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/# ).

Management of Helicobacter pylori infection.

Helicobacter pylori infection exhibits a wide disease spectrum ranging from asymptomatic gastritis, peptic ulcer disease, to gastric cancer. H. pylori can induce dysbiosis of gastric microbiota in the pathway of carcinogenesis and successful eradication can restore gastric homeostasis. Diagnostic testing and treatment for H. pylori infection is recommended in patients with active or past history of peptic ulcer, chronic dyspepsia, chronic non-steroidal anti-inflammatory drugs (NSAID) or aspirin use, precancerous gastric lesions, gastric cancer, mucosa-associated lymphoid tissue (MALT) lymphoma, family history of gastric cancer, family history of peptic ulcers, household family member having active H. pylori infection, iron deficiency anemia, idiopathic thrombocytopenic purpura, or vitamin B12 deficiency. Recommended first-line regimens for H. pylori eradication are classified according to clarithromycin resistance. In areas of high clarithromycin resistance (≥15%), we recommend 14-day concomitant therapy or 14-day bismuth quadruple therapy (BQT) as first-line regimen. In areas of low clarithromycin resistance (<15%), we recommend 14-day triple therapy or 14-day BQT as first-line treatment. Second-line regimens are 14-day levofloxacin triple therapy or 14-day BQT if BQT is not previously used. For patients with multiple treatment failure, antimicrobial susceptibility testing (AST) should be performed. If AST is not available, we recommend using antibiotics not previously used or for which resistance is unlikely, such as amoxicillin, tetracycline, bismuth, or furazolidone. High-dose potent proton pump inhibitor or vonoprazan is recommended to achieve adequate acid suppression. Probiotics can be used as an adjuvant treatment to reduce the side effects of antibiotics and enhance eradication rate.

Efficacy of Zinc Supplement in Minimal hepatic Encephalopathy: A prospective, Randomized Controlled Study (Zinc-MHE Trial).

BACKGROUND: Minimal hepatic encephalopathy (MHE) in patients with cirrhosis of the liver has a negative impact on the quality of daily life by impairing attention, memory and visuomotor coordination, and resulting in cognitive decline. Ammonia is thought to be part of the pathogenesis of hepatic encephalopathy. Zinc is an essential trace element, one of the cofactor enzymes that is essential for the conversion of ammonia to urea. AIM: To assess the effect of zinc supplementation on psychomotor performance in cirrhotic patients with MHE. METHODS: This prospective, randomized, controlled trial recruited 69 cirrhotic patients (age 18-75 years) diagnosed with MHE by neuropsychometric (NP) tests comprised of the number connection test part A (NCT-A), number connection test part B (NCT-B), serial dot test (SDT), line tracing test (LTT) and digit symbol test (DST). Eligible patients were randomly assigned (1:1) by a computer-based system block of four randomizations to receive 45 mg of elemental zinc or placebo for 12 weeks. The primary endpoint was the absolute change in NP tests from baseline to 12-weeks of zinc supplement compared with placebo. The assessment of changes of the health-related quality of life (HRQOL) using the Short Form survey-36 (SF-36) questionnaire, as well as biochemical parameters including serum ammonia, was also conducted in both groups. RESULTS: From January to December 2020, 125 eligible cirrhotic patients were diagnosed with liver cirrhosis, of whom 69 (55%) had MHE and were randomly assigned to treatment: 35 patients were assigned to receive 45 mg of elemental zinc and the others 34 patients to receive placebo. Significant improvements in NP tests were established in the zinc supplement group when compared with the placebo group (NCT-A, p = 0.029; NCT-B, p = 0.008; SDT, p = 0.002; DST, p = <0.001). A significant improvement of HRQOL assessed by the SF-36 score was only seen in the zinc group (p<0.001). In the zinc supplement group, not only was an improvement in psychomotor performance reported, but quality of life was also improved, irrespective of baseline zinc level. CONCLUSION: Twelve weeks of zinc supplement in cirrhotic patients with MHE not only had a positive effect on psychomotor performance but also improved HRQOL irrespective to baseline zinc level.

Anti-Helicobacter pylori, Anti-Inflammatory, Cytotoxic, and Antioxidant Activities of Mace Extracts from Myristica fragrans.

The aril (mace) of Myristica fragrans, known as Dok-Chan, is a spice that has long been used for treating stomach discomfort, peptic ulcer, and nausea. It is an ingredient in many remedies in Thai traditional medicine, e.g., Ya-Hom-Thep-Bha-Jit, Ya-Hom-Nao-Wa-Kot, and Ya-That-Bun-Job, which are used to treat dyspepsia and other gastrointestinal tract symptoms. The aqueous and ethanolic extracts of mace were used for all tests. Anti-H. pylori activities were determined by the disc diffusion method and agar dilution. Anti-inflammatory activity was determined by the LPS-induced nitric oxide (NO) inhibition in a RAW264.7 cell line, and cytotoxicity was determined against gastric cancer cell lines (Kato III) using the sulphorhodamine B (SRB) assay. The DPPH radical scavenging and ABTS radical cation decolorization assays were used to determine the antioxidant activities. The result found that the ethanolic extract of mace exhibited antimicrobial activity against H. pylori ATCC 43504 and six clinical strains with MIC values of 125-250 µg/ml. The aqueous extract MICs against H. pylori ATCC reference strain and six clinical strains were 500 µg/ml compared with 0.5 µg/ml for the positive control, clarithromycin. The inhibitory effect of LPS-induced NO release and cytotoxic activity of the ethanolic extract had IC50 values of 82.19 µg/ml and 26.06 µg/ml, respectively, and the EC50 values for the DPPH and ABTS antioxidant assays were 13.41 µg/ml and 12.44 µg/ml, respectively. The mace extract also had anticancer properties. In conclusion, the ethanolic mace extract had anti-H. pylori, anti-inflammatory, antioxidant, and anticancer activities. These data support further preclinical and clinical investigation to see if the mace extract could have a role in treating patients with dyspepsia, peptic ulcers, and possibly gastric cancer.

Characterization and Antibacterial Activity Against Helicobacter pylori of Lactic Acid Bacteria Isolated from Thai Fermented Rice Noodle.

A total of 32 lactic acid bacteria (LAB) were isolated from Khanom-jeen, a Thai traditional fermented rice noodle. They belonged to the genus Leuconostoc (Ln), Lactobacillus (Lb), Enterococcus (E), Lactococcus (Lc), and Weissella (W), based on their phenotypic characteristics and 16S rRNA gene sequence analyses. The strains were identified as Ln. pseudomesenteroides (group 1, two strains), Ln. citreum (group 2, three strains), Ln. lactis (group 3, three strains), Lb. paracasei subsp. tolerans (group 4, two strains), E. faecium (group 5, three strains), Lc. lactis subsp. lactis (group 6, one strain), W. confusa (group 7, six strains), Lb. fermentum (group 8, seven strains), and Lb. plantarum subsp. plantarum and Lb. pentosus (group 9, five strains). Fifteen strains exhibited the inhibitory activity against Helicobacter pylori clinical isolates by spot-on-lawn method. Lb. fermentum P43-01 resisted to bile acids showed the broad spectrum of antimicrobial activity against H. pylori strains MS83 and BK364. These antagonistic effects were associated with proteinaceous compounds which are sensitive to α-chymotrypsin and pepsin. Results indicated that production of bacteriocin-like substances of selected strain might be the significant mechanism that exerted the inhibition on H. pylori. A potential strain could be used as probiotics in alternative or adjunctive therapy for a patient suffering from H. pylori infection.

Antibiotic Resistant Pattern of Helicobacter Pylori Infection Based on Molecular Tests in Laos.

BACKGROUND: The efficacy of standard treatment of Helicobacter pylori (H. pylori) is declining because of antibiotic resistance. Clarithromycin resistance is also increasing in many Asian countries. The aim of this study was to determine the antibiotic susceptibility patterns of H. pylori infection and clinical association in Laos. MATERIALS AND METHODS: A total of 329 Lao dyspeptic patients who underwent gastroscopy at Mahosot Hospital, Vientiane, Laos during December 2010-March 2012 were enrolled in this study. During gastroscopy, 4 biopsies were collected (2 each from the antrum and body) for CLO-test and histopathology. Only the positive CLO-test gastric tissues was stored at -80° in a freezer until DNA was extracted and a GenoType®HelicoDR test was conducted for detecting mutations in the rrl gene encoding 23S rRNA (clarithromycin resistance) and mutations in gyrA gene (fluoroquinolone resistance) . RESULTS: Of the total, 119 Lao patients (36.2%) were infected with H. pylori including 59 males (49.6%) and 60 females (50.4%) with a mean age of 46 years. Clarithromycin and fluoroquinolone resistance of H. pylori infection was demonstrated in 15 (12.6%) and 16 strains (13.4%) respectively. In clarithromycin resistance, the number of patients who had education above primary school and BMI≥ 25 kg/m2 were significantly higher than those who had education below primary school and BMI< 25 kg/m2 (23.1% vs 7.5%, P-value= 0.036 and 20.5% vs 8%, P-value= 0.048, respectively). In fluoroquinolone resistance, the number of lowland Lao was significantly higher than those of non- lowland (highland and midland) Lao ethnic groups (16.7% vs 0%, P-value= 0.039). CONCLUSIONS: H. pylori infections remain common in Laos. Clarithromycin and fluoroquinolone resistance with H. pylori infection are growing problems. Education above primary school and BMI ≥ 25 kg/m2 might be predictors for clarithromycin resistance and lowland Lao ethnicity might be predictors for fluoroquinolone resistance with H. pylori infection in Laos.

Extremely High Prevalence of Metronidazole-Resistant Helicobacter pylori Strains in Mountain People (Karen and Hmong) in Thailand.

This study aimed to survey the prevalence, patterns of antibiotic resistance, and clinical factors associated with antibiotic resistance in Helicobacter pylori among the Karen and Hmong mountain people of Thailand. We recruited dyspeptic patients in the Maesod district, Tak Province, Thailand. All subjects underwent upper gastrointestinal endoscopy, and three antral gastric biopsies were obtained for rapid urease tests and culture. An epsilometer was used to determine the minimum inhibitory concentrations of amoxicillin (AMX), clarithromycin (CLR), metronidazole (MNZ), levofloxacin (LVX), ciprofloxacin (CIP), and tetracycline (TET). A total of 291 subjects were enrolled; 149 (51.2%) were infected with H. pylori. Helicobacter pylori infection was present in 47.1% of Thai, 51.7% of Karen, and 58.7% of Hmong subjects. Antibiotic resistance was present in 75.8% including AMX (0.8%), TET (0%), CLR (5.6%), MNZ (71.8%), CIP (19.4%), LVX (19.4%), and multidrug resistance in 21.8%. Karen subjects had the highest prevalence of MNZ resistance (84.6%), and Hmong subjects had the highest prevalence of fluoroquinolone (27.3%) and multidrug (34.1%) resistance. MNZ plus fluoroquinolone (14.5%) was the most common multidrug resistance. There was no association between clinical factors and antibiotic resistance. MNZ resistance was prevalent, whereas fluoroquinolone- and multidrug-resistant H. pylori infections are important problems in mountain people of Thailand.

High Efficacy of Levofloxacin-Dexlansoprazole-Based Quadruple Therapy as a First Line Treatment for Helicobacter pylori Eradication in Thailand.

BACKGROUND: Levofloxacin is an effective medication for second line Helicobacter pylori (H. pylori) eradication. However, limited studies have approved its use as an effective antibiotic in first line therapy. Dexlansoprazole is a new PPI and lacks of evidence in support of a role in H. pylori eradication. This study was designed to evaluate efficacy of levofloxacin-dexlansoprazole-based quadruple therapy for H. pylori eradication in Thailand. MATERIALS AND METHODS: This prospective randomized control study was performed during June 2014 to December 2014. H. pylori infected gastritis patients were randomized to receive 7- or 14-day levofloxacin-dexlansoprazole based on quadruple therapy (levofloxacin 500 mg OD, dexlansoprazole 60 mg bid, clarithromycin MR 1000 mg OD, bismuth subsalicylate 1048 mg bid). CYP2C19 genotyping and antibiotic susceptibility tests were conducted for all patients. A 13C urea breath test was performed to confirm H. pylori eradication at least 4 weeks after treatment. RESULTS: A total of 100 patients were enrolled, comprising 44 males and 56 females (mean age of 52.6 years). Eradication rate by PP analysis was 85.7% (42/49) with the 7-day regimen and 98% (48/49) with the 14-day regimen (85.7% vs 98%; p-value=0.059). ITT analysis was 84% and 96% with 7- and 14-day regimens, respectively (84% vs 96%; p-value=0.092). Antibiotic susceptibility testing demonstrated 35.1% resistance to metronidazole, 18.3% to clarithromycin, and 13.5% to levofloxacin. CYP2C19 genotyping revealed 54.1% RM, 34.7% IM and 11.2% PM. The 14-day regimen provided 100% eradication in patients with clarithromycin or dual clarithromycin and metronidazole H. pylori resistant strains. Moreover, the eradication rate was 96.6% in patients with CYP2C19 genotype RM. CONCLUSIONS: The 14-day levofloxacin-dexlansoprazole based quadruple therapy provides high H. pylori eradication regardless of CYP2C19 genotype, clarithromycin or dual clarithromycin and metronidazole resistant strains. This regimen could be use as an alternative first line therapy for H. pylori eradication in Thailand.

Improved eradication rate of standard triple therapy by adding bismuth and probiotic supplement for Helicobacter pylori treatment in Thailand.

BACKGROUND: Helicobacter pylori (H. pylori) remains an important cause of gastric cancer and peptic ulcer disease worldwide. Treatment of H. pylori infection is one of the effective ways to prevent gastric cancer. However, standard triple therapy for H. pylori eradication is no longer effective in many countries, including Thailand. This study was designed to evaluate the efficacy of adding bismuth and probiotic to standard triple therapy for H. pylori eradication. MATERIALS AND METHODS: In this prospective single center study, H. pylori infected gastritis patients were randomized to receive 7- or 14-day standard triple therapy plus bismuth with probiotic or placebo. Treatment regimen consisted of 30 mg lansoprazole twice daily, 1 g amoxicillin twice daily, 1 g clarithromycin MR once daily and 1,048 mg bismuth subsalicylate twice daily. Probiotic bacteria composed of Bifidobacterium lactis, Lactobacillus acidophilus and Lactobacillus paracasei. Placebo was conventional drinking yogurt without probiotic. CYP2C19 genotyping and antibiotic susceptibility tests were also done. H pylori eradication was defined as a negative 13C-urea breath test at least 2 weeks after completion of treatment. RESULTS: One hundred subjects were enrolled (25 each to 7- and 14-day regimens with probiotic or placebo). Antibiotic susceptibility tests showed 36.7% metronidazole and 1.1% clarithromycin resistance. CYP2C19 genotyping revealed 40.8%, 49% and 10.2% were rapid, intermediate and poor metabolizers, respectively. The eradication rates of 7- or 14 regimens with probiotics were 100%. Regarding adverse events, the incidence of bitter taste was significantly lower in the 7- day regimen with the probiotic group compared with 7- day regimen with placebo (40% vs. 64%; p=0.04). CONCLUSIONS: The 7-day standard triple therapy plus bismuth and probiotic can provide an excellent cure rate of H. pylori (100%) in areas with low clarithromycin resistance such as Thailand, regardless of CYP2C19 genotype. Adding a probiotic also reduced treatment-related adverse events.

Improved efficacy of proton pump inhibitor - amoxicillin - clarithromycin triple therapy for Helicobacter pylori eradication in low clarithromycin resistance areas or for tailored therapy.

OBJECTIVE: Standard triple therapy for Helicobacter pylori eradication is no longer effective as an empiric choice in most areas. Even in low clarithromycin resistance areas, results ≥95% are infrequently achieved. This study was designed to search for a version of standard triple therapy for use low prevalence areas or as tailored therapy that is highly effective irrespective of CYP2C19 genotype. DESIGN: Two prospective pilot single center studies were performed in Thailand. H. pylori-infected subjects were randomized to 7- or 14-day regimens using a high-dose proton pump inhibitor (PPI) triple therapy consisting of lansoprazole (60 mg) twice daily, amoxicillin 1 g twice daily, and long-acting clarithromycin MR 1 g once daily. H. pylori was defined as positive H. pylori culture; or two positive tests (rapid urease test and histology); CYP2C19 genotyping was performed. H. pylori eradication was evaluated by (13) C-UBT 4 or more weeks after treatment. RESULTS: Hundred and ten subjects were enrolled (55 each to the 7- and 14-day regimens). Antibiotic susceptibility testing (25 strains) showed 40% metronidazole resistance but no clarithromycin resistance. CYP2C19 genotyping (64 subjects) revealed 56.3% rapid metabolizer, 29.7% intermediate metabolizer, and 14% poor metabolizer. The eradication rate with the 14-day regimen was 100% (95% CI = 93.5-100%) and 92.7% (95% CI = 82-97%) with the 7-day regimen. The difference was related to improved eradication at 14 days in rapid metabolizers (i.e. 100 vs 88.2%). CONCLUSION: Triple therapy using a 14-day high-dose PPI and long-acting clarithromycin provided an excellent cure rate (100%) regardless of the CYP2C19 genotype.

CagA genotype and metronidazole resistant strain of Helicobacter pylori in functional dyspepsia in Thailand.

BACKGROUND AND AIM: Many previous studies indicated relationship between H. pylori infection and functional dyspepsia (FD) but pathogenesis remains unclear. The aim of this study was to determine relationship between cagA genotype and metronidazole resistant strains of H. pylori in Thai FD patients. METHODS: Total of 412 Thai FD patients who underwent gastroscopy at Thammasat University Hospital, Thailand between June 2008 and May 2010 were enrolled. Two antral gastric biopsies were obtained for CLO test, cultures and E-test for metronidazole. Cag A genotype was determined by PCR. FD patients were diagnosed by Rome III criteria and categorized as epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS). RESULTS: 133 FD patients (31%) were infected with H. pylori (56 male, 77 female). There were 37 patients with EPS and 96 patients with PDS. Cag A genotype was performed in 114 patients and CagA 1a was demonstrated in 24.6%. Cag A 1a was relatively higher prevalence in PDS than EPS without statistical significance (26% vs 22%; P > 0.05). E-test for metronidazole was performed in 100 patients (32 EPS and 68 PDS patients) and metronidazole resistant strains were found in 30%. Metronidazole resistant strains were significantly higher in PDS than EPS patients (38.2% vs 12.5%; P = 0.03). In EPS patients, presence of cagA 2a gene was significantly higher in metronidazole resistant than metronidazole sensitive strains (100% vs 74.1%; OR = 4.8, 95% CI = 1.2-26.8, P = 0.01). CONCLUSIONS: PDS was the predominant type of FD in Thailand. Metronidazole resistant strains and cagA 2a gene of H. pylori infection was commonly found in Thai FD patients. In EPS patients, cagA 2a gene might be related to metronidazole resistant strains of H. pylori infection in Thailand.

Asia-Pacific consensus guidelines on gastric cancer prevention.

BACKGROUND AND AIM: Gastric cancer is a major health burden in the Asia-Pacific region but consensus on prevention strategies has been lacking. We aimed to critically evaluate strategies for preventing gastric cancer. METHODS: A multidisciplinary group developed consensus statements using a Delphi approach. Relevant data were presented, and the quality of evidence, strength of recommendation, and level of consensus were graded. RESULTS: Helicobacter pylori infection is a necessary but not sufficient causal factor for non-cardia gastric adenocarcinoma. A high intake of salt is strongly associated with gastric cancer. Fresh fruits and vegetables are protective but the use of vitamins and other dietary supplements does not prevent gastric cancer. Host-bacterial interaction in H. pylori infection results in different patterns of gastritis and differences in gastric acid secretion which determine disease outcome. A positive family history of gastric cancer is an important risk factor. Low serum pepsinogens reflect gastric atrophy and may be useful as a marker to identify populations at high risk for gastric cancer. H. pylori screening and treatment is a recommended gastric cancer risk reduction strategy in high-risk populations. H. pylori screening and treatment is most effective before atrophic gastritis has developed. It does not exclude the existing practice of gastric cancer surveillance in high-risk populations. In populations at low risk for gastric cancer, H. pylori screening is not recommended. First-line treatment of H. pylori infection should be in accordance with national treatment guidelines. CONCLUSION: A strategy of H. pylori screening and eradication in high-risk populations will probably reduce gastric cancer incidence, and based on current evidence is recommended by consensus.