Predictive Factors Associated with Survival in Female Gastric Cancer Patients in Southeast Asia.

Introduction: Association of Southeast Asian Nations (ASEAN) countries have high Helicobacter pylori infections, and gastric cancer (GC) is a leading fatal cancer in this region, especially in female patients. This study aimed to compare clinical manifestations, histopathological subtypes, and prognostic factors associated with the overall survival rate of female GC patients in this important region. Methods: This retrospective cohort study was conducted between 2007 and 2022 at a tertiary care center in Thailand. All clinical information, endoscopic findings, and histological types were extensively reviewed. Furthermore, all qualified studies in ASEAN published in PubMed and Scopus between 2000 and 2022 were extracted and thoroughly analyzed. Young female GC patients are defined as those ≤50 years of age. Results: A total of 98 Thai female GC patients were included, with a mean age of 58.99 ± 14 years; 70.4% were elderly women. The common presenting symptoms were weight loss (69.4%) and dyspepsia (68.4%). Younger female GC patients had significantly more common diffuse-type GC than elderly female GC patients (82.8% vs. 53.6%, p-value = 0.007). Moreover, elderly female GC patients demonstrated significantly better survival than younger female GC patients (44.8% vs. 20.7%, odds ratio = 3.49; 95% confidence interval: 1.20-10.14, p-value = 0.022). Furthermore, a total of 1,491 female GC patients from ASEAN were reviewed and included in this study, aged 15 to 93 years. The top three countries with the highest proportion of female GC from ASEAN were Indonesia (66.7%), Thailand (44.9%), and Singapore (38.4%). Conclusion: GC in women is not uncommon in ASEAN and presents at an advanced stage with a grave prognosis. This study showed that ASEAN countries with the highest disease burden were Indonesia, Thailand, and Singapore. Overall, survival rates for female GC patients in ASEAN countries were relatively low, highlighting the need for proactive measures such as intensive H. pylori eradication and the development of early detection methods for GC.

Simultaneous detection of Helicobacter pylori infection comparing between white light and image-enhanced endoscopy.

BACKGROUND: Helicobacter pylori (H. pylori) is associated with gastric cancer. Early and accurate diagnosis of H. pylori infection can reduce risk of gastric cancer. Conventional white light imaging (WLI) and image-enhanced endoscopic (IEE) techniques such as narrow-band imaging (NBI), linked color imaging (LCI) and blue laser imaging (BLI) plays pivotal role in H. pylori diagnosis. This study aimed to determine diagnostic performance of real-time endoscopy between WLI and other IEE techniques for diagnosis of H. pylori infection. METHODS: This prospective study compared endoscopic images by gastroscopy using WLI and IEE techniques (LCI, Magnifying-BLI, and Magnifying-NBI) at Thammasat University Hospital, Thailand between January 2020, and July 2021. All participants underwent gastroscopy. Three biopsies at gastric antrum and two biopsies at body were obtained for H.pylori diagnosis. H. pylori infection was defined as a positive test of either one of the following tests: rapid urease test, histopathology, H. pylori culture. RESULTS: Of 167 dyspeptic patients undergoing gastroscopy, 100 were enrolled in this study. Overall H. pylori infection was 40%. Patients had the mean age of 59.1 years and 53% were males. Enlarged gastric folds and antral nodularity can predict H. pylori infection with 100% PPV, while fundic gland polyps and red streak provided 100% PPV for exclusion of H. pylori infection on WLI. Sensitivity, specificity, PPV, NPV and accuracy for diagnosis of H. pylori infection for WLI were 80%, 71.7%, 65.3%, 84.3% and 75% respectively, while those for LCI were 90%, 70%, 66.7%, 91.3% and 78% respectively. M-NBI and M-BLI endoscopy demonstrated elongated pits in H. pylori-positive patients. Sensitivity, specificity, PPV, NPV and accuracy for M-BLI were 95%, 80%, 76%, 96% and 86% respectively, whereas those for M-NBI were 92.5%, 86.7%, 82.2%, 94.6% and 89% respectively. Sensitivity of M-BLI was better than WLI, while sensitivities of LCI and M-NBI were also numerically higher than WLI without statistical difference (M-BLI 95%vs.WLI 80%, p = 0.03; M-NBI 92.5%vs.WLI 80%, p = 0.13; LCI 90%vs.WLI 80%, p = 0.22). Sensitivities of all IEE modes were not different from one another (LCI 90%vs.M-BLI 95%, p = 0.50; LCI 90%vs.M-NBI 92.5%, p = 1.00, M-BLI 95%vs.M-NBI 92.5%, p = 1.00). CONCLUSIONS: M-BLI significantly improved sensitivity of real-time endoscopic diagnosis of H. pylori infection compared with WLI. Enlarged gastric folds and antral nodularity could be reliable predictors for H. pylori infection, while fundic gland polyps and red streak could be important endoscopic findings for H. pylori-negative mucosa.

Correlation between Cumulative Methotrexate Dose, Metabolic Syndrome and Hepatic Fibrosis Detected by FibroScan in Rheumatoid Arthritis Patients.

Background and Objectives: Methotrexate (MTX) is routinely prescribed for rheumatoid arthritis (RA) patients, but high cumulative doses may lead to hepatic fibrosis. Additionally, a high proportion of RA patients suffer from metabolic syndrome, which also increases the risk of hepatic fibrosis. This cross-sectional study aimed to explore the association between a cumulative MTX dose, metabolic syndrome, and hepatic fibrosis in patients diagnosed with RA. Materials and Methods: RA patients undergoing treatment with MTX were examined using transient elastography (TE). All patients, regardless of having hepatic fibrosis, were compared to identify the risk factors. Results: Two hundred and ninety-five rheumatoid arthritis patients were examined using FibroScan. One hundred and seven patients (36.27%) were found to have hepatic fibrosis (TE > 7 kPa). After multivariate analysis, only BMI (OR = 14.73; 95% CI 2.90-74.79; p = 0.001), insulin resistance (OR = 312.07; 95% CI 6.19-15732.13; p = 0.04), and cumulative MTX dosage (OR 1.03; 95% CI 1.01-1.10; p = 0.002) were associated with hepatic fibrosis. Conclusions: While the cumulative MTX dose and metabolic syndrome are both the risk factors of hepatic fibrosis, metabolic syndrome, including a high BMI and insulin resistance, poses a greater risk. Therefore, MTX-prescribed RA patients with metabolic syndrome factors should be attentively monitored for signs of liver fibrosis.

Branched-chain amino acids supplementation improves liver frailty index in frail compensated cirrhotic patients: a randomized controlled trial.

BACKGROUND: Physical frailty is related with morbidity and mortality in patients with cirrhosis. Currently, there is no approved treatment of frailty in these patients. Here, we evaluated the efficacy of 16 weeks branched-chain amino acids (BCAA) supplementation on frailty in frail compensated cirrhotic patients. METHODS: After a 4-week run-in period consisted of dietary and exercise counseling, compensated cirrhotic patients with frailty, defined by liver frailty index (LFI)≥4.5, were randomly assigned (1:1) to BCAA or control group. The BCAA group received twice daily BCAAs supplementation (210 kcal, protein 13.5 g, BCAA 2.03 g) for 16 weeks. The primary outcome was frailty reversion. The secondary outcomes were changes in biochemistries, body composition evaluated by bioelectrical impedance analysis, and quality of life (QoL). RESULTS: 54 patients were prospectively enrolled (age 65.5 ± 9.9 years, 51.9% female, Child-Pugh A/B 68.5%/31.5%, MELD 10.3 ± 3.1). Baseline characteristics were similar between both groups. At week 16, BCAA group had a significant improvement in LFI (-0.36 ± 0.3 vs. -0.15 ± 0.28, P = 0.01), BMI (+ 0.51 ± 1.19 vs. -0.49 ± 1.89 kg/m2, P = 0.03), and serum albumin (+ 0.26 ± 0.27 vs. +0.06 ± 0.3 g/dl, P = 0.01). The proportion of frailty reversion at week 16 was significantly higher in BCAA group (36% vs. 0%, P < 0.001). Compared with baseline, BCAA group had a significant increase in skeletal muscle index (7.5 ± 1.6 to 7.8 ± 1.5 kg/m2, P = 0.03). Regarding the QoL, only the BCAA group had a significant improvement in all 4 domains of physical component score of the SF-36 questionnaire. CONCLUSIONS: A 16-week BCAA supplementation improved frailty in frail compensated cirrhotic patients. In addition, this intervention resulted in an improvement of muscle mass and physical domain of QoL in these patients. TRIAL REGISTRATION: This study was registered with Thai Clinical Trial Registry (TCTR20210928001; https://www.thaiclinicaltrials.org/# ).

Plasma Cystatin C Level is a Prognostic Marker of Morbidity and Mortality in Hospitalized Decompensated Cirrhotic Patients.

Introduction : Cystatin C (CysC) is biomarker for early detection of acute kidney injury (AKI). However, there is limited evidence in decompensated cirrhotic patients without AKI at admission. This study aimed to assess CysC as a predictor of 90-day mortality. Methods : Decompensated cirrhotic patients without AKI were prospectively enrolled. CysC and creatinine were measured within 24 hours of admission and compared between patients with in-hospital complications (AKI, hepatorenal syndrome (HRS), acute-on-chronic liver failure (ACLF)) vs. those without, and survivors vs. non-survivors. The AUROC and cut-off point of CysC in predicting 90-day mortality were determined. Results : Of 137 decompensated cirrhotic patients, 46 without AKI at admission were included (58.7% male, age 60.8 ±â€†11.2years, MELD 13.1 ±â€†5.1, ChildA / B / C 43.5% / 39.1% / 17.4%). The mean CysC level tended to be higher in patients with ACLF (1.52 ±â€†0.60 vs. 1.11 ±â€†0.28, p = 0.05), and significantly higher in non-survivors than survivors (1.61 ±â€†0.53 vs. 1.08 ±â€†0.28, p = 0.013). The 90-day mortality rate was 21.7%. After adjusting with age and bacterial infection on admission, CysC level  ≥ 1.25 mg / L was significantly associated with 90-day mortality. The CysC cut-off level  ≥ 1.25 mg / L provided 80% sensitivity and 75% specificity for predicting 90-day mortality. Conclusion : Plasma CysC within 24 hours could be used as a predictor for 90-day mortality and development of ACLF in decompensated cirrhotic patients. J. Med. Invest. 68 : 302-308, August, 2021.

Frailty as tested by the Liver Frailty Index is associated with decompensation and unplanned hospitalization in patients with compensated cirrhosis.

BACKGROUND AND AIMS: Frailty is associated with morbidity and mortality in advanced cirrhosis. However, the information on the association between frailty and outcome in compensated cirrhosis is scarce. We aimed to explore the prognostic impact of frailty in compensated cirrhosis. METHODS: Compensated cirrhotic patients were prospectively enrolled. Frailty was defined by the Liver Frailty Index (LFI). Development of new hepatic decompensation (worsening ascites, portal hypertension-related bleeding, hepatic encephalopathy, or acute kidney injury), unplanned hospitalization, and decompensation-free survival were recorded. Quality of life (QoL) was assessed by SF-36 questionnaire. RESULTS: 152 patients were included (MELD 9.2 ± 3.4, Child-Pugh A/B 84.9%/15.1%), and 24.3% were frail. By multivariable logistic regression analysis, age > 65 years, MELD score > 10, and Child-Pugh B were associated with frailty. Compared to the robust group, pre-frail and frail patients had significantly higher cumulative 1-year probabilities of developing decompensation (0% vs. 8.5% vs. 18.4%, p = .009), and unplanned hospitalization (0% vs. 13.5% vs. 34.2%, p < .001), and lower 1-year decompensation-free survival (100% vs. 90.8% vs. 80.4%, p = .014). Two models of multivariable Cox regression analysis were done adjusted with MELD-Na and Child-Pugh B, frailty was associated with developing decompensation (HR 3.01, p = .04; and 2.98, p = .04, respectively) and unplanned hospitalization (HR 2.46, p = .02; and 2.39, p = .03, respectively), but not the decompensation-free survival. By multivariable linear regression analysis, Child-Pugh B and frailty significantly decreased both physical and mental component scores of the SF-36 questionnaire. CONCLUSION: Frailty is prevalent in compensated cirrhosis. The LFI provides additional prognostic values to recognized risk scores regarding the development of decompensation, hospitalization, and impaired QoL.

Predictors for regression and progression of intestinal metaplasia (IM): A large population-based study from low prevalence area of gastric cancer (IM-predictor trial).

BACKGROUND: Gastric intestinal metaplasia (IM) can lead to gastric cancer. Until now, there have been limited studies of predictors for regression and progression of IM. This study aimed to determine risk factors associated with regression or progression of IM for guiding proper management and prevention of gastric cancer. METHODS: 2,025 patients undergoing gastroscopy in Thammasat University Hospital, Thailand were enrolled during September 2017-August 2019. Patients' data including baseline characteristics, laboratory results, and histopathology of gastric biopsies from University medical database were extensively reviewed. RESULTS: 2,025 patients had mean age of 61.3 years and 44.2% were males. Overall H. pylori prevalence was 47.5%. There were 1,551(76.6%) patients with chronic gastritis and 361(17.8%) with IM. Of 400 patients with chronic gastritis having follow-up endoscopy and repeated gastric biopsies, 104(26%) had persistent H. pylori infection and 27(26%) developed IM during mean follow-up time of 24 months. Persistent H. pylori infection was significantly associated with development of IM (OR 3.16, 95%CI 1.56-6.39, p = 0.001). Regression, persistence, and progression of IM were demonstrated in 57.3%, 39.2%, and 3.5% of patients, respectively. Age >65 years, persistent H. pylori infection, and diabetes mellitus were significantly associated with persistent IM or progression to dysplasia with OR 2.47(95%CI 1.33-4.61, p = 0.004), OR 2.64(95%CI 1.13-6.18, p = 0.025), and OR 2.54(95%CI 1.16-5.54, p = 0.019), respectively. Patients without H. pylori infection had more IM regression than patients with persistent infection (60.4%vs.39.4%, p = 0.035). Patients with persistent H. pylori infection significantly had higher IM progression to dysplasia (15.2%vs.2.1%; OR 11.15, 95%CI 1.18-105.24, p = 0.035) than noninfected. During 24 months of study, 30 patients (1.5%) were diagnosed with gastric cancer. CONCLUSION: Regression of IM could be achieved by successful H. pylori eradication. Persistent H. pylori infection was significantly associated with development and progression of IM to dysplasia. Age >65 years and diabetes mellitus were also significant predictors for IM progression.

Clinical Features and Overall Survival of Females with Hepatocellular Carcinoma: A Retrospective Study and Review of the Literature in the Association of Southeast Asian Nations.

INTRODUCTION: Hepatocellular carcinoma (HCC) causes more than 200,000 women deaths annually. This study aimed to investigate the clinical features, provide prognostic factors for female patients with HCC, and performed a literature review on them in the Association of Southeast Asian Nations (ASEAN). MATERIALS AND METHODS: We conducted a retrospective cohort study of female patients with HCC at Thammasat University Hospital, Thailand between January 2009 and January 2019. Furthermore, important aspects of female patients with HCC in the ASEAN published in PubMed and Scopus up to October 2020 were extensively reviewed. RESULTS: A total of 187 female patients with HCC were included (mean age 65.7±11.9 years). Elderly females were diagnosed with HCC at a more advanced stage than younger individuals (37.0% vs 23.2%, p=0.049, OR 1.94, 95% CI 1.00-3.78) and the younger group had a significantly higher overall 2-year survival rate than the elderly group (65.0% vs 45.5%, p=0.03, OR 2.23, 95% CI 1.09-4.57). Abdominal pain (HR 9.89, 95% CI 2.85-34.38, p<0.001), ascites at presentation (HR 2.77, 95% CI 1.11-6.92, p=0.03), ruptured hepatoma (HR 14.68, 95% CI 12.60-83.09, p=0.002), advanced-stage HCC (HR 9.74, 95% CI 1.89-50.26; p=0.007), and serum hypoalbuminemia (HR 4.67, 95% CI 1.62-13.50, p=0.004) were significantly associated with poor survival rate. From the ASEAN, a total of 543 females HCC patients from 6 studies were extensively reviewed. Chronic hepatitis B infection was among the pre-existing liver disease leading to HCC in ASEAN. HCC in females of the ASEAN occurred most often at an advanced age and had a grave prognosis. CONCLUSION: HCC affects a large number of females, especially in Thailand and the ASEAN, is diagnosed at an advanced stage and had a grave prognosis. Abdominal pain, ascites, ruptured HCC, advanced-stage HCC, and serum hypoalbuminemia are associated with poor prognosis. Early detection of HCC and prompt treatment in patients at risk could result in better survival outcomes.

Predictors for development of complete and incomplete intestinal metaplasia (IM) associated with H. pylori infection: A large-scale study from low prevalence area of gastric cancer (IM-HP trial).

BACKGROUND: Gastric intestinal metaplasia (IM) is precancerous lesion of gastric cancer related to H. pylori infection. There has been limited data about IM and associated risk factors. This study aimed to determine risk factors related to development of IM to guide proper management. METHODS: 1,370 patients undergoing UGI endoscopy at Thammasat University Hospital, Thailand were included between January 2018-August 2019. Patients' data including baseline characteristics, laboratory results, and histopathology from medical database were extensively reviewed. Immunohistochemical staining for p53 expression from gastric biopsies was also performed. RESULTS: Overall H. pylori prevalence was 43.8%. Mean age was 60.7 years and 45% of whom were males. Chronic gastritis was observed in 1,064(77.7%) patients, while 223(16.3%) had IM. Of 223 patients with IM, 194(87%) patients had complete IM, while 29 (13%) had incomplete IM. In groups of complete and incomplete IM, current H. pylori infection rates were 66.5% and 58.6%, respectively. The BMI of incomplete IM group(27.4) was significantly higher than BMI of complete IM group (23.6). Overweight and obese patients (BMI ≥23 kg/m2) were significantly associated with higher risk for the development of incomplete IM (OR 3.25; 95%CI 1.14-9.27, p = 0.027). Males, age >50 years, and current H. pylori infection were significantly higher in IM than chronic gastritis group with OR 1.43 (95%CI 1.01-2.03, p = 0.048), OR 1.67 (95% CI 1.08-2.57, p = 0.021), and OR 3.14 (95% CI 2.29-4.30, p<0.001), respectively. During 20 months of study, there were 15 patients (1.1%) diagnosed with gastric cancer and 1-year survival rate was only 60%. CONCLUSIONS: Males, age >50 years, and current H. pylori infection are significant predictors for the presence of intestinal metaplasia. BMI might be beneficial for using as a predictive risk factor to reduce the development of incomplete intestinal metaplasia. H. pylori eradication could be an effective way to prevent the development of gastric precancerous lesions.

Real-world effectiveness and safety of sofosbuvir and nonstructural protein 5A inhibitors for chronic hepatitis C genotype 1, 2, 3, 4, or 6: a multicentre cohort study.

BACKGROUND: We investigated real-world effectiveness and safety of sofosbuvir and the nonstructural protein 5A inhibitors in the treatment of patients infected with hepatitis C virus (HCV) genotypes 1, 2, 3, 4, or 6. METHODS: We analyzed data from 1021 patients with HCV infection (506 with genotype 1; 16 with genotype 2; 314 with genotype 3; 13 with genotype 4; 166 with genotype 6) who received 12 to 24 weeks of daclatasvir plus sofosbuvir (n = 767), ledipasvir/sofosbuvir (n = 197), or sofosbuvir/velpatasvir (n = 57), with or without ribavirin in 12 centers across Thailand to estimate sustained virologic response at post-treatment week 12 (SVR12). RESULTS: Overall, SVR12 rate was 98.0% (95% confidence interval [CI], 96.7-98.8%) with daclatasvir plus sofosbuvir, 97.9% (95% CI, 94.8-99.2%) with ledipasvir/sofosbuvir, and 96.5% (95% CI, 88.1-99.0%) with sofosbuvir/velpatasvir. SVR12 was achieved by 99.2% (95% CI, 97.9-99.7%) of subjects with genotype 1 infection, 100% (95% CI, 78.5-100%) of those with genotype 2 infection, 96.7% (95% CI, 94.0-98.2%) of those with genotype 3 infection, 90.9% (95% CI, 62.3-98.4%) of those with genotype 4 infection, and 96.7% (95% CI 92.5-98.6%) of those with genotype 6 infection. Patients with advanced liver disease were at risk of treatment failure. Only four patients discontinued treatment before week 4 due to non-hepatic adverse events. CONCLUSIONS: In this large cohort of patients with various HCV genotypes managed in the real-world practice setting, daclatasvir plus sofosbuvir, ledipasvir/sofosbuvir, and sofosbuvir/velpatasvir achieved high SVR rates with good safety profile, comparable to those observed in clinical trials.

N-Acetylcysteine Prevents Post-embolization Syndrome in Patients with Hepatocellular Carcinoma Following Transarterial Chemoembolization.

BACKGROUND: Post-embolization syndrome is a common complication after transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). N-acetylcysteine (NAC) is known to ameliorate liver damage from several causes. AIM: To determine the efficacy of intravenous NAC in the prevention of post-embolization syndrome in HCC patients following TACE. METHODS: In this study, patients with HCC admitted for TACE were prospectively enrolled. All patients were randomized stratified by Child A or B to receive NAC or placebo. The NAC group received intravenous NAC 24 h prior to TACE (150 mg/kg/h for 1 h followed by 12.5 mg/kg/h for 4 h, then continuous infusion 6.25 mg/h for 48 h after the procedure). The placebo group received an infusion of 5% glucose solution until 48 h after procedure. The post-embolization syndrome was defined as: T ≥ 38.5 c and serum ALT > 3 times of pretreatment value. RESULTS: In total, 111 HCC patients were enrolled; 57 were randomly assigned to NAC group and 54 to placebo group. The incidence of post-embolization syndrome was lower in NAC group (24.6%) compared to placebo group (48.2%); P = 0.01. On multivariate analysis, receiving IV NAC (P = 0.03) and HCC diameter (P < 0.01) were associated with developing post-embolization syndrome. Post-TACE liver decompensation was documented in 26/111 (23.4%) patients. There was no difference in the incidence of post-TACE liver decompensation between NAC and placebo group. CONCLUSIONS: In this study, intravenous NAC administration reduces the incidence of post-embolization syndrome after TACE in patients with HCC. However, it does not prevent post-TACE liver decompensation. TRIAL REGISTRATION NUMBER: This study was registered with Thai Clinical Trial Registry (TCTR20150313002).

Association between cumulative methotrexate dose, non-invasive scoring system and hepatic fibrosis detected by Fibroscan in rheumatoid arthritis patients receiving methotrexate.

BACKGROUND: Methotrexate (MTX) is recommended by recent American College of Rheumatology and European League against Rheumatism guidelines as a first-line drug for rheumatoid arthritis (RA). Liver fibrosis, which occurs as a long-term side effect is of major concern. Monitoring aminotransferase and albumin is suggested in the guidelines, unfortunately this method is unreliable for detecting liver fibrosis. We try to find the association between clinical parameters, cumulative MTX dosage, liver fibrosis scoring systems and the presence of liver fibrosis assessed by transient elastography (TE; Fibroscan®). METHOD: Rheumatoid arthritis patients prescribed MTX were evaluated for liver fibrosis with TE. Two subgroups of patients were compared: non-fibrosis and fibrosis (TE > 7 kPa). Univariate and multivariate logistic regression analysis was performed to identify factors associated with liver fibrosis. RESULTS: One hundred and eight patients were recruited. Twenty-nine patients (26.8%) were classified by transient elastography as liver fibrosis cases. The multivariate analysis demonstrated statistical significance only in the association of body mass index (odds ratio [OR] = 1.22; 95% CI 1.05-1.41; P = 0.01); fatty liver (OR = 2.32; 95% CI 1.58-9.19; P = 0.02); alanine transaminase (OR = 1.04; 95% CI 1.02-1.09; P = 0.04) and cumulative MTX dosage (OR = 1.03; 95% CI 1.01-1.04; P = 0.001). CONCLUSIONS: Liver fibrosis measured with Fibroscan was associated with cumulative MTX. RA patients with metabolic syndrome including high body mass index and fatty liver, had a higher risk of MTX-induced hepatic fibrosis. RA patients with high cumulative MTX dose, especially patients with concurrent metabolic syndrome, should be cautiously monitored for liver fibrosis.

Epidemiology and treatment of hepatocellular carcinoma in Thailand.

Hepatocellular carcinoma (HCC) is the most frequent type of malignant liver tumor in Thailand. The high incidence rate of HCC reflects from chronic HBV infection in this endemic area. Some patients are asymptomatic at presentation whereas many of them presented at advanced stage of HCC with limited treatment options and grave outcome. The Barcelona Clinic Liver Cancer (BCLC) staging system and management allocation for HCC is widely accepted and used in many international guidelines including Thailand. Curative treatment is expected in early stage of HCC while palliative treatment, combination treatment and best supportive care are offered to advanced stage of HCC. The most effective strategy to prevent the development of HCC is prevention of HBV vertical transmission and treatment HBV or HCV infection. The purpose of this article is to update information of HCC in Thailand including epidemiology, diagnosis, clinical manifestation, and treatment.

Effect of IL-1 Polymorphisms, CYP2C19 Genotype and Antibiotic Resistance on Helicobacter pylori Eradication Comparing Between 10-day Sequential Therapy and 14-day Standard Triple Therapy with Four-Times-Daily-Dosing of Amoxicillin in Thailand: a Prospective Randomized Study.

BACKGROUND: Studies of effects of IL-1 polymorphisms, CYP2C19 genotype together with antibiotic resistance for H. pylori eradication are rare worldwide. The present study was designed to evaluate efficacy of 10-day sequential therapy (SQT) and 14-day standard triple therapy (STT) with four- times-daily dosing of amoxicillin for H. pylori eradication related to these important host and bacterial factors in Thailand. MATERIALS AND METHODS: This prospective randomized study was performed during March 2015 to January 2016. H. pylori infected gastritis patients were randomized to receive 10-day sequential therapy and 14-day standard triple therapy. CYP2C19 genotyping, IL1 polymorphism (IL-1B and IL-1RN genotypes) and antibiotic susceptibility tests were performed in all patients. 13C-UBT was conducted to confirm H. pylori eradication at least 4 weeks after treatment. RESULTS: A total of 100 patients (33 males and 67 females, mean age=51.1 years) were enrolled. Eradication rate by PP analysis was 97.9% (47/48) with the 10-day SQT regimen and 87.8% (43/49) with 14-day STT regimen (97.9% vs 87.8%; p-value=0.053). Antibiotic susceptibility testing demonstrated 45% resistance to metronidazole, 14.8% to clarithromycin, and 24.1% to levofloxacin. CYP2C19 genotyping revealed 44.9% RM, 49% IM and 6.1% PM. IL-1B and IL-1RN genotypes were demonstrated as 21.4% for CC, 48.1% for TC, 36.8% for TT, 72.7% for 1/1, and 21.2% for 1/2 genotypes, respectively. The 10-day SQT regimen provided 100% eradication in patients with clarithromycin or dual clarithromycin and levofloxacin H. pylori resistant strains. Moreover, the 10-day SQT regimen resulted in a 100% eradication rate in all patients with CYP2C19 genotype RM and almost type of IL-1B (TC and TT) and IL1-RN genotypes ( 1/2 and other). CONCLUSIONS: Treatment with 10-day sequential therapy is highly effective for H. pylori eradication regardless of the effects of clarithromycin resistance, dual clarithromycin and levofloxacin resistance, CYP2C19 genotype, IL-1B and IL1-RN genetic polymorphisms and can be used as effective first line therapy in Thailand.

Treatment outcomes and validation of the stopping rule for response to peginterferon in chronic hepatitis B: A Thai nationwide cohort study.

BACKGROUND AND AIMS: Peginterferon has demonstrated effectiveness in clinical trials in patients with chronic hepatitis B (CHB). However, its efficacy in real-life settings remains unclear. We investigated the efficacy of peginterferon for CHB and validated the performance of previously identified response predictors in clinical practice. METHODS: We analyzed prospectively collected data from a Thai nationwide cohort of CHB patients treated with peginterferon alfa-2a (180 µg/week, 48 weeks). RESULTS: Among a total of 233 patients, mostly with genotype B or C, sustained response was observed in 23% of 135 hepatitis B e antigen (HBeAg)-positive patients (HBeAg seroconversion with hepatitis B virus [HBV] DNA < 2000 IU/mL) and 42% of 98 HBeAg-negative patients (HBV DNA < 2000 IU/mL with aminotransferase normalization) at 24 weeks after treatment. Age, sex, presence of cirrhosis, genotype, and pretreatment levels of aminotransferase, HBV DNA, and hepatitis B surface antigen (HBsAg) were not identified as significant predictors of sustained response. In HBeAg-positive patients, HBsAg > 20 000 IU/mL at week 12 provided a good stopping rule, with a negative predictive value of 96%. In HBeAg-negative patients, the performance of 12-week stopping rules of no decline in HBsAg with a < 2log10 decline in HBV DNA and a < 10% log10 decline in HBsAg showed modest negative predictive values of 80% and 66%, respectively, for achieving sustained response. CONCLUSION: Outcomes in CHB patients treated with peginterferon in a clinical setting are similar to those demonstrated in clinical trials. Application of the early stopping rule based on HBsAg quantification may allow individualization of therapy, particularly in HBeAg-positive patients.

CYP2C19 Genotype Could be a Predictive Factor for Aggressive Manifestations of Hepatocellular Carcinoma Related with Chronic Hepatitis B Infection in Thailand.

BACKGROUND: Chronic hepatitis B virus (HBV) infection related hepatocellular carcinoma (HCC) is a major health problem in the Asia-Pacific region including Thailand. Several factors have been proposed as contributing to hepatocarcinogenesis. This study was aimed to investigate the impact of CYP2C19 genotypic polymorphism in HCC related to chronic HBV infection in Thailand. MATERIALS AND METHODS: A cross-sectional study was performed between April 2014 and January 2015. Chronic HBV patients with HCC (n=50) and without HCC (n=50) were included. Clinical information and blood samples of all patients were collected. The CYP2C19 genotype was determined by polymerase chain reaction-restriction fragment length polymorphism method, and was classified as rapid metabolizer (RM), intermediate metabolizer (IM) or poor metabolizer (PM). RESULTS: The CYP2C19 genotype frequencies of RM, IM and PM in HBV patients were found to be 19/50 (38%), 25/50 (50%) and 6/50 (12%), respectively. The CYP2C19 genotype frequencies of RM, IM and PM in HBV with HCC patients were 21/50 (42%), 25/50 (50%) and 4/50 (8%), respectively. The distribution of CYP2C19 genotype was not different between patients with and without HCC. Interestingly, among HBV with HCC patients, the RM genotype of CYP2C19 tended to increase risk of aggressive manifestation (OR=2.89, 95%CI=0.76-11.25, P-value = 0.07), compared with non RM genotype carriers. CONCLUSIONS: CYP2C19 genotype IM was the most common genotype in Thai patients with chronic HBV infection. In addition, genotype RM could be an associated factor for aggressive presentation in HCC related to chronic HBV infection.