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.

Risk factors of active upper gastrointestinal bleeding in patients with COVID-19 infection and the effectiveness of PPI prophylaxis.

BACKGROUND: Gastrointestinal (GI) bleeding is one of the most impactful complications in patients hospitalized from COVID-19 infection. Limited study has focused on patients with upper GI bleeding (UGIB). This study aimed to identify the risk factors of patients who were hospitalized from COVID-19 infection and developed UGIB as well as the effectiveness of proton pump inhibitor (PPI) prophylaxis in those patients. METHODS: This study was comprised of two phases. The first phase was the retrospective enrollment of patients who were admitted due to COVID-19 infection and developed UGIB between April and August 2021 to evaluate the associated factors of active UGIB. The second phase was a retrospective analysis after PPI prophylaxis protocol from September - October 2021 to assess the benefit of PPI use in those patients. RESULTS: Of 6,373 patients hospitalized, 43 patients (0.7%) had evidence of UGIB. The majority were male 28 (65.1%) with a mean age of 69.1 ± 11.8 years. Twenty-four of 43 patients (55.8%) needed mechanical ventilation, 35 patients (81.4%) received systemic corticosteroids, and 10 patients (23.3%) were taking anticoagulants for venous thromboembolic prophylaxis. Seven of 43 patients (16%) had active UGIB. There was no significant difference in the number of patients taking antiplatelets, anticoagulants, or steroids and the severity of COVID-19 infection between the two groups. An emergency endoscopy or endoscopic hemostasis were performed in 6/7 (85.7%) patients. The multivariate logistic regression analysis revealed two significant factors associated with active UGIB including higher of Glasgow-Blatchford score (GBS) per point (OR = 7.89; 95%CI 1.03-72.87; p = 0.04) and an absence of PPI use (OR 4.29; 95%CI 1.04-19.51; p = 0.04). After prescribing PPI as a prophylaxis, there was a slightly lower incidence of UGIB (0.6% vs 0.7%) in addition to an absence of active UGIB (0% vs 16%). CONCLUSION: Our study demonstrated that the absence of PPI and higher GBS were significant risk factors for active UGIB which required therapeutic endoscopy in patients with COVID-19 infection. We suggest that short-term PPI prophylaxis should be prescribed in those patients once they need hospitalization regardless of the severity of COVID-19 infection to minimize the severity of UGIB.

Prevalence and genotype distribution of hepatitis C virus within hemodialysis units in Thailand: role of HCV core antigen in the assessment of viremia.

BACKGROUND: Individuals with end-stage renal disease have a higher risk of hepatitis C virus (HCV) acquisition during long-term hemodialysis (HD). Our report was designed to investigate HCV prevalence and genotype, in addition to the clinical use of HCV core antigen (HCVcAg), within multiple HD facilities in Thailand. METHODS: This cross-sectional report was investigated between January and June 2019. HCV infection was assessed by anti-HCV and confirmed active infection by measuring HCV RNA and HCVcAg. HCV genotype was determined by phylogenetic analysis using nucleotide sequences of NS5B region. RESULTS: Overall, 140 of 3,305 (4.2%) patients in 15 dialysis centers had anti-HCV positive. Among them, HCV RNA was further assessed in 93 patients and was detectable in 59 (63.4%) persons. Considering HCV viremia, HCVcAg measurement exhibited high accuracy (96.8%), sensitivity (94.9%) and specificity (100%) in comparison with HCV RNA testing. Moreover, individuals infected with HCV received a longer duration of dialysis vintage when compared to anti-HCV negative controls. The major sub-genotypes were 1a, 1b, 3a, 3b, 6f and 6n. Regarding phylogenetic analysis, there were 7 clusters of isolates with high sequence homology affecting 17 individuals, indicating possible HCV transmission within the same HD centers. CONCLUSIONS: HCV frequency and common sub-genotypes in HD centers were different from those found in the Thai general population. HCVcAg might be an alternate testing for viremia within resource-limited countries. Enhanced preventive practices, dialyzer reuse policy and better access to antiviral therapy are crucial for HCV micro-elimination within HD facilities.

Amount of contamination on the face shield of endoscopists during upper endoscopy between patients in two positions: A randomized study.

BACKGROUND AND AIM: During the Coronavirus Disease 2019 pandemic, esophagogastroduodenoscopy (EGD) has been recognized as an aerosol-generating procedure. This study aimed to systematically compare the degree of face shield contamination between endoscopists who performed EGD on patients lying in the left lateral decubitus (LL) and prone positions. METHODS: This is a randomized trial in patients scheduled for EGD between April and June 2020. Eligible 212 patients were randomized with 1:1 allocation. Rapid adenosine triphosphate test was used to determine contamination level using relative light units of greater than 200 as a cutoff value. All eligible patients were randomized to lie in either the LL or prone position during EGD. The primary outcome was the rate of contamination on the endoscopist's face shield. RESULTS: The majority of patients were female (63%), with a mean age of 60 ± 13 years. Baseline characteristics were comparable between the two groups. There was no face shield contamination after EGD in either group. The number of coughs in the LL group was higher than the prone group (1.38 ± 1.8 vs 0.89 ± 1.4, P = 0.03). The mean differences in relative light units on the face shield before and after EGD in the LL and prone groups were 9.9 ± 20.9 and 4.1 ± 6 (P = 0.008), respectively. CONCLUSION: As measured by the adenosine triphosphate test, performing diagnostic EGD does not lead to contamination on the face shield of the endoscopist. However, placing patients in the prone position may further mitigate the risk.

Development of a diagnostic support system for the fibrosis of nonalcoholic fatty liver disease using artificial intelligence and deep learning.

Liver fibrosis is a pathological condition characterized by the abnormal proliferation of liver tissue, subsequently able to progress to cirrhosis or possibly hepatocellular carcinoma. The development of artificial intelligence and deep learning have begun to play a significant role in fibrosis detection. This study aimed to develop SMART AI-PATHO, a fully automated assessment method combining quantification of histopathological architectural features, to analyze steatosis and fibrosis in nonalcoholic fatty liver disease (NAFLD) core biopsies and employ Metavir fibrosis staging as standard references and fat assessment grading measurement for comparison with the pathologist interpretations. There were 146 participants enrolled in our study. The correlation of Metavir scoring system interpretation between pathologists and SMART AI-PATHO was significantly correlated (Agreement = 68%, Kappa = 0.59, p-value <0.001), which subgroup analysis of significant fibrosis (Metavir score F2-F4) and nonsignificant fibrosis (Metavir score F0-F1) demonstrated substantial correlated results (agreement = 80%, kappa = 0.61, p-value <0.001), corresponding with the correlation of advanced fibrosis (Metavir score F3-F4) and nonadvanced fibrosis groups (Metavir score F0-F2), (agreement = 89%, kappa = 0.74, p-value <0.001). SMART AI-PATHO, the first pivotal artificially intelligent diagnostic tool for the color-based NAFLD hepatic tissue staging in Thailand, demonstrated satisfactory performance as a pathologist to provide liver fibrosis scoring and steatosis grading. In the future, developing AI algorithms and reliable testing on a larger scale may increase accuracy and contribute to telemedicine consultations for general pathologists in clinical practice.

Machine learning improves the prediction of significant fibrosis in Asian patients with metabolic dysfunction-associated steatotic liver disease - The Gut and Obesity in Asia (GO-ASIA) Study.

BACKGROUND: The precise estimation of cases with significant fibrosis (SF) is an unmet goal in non-alcoholic fatty liver disease (NAFLD/MASLD). AIMS: We evaluated the performance of machine learning (ML) and non-patented scores for ruling out SF among NAFLD/MASLD patients. METHODS: Twenty-one ML models were trained (N = 1153), tested (N = 283), and validated (N = 220) on clinical and biochemical parameters of histologically-proven NAFLD/MASLD patients (N = 1656) collected across 14 centres in 8 Asian countries. Their performance for detecting histological-SF (≥F2fibrosis) were evaluated with APRI, FIB4, NFS, BARD, and SAFE (NPV/F1-score as model-selection criteria). RESULTS: Patients aged 47 years (median), 54.6% males, 73.7% with metabolic syndrome, and 32.9% with histological-SF were included in the study. Patients with SFvs.no-SF had higher age, aminotransferases, fasting plasma glucose, metabolic syndrome, uncontrolled diabetes, and NAFLD activity score (p < 0.001, each). ML models showed 7%-12% better discrimination than FIB-4 to detect SF. Optimised random forest (RF) yielded best NPV/F1 in overall set (0.947/0.754), test set (0.798/0.588) and validation set (0.852/0.559), as compared to FIB4 in overall set (0.744/0.499), test set (0.722/0.456), and validation set (0.806/0.507). Compared to FIB-4, RF could pick 10 times more patients with SF, reduce unnecessary referrals by 28%, and prevent missed referrals by 78%. Age, AST, ALT fasting plasma glucose, and platelet count were top features determining the SF. Sequential use of SAFE < 140 and FIB4 < 1.2 (when SAFE > 140) was next best in ruling out SF (NPV of 0.757, 0.724 and 0.827 in overall, test and validation set). CONCLUSIONS: ML with clinical, anthropometric data and simple blood investigations perform better than FIB-4 for ruling out SF in biopsy-proven Asian NAFLD/MASLD patients.

Validation of the albumin-bilirubin score for identifying decompensation risk in patients with compensated cirrhosis.

BACKGROUND: The albumin-bilirubin (ALBI) score is an index of liver function recently developed to assess prognosis in patients with hepatocellular carcinoma (HCC). It can detect small changes in liver dysfunction and has been successfully applied to the prediction of survival in patients with non-malignant liver diseases of various etiologies. AIM: To investigate the ALBI score for identifying decompensation risk at the 3-year follow-up in patients with compensated cirrhosis. METHODS: One-hundred and twenty-three patients with compensated cirrhosis without HCC in King Chulalongkorn Memorial Hospital diagnosed by imaging were retrospectively enrolled from January 2016 to December 2020. A total of 113 patients (91.9%) had Child A cirrhosis with a median model for end-stage liver disease (MELD) score of less than 9. Baseline clinical and laboratory variables and decompensation events were collected. The ALBI score was calculated and validated to classify decompensation risk into low-, middle-, and high-risk groups using three ALBI grade ranges (ALBI grade 1: ≤ -2.60; grade 2: > -2.60 but ≤ -1.39; grade 3: > -1.39). Decompensation events were defined as ascites development, variceal bleeding, or grade 3 or 4 hepatic encephalopathy. RESULTS: Among 123 cirrhotic patients enrolled, 13.8% (n = 17) developed decompensating events at a median time of 25 [95% confidence interval (CI): 17-31] mo. Median baseline ALBI score in compensated cirrhosis was significantly lower than that of patients who developed decompensation events [-2.768 (-2.956 to -2.453) vs -2.007 (-2.533 to -1.537); P = 0.01]. Analysis of decompensation risk at 3 years showed that ALBI score had a time-dependent area under the curve (tAUC) of 0.86 (95%CI: 0.78-0.92), which was significantly better than that of ALBI-Fibrosis-4 (ALBI-FIB4) score (tAUC = 0.77), MELD score (tAUC = 0.66), Child-Pugh score (tAUC = 0.65), and FIB-4 score (tAUC = 0.48) (P < 0.05 for all). The 3-year cumulative incidence of decompensation was 3.1%, 22.6%, and 50% in the low-, middle-, and high-risk groups, respectively (P < 0.001). The odds ratio for decompensation in patients of the high-risk group was 23.33 (95%CI: 3.88-140.12, P = 0.001). CONCLUSION: The ALBI score accurately identifies decompensation risk at the 3-year follow-up in patients with compensated cirrhosis. Those cirrhotic patients with a high-risk grade of ALBI score showed a 23 times greater odds of decompensation.

Modified albumin-bilirubin predicted survival of unresectable hepatocellular carcinoma patients treated with immunotherapy.

BACKGROUND: Modified albumin-bilirubin (mALBI) grade has been established as a survival determinant in hepatocellular carcinoma (HCC) patients who receive locoregional and targeted therapies. AIM: To investigate whether mALBI could predict survival in unresectable HCC (uHCC) patients who were treated with atezolizumab plus bevacizumab (AB). METHODS: A single-center, retrospective cohort study enrolled uHCC patients who received AB treatment between September 2020 and April 2023 and were followed up until June 2023. An association between mALBI and patient survival was determined using Cox proportional hazards analysis. RESULTS: Of the 83 patients, 67 patients (80.7%) were male with the mean age of 60.6 years. Among them, 22 patients (26.5%) were classified as Barcelona Clinic Liver Cancer B, and 61 patients (73.5%) were classified as Barcelona Clinic Liver Cancer C. Cirrhosis was present in 76 patients (91.6%), with 58 patients classified as Child-Turcotte-Pugh (CTP) A and 18 as CTP B. The median overall survival (OS) and progression-free survival were 13.0 mo [95% confidence interval (CI): 5.2-20.8] and 9.0 mo (95%CI: 5.0-13.0), respectively. The patients were divided into two groups based on mALBI grades: 42 patients (50.6%) in the mALBI 1 + 2a group; and 41 patients (49.4%) in the mALBI 2b + 3 group. During the median follow-up period of 7.0 mo, the mALBI 1 + 2a group exhibited significantly better survival compared to the mALBI 2b + 3 group, with a median OS that was not reached vs 3.0 mo (95%CI: 0.1-6.0, P < 0.001). In a subgroup of patients with CTP A, the mALBI 1 + 2a group also showed significantly longer survival compared to the mALBI 2b + 3 group, with a median OS that was not reached vs 6.0 mo (95%CI: 3.4-8.6, P < 0.001). In the multivariate analysis, both CTP class and mALBI grade were independently associated with survival, with adjusted hazard ratios (95%CI) of 2.63 (1.19-5.78, P = 0.020) and 3.90 (1.71-8.90, P = 0.001), respectively. CONCLUSION: mALBI grades can determine survival of uHCC patients receiving AB treatment, particularly those who have mildly impaired liver function. This highlights the importance of assessing mALBI before initiating AB treatment to optimize therapeutic efficacy in clinical practice.

Acupuncture-Associated Mycobacterium massiliense and Scedosporium Infections Superimposed by Tetanus.

Background: Tetanus has rarely been reported in Thailand since 1982 due to 100% tetanus vaccination coverage during the neonatal period of life. However, the reemergence of tetanus has been observed in our country during the past decade, mainly due to the increasing number of migrants traveling from neighboring countries in search of work. Acupuncture has become an essential part of alternative and complementary medicine. To our knowledge, acupuncture-associated Mycobacterium abscessus and Scedosporium infections superimposed by tetanus have never been reported. Case Presentation. A 55-year-old Thai female with schizophrenia was hospitalized due to a 4-day course of trismus, dysphagia, and back muscle spasms. Upon admission, a clinical diagnosis of tetanus was made, which included muscle rigidity and reflex muscle spasms, despite a recent history of diphtheria-tetanus (dT) vaccination for tetanus prophylaxis after 2 episodes of falling complicated by two lacerations on the left shoulder and head. Endotracheal intubation for airway protection was given, in addition to tetanus immunoglobulin, metronidazole, and diazepam which were prescribed to the patient. Incision and drainage of the wound on the left shoulder yielded 40 mL of pus, which subsequently grew Clostridium species, Mycobacterium massiliense, and Scedosporium on anaerobic bacterial, mycobacterial, and fungal cultures, respectively. An incision of an acupuncture wound on the abdominal wall yielded 1 mL of pus, which exhibited positive acid-fast bacilli (AFB) on AFB stain. Mycobacterial culture finally grew M. massiliense. The organism was susceptible to amikacin and clarithromycin. Amikacin, clarithromycin, ciprofloxacin, and voriconazole were then added. The patient gradually improved and was discharged after one month of hospitalization. The patient was reported to be doing well, with no neurological sequelae, when last seen one month after discharge. Conclusions: To our knowledge, this is the first case of acupuncture-associated M. massiliense and Scedosporium infections superimposed by tetanus. In Thailand, the occurrence of acupuncture by nonqualified individuals and the reemergence of tetanus remain prevalent. Hence, it is not uncommon to see tetanus in association with acupuncture-related nontuberculous mycobacterial/fungal infection.

Nephrotic Syndrome Induced by Lenvatinib Treatment for Hepatocellular Carcinoma.

Lenvatinib, an oral small-molecule multiple tyrosine kinase inhibitor (TKI), has been approved for first-line therapy for unresectable hepatocellular carcinoma (HCC). Proteinuria is one of the most common adverse events associated with lenvatinib treatment. We reported a 67-year-old Thai female was diagnosed with NASH cirrhosis and HCC BCLC B with TACE refractoriness. She received 8 mg of lenvatinib for 2 weeks and began to experience worsening hypertension, bilateral pleural effusion, pedal edema, hypoalbuminemia, hypercholesterolemia, and proteinuria. After exclusion of all possible causes, lenvatinib-induced nephrotic syndrome (NS) was diagnosed. One week after discontinuing the drug, her symptoms gradually improved. To date, there have been only a handful of reported cases of lenvatinib-induced nephrotoxicity. We report herein the case of lenvatinib-induced NS in a cirrhotic patient with HCC with resolution of symptoms in a short period after drug discontinuation. In addition, we reviewed all reported cases of lenvatinib-induced nephrotoxicity.

Successful hemostasis by percutaneous transhepatic cyanoacrylate injection for hepatic artery pseudoaneurysm causing hemobilia.

A 73-year-old man, post-liver transplantation, was scheduled for ERCP to evaluate anastomotic biliary stricture. The patient developed massive bleeding from hepatic artery pseudoaneurysm. Angiography via femoral artery could not identified feeding artery of the pseudoaneurysm. Thus, trans-abdominal ultrasonography was performed and percutaneous transhepatic glue embolization successfully.

Application of artificial intelligence for diagnosis of pancreatic ductal adenocarcinoma by EUS: A systematic review and meta-analysis.

EUS-guided tissue acquisition carries certain risks from unnecessary needle puncture in the low-likelihood lesions. Artificial intelligence (AI) system may enable us to resolve these limitations. We aimed to assess the performance of AI-assisted diagnosis of pancreatic ductal adenocarcinoma (PDAC) by off-line evaluating the EUS images from different modes. The databases PubMed, EMBASE, SCOPUS, ISI, IEEE, and Association for Computing Machinery were systematically searched for relevant studies. The pooled sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver operating characteristic curve were estimated using R software. Of 369 publications, 8 studies with a total of 870 PDAC patients were included. The pooled sensitivity and specificity of AI-assisted EUS were 0.91 (95% confidence interval [CI], 0.87-0.93) and 0.90 (95% CI, 0.79-0.96), respectively, with DOR of 81.6 (95% CI, 32.2-207.3), for diagnosis of PDAC. The area under the curve was 0.923. AI-assisted B-mode EUS had pooled sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 0.91, 0.90, 0.94, and 0.84, respectively; while AI-assisted contrast-enhanced EUS and AI-assisted EUS elastography had sensitivity, specificity, PPV, and NPV of 0.95, 0.95, 0.97, and 0.90; and 0.88, 0.83, 0.96 and 0.57, respectively. AI-assisted EUS has a high accuracy rate and may potentially enhance the performance of EUS by aiding the endosonographers to distinguish PDAC from other solid lesions. Validation of these findings in other independent cohorts and improvement of AI function as a real-time diagnosis to guide for tissue acquisition are warranted.

Validation model of fibrosis-8 index score to predict significant fibrosis among patients with nonalcoholic fatty liver disease.

BACKGROUND: Identifying hepatic fibrosis is crucial for nonalcoholic fatty liver disease (NAFLD) management. The fibrosis-8 (FIB-8) score, recently developed by incorporating four additional variables into the fibrosis-4 (FIB-4) score, showed better performance in predicting significant fibrosis in NAFLD. AIM: To validate the FIB-8 score in a biopsy-proven NAFLD cohort and compare the diagnostic performance of the FIB-8 and FIB-4 scores and NAFLD fibrosis score (NFS) for predicting significant fibrosis. METHODS: We collected the data of biopsy-proven NAFLD patients from three Asian centers in three countries. All the patients with available variables for the FIB-4 score (age, platelet count, and aspartate and alanine aminotransferase levels) and FIB-8 score (the FIB-4 variables plus 4 additional parameters: The body mass index (BMI), albumin to globulin ratio, gamma-glutamyl transferase level, and presence of diabetes mellitus) were included. The fibrosis stage was scored using nonalcoholic steatohepatitis CRN criteria, and significant fibrosis was defined as at least fibrosis stage 2. RESULTS: A total of 511 patients with biopsy-proven NAFLD and complete data were included for validation. Of these 511 patients, 271 (53.0%) were female, with a median age of 51 (interquartile range: 41, 58) years. The median BMI was 29 (26.3, 32.6) kg/m2, and 268 (52.4%) had diabetes. Among the 511 NAFLD patients, 157 (30.7%) had significant fibrosis (≥ F2). The areas under the receiver operating characteristic curves of the FIB-8 and FIB-4 scores and NFS for predicting significant fibrosis were 0.774, 0.743, and 0.680, respectively. The FIB-8 score demonstrated significantly better performance for predicting significant fibrosis than the NFS (P = 0.001) and was also clinically superior to FIB-4, although statistical significance was not reached (P = 0.073). The low cutoff point of the FIB-8 score for predicting significant fibrosis of 0.88 showed 92.36% sensitivity, and the high cutoff point of the FIB-8 score for predicting significant fibrosis of 1.77 showed 67.51% specificity. CONCLUSION: We demonstrated that the FIB-8 score had significantly better performance for predicting significant fibrosis in NAFLD patients than the NFS, as well as clinically superior performance vs the FIB-4 score in an Asian population. A novel simple fibrosis score comprising commonly accessible basic laboratories may be beneficial to use for an initial assessment in primary care units, excluding patients with significant liver fibrosis and aiding in patient selection for further hepatologist referral.

Circulating tumor cells as a prognostic biomarker in patients with hepatocellular carcinoma.

Circulating tumor cells (CTCs) have been shown as a surrogate for cancer progression and prognostication. We aimed to determine an association between CTCs and survival of hepatocellular carcinoma (HCC) patients. Peripheral blood was obtained from 73 HCC patients to enumerate for epithelial CTCs/8 mL blood. CTCs were detected by immunoaffinity-based method using epithelial cell adhesion molecule (EpCAM) and mucin1 (MUC1). The CTCs detection rates of BCLC stages A, B, and C patients were 65.4% (17/26), 77.3% (17/22), and 96% (24/25), respectively, p = 0.018. Patients with CTCs < 5 cells/8 mL had significantly longer survival than those with CTCs ≥ 5 cells/8 mL (>36 vs. 4.6 months, p < 0.001). In multivariate analysis, CTP B, BCLC B, BCLC C, AFP ≥ 400 ng/mL, and CTC ≥ 5 cells/8 mL were independently associated with survival, with adjusted HRs (95%CI) of 4.1 (2.0-8.4), 3.5 (1.1-11.4), 4.7 (1.4-15.4), 2.4 (1.1-5.0), and 2.6 (1.2-8.4); p < 0.001, 0.036, 0.011, 0.025 and 0.012, respectively. The combination of CTCs ≥ 5 cells/8 mL and AFP ≥ 400 ng/mL provided additively increased HR to 5.3 (2.5-11.1), compared to HRs of 4.0 (2.0-8.0) and 3.5 (1.8-6.7) for CTCs ≥ 5 cells/8 mL and AFP ≥ 400 ng/mL, p < 0.001, respectively. The larger number of peripheral CTCs is correlated with higher tumor aggressive features and poorer survival of HCC patients. CTCs can potentially become novel prognostic biomarker in HCC.

Pharmacological Therapeutics: Current Trends for Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD).

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new term from nonalcoholic fatty liver disease (NAFLD) and is a positive diagnosis based on histopathology, imaging, or blood biomarkers. MAFLD is one of the common causes of liver dysfunction worldwide, likely due to the increase in metabolic syndrome as well as the high burden of disease and its relationship to other extrahepatic conditions. However, effective pharmacological therapeutic agents are still lacking; current management largely focuses on weight reduction and lifestyle modification. The purpose of this review was to summarize the updated evidence of novel therapies targeting different pathogenetic pathways in MAFLD.

A randomized controlled trial of comparative effectiveness between the 2 dose and 3 dose regimens of hepatitis a vaccine in kidney transplant recipients.

Hepatitis A virus (HAV) is able to cause a spectrum of illnesses ranging from no symptom to fulminant hepatitis which may lead to acute kidney injury. Although hepatitis A vaccine is recommended in non-immune solid organ transplant recipients who live in or travel to endemic areas, the standard 2-dose vaccination regimen demonstrated less favorable immunogenicity among these population. The 3-dose regimen showed higher response rate and immune durability in patients with human immunodeficiency virus. However, this strategy has never been studied in solid organ transplant recipients. A single-center, open-labeled, computer-based randomized controlled trial (RCT) with a 2:1 allocation ratio was conducted from August 2017 to December 2018. The study compared the seroconversion rate after receiving 2- or 3-dose regimen of hepatitis A vaccine at 0, 6 and 0, 1, 6 months, respectively, in non-immune kidney transplant recipients. A total of 401 adult kidney transplant recipients were screened for anti-HAV IgG and 285 subjects had positive results so the seroprevalence was 71.1%. Of 116 seronegative recipients, 93 (80.2%) completed vaccination; 60 and 33 participants completed 2- and 3-dose vaccination, respectively. The baseline characteristics were comparable between both groups. The seroconversion rate at 1 month after vaccination was 51.7% in the standard 2-dose regimen and 48.5% in the 3-dose regimen (p = 0.769). Overall, the seroconversion rate appeared to be associated with high estimated glomerular infiltration rate, high serum albumin, and low intensity immunosuppressive regimen. Seroconversion rate after hepatitis A vaccination in kidney transplant recipients was less favorable than healthy population. Three-dose regimen did not show superior benefit over the standard 2-dose regimen. Other strategies of immunization may increase immunogenicity among kidney transplant recipients.