Peg-interferon and ribavirin treatment in HIV/HCV co-infected patients in Thailand: efficacy, safety and pharmacokinetics.

OBJECTIVE: In Thailand, 7.2% of HIV patients are co-infected with hepatitis C virus (HCV), and these patients are treated with peg-interferon + ribavirin (PR) for their HCV infection. This study evaluates efficacy and safety of PR treatment and pharmacokinetics of ribavirin in this population. METHODS: HIV/HCV co-infected Thai patients were treated with PR for 24 or 48 weeks. Sustained virological response 24 weeks after the end of treatment (SVR24) was used to describe efficacy. (laboratory) safety parameters and ribavirin plasma concentrations were evaluated during study visits. Ribavirin concentrations were compared with t-tests for patients with and without anaemia (haemoglobin <10 g/dl) and SVR24. RESULTS: A total of 101 HIV/HCV co-infected patients were included; 88% were male (n = 88), and 46% were infected with genotype 3. The median (IQR) start dose was 14.28 mg/kg/day. SVR24 rate was 56%. All patients reported at least one (serious) adverse event, of which 28% of patients developed anaemia. Seven patients discontinued treatment due to toxicity issues. Geometric mean (IQR) ribavirin concentration was 1.81 (1.42-2.32) mg/l at week 8 of treatment. At week 8, patients with and without anaemia and SVR had ribavirin concentrations of 2.29 and 1.63 mg/l and 1.91 and 1.74 mg/l, respectively. CONCLUSIONS: PR treatment has comparable response rates and toxicity profile in Thai HIV/HCV co-infected patients as in Western HIV/HCV patients. However, ribavirin plasma concentrations were comparable with previously published studies in HIV/HCV co-infected patients, but both, just as SVR rate, were lower than in mono-infected patients.

A randomized clinical trial of peginterferon alpha-2b with or without entecavir in patients with HBeAg-negative chronic hepatitis B: Role of host and viral factors associated with treatment response.

Combining peginterferon (PEG-IFN) and a potent nucleoside/nucleotide analogue might improve treatment response in patients with chronic hepatitis B (CHB). The aims of this study were to compare the efficacy of PEG-IFN alpha-2b with or without entecavir in HBeAg-negative CHB and to investigate predictors of response. A total of 126 treatment-naïve patients were randomly assigned to receive monotherapy (n = 63) or combination therapy (n = 63) for 48 weeks. Virological response (VR) was defined as HBV DNA level <2000 IU/mL at week 96. Baseline factors including polymorphisms in the IFNL3 (rs12979860) and HLA-DPA1 (rs3077) genes and on-treatment viral kinetics were determined. At week 48, rates of undetectable HBV DNA were lower in the monotherapy than combination groups, but rates of HBsAg clearance and decline were comparable. At week 96, there was no difference between the corresponding groups regarding virological response (41.3% vs 38.1%, P = 0.856), HBsAg clearance (9.5% vs 4.8%, P = 0.491) and HBsAg decline. Baseline HBsAg level [odds ratio (OR): 3.14 (1.34-7.69), P = 0.012] and rs3077 polymorphism [OR: 2.78 (1.27-6.11), P = 0.011] were independent predictors of response. Patients carried GG genotype of rs3077 with low baseline HBV (<1000 IU/mL) had high probability of achieving VR (76.5%) and HBsAg clearance (29.4%). None of the patients without decrease in HBsAg combined with <2 log10 HBV DNA decline at week 12 achieved a virological response. In conclusion, the combination therapy lead to greater on-treatment HBV DNA suppression but did not improve virological response and HBsAg clearance/decline over monotherapy. Host and viral factors could help optimize decision-making at baseline and during PEG-IFN-based therapy.

Gene polymorphisms of interleukin 28B and the risk to chronic hepatitis B virus infection in Thai.

In this study, we aimed to evaluate the effect of two single nucleotide polymorphisms (SNPs) of interleukin 28B (IL28B) (rs12979860C/T and rs8099917G/T) on chronic hepatitis B virus (CHB) infection in Thai population. We studied 375 subjects: 83 CHB with hepatocellular carcinoma (HCC) patients, 128 CHB without HCC and 164 individuals with self-limited HBV infection, by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and TaqMan allelic discrimination assay. Results revealed significant risk of IL28B rs8099917T allele associated with CHB without HCC compared with self-limited HBV [odds ratio (OR) (95% confidence interval (CI)) = 2.56 (1.08-6.28), P = 0.019]. The effect of this T allele was similar to that of an autosomal recessive gene in the presence of TT genotype compared with GG and GT genotype [OR (95% CI) = 2.70 (1.11-6.77), P = 0.016, P (logistic regression) = 0.048]. The two locus haplotype analysis of the two IL28B SNP loci did not show any association with CHB (P > 0.05). In conclusion, these results suggested a IL28B rs8099917T allele predispose for susceptibility to chronic HBV infection but not leading to HCC in Thai population.

Association of IFNAR2 and IL10RB genes in chronic hepatitis B virus infection.

In this study, we investigated the effects of two functional polymorphisms, type I interferon receptor 2 gene (IFNAR2)-F8S and interleukin-10 receptor subunit beta gene (IL10RB)-K47E, on chronic hepatitis B virus (HBV) infection. We included 227 Thai patients with chronic HBV infection [100 with hepatocellular carcinoma (HCC) and 127 non-HCC], 170 individuals with self-limited HBV infection and 150 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to analyze these two single nucleotide polymorphisms (SNPs). In this study, the C allele of IFNAR2-F8S was found to be significantly increased in chronic HBV patients when compared with healthy controls [odds ratio, OR (95% confidence interval, CI)= 3.31 (2.11-5.21), P = 6.214 × 10(-9) and corrected P-value, P(c)= 1.864 × 10(-8)]. The effect of this allele was similar to that of an autosomal dominant gene in the presence of CC and CT genotype, when compared to TT with an OR of 4.02 (P = 4.631 × 10(-9) and P(c)= 1.389 × 10(-8)). Furthermore, AA genotype of IL10RB-K47E was found to be significantly decreased in chronic HBV patients compared with individuals with self-limited HBV infection (P = 0.006, P(c)= 0.018 and OR = 0.45). For haplotype analysis, we found CA and CG haplotypes were associated with susceptibility to chronic HBV (P = 0.014, OR = 6.84 and P = 0.002, OR = 3.75, respectively) when compared with healthy individuals. This study suggests that IFNAR2-F8S polymorphisms might be involved in the susceptibility to chronic HBV infection. Moreover, AA genotype of IL10RB-K47E may provide a protective effect in this disease. However, an association study using a larger sample size should be performed to confirm these findings.

Molecular epidemiology and genetic history of hepatitis C virus subtype 3a infection in Thailand.

OBJECTIVE: Among all hepatitis C virus (HCV) infections, subtype 3a is the most common genotype in Thailand. This study investigates the molecular epidemiology and epidemic history of HCV subtype 3a in Thailand. METHODS: Three hundred and fifty-six serum samples were collected from HCV-infected Thai patients. The virus was isolated, after which the core and NS5B regions were sequenced. Subsequently, the HCV genotype was classified by phylogenetic analysis based on the core and NS5B regions. Molecular evolution analysis of HCV subtype 3a was estimated using BEAST (Bayesian Evolutionary Analysis by Sampling Trees) v.1.5.4. RESULTS: Based on our phylogenetic analyses, subtype 3a (38.5%) was the most prevalent, followed by 1a (21%), 1b (13.8%), genotype 6 (19.9%) [comprised of subtypes 6e (0.3%), 6f (11%), 6i (1.9%), 6j (1.9%) and 6n (4.8%)] and 3b (5.6%). Our phylogenetic tree indicates the existence of a specific group of HCV subtype 3a strains in the Thai population. Molecular evolutionary analysis dated the most recent common ancestor of the Thai HCV subtype 3a strains as existing approximately 200 ago, and a Bayesian skyline plot showed that this particular strain spread to Thailand during the mid-1970s and early 1980s. This period overlaps with the Vietnam War (1955-1975) and the widespread use of injection stimulants introduced by the US Army during this time. CONCLUSION: The estimated history of HCV subtype 3a infection in Thailand may help to predict the future burden of HCV-related diseases and facilitate better public health control and surveillance.

Association of interferon-alpha gene polymorphisms with chronic hepatitis B virus infection.

In this study, the association between the risk of chronic hepatitis B virus infection and the polymorphisms within promoter regions of IFN-α1 and five genes was explored. This association study was performed on 180 Thai patients with chronic HBV infection [hepatocellular carcinoma (HCC) = 65 and non-HCC = 115], 173 individuals with self-limited HBV infection and 140 healthy controls. Our results showed that the A allele of -1823G/A SNP within IFNA1 gene was significantly associated with an increased risk of chronic HBV infection as compared to healthy individuals and self-limited HBV group [OR (95% CI) = 2.20 (1.51-3.19), P = 0.000014 and OR (95% CI) = 1.61 (1.12-2.33), P = 0.0073, respectively]. The effect of A allele was similar to autosomal recessive in which the presence of AA genotype when compared to GG and GA conferred the OR of 2.79 (95% CI = 1.72-4.52, P = 0.0000085). By multifactor dimensionality reduction analysis, we found the interaction between IFNA5 (-2529) and IFNA1 (-1823) genes that gave the risk to chronic HBV infection, with the OR (95% CI) of the high-risk to low-risk group was 2.79 (1.77-4.40), P < 0.0001. However, further study in functional significance is required.

Response-guided therapy for patients with hepatitis C virus genotype 6 infection: a pilot study.

The optimal duration of treatment with pegylated interferon (PEG-IFN) plus ribavirin (RBV) in patients with hepatitis C virus (HCV) genotype 6 is unknown. This study was aimed at determining treatment response on the basis of rapid virological response (RVR) of HCV genotype 6 in comparison with genotypes 1 and 3. Sixty-six treatment naïve patients were treated with PEG-IFN-α2a (180 µg/week) plus weight-based RBV (1000-1200 mg/day). Patients with genotype 1 n = 16) and genotype 3 (n = 16) were treated for a fixed duration of 48 and 24 weeks, respectively. Patients with genotype 6 (n = 34) who achieved RVR were treated for 24 weeks (response-guided therapy) and the remaining patients were treated for 48 weeks (standard therapy). The mean baseline HCV RNA levels were not statistically different between groups (6.4 ± 0.8, 6.0 ± 1.0 and 6.5 ± 0.8 Log(10) IU/mL for genotypes 1, 3 and 6, respectively). Patients with genotypes 1, 3 and 6 achieved RVR in 43.8%, 87.5% and 73.5% of cases, respectively. One patient with genotype 1 and 3 with genotype 6 were considered nonresponders and discontinued therapy. Sustained virological response (SVR) was achieved in 62.5%, 81.3% and 76.5% of patients with genotypes 1, 3 and 6, respectively. The SVR rate in patients with genotype 6 who underwent response-guided therapy was 88%. This pilot study suggested that the SVR rate of HCV genotype 6 was at an intermediate level between those of genotypes 3 and 1. Treatment with PEG-IFN plus RBV for 24 weeks may be sufficient for patients with genotype 6 who achieve RVR. Prospective randomized trials are required to evaluate this response-guided strategy in a larger number of patients with genotype 6.

Hepatitis B among pregnant women attending health care facilities in rural Bangladesh.

This study assessed hepatitis B prevalence among pregnant women attending health care facilities in rural Bangladesh. Blood samples were collected from 480 participants. HBsAg was positive in 0.4% of subjects, anti-HBc was positive in 21.5% and anti-HBs was positive in 8.5% of subjects. HBsAg was more prevalent among the older age group. Hepatitis B has a low prevalence among pregnant women in rural Bangladesh. Existing hepatitis B vaccination schedule in the Expanded Program on Immunization (EPI) to vaccinate the children in rural Bangladesh is appropriate.

Predictive role of serum HBsAg and HBcrAg kinetics in patients with HBeAg-negative chronic hepatitis B receiving pegylated interferon-based therapy.

OBJECTIVES: To investigate the role of serum hepatitis B core-related antigen (HBcrAg) kinetics in predicting long-term outcome of pegylated interferon (PEG-IFN)-based therapy in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). METHODS: A total of 121 Thai patients with HBeAg-negative CHB recruited from a previous randomized trial of 48-week PEG-IFN alone or combined with entecavir were enrolled. Hepatitis B surface antigen (HBsAg) and HBcrAg levels were serially examined. Paired biopsy samples taken at baseline and after treatment were assessed for intrahepatic covalently closed circular DNA (cccDNA). RESULTS: Persistent virologic remission (PVR, defined by persistent hepatitis B virus (HBV) DNA <2000 IU/mL) and HBsAg clearance at 3 years after treatment were 29% (35/121) and 9% (11/121) respectively. Baseline HBcrAg correlated with HBV DNA and cccDNA but not with HBsAg. Baseline HBsAg, as well as HBsAg and HBcrAg, declines were associated with PVR, while HBsAg decline was predictive of HBsAg clearance. High baseline antigen levels (HBsAg ≥3.4 log10 IU/mL plus HBcrAg ≥3.7 log10 U/mL) yielded high negative predictive values of PVR (45/50, 90%) and HBsAg clearance (50/50, 100%). At week 12, declines of HBsAg, HBcrAg and both antigens combined of <0.5 log10 yielded negative predictive values for PVR of 90% (71/79), 82% (61/74) and 96% (48/50) respectively. CONCLUSIONS: Quantitative HBcrAg was significantly associated with cccDNA in HBeAg-negative CHB. This novel antigen, together with HBsAg, could identify patients with low probability of PVR and HBsAg clearance in long-term follow-up.

Telomerase assay for differentiating between malignancy-related and nonmalignant ascites.

The differential diagnosis between malignancy-related ascites (MRAs) and nonmalignant ascites (NMAs) has remained an essential problem in clinical practice. Our purpose was to determine the diagnostic value of ascitic fluid telomerase activity in discriminating these two categories compared with that of cytological examination. Twenty-five MRAs and 47 NMAs as the control group were enrolled in our study. In the MRA group, telomerase activity was detected in 13 of 16 (81.3%) cases of peritoneal carcinomatosis and in 6 of 9 (66.7%) cases of hepatocellular carcinoma (HCC)-associated ascites. Contrasting that, cytological examination was positive in only 9 of 16 (56.3%) and 1 of 9 (11.1%) cases, respectively. In the NMA group, telomerase-positive ascitic fluid samples were found in 2 of 47 (4.3%) cases, all belonging to subgroups that contained large numbers of lymphocytes in the ascites. In our study, the telomerase activity and cytological examination exhibited a sensitivity of 76% and 40% and a specificity of 95.7% and 100%, respectively. Regarding subgroups of MRAs, the telomerase activity and cytological examination demonstrated a sensitivity of 81.3% and 56.3%, respectively, in peritoneal carcinomatosis and a sensitivity of 66.7% and 11.1%, respectively, in HCC-associated ascites. In conclusion, telomerase activity is a more sensitive marker than cytological examination for differentiating between MRAs and NMAs. It may also serve as a useful indicator for detecting early i.p. metastasis in HCC-associated ascites.

Association of hepatitis viruses with hepatocellular carcinoma in Thailand.

Hepatocellular carcinoma (HCC) represents the most common form of malignant tumor among males in Thailand, an area endemic for hepatitis B virus (HBV) infection. Various risk factors have been associated with the development of HCC, among them exposure to certain toxins, and infection with hepatitis viruses, in particular HBV, as well as HCV in areas non-endemic for HBV infection. To examine the association of hepatitis viruses with HCC, our group investigated 101 patients who had been clinically, mainly via alpha fetoprotein level, and/or histologically diagnosed with hepatocellular carcinoma. We also examined 200 voluntary blood donors as controls. All subjects underwent serological tests for the presence of hepatitis B surface antigen (HBsAg) and anti-HCV with polymerase chain reaction (PCR) used for the detection of HBV and TT virus (TTV) DNA, and reverse transcription (RT)-PCR for the detection of HCV RNA and HGV RNA. Besides showing a clear preponderance of HCC among males, with a peak incidence the age group 51-70 years, the results obtained in the HCC patients demonstrated that the prevalence of HBV was 65%, four times that of HCV (17%), ten times that of HGV (6%), and seven times that of TTV (9%). In the controls, the prevalence of HBV was 0.5%; that of HCV, 0.5%: that of HGV, 5%; and that of TTV, 7%. These findings confirmed that hepatitis B virus was associated with the development of hepatocellular carcinoma among the Thai population, among whom case histories of chronic hepatitis and cirrhosis have also been encountered quite frequently.

Clinical significance of p53 antigen and anti-p53 antibodies in the sera of hepatocellular carcinoma patients.

BACKGROUND: To analyze the clinical significance of serum p53 protein and anti-p53 antibodies as serological markers for hepatocellular carcinoma (HCC). METHODS: We studied clinical data, i.e., age, sex, etiology, serum alpha-fetoprotein (AFP) level. TMN staging, and Okuda staging in 141 patients with HCC. The sera of these patients were analyzed for serum p53 protein and serum anti-p53 antibodies by enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum p53 antigen and serum anti-p53 antibodies were detected in the sera of 32 of the 141 (22.7%) patients and 26 of the 141 patients (18.4%), respectively. Of note, the HCC patients who were positive for p53 antigen (32/141) had no circulating anti-p53 antibodies. When both these groups of patients were combined as a serum p53 status-positive group, the total number in this group was 58 (41.1 %). Positive status of p53 was not associated with age (P = 0.206), serum alpha-fetoprotein level (P = 0.851). Okuda staging (P = 0.243), or survival (P = 0.078), but was correlated significantly with TMN staging (P = 0.049). Interestingly, a shorter survival time (mean, 3.9 months) was noted in the serum p53 status-positive group. in comparison with the longer survival time (mean, 6.5 months) in the serum p53 status-negative group. CONCLUSIONS: Combination of the detection of serum p53 antigen and antibodies by ELISA may represent a suitable noninvasive investigation in assessing the clinical implications and prognoses of patients with HCC.

Transfusion transmissible virus TTV and its putative role in the etiology of liver disease.

TTV, the transfusion transmissible hepatitis virus infects mainly patients at risk for parenteral exposure and hence, prone to develop chronic liver disease, as well as healthy populations worldwide. Most TTV infections appear to occur parenterally, with viremia detected frequently in blood donors and blood products. The substantial proportion of asymptomatic individuals never exposed to blood-borne agents, and its high prevalence among healthy subjects implicates the fecal-oral route as another potential for transmission. According to the TTV DNA levels detected in liver tissue, it apparently replicates in hepatocytes, and TTV DNA is present in sera of patients with posttransfusion hepatitis of unknown etiology closely correlated with ALT levels. However, TTV initiating the development of chronic liver disease or causing posttransfusion hepatitis could not be confirmed, as most patients positive for TTV DNA remain asymptomatic and those progressing towards chronic liver disease are invariably coinfected with either the hepatitis B or C virus. Also, TTV coinfection does not aggravate the symptoms associated with hepatitis B or C. Similarly, it does not cause posthepatitis aplastic anemia, and high-risk patients can immunologically clear the viral DNA. In conclusion, being widely distributed and apparently nonpathogenic, TTV might represent an opportunistic but innocent virus reminiscent of hepatitis G virus, with a negligible role in the etiology of chronic liver disease.

TT virus infection in chronic liver disease.

BACKGROUND/AIMS: The exact role of the novel hepatotropic TT virus regarding the etiology of viral hepatitis, as well as the progression towards chronic liver disease has as yet not been defined. Moreover, the contribution of TTV infection to the course of chronic hepatitis B or C virus infections also still awaits clarification. Hence, the aim of our study was to investigate the impact of TTV infection on clinical severity and histology of chronic liver disease originating from HBV and/or HCV infections in Thai patients concomitant with the determination of TTV's association with non-B, non-C chronic liver disease and compared to its prevalence among voluntary blood donors. METHODOLOGY: DNA was extracted from the sera collected from 115 hepatitis B patients, 41 hepatitis C, and 48 negative for either viral marker, who had all been diagnosed with chronic liver disease ranging from chronic hepatitis over cirrhosis to hepatocellular carcinoma. The sera obtained from 200 voluntary blood donors served as controls. TTV DNA was amplified by seminested polymerase chain reaction (PCR) employing primers derived from the genome's most conserved region. The PCR products were analyzed by gel electrophoresis. Liver function tests were performed by means of a chemical analyzer. RESULTS: TTV DNA was detected in 20% of the HBV-positive and 19.5% of the HCV-positive chronic liver disease patients. Within the group of patients seronegative for both viral markers, TTV was detected in 8.3%. Furthermore, its DNA was identified in 6.8% of the HCC patients and finally, in 7% of the blood donors. Yet, no significant differences between TTV infected and non-infected patients were found as to demographic data, assumed source of infection, biochemical abnormalities, or severity of liver histology. CONCLUSIONS: TTV appears to be highly prevalent on a worldwide scale but regarding etiology of and progression towards serious liver disease, its contribution seems to be minor if not altogether non-existent. Hence, regarding clarification of its clinical significance, further studies are certainly required.

Proliferating ductules are a diagnostic discriminator for intrahepatic cholangiocarcinoma in FNA biopsies.

The histologic distinction of cholangiocarcinoma (CC) from metastatic carcinoma and hepatocellular carcinoma (HCC) is difficult. In particular, the distinction of CC from metastatic carcinoma on morphologic features alone is not possible and is dependent on the identification of an extrahepatic primary carcinoma. The proliferative response to many types of liver injury is characterized by a proliferation of either hepatocyte ductular clusters (HDC) or biliary ductular clusters (BDC). This study examined the presence of such ductular reactions in fine needle aspiration biopsies of 20 consecutive cases each of CC and HCC, and compared the findings to those of 20 cases of hepatic metastases from a wide variety of sites. All 18 cases of CC with adequate smears showed ductular proliferation of either HDC or BDC type, the latter being more common; in 13 cases, there were more than 10 ductular clusters per smear. In contrast, only one case of metastatic carcinoma displayed so many ductular clusters, this being a case with multiple hepatic deposits. Five cases of HCC showed more than 10 clusters. The presence of more than 10 ductular clusters associated with malignant cells is a useful discriminator to separate CC from metastatic carcinoma.

The correlation between markers of oxidative stress and risk factors of coronary artery disease in Thai patients.

An imbalance between oxidative damage and antioxidative protection in association with the pathophysiology of atherosclerosis has been suggested. The aim of our study was to investigate the relationship between plasma lipids, the antioxidant system and oxidative damage in Thai patients with stable coronary artery disease (CAD). Sixty-one patients (40 males, 21 females), who were angiographically defined as having CAD and were clinically stable, participated in this study. Thirty-two healthy subjects (20 males, 12 females) served as normal controls. The investigation included the measurements of plasma lipid profiles and plasma total antioxidative status (TAS) such as plasma vitamin E erythrocyte glutathione (GSH) and glutathione peroxidase (GPx), as well as malondialdehyde (MDA) and total plasma total protein thiols (P-SH). In patients with CAD, erythrocyte GSH and GPx were significantly lower than those found in controls. However plasma TAS and vitamin E were not significantly different between groups. Patients with CAD also had higher MDA and lower P-SH levels than the controls, which represents the oxidative damage products of lipid and proteins. Multiple regression analysis revealed negative correlations between GSH and cholesterol, GSH and low density lipoprotein (LDL), vitamin E and MDA, as well as P-SH and MDA. This study demonstrated the status of oxidative stress in patients with stable CAD. Since oxidative stress is the imbalance between the total oxidants and antioxidants in the body, any single oxidant/antioxidant parameter may not reflect the overall oxidative stress system. Thus, in patients with CAD, diets with various types of antioxidants may be more beneficial in increasing antioxidant activity than any particular antioxidant supplementation.

Current status of infection-related gastrointestinal and hepatobiliary diseases in Thailand.

The objective of this overview is to assess the present situation with regards to gastrointestinal and hepatobiliary diseases prevailing in Thailand. In that context, special emphasis has been put on those forms of viral hepatitis prevalent in the region, namely, hepatitis A the frequency of which has undergone a change from hyper- to hypoendemic with a resulting decline in naturally acquired immunity; hepatitis B with its tendency to cause chronic liver disease mainly due to asymptomatic infections during early childhood and the impact of mass vaccination programs on its endemicity; hepatitis C which can also lead to chronicity; hepatitis D solely found as a coinfection with hepatitis B; hepatitis E acute cases of which can sporadically be found; hepatitis G encountered in healthy subjects at a prevalence similar to that seen in patients with chronic liver disease and rather more prevalent among people at risk for contracting blood borne agents; finally the novel hepatitis TT virus with a distribution comparable to that of hepatitis G virus and a similarly unclear role as to the etiology of serious liver disease. Particularly in connection with hepatitis B we have examined the situation regarding hepatocellular carcinoma which represents one of the most common malignancies among the Thai population. Cholangiocarcinoma caused by the liver fluke Opisthorchis viverrini is the most common form of liver cancer in the northeastern part of Thailand where an estimated 70% of the population are infested with the parasite. Peptic ulcer caused by Helicobacter pylori constitutes another common gastrointestinal affliction with the overall prevalence of antibodies to the agent amounting to 63 to 74% in patients exhibiting gastroduodenal symptoms. The final part of the paper deals with HIV-related gastrointestinal and liver disease and with amebic and pyogenic liver abscesses.

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.

Hepatitis GBV-C infection in intravenous drug users.

Our group has investigated 204 intravenous drug users for the presence of GBV-C-RNA by means of reverse transcriptase polymerase chain reaction (RT-PCR). The majority of the individuals tested were male, their age ranging from 16 to 63 years, and the duration of intravenous drug use from one to 40 years. We detected GBV-C-RNA in 46 of the 204 IVDUs (22.5%) with its prevalence peaking in the age group between 21 to 30 years while decreasing with advancing age. Similarly, its frequency was found in inverted relation to the duration of drug use. The present findings strongly hint at the host's immune system's capacity to clear hepatitis GBV-C as opposed to the other blood-borne hepatitis viruses. From the liver function tests performed we could not detect any statistically significant difference regarding ALT elevation observed in GBV-C-positive as compared to GBV-C-negative individuals. To date, GBV-C in most cases does not appear to cause any serious liver disease.

Short-term effects of branched-chain amino acids on liver function tests in cirrhotic patients.

A randomized study was conducted in 29 ambulatory cirrhotic patients to determine the short-term effects of branched-chain amino acids (BCAA) on nutritional status, biochemical liver function tests and caffeine clearance. Each patient received a 4-week period of isonitrogenous and isocaloric regimens, either a standardized diet contained 40 g protein with supplementation of BCAA 150 g daily (group I) or only a standardized diet contained 80 g protein daily (group II). At the end of treatment, only group I showed significant improvements in transaminase levels as well as the caffeine clearance test compared with those of the pre-treatment levels. Nonetheless, significant improvements in nutritional parameters and additional liver function tests were not yet detected. We conclude that the short-term nutritional supplementation of BCAA is well tolerated and leads to improvement in hepatic metabolic capacity assessed by the caffeine clearance test.