HBV DNA and HBsAg Levels at 24 Weeks Off-Treatment Predict Clinical Relapse and HBsAg Loss in HBeAg-Negative Patients Who Discontinued Antiviral Therapy.

BACKGROUND & AIMS: Patients who discontinue nucleo(s)tide analogue therapy are at risk of viral rebound and severe hepatitis flares, necessitating intensive off-treatment follow-up. METHODS: We studied the association between hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA levels at off-treatment follow-up week 24 (FU W24), with subsequent clinical relapse, and HBsAg loss in a multicenter cohort of hepatitis B e antigen (HBeAg)-negative patients with chronic hepatitis B who discontinued nucleo(s)tide analogue therapy. RESULTS: We studied 475 patients, 82% Asian, and 55% treated with entecavir. Patients with higher HBV DNA levels at FU W24 had a higher risk of clinical relapse (hazard ratio [HR], 1.576; P < .001) and a lower chance of HBsAg loss (HR, 0.454; P < .001). Similarly, patients with higher HBsAg levels at FU W24 had a higher risk of clinical relapse (HR, 1.579; P < .001) and a lower chance of HBsAg loss (HR, 0.263; P < .001). A combination of both HBsAg <100 IU/mL and HBV DNA <100 IU/mL at FU W24 identified patients with excellent outcomes (9.9% clinical relapse and 58% HBsAg loss at 216 weeks of follow-up). Conversely, relapse rates were high and HBsAg loss rates negligible among patients with both HBsAg >100 IU/mL and HBV DNA >100 IU/mL (P < .001). CONCLUSIONS: Among HBeAg-negative patients with chronic hepatitis B who discontinued antiviral therapy and who did not experience clinical relapse before FU W24, serum levels of HBV DNA and HBsAg at FU W24 can be used to predict subsequent clinical relapse and HBsAg clearance. A combination of HBsAg <100 IU/mL with HBV DNA <100 IU/mL identifies patients with a low risk of relapse and excellent chances of HBsAg loss and could potentially be used as an early surrogate end point for studies aiming at finite therapy in HBV.

Comparing serial and current liver stiffness measurements to predict decompensation in compensated advanced chronic liver disease patients.

BACKGROUND AND AIMS: The utility of serial liver stiffness measurements (LSM) to predict decompensation in patients with compensated advanced chronic liver disease (cACLD) remains unclear. We aimed to validate whether comparing serial LSM is superior to using the current LSM to predict liver-related events (LRE) in patients with cACLD. APPROACH AND RESULTS: In this retrospective analysis of an international registry, patients with cACLD and serial LSM were followed up until index LRE. We compared the performance of both the dynamic LSM changes and the current LSM in predicting LRE using Cox regression analysis, considering time zero of follow-up as the date of latest liver stiffness measurement. In all, 480 patients with cACLD with serial LSM were included from 5 countries. The commonest etiology of cACLD was viral (53%) and MASLD (34%). Over a median follow-up of 68 (IQR: 45 -92) months, 32% experienced a LSM decrease to levels below 10kPa (resolved cACLD) and 5.8% experienced LRE. Resolved cACLD were more likely to be nondiabetic and had better liver function. While a higher value of the current LSM was associated with higher LREs, LSM changes over time (LSM slope) were not associated with LRE. In multivariable Cox regression, neither the prior LSM nor the LSM slope added predictive value to latest liver stiffness measurement. CONCLUSIONS: Once the current LSM is known, previous LSM values do not add to the prediction of LREs in patients with cACLD.

Sequential SAFE Score and Transient Elastography for Detecting Significant Fibrosis in Asian Patients with MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD),1 represents a global public health issue. Fibrosis stage is the most important risk for long-term undesirable outcomes.2,3 From recent meta-analyses, all-cause and liver-related mortalities significantly increased from fibrosis stage 2 (significant fibrosis; F≥2) onward.4,5 In primary care setting, those with F≥2 should be referred to hepatologists; therefore, noninvasive tests to stratify risk of patients with MASLD are crucial. Steatosis-associated fibrosis estimator (SAFE) was recently developed to predict F≥2.6 SAFE has been externally validated and outperformed fibrosis-4 (FIB-4) and NAFLD fibrosis score (NFS).7,8 Recently, international guidelines proposed sequential diagnostic steps, initially using FIB-4 and then transient elastography (TE) in non-low-risk patients.9,10 However, the guidelines focused on identifying advanced fibrosis (F≥3), which might be too late. This study aimed to compare the performance among SAFE, FIB-4, and NFS, and evaluate SAFE-TE sequential approach. We hypothesized that by initially using SAFE, the proportion of patients misclassified as low risk despite already having F≥2 could be diminished.

Longitudinal Outcomes Associated With Metabolic Dysfunction-Associated Steatotic Liver Disease: A Meta-analysis of 129 Studies.

BACKGROUND & AIMS: The progression of metabolic dysfunction-associated steatotic liver disease (MASLD) has been found to manifest in a series of hepatic and extrahepatic complications. A comprehensive meta-analysis of the longitudinal outcomes associated with MASLD has yet to be conducted. METHODS: To investigate the longitudinal outcomes associated with MASLD, Medline and Embase databases were searched to identify original studies that evaluated the longitudinal risks of incident clinical outcomes among MASLD patients compared with non-MASLD individuals. DerSimonian Laird random-effects meta-analysis was performed. Pooled effect estimates were calculated, and heterogeneity among studies was evaluated. RESULTS: One hundred twenty-nine studies were included in the meta-analysis. Meta-analysis revealed a significant increase in the risk of cardiovascular outcomes (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.27-1.60; P < .01), various metabolic outcomes such as incident hypertension (HR, 1.75; 95% CI, 1.46-2.08; P < .01), diabetes (HR, 2.56; 95% CI, 2.10-3.13; P < .01), pre-diabetes (HR, 1.69; 95% CI, 1.22-2.35; P < .01), metabolic syndrome (HR, 2.57; 95% CI, 1.13-5.85; P = .02), chronic kidney disease (HR, 1.38; 95% CI, 1.27-1.50; P < .01), as well as all cancers (HR, 1.54; 95% CI, 1.35-1.76; P < .01) among MASLD patients compared with non-MASLD individuals. By subgroup analysis, MASLD patients with advanced liver disease (HR, 3.60; 95% CI, 2.10-6.18; P < .01) were also found to be associated with a significantly greater risk (P = .02) of incident diabetes than those with less severe MASLD (HR, 1.63; 95% CI, 1.0-2.45; P = .02) when compared with non-MASLD. CONCLUSIONS: The present study emphasizes the association between MASLD and its clinical outcomes including cardiovascular, metabolic, oncologic, and other outcomes. The multisystemic nature of MASLD found in this analysis requires treatment targets to reduce systemic events and end organ complications.

Lower Risks of New-Onset Hepatocellular Carcinoma in Patients With Type 2 Diabetes Mellitus Treated With SGLT2 Inhibitors Versus DPP4 Inhibitors.

BACKGROUND: Type 2 diabetes mellitus (T2DM) may be a risk factor for development of hepatocellular carcinoma (HCC). The association between risk of developing HCC and treatment with sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus dipeptidyl peptidase-4 inhibitors (DPP4i) is currently unknown. This study aimed to compare the risk of new-onset HCC in patients treated with SGLT2i versus DPP4i. METHODS: This was a retrospective cohort study of patients with T2DM in Hong Kong receiving either SGLT2i or DPP4i between January 1, 2015, and December 31, 2020. Patients with concurrent DPP4i and SGLT2i use were excluded. Propensity score matching (1:1 ratio) was performed by using the nearest neighbor search. Multivariable Cox regression was applied to identify significant predictors. RESULTS: A total of 62,699 patients were included (SGLT2i, n=22,154; DPP4i, n=40,545). After matching (n=44,308), 166 patients (0.37%) developed HCC: 36 in the SGLT2i group and 130 in the DPP4i group over 240,269 person-years. Overall, SGLT2i use was associated with lower risks of HCC (hazard ratio [HR], 0.42; 95% CI, 0.28-0.79) compared with DPP4i after adjustments. The association between SGLT2i and HCC development remained significant in patients with cirrhosis or advanced fibrosis (HR, 0.12; 95% CI, 0.04-0.41), hepatitis B virus (HBV) infection (HR, 0.32; 95% CI, 0.17-0.59), or hepatitis C virus (HCV) infection (HR, 0.41; 95% CI, 0.22-0.80). The results were consistent in different risk models, propensity score approaches, and sensitivity analyses. CONCLUSIONS: SGLT2i use was associated with a lower risk of HCC compared with DPP4i use after adjustments, and in the context of cirrhosis, advanced fibrosis, HBV infection, and HCV infection.

Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors for new-onset gastric cancer and gastric diseases in patients with type 2 diabetes mellitus: a population-based cohort study.

OBJECTIVE: To compare the risks of gastric cancer and other gastric diseases in patients with type-2 diabetes mellitus (T2DM) exposed to sodium-glucose cotransporter 2 inhibitors (SGLT2I), dipeptidyl peptidase-4 inhibitors (DPP4I) or glucagon-like peptide-1 receptor agonists (GLP1a). DESIGN: This was a population-based cohort study of prospectively collected data on patients with T2DM prescribed SGLT2I, DPP4I or GLP1a between January 1st 2015 and December 31st 2020 from Hong Kong. The outcomes were new-onset gastric cancer, peptic ulcer (PU), acute gastritis, non-acute gastritis, and gastroesophageal reflux disease (GERD). Propensity score matching (1:1) using the nearest neighbour search was performed, and multivariable Cox regression was applied. A three-arm comparison between SGLT2I, DPP4I and GLP1a was conducted using propensity scores with inverse probability of treatment weighting. RESULTS: A total of 62,858 patients (median age: 62.2 years old [SD: 12.8]; 55.93% males; SGLT2I: n = 23,442; DPP4I: n = 39,416) were included. In the matched cohort, the incidence of gastric cancer was lower in SGLT2I (Incidence rate per 1000 person-year, IR: 0.32; 95% confidence interval, CI 0.23-0.43) than in DPP4I (IR per 1000 person-year: 1.22; CI 1.03-1.42) users. Multivariable Cox regression found that SGLT2I use was associated with lower risks of gastric cancer (HR 0.30; 95% CI 0.19-0.48), PU, acute gastritis, non-acute gastritis, and GERD (p < 0.05) compared to DPP4I use. In the three-arm analysis, GLP1a use was associated with higher risks of gastric cancer and GERD compared to SGLT2I use. CONCLUSIONS: The use of SGLT2I was associated with lower risks of new-onset gastric cancer, PU, acute gastritis, non-acute gastritis, and GERD after matching and adjustments compared to DPP4I use. SGLT2I use was associated with lower risks of GERD and gastric cancer compared to GLP1a use.

Proton Pump Inhibitors Increases Longitudinal Risk of Mortality, Decompensation, and Infection in Cirrhosis: A Meta-Analysis.

BACKGROUND/AIMS: Proton pump inhibitors (PPIs) are frequently prescribed to cirrhotic patients, but there is limited longitudinal evidence regarding their effects. This study aimed to assess the impact of PPIs on adverse events in cirrhotic patients. METHODS: A comprehensive search was conducted using the Medline and Embase databases to identify relevant articles. Pooled hazard ratios (HRs) using DerSimonian and Laird random-effects model were calculated to evaluate the risk of adverse events such as long-term mortality, hepatic decompensation, hepatic encephalopathy (HE), spontaneous bacterial peritonitis (SBP), and overall infection in cirrhotic patients with PPI use. RESULTS: The analysis included 28 studies with 260,854 cirrhotic patients. The prevalence of PPI use among cirrhotic patients was 55.93%. The use of PPIs was not significantly associated with short-term mortality in cirrhotic patients. However, long-term mortality (HR 1.321, 95% CI 1.103-1.581, P = 0.002), decompensation (HR 1.646, 95% CI 1.477-1.835, P < 0.001), HE (HR 1.968, 95% CI 1.372-2.822, P < 0.001), SBP (HR 1.751, 95% CI 1.649-1.859, P < 0.001), and infection (HR 1.370, 95% CI 1.148-1.634, P < 0.001) were significantly associated with PPI use. Sensitivity analysis with prospective studies yielded similar results. CONCLUSION: PPIs should be reserved for appropriate indications at lowest effective dose for cirrhotic patients due to the potential harm.

Ethnic disparities in waitlist outcomes of patients with nonalcoholic steatohepatitis listed for liver transplantation in the US.

NASH is the fastest-growing cause of liver cirrhosis and is the leading indication for liver transplantation (LT). However, significant racial and ethnic disparities in waitlist outcomes and LT allocation may unfairly disadvantage minorities. Our aim was to characterize racial and ethnic disparities in waitlist mortality and transplantation probability among patients with NASH. This is a retrospective analysis of the United Network for Organ Sharing registry data of LT candidates from January 1, 2000 to December 31, 2021. Outcomes analysis was performed using competing risk analysis with the Fine and Gray model. The multivariable adjustment was conducted, and mixed-effect regression was used to compare the model for end-stage liver disease scores at listing and removal. Of 18,562 patients with NASH cirrhosis, there were 14,834 non-Hispanic Whites, 349 African Americans, 2798 Hispanics, 312 Asians, and 269 of other races/ethnicities; African American (effect size: 2.307, 95% CI: 1.561-3.053, and p < 0.001) and Hispanic (effect size: 0.332, 95% CI: 0.028-0.637, p = 0.032) patients were found to have a significantly higher model for end-stage liver disease scores at the time of listing than non-Hispanic Whites. African Americans had a higher probability of receiving LT relative to non-Hispanic Whites (subdistribution HR: 1.211, 95% CI: 1.051-1.396, and p = 0.008). However, Hispanic race/ethnicity was associated with a lower transplantation probability (subdistribution HR: 0.793, 95% CI: 0.747-0.842, and p < 0.001) and increased waitlist mortality (subdistribution HR: 1.173, CI: 1.052-1.308, and p = 0.004) compared with non-Hispanic Whites. There are significant racial and ethnic disparities in waitlist outcomes of patients with NASH in the US. Hispanic patients are less likely to receive LT and more likely to die while on the waitlist compared with non-Hispanic Whites despite being listed with a lower model for end-stage liver disease scores.

Probability of HBsAg loss after nucleo(s)tide analogue withdrawal depends on HBV genotype and viral antigen levels.

BACKGROUND & AIMS: Nucleo(s)tide analogue (NUC) withdrawal may result in HBsAg clearance in a subset of patients. However, predictors of HBsAg loss after NUC withdrawal remain ill-defined. METHODS: We studied predictors of HBsAg loss in a global cohort of HBeAg-negative patients with undetectable HBV DNA who discontinued long-term NUC therapy. Patients requiring retreatment after treatment cessation were considered non-responders. RESULTS: We enrolled 1,216 patients (991 with genotype data); 98 (8.1%) achieved HBsAg loss. The probability of HBsAg loss was higher in non-Asian patients (adjusted hazard ratio [aHR] 8.26, p <0.001), and in patients with lower HBsAg (aHR 0.243, p <0.001) and HBV core-related antigen (HBcrAg) (aHR 0.718, p = 0.001) levels. Combining HBsAg (<10, 10-100 or >100 IU/ml) and HBcrAg (<2log vs. ≥2 log) levels improved prediction of HBsAg loss, with extremely low rates observed in patients with HBsAg >100 IU/ml with detectable HBcrAg. HBsAg loss rates also varied with HBV genotype; the highest rates were observed for genotypes A and D, and none of the patients with HBV genotype E experienced HBsAg loss (p <0.001 for the overall comparison across genotypes; p <0.001 for genotypes A/D vs. genotypes B/C). HBV genotype C was independently associated with a higher probability of HBsAg loss when compared to genotype B among Asian patients (aHR 2.494; 95% CI 1.490-4.174, p = 0.001). CONCLUSIONS: The probability of HBsAg loss after NUC cessation varies according to patient ethnicity, HBV genotype and end-of-treatment viral antigen levels. Patients with low HBsAg (<100 IU/ml) and/or undetectable HBcrAg levels, particularly if non-Asian or infected with HBV genotype C, appear to be the best candidates for treatment withdrawal. LAY SUMMARY: A subset of patients may achieve clearance of hepatitis B surface antigen (HBsAg) - so-called functional cure - after withdrawal of nucleo(s)tide analogue therapy. In this multicentre study of 1,216 patients who discontinued antiviral therapy, we identified non-Asian ethnicity, HBV genotype C, and low hepatitis B surface antigen and hepatitis B core-related antigen levels as factors associated with an increased chance of HBsAg loss.

Prediction of Sustained Response After Nucleo(s)tide Analogue Cessation Using HBsAg and HBcrAg Levels: A Multicenter Study (CREATE).

BACKGROUND & AIMS: Predictors of successful nucleo(s)tide analogue (NA) therapy withdrawal remain elusive. We studied the relationship between end-of-treatment levels of hepatitis B core-related antigen (HBcrAg) and hepatitis B surface antigen (HBsAg) and outcome after therapy cessation. METHODS: Patients who discontinued NA therapy in centers in Asia and Europe were enrolled. HBcrAg and HBsAg were measured at treatment cessation, and associations with off-treatment outcomes were explored. The SCALE-B (Surface antigen, Core-related antigen, Age, ALT, and tenofovir for HBV) score was calculated as previously reported. End points included sustained virologic response (VR; hepatitis B virus DNA level <2000 IU/mL), HBsAg loss, and alanine aminotransferase (ALT) flares (>3× upper limit of normal). Re-treated patients were considered nonresponders. RESULTS: We analyzed 572 patients, 457 (80%) were Asian and 95 (17%) were hepatitis B e antigen positive at the start of NA therapy. The median treatment duration was 295 weeks. VR was observed in 267 (47%), HBsAg loss was observed in 24 (4.2%), and ALT flare was observed in 92 (16%). VR (67% vs 42%) and HBsAg loss (15% vs 1.5%) was observed more frequently in non-Asian patients when compared to Asian patients (P < .001). Lower HBcrAg levels were associated with higher rates of VR (odds ratio [OR], 0.701; P < .001) and HBsAg loss (OR, 0.476; P < .001), and lower rates of ALT flares (OR, 1.288; P = .005). Similar results were observed with HBsAg (VR: OR, 0.812; P = .011; HBsAg loss: OR, 0.380; P < .001; and ALT flare: OR, 1.833; P < .001). Lower SCALE-B scores were associated with higher rates of VR, HBsAg loss, and lower rates of ALT flares in both Asian and non-Asian patients (P < .001). CONCLUSIONS: In this multicenter study, off-treatment outcomes after NA cessation varied with ethnicity. Lower levels of HBcrAg and HBsAg were associated with favorable outcomes. A risk score comprising both factors can be used for risk stratification.

Utility of handgrip strength (HGS) and bioelectrical impedance analysis (BIA) in the diagnosis of sarcopenia in cirrhotic patients.

BACKGROUND: Sarcopenia is associated with disability, mortality, and poorer survival in cirrhotic patients. For the evaluation of muscle volume, computed tomography (CT) is the most accurate tool. Unfortunately, it would be hard to apply a muscle mass measuring CT to daily practice. This research aims to study the utility of handgrip strength (HGS) and bioelectrical impedance analysis (BIA) to detect sarcopenia in cirrhotic patients compared with CT as the reference. METHODS: In cirrhotic patients who met inclusions criteria (age 20-70 years, ascites < grade 2 of International Ascites Club grading system, no active malignancy, and no cardiac implanted device), HGS were measured using a Jamar dynamometer. Subsequently, patients with low muscle strength (defined as JSH criteria, < 26 kg in male, < 18 kg in female) were then underwent CT and BIA (Tanita MC780 MA) on the same day to measure muscle volume, the definition of sarcopenia by CT was according to the Japan Society of Hepatology (JSH). We also collected data from patients with normal HGS whose CT results were available in the study period. RESULTS: From 146 cirrhotic patients who underwent HGS, 30 patients (20.5%) had diagnosed low HSG. Data from 50 patients whose available CT results included 30 low HGS and 20 patients with normal HSG. The HGS was strongly correlated with skeleton muscle index (SMI) by CT (r = 0.81, p < 0.001) and had an excellent diagnostic performance for detecting sarcopenia by using JSH criteria the sensitivity, specificity, NPV and PPV were 88.2%, 100%, 100%, and 98.7% respectively. In contrast, only 6 of 30 patients (20%) met sarcopenic criteria by BIA. Among sarcopenic patients, the result showed a fair correlation between SMI and BIA (r = 0.54; p < 0.002). CONCLUSION: Our study demonstrated an excellent correlation between HGS and SMI by CT in the mixed cirrhotic population from the sarcopenia and non-sarcopenia groups. The HGS using the JSH criteria showed an excellent performance in detecting sarcopenia compared to CT. Nonetheless, for the BIA by using the current cut-offs demonstrated unacceptable rate to detect sarcopenia.

Diagnostic performance of endoscopic ultrasound-guided tissue acquisition by EUS-FNA versus EUS-FNB for solid pancreatic mass without ROSE: a retrospective study.

BACKGROUND: Endoscopic ultrasound-guided tissue acquisition (EUS-TA) is an established diagnostic procedure for solid pancreatic mass. However, the diagnostic yield between fine-needle aspiration (FNA) and fine-needle biopsy (FNB) remains unclear. We aimed to evaluate and compare the diagnostic yields between FNA and FNB using conventional FNA and Franseen needles of the same size 22-gauge needle, in patients with solid pancreatic mass who underwent EUS-TA without rapid onsite cytopathology evaluation (ROSE). METHODS: All cases of EUS-TA by FNA or FNB for solid pancreatic mass between January 2017 and October 2020 in a single-centre university hospital were retrospectively reviewed. All procedures were performed without an onsite cytologist. Before the endoscopist finished the procedure, macroscopic onsite evaluation (MOSE) was confirmed. The diagnostic yield and the average number of needle passes between FNB and FNA were then compared. RESULTS: A total of 151 patients (FNA, n = 77; FNB, n = 74) with solid pancreatic mass detected by cross-sectional imaging underwent EUS-TA. The mean age was 62.3 ± 12.8 years, with 88 (58.3%) males. Age, sex, mass location, tumour size and disease stage from imaging were not significantly different between the two groups. The diagnostic performance was higher in EUS-FNB (94.6%) than in EUS-FNA (89.6%). The mean number of needle passes was clearly fewer in FNB than in FNA (2.8 vs. 3.8, p < 0.001). The total procedure time was shorter in FNB (34.7 min) than in FNA (41 min). The adverse event rate between FNB and FNA was not significantly different. CONCLUSIONS: The diagnostic yield of solid pancreatic mass was higher in FNB using the Franseen needle than in FNA using the conventional FNA needle in a centre where ROSE is unavailable, without serious adverse event. In addition, FNB had fewer needle passes and shorter total procedure time.

Hepatitis B surface antigen, core-related antigen and HBV RNA: Predicting clinical relapse after NA therapy discontinuation.

BACKGROUND & AIMS: The safe discontinuation of nucleos(t)ide analogue therapy remains challenging in chronic hepatitis B. We investigated the potential role of quantitative hepatitis B surface antigen, hepatitis B core-related antigen and hepatitis B virus RNA at the end of treatment in predicting off-therapy relapse. METHODS: Patients who fulfilled the stopping criteria of the Asian Pacific Association for the Study of the Liver guideline were enrolled. Virological relapse was defined as hepatitis B virus DNA level greater than 2000 IU/mL, and clinical relapse was defined as virological relapse plus alanine aminotransferase level of more than twice the upper limit of normal. RESULTS: Ninety-two patients participated. The combination of end-of-treatment hepatitis B core-related antigen and hepatitis B virus RNA levels was most predictive of clinical relapse. Multivariate analysis revealed that end-of-treatment hepatitis B core-related antigen and hepatitis B virus RNA were independently associated with clinical relapse. During follow-up, no patients with undetectable hepatitis B core-related antigen (<3.0 log10 U/mL) and hepatitis B virusRNA (<2.0 log10 copies/mL) at end of treatment developed clinical relapse, in comparison with 22.9% and 62.5% patients with detectable levels of one or both biomarkers respectively. End-of-treatment quantitative hepatitis B surface antigen was linked to a likelihood of hepatitis B surface antigen clearance. CONCLUSIONS: The combined hepatitis B core-related antigen and hepatitis B virus RNA assays at end of treatment were highly predictive of subsequent clinical relapse. These novel biomarkers could potentially be used to identify patients who could safely discontinue nucleos(t)ide analogue therapy.

Prevalence and virulence factors of Helicobacter pylori isolated from oral cavity of non-disease, gastritis, and gastric cancer patients.

Background/purpose: The oral cavity is considered a reservoir of Helicobacter pylori associated with gastric infection. It aimed to examine the prevalence of H. pylori strains from the oral cavity and gastric tissue of patients with different stage of gastric-diseases. Strains were further characterized for virulence genes, adhesion ability, and inflammation responses. Materials and methods: 11 non-disease, 15 gastritis, and 15 gastric cancer participated in the study. After clinical examination, gastric biopsies, saliva and plaque samples were collected and H. pylori levels were examined by real-time PCR and cultivation. The cagA and vacA genes were investigated from the culture strains. Adhesion ability and pro-inflammatory responses were analyzed in comparison between the presence of virulent genes and disease status. Results: Relatively poor periodontal condition was found among gastric cancer patients. Prevalence of H. pylori-positive was 84.8% and 19.5% by real-time PCR and cultivation, respectively. The cagA and vacA gene-positive strains were 52.6% and 5.3%, respectively, which were found more in gastric cancer patients. The cagA gene-positive strains were found to be higher in gastric cancer patients, and strains had significantly higher adhesion ability and pro-inflammation expressions than the cagA gene-negative strains. Conclusion: Colonization by H. pylori in oral cavity was confirmed, and the cagA gene-positive strains play a crucial role in both adhesion and inflammatory responses. The presence of H. pylori and its virulence gene in oral cavity should be received attention. An eradication of such strains from oral cavity may help to prevent the transmission and recolonization to gastric organs.

Non-Invasive Serum Biomarkers for the Diagnosis of Cirrhosis in Patients with Autoimmune Hepatitis (AIH) and AIH-Primary Biliary Cholangitis Overlap Syndrome (AIH-PBC): Red Cell Distribution Width to Platelet Ratio (RPR) Yielded the Most Promising Result.

Several serum biomarkers for fibrosis assessment have been proposed in various liver diseases, but in autoimmune hepatitis (AIH) or overlap with primary biliary cholangitis (PBC; AIH-PBC) patients, the data are scarce. This retrospective cross-sectional study was conducted to validate six non-invasive biomarkers in the diagnosis of cirrhosis (F4 fibrosis) in such patients. We included adult patients diagnosed with AIH or AIH-PBC overlap syndrome who underwent a liver biopsy between 2011 and 2021. Laboratory data were collected to calculate the following scores: red cell distribution width to platelet ratio (RPR), aspartate aminotransferase/platelet ratio index (APRI), Fibrosis-4 index (FIB-4), aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR), neutrophil-to-lymphocyte ratio (NLR), and lymphocyte-to-platelet ratio (LPR). A total of 139 patients were eligible (111 AIH and 28 AIH-PBC). The prevalence of cirrhosis was 35.3% (36% in AIH and 32.1% in AIH-PBC). The AUROCs of the RPR, FIB-4, APRI, AAR, LPR, and NLR in all patients were 0.742, 0.724, 0.650, 0.640, 0.609, and 0.585, respectively. RPR was significantly superior to APRI, NLR, and LPR. Moreover, RPR showed the highest AUROC (0.915) in the overlap AIH-PBC subgroup. In conclusion, RPR yielded the highest diagnostic accuracy to predict cirrhosis in AIH and AIH-PBC overlap syndrome patients, while FIB-4 was considerably optimal.

Liver Transplantation in Chronic Liver Disease and Acute on Chronic Liver Failure- Indication, Timing and Practices.

Liver transplantation (LT) is the second most common solid organ transplantation worldwide. LT is considered the best and most definitive therapeutic option for patients with decompensated chronic liver disease (CLD), hepatocellular carcinoma (HCC), acute liver failure (ALF), and acute-on-chronic liver failure (ACLF). The etiology of CLD shows wide geographical variation, with viral hepatitis being the major etiology in the east and alcohol-related liver disease (ALD) in the west. Non-alcoholic fatty liver disease (NAFLD) is on an increasing trend and is expected to be the most common etiology on a global scale. Since the first successful LT, there have been radical changes in the indications for LT. In many circumstances, not just the liver disease itself but factors such as extra-hepatic organ dysfunction or failures necessitate LT. ACLF is a dynamic syndrome that has extremely high short-term mortality. Currently, there is no single approved therapy for ACLF, and LT seems to be the only feasible therapeutic option for selected patients at high risk of mortality. Early identification of ACLF, stratification of patients according to disease severity, aggressive organ support, and etiology-specific treatment approaches have a significant impact on post-transplant outcomes. This review briefly describes the indications, timing, and referral practices for LT in patients with CLD and ACLF.

Lyophilized cell-free supernatants of Limosilactobacillus fermentum T0701 exhibited antibacterial activity against Helicobacter pylori.

Helicobacter pylori is a prominent gastrointestinal pathogen associated with various gastrointestinal illnesses. It presents substantial health risks due to its antibiotic resistance. Therefore, it is crucial to identify alternative treatments for H. pylori infections. Limosilactobacillus spp exhibit probiotic properties with beneficial effects in humans; however, the mechanisms by which it counteracts H. pylori infection are unknown. This study aimed to evaluate the potential of Limosilactobacillus fermentum T0701 lyophilized cell-free supernatants (LCFS) against H. pylori. The LCFS has varying antimicrobial activities, with inhibition zones of up to 10.67 mm. The minimum inhibitory concentration and minimum bacterial concentration of LCFS are 6.25-25.00 mg/mL and 6.25 mg/mL to > 50.00 mg/mL, respectively, indicating its capability to inhibit H. pylori. There is morphological damage observed in H. pylori treated with LCFS. Additionally, H. pylori adhesion to AGS cells (human gastric adenocarcinoma epithelial cells) reduces by 74.23%, highlighting the LCFS role in preventing bacterial colonization. Moreover, LCFS exhibits no cytotoxicity or morphological changes in AGS cells, and with no detected virulence or antimicrobial resistance genes, further supporting its safety profile. L. fermentum T0701 LCFS shows promise as a safe and effective non-toxic agent against H. pylori, with the potential to prevent gastric colonization.

Effect of mouthwash containing poly l-Lysine and glycerol monolaurate on oral Helicobacter pylori relating to biofilm eradication, anti-adhesion, and pro-inflammatory cytokine suppression.

Background/purpose: Helicobacter pylori has been found to be related to periodontitis, and the oral cavity has been considered a reservoir for H. pylori gastritis infection. Thus, this study evaluated the effect of mouthwash containing poly l-Lysine and glycerol monolaurate on inhibiting H. pylori growth, biofilm formation, cell cytotoxicity, adhesion ability, cagA mRNA expression, and pro-inflammatory cytokines stimulated by H. pylori. Materials and methods: Nineteen H. pylori strains were isolated from the oral cavity. The effectiveness of mouthwash containing poly l-Lysine and glycerol monolaurate was examined for its ability to inhibit H. pylori growth and biofilm formation and was tested for cell viability in oral epithelial cells (H357), gastric adenocarcinoma cells (AGS), and periodontal ligament cells (PDL). Additionally, the mouthwash was tested for reducing cagA mRNA expression, adhesion ability to H357 and AGS cells, and pro-inflammatory cytokines stimulated with H. pylori in AGS and PDL cells. Results: The mouthwash containing poly l-Lysine and glycerol monolaurate could eradicate the biofilm by 14.9-19.9% after incubation at 5 min, and cell viability revealed 77.2, 79.8, and 100.0% for AGS, H357, and PDL cells, respectively. Moreover, the mouthwash containing poly l-Lysine and glycerol monolaurate could down-regulate cagA mRNA expression, reduce adhesion of H. pylori by approximately 9.5-47.8% for H357 cells and 24.5-62.9% for AGS cells, and decrease pro-inflammatory cytokines, especially interleukin-8, stimulated with H. pylori. Conclusion: Mouthwash containing poly l-Lysine and glycerol monolaurate could inhibit H. pylori growth and reduce their virulence expression. The mouthwash also revealed low cytotoxicity to oral and gastric cells.

Effect of smartphone-assisted lifestyle intervention in MASLD patients: a randomized controlled trial.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is emerging globally as a significant problem. The mainstay of treatment is lifestyle intervention (LSI). We hypothesized that providing information regarding LSI and MASLD through a social media application generally used in the respective society would improve clinical outcomes in MASLD more than standard of care (SOC). This is a randomized controlled study in noncirrhotic MASLD patients aged 18-65 years in Thailand. Eligible patients were randomly assigned to either the control (SOC) or intervention arm. Patients in both groups received standard LSI advice. Infographics about MASLD and LSI information were sent to the intervention group every 3-7 days via the LINE official account. The outcomes are changes in liver steatosis and liver stiffness by FIBROSCAN at 24 weeks, as well as weight loss, body composition, and serum alanine aminotransferase (ALT) level between the two groups. A total of 122 patients were enrolled. The median age of eligible participants was 53 years, 64.7% were female, and median body mass index was 27.3 kg/m2. After a complete 24-week study period, both groups had an improvement in weight, ALT level, liver steatosis, and fat mass, but the differences in those changes between groups were not statistically significant. Interestingly, a significant improvement in liver stiffness was observed in the intervention group than in the control group (- 0.7 ± 1.8 kPa vs. 0.1 ± 2.4 kPa, P = 0.035). Encouraging LSI and delivering MASLD information via a social media application (LINE official account) to patients with MASLD demonstrated a better outcome of liver stiffness measurement than SOC.Clinical trial number: TCTR20210304002 (04/03/2021) ( http://www.thaiclinicaltrials.org/show/TCTR20210304002 ).

Health-related quality of life in Thai patients with chronic hepatitis B.

Background: Chronic hepatitis B (CHB) significantly impacts the health-related quality of life (HRQoL), but remains underexplored in the Thai population. Health state utilities (HSU) are indicators reflecting HRQoL which serve as fundamental inputs for economic evaluation analyses. This study aimed at assessing differences in HRQoL across five CHB stages in Thai patients, including non-cirrhotic CHB, compensated cirrhosis, decompensated cirrhosis, early-/intermediate-stage hepatocellular carcinoma (HCC) and advanced-/terminal-stage HCC. Methods: We conducted a cross-sectional study to collect HRQoL data from patients with CHB at five stages. The study included patients with CHB who were followed up at a super-tertiary care centre between March 2021 and February 2022. The participants completed the EQ-5D-5L questionnaire and provided demographic data. Disease stage and relevant data were obtained from medical records. HSU and Euroqol-visual analogue scale (EQ-VAS) scores, calculated using Thai-specific conversion coefficients, were assessed. Results: Among 422 patients, 236 did not have cirrhosis, 92 had compensated cirrhosis, 13 had decompensated cirrhosis, 55 had early-/intermediate-stage HCC, and 26 had advanced-/terminal-stage HCC. The HSU scores for non-cirrhotic, compensated cirrhosis, decompensated cirrhosis, early-/intermediate-stage HCC and advanced-/terminal-stage HCC were 0.95 ± 0.08, 0.89 ± 0.16, 0.79 ± 0.19, 0.89 ± 0.12 and 0.52 ± 0.39, respectively. Similarly, the EQ-VAS scores for various CHB stages were 83.56 ± 12.90, 80.48 ± 13.03, 68.76 ± 17.40, 79.00 ± 14.38 and 62.92 ± 20.62, respectively. A significant correlation (r = 0.469, P < 0.001) was observed between the HSU and EQ-VAS scores. The disease progression led to a notable HSU decline, particularly in the advanced-/terminal-stage HCC group (regression coefficient: -0.436, P < 0.001). The EQ-VAS scores indicated reduced quality of life in advanced liver disease. Conclusions: Later CHB stages compromise the HRQoL. Decompensated cirrhosis and advanced-/terminal-stage HCC profoundly affect physical health and quality of life, whereas patients with compensated cirrhosis and early-/intermediate-stage HCC report better HRQoL.