to South China,South-East Asia,and it is also occasionally found in migrant patients from endemic countries.HCV-6 has considerable genetic diversity with23 subtypes(a to w).Although direct sequencing followed by phylogenetic analysis is the gold standard for HCV-6 genotyping and subtyping,there are also now rapid genotyping tests available such as the reverse hybridization line probe assay(INNO-LiPAⅡ;Innogenetics,Zwijnaarde,Belgium).HCV-6 patients present with similar clinical manifestations as patients infected with other genotypes.Based on current evidence,the optimal treatment duration of HCV-6 with pegylated interferon/ribavirin should be 48 wk,although a shortened treatment duration of 24 wk could be sufficient in patients with low pretreatment viral load who achieve rapid virological response.In addition,the development of direct-acting antiviral agents is ongoing,and they give high response rate when combined with standard therapy.Herein,we review the epidemiology,classification,diagnosis and treatment as it pertain to HCV-6.     

Genotypes and subtypes of hepatitis B virus in Thailand

Hepatitis B virus exhibits considerable variability evident in its various antigenic subtypes, which complicates the characterization of epidemiological factors, particularly in areas endemic for hepatitis B. Our group investigated the genotypes and subtypes prevalent in Thailand employing nested PCR and sequencing of the a determinant, as well as the sub-determinants located on the S gene. The sera examined originated from a mixed range of HBV-infected individuals. The results were mostly consistent with those reported for Southeast Asia in that genotype C (54.4%) dominates over genotypes A (22.1%) and B1 (23.5%). Regarding the subtypes, we have exclusively found adw2 (45.6%) and adr (54.4%) as expected for this area, with one case of subtype adw representing the exception. While genotype and/or subtype of HBV do not predispose to clinical disease, they nevertheless may account for those few cases reported in which a mutation, particularly within the a determinant of the S gene, causes evasion of routine detection by commercial kits, particularly as long as the respective individuals remain asymptomatic carriers solely expressing anti-HBc.     

Coinfections with hepatitis g and/or c virus in hepatitis B-related chronic liver disease

Concurrent infections with HGV and/or HCV (HGV/HCV) were investigated in 196 patients with HBV-related chronic liver disease (115 chronic hepatitis, 31 liver cirrhosis, 50 hepatocellular carcinoma), and in 100 HBsAg carriers. Coinfections were detected in 18 (9.2%) patients with HGV (10) or HCV (5) or both agents (3), but in none of the HBsAg carriers. Patients with coinfection were more frequently exposed to blood transfusions (55.6% vs 5.6%) and also were more commonly anti-HBe positive. Serum levels of HBV-DNA were lower in patients with HCV coinfection than in those coinfected with HGV. Interferon was administered to 39 patients with chronic active hepatitis including 7 patients with HGV/HCV coinfection. Sustained clearance of HBV-DNA was observed in 10 (25.6%) patients who were solely infected with HBV. These patients were significantly younger and had much lower histological scores than non-responders. Patients with HCV coinfection had significantly higher pre-treatment histological scores than those without HCV. After interferon treatment, a significant reduction in histological scores was observed in all patients except those coinfected with HGV/HCV. None of the 7 patients with coinfection had sustained clearance of HBV-DNA or HCV-RNA, and only one had cleared HGV-RNA. These results suggest that parenteral exposure is a risk factor for HGV/HCV coinfection in chronic HBV infection. HGV infection shows no significant impact on chronic HBV infection. HCV coinfection appears to inhibit HBV replication, but causes more severe chronic hepatitis and increases resistance to interferon therapy.     

Alpha-L-fucosidase as a serum marker of hepatocellular carcinoma in Thailand

To evaluate the role of serum alpha-L-fucosidase (AFU) in the diagnosis of hepatocellular carcinoma (HCC), we simultaneously studied both AFU activity and alpha-fetoprotein (AFP) level in 60 patients with HCC, 60 patients with cirrhosis and chronic hepatitis each, 30 patients with other liver tumors and 60 healthy subjects. Serum AFU activity in patients with HCC (1,418.62 +/- 575.76 nmol/ml/hr) was significantly higher than that found in cirrhosis (831.25 +/- 261.13 nmol/ml/hr), chronic hepatitis (717.71 +/- 205.86 nmol/ ml/hr) or other tumors (706.68 +/- 197.67 nmol/ml/hr) and in controls (504.18 +/- 121.88 nmol/ml/hr, p < 0.05). With 870 nmol/ml/hr (mean value of controls plus 3 standard deviations) considered as the cut-off point, AFU was more sensitive (81.7 vs 39.1%) but less specific (70.7 vs 99.3%) than AFP at a level of > 400 ng/ml as a tumor marker of HCC. With both markers combined, the sensitivity was improved to as much as 82.6%. AFU activity in HCC patients was correlated to tumor size (r = 0.3529, p = 0.006) but not associated with tumor staging classified by Okuda's criteria (p = 0.1). The AFU activity in the viral hepatitis group (hepatitis B or C) was also significantly higher than in the non-viral group (p = 0.0005). We conclude AFU to be a useful marker, in conjunction with AFP and ultrasonography, for detecting HCC, particularly in patients with underlying viral hepatitis and cirrhosis.     

A review of Hib epidemiology in Asia.

Meningitis due to an invasive Haemophilus influenzae type b (Hib) infection, has been previously perceived to be relatively uncommon in Asia. However, the incidence of disease and its impact may have been underestimated. In addition to a lack of microbiological facilities in some hospitals, difficulties in culturing the organism and the widespread use of antibiotics may have hidden the true incidence of the disease in some countries. Furthermore, the reported disease burden probably underestimates the incidence of Hib pneumonia. The epidemiology of invasive Hib disease for various Asian nations is reviewed in this paper. Hospital-based studies show that Hib is a major cause of bacterial meningitis and/or pneumonia in the Philippines, India, Thailand, Malaysia, Indonesia and Vietnam. Singapore and Hong Kong have a low incidence of infection compared with Western and other Asian nations. This low incidence is not due to a higher level of natural protective antibodies, but may be related to an interaction between environmental and genetic factors. Therefore the widespread belief that Hib infection is unimportant in Asia does not refer to Asia as a whole and possibly to Chinese patients only, and failure to recognize this has serious implications. The inclusion of Hib vaccine in the routine infant immunization schedule in many industrialized nations has significantly reduced the incidence of invasive disease. Recent studies have shown Hib vaccination is also effective in preventing invasive disease in children in developing countries. While population-based data may be required to confirm the need for public-funded infant Hib immunization in Asia, its introduction in countries with a high incidence of Hib meningitis and/or pneumonia has the potential to significantly improve pediatric health and survival.