Diagnostic and prognostic performances of GALAD score in staging and 1-year mortality of hepatocellular carcinoma: A prospective study.

BACKGROUND: The GALAD score has improved early hepatocellular carcinoma (HCC) detection rate. The role of the GALAD score in staging and predicting tumor characteristics or clinical outcome of HCC remains of particular interest. AIM: To determine the diagnostic/prognostic performances of the GALAD score at various phases of initial diagnosis, tumor features, and 1-year mortality of HCC and compare the performance of the GALAD score with those of other serum biomarkers. METHODS: This prospective, diagnostic/prognostic study was conducted among patients with newly diagnosed HCC at the liver center of Vajira Hospital. Eligible patients had HCC staging allocation using the Barcelona Clinic Liver Cancer (BCLC) categorization. Demographics, HCC etiology, and HCC features were recorded. Biomarkers and the GALAD score were obtained at baseline. The performance of the GALAD score and biomarkers were prospectively assessed. RESULTS: Exactly 115 individuals were diagnosed with HCC. The GALAD score increased with disease severity. Between BCLC-0/A and BCLC-B/C/D, the GALAD score predicted HCC staging with an area under the curve (AUC) of 0.868 (95%CI: 0.80-0.93). For identifying the curative HCC, the AUC of GALAD score was significantly higher than that of Alpha-fetoprotein (AFP) (0.753) and Lens culinaris agglutinin-reactive fraction of AFP-L3 (0.706), and as good as that of Protein induced by vitamin K absence-II (PIVKA-II) (0.897). For detecting aggressive features, the GALAD score gave an AUC of 0.839 (95%CI: 0.75-0.92) and significantly outperformed compared to that of AFP (0.761) and AFP-L3 (0.697), with a trend of superiority to that of PIVKA-II (0.772). The performance to predict 1-year mortality of GALAD score (AUC: 0.711, 95%CI: 0.60-0.82) was better than that of AFP (0.541) and as good as that of PIVKA-II (0.736). The optimal cutoff value of GALAD score was ≥ 6.83, with a specificity of 72.63% for exhibiting substantial reduction in the 1-year mortality. CONCLUSION: The GALAD model can diagnose HCC at the curative stage, including the characteristic of advanced disease, more than that by AFP and AFP-L3, but not PIVKA-II. The GALAD score can be used to predict the 1-year mortality of HCC.

Intravenous metoclopramide for increasing endoscopic mucosal visualization in patients with acute upper gastrointestinal bleeding: a multicenter, randomized, double-blind, controlled trial.

Acute upper gastrointestinal hemorrhage (UGIH) is the most common emergency condition that requires rapid endoscopic treatment. This study aimed to evaluate the effects of pre-endoscopic intravenous metoclopramide on endoscopic mucosal visualization (EMV) in patients with acute UGIH. This was a multicenter, randomized, double-blind controlled trial of participants diagnosed with acute UGIH. All participants underwent esophagogastroduodenoscopy within 24 h. Participants were assigned to either the metoclopramide or placebo group. Modified Avgerinos scores were evaluated during endoscopy. In total, 284 out of 300 patients completed the per-protocol procedure. The mean age was 62.8 ± 14.3 years, and 67.6% were men. Metoclopramide group achieved a higher total EMV and gastric body EMV score than the other group (7.34 ± 1.1 vs 6.94 ± 1.6; P = 0.017 and 1.80 ± 0.4 vs 1.64 ± 0.6; P = 0.006, respectively). Success in identifying lesions was not different between the groups (96.5% in metoclopramide and 93.6% in placebo group; P = 0.26). In the metoclopramide group, those with active variceal bleeding compared with the control group demonstrated substantial improvements in gastric EMV (1.83 ± 0.4 vs 1.28 ± 0.8, P = 0.004), antral EMV (1.96 ± 0.2 vs 1.56 ± 0.6, P = 0.003), and total EMV score (7.48 ± 1.1 vs 6.2 ± 2.3, P = 0.02). Pre-endoscopic intravenous metoclopramide improved the quality of EMV in variceal etiologies of UGIH, which was especially prominent in those who had signs of active bleeding based on nasogastric tube assessment.Trial Registration: Trial was registered in Clinical Trials: TCTR 20210708004 (08/07/2021).

Nonvitamin K oral anticoagulants with proton pump inhibitor cotherapy ameliorated the risk of upper gastrointestinal bleeding.

Proton pump inhibitors (PPIs) can reduce the risk of upper gastrointestinal bleeding (UGIB) in patients who are taking oral anticoagulants. This study aimed to identify the association between NOACs with PPI cotherapy and UGIB. This retrospective cohort analysis included patients over the age of 18 years who were using NOACs between 2013 and 2020. NOAC categories, concomitant medications, endoscopic findings, the HAS-BLED score and the Charlson Comorbidity Index score were recorded. Using Poisson regression models, the relationship between UGIB events and risk factors was analyzed. Throughout a mean follow-up of 29.5 months, 14 (5.1%) individuals experienced UGIB. The incidence of UGIB was greater in patients receiving NOACs without PPIs (2.7 [1.26-5.60] per 1000) than in those receiving NOACs with PPIs (1.3 [0.61-2.67] per 1000). Patients receiving NOACs with PPIs had a 79.2% lower incidence of UGIB than patients receiving NOAC monotherapy (RR 0.208, 95% CI 0.061-0.706; p = 0.012). Female sex and the HAS-BLED score were associated with UGIB (RR 5.043; 95% CI 1.096-23.20; p = 0.038; RR 2.024; 95% CI 1.095-3.743; p = 0.024, respectively). Patients receiving NOAC and PPI cotherapy had a lower incidence of UGIB than those receiving NOACs alone, and female sex was a risk factor for UGIB in NOAC-treated patients.

Real world for management of hepatocellular carcinoma: a large population-based study.

OBJECTIVES: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death. This study investigated the risk factors, treatment responses and survival outcomes in real-world patients with HCC. MATERIALS AND METHODS: This was a large, retrospective cohort study of patients newly diagnosed with HCC at tertiary referral centers in Thailand between 2011 and 2020. Survival time was defined as the time from the date of HCC diagnosis to the date of death or last follow-up. RESULTS: A total of 1145 patients with a mean age of 61.4 ± 11.7 years were included. Next, 568 (48.7%), 401 (34.4%) and 167 (15.1%) patients were classified as Child-Pugh score A, B and C, respectively. Over half of the patients (59.0%) were diagnosed with noncurative-stage HCC (BCLC B-D). Patients with Child-Pugh A scores were more likely to be diagnosed with curative-stage HCC (BCLC 0-A) than noncurative stage (67.4% vs. 37.2%, p < .001). Patients with curative-stage HCC and Child-Pugh A cirrhosis underwent more liver resections than radiofrequency ablation (RFA) (91.8% vs. 69.7%, p < .001). For BCLC 0-A patients with portal hypertension, RFA was selected more frequently than liver resection (52.1% vs. 28.6%, p < .001). Patients who received RFA monotherapy tended to experience increased median survival times compared to those who underwent resection (55 vs. 36 months; p = .058). CONCLUSIONS: Surveillance programs should be encouraged to detect early-stage HCC, which is suitable for curative treatment improving survival outcomes. RFA may be an appropriate first-line treatment for curative-stage HCC. Sequential multi-modality treatment in the curative stage can achieve favorable 5-year survival.

Efficacy of dexamethasone and N-acetylcysteine combination in preventing post-embolization syndrome after transarterial chemoembolization in hepatocellular carcinoma.

BACKGROUND: Conventional transarterial chemoembolization (cTACE) is the current standard treatment for intermediate-stage hepatocellular carcinoma (HCC). Post-embolization syndrome (PES) is complex clinical syndrome that presents as fever, abdominal pain, nausea, and vomiting. Either dexamethasone (DEXA) or N-acetylcysteine (NAC) is used to prevent PES; however, the synergistic effect of their combined therapy for preventing PES and liver decompensation has not been determined. AIM: To evaluate the efficacy of DEXA and NAC combination in preventing PES and liver decompensation after cTACE. METHODS: Patients with Barcelona Clinic Liver Cancer stage A or B HCC who were scheduled for TACE were prospectively enrolled. All patients were randomly stratified to receive NAC and DEXA or placebo. The dual therapy (NAC + DEXA) group received intravenous administration of 10 mg DEXA every 12 h, NAC 24 h prior to cTACE (150 mg/kg/h for 1 h followed by 12.5 mg/kg/h for 4 h), and a continuous infusion of 6.25 mg/h NAC plus 4 mg DEXA every 12 h for 48 h after cTACE. The placebo group received an infusion of 5% glucose solution until 48 h after procedure. PES was defined by South West Oncology Group toxicity code grading of more than 2 that was calculated using incidence of fever, nausea, vomiting, and pain. RESULTS: One-hundred patients were enrolled with 50 patients in each group. Incidence of PES was significantly lower in the NAC + DEXA group compared with in the placebo group (6% vs 80%; P < 0.001). Multivariate analysis showed that the dual treatment is a protective strategic therapy against PES development [odds ratio (OR) = 0.04; 95% confidence interval (CI): 0.01-0.20; P < 0.001). Seven (14%) patients in the placebo group, but none in the NAC + DEXA group, developed post-TACE liver decompensation. A dynamic change in Albumin-Bilirubin score of more than 0.5 point was found to be a risk factor for post-TACE liver decompensation (OR = 42.77; 95%CI: 1.01-1810; P = 0.049). CONCLUSION: Intravenous NAC + DEXA administration ameliorated the occurrence of PES event after cTACE in patients with intermediate-stage HCC.

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.

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.

Recall Type vs Problem-based Tests for Formative Assessment in Undergraduate Medical Students.

We studied two types of formative assessment: recall type, and problem-based questions, with summative scores and previous grades in 77 fourth-year medical students. We found that the formative scores did not correlate well with the summative scores, but were associated with the Grade point average in the preclinical period.

Quantitative histological-hemodynamic correlations in cirrhosis.

UNLABELLED: We have previously shown, in a semiquantitative analysis of liver biopsies showing cirrhosis, that thickness of fibrous septa separating cirrhotic nodules and small size of cirrhotic nodules correlated independently with portal pressure (as determined by the hepatic venous pressure gradient; HVPG) and were independent predictors of the presence of clinically significant portal hypertension (PH). This study aimed to confirm these results using quantitative analysis of these biopsies using digital image analysis. Biopsies of 42 patients with cirrhosis and HVPG measurements within 6 months of the biopsy were included in the study. The following parameters were scored quantitatively and without knowledge of HVPG results: total fibrosis area, septal thickness, nodule size, and number of nodules per millimeter of length of liver biopsy. Fibrosis area was the only parameter that independently correlated with HVPG (r = 0.606; P < 0.0001). Correlation was significant, even among patients with clinically significant PH (r = 0.636; P < 0.005). Fibrosis area and nodule size were both independently predictive of the presence of clinically significant PH (r = 0.57; P = 0.003). CONCLUSIONS: On quantitative analysis, fibrosis area was the parameter that correlated best with HVPG and the presence of clinically significant PH. Beyond pathophysiological implications, this also has methodological implications that are discussed in this article.

Intestinal and plasma VEGF levels in cirrhosis: the role of portal pressure.

Increased levels of intestinal VEGF are thought to worsen portal hypertension. The cause of the increase in the level of intestinal VEGF found during cirrhosis is not known. The aim of this study is to demonstrate a relationship between portal pressure (PP) and intestinal/ plasma VEGF levels in different stages of fibrosis/cirrhosis. In this experiment, rats were exposed to carbon tetrachloride (CCl(4) ) for 6, 8 and 12 weeks. At the end of exposure, the three groups of rats exhibited three different stages of pathology: non-cirrhotic, early fibrotic and cirrhotic, respectively. For those rats and their age-matched controls, PP and intestinal/plasma VEGF levels were measured. Rats inhaling CCl(4) for 12 weeks developed portal hypertension (18.02 ± 1.07 mmHg), while those exposed for 6 weeks (7.26 ± 0.58 mmHg) and for 8 weeks (8.55 ± 0.53 mmHg) did not. The rats exposed for 12 weeks also showed a 40% increase in the level of intestinal VEGF compared to the controls (P < 0.05), while those rats exposed to CCl(4) inhalation for 6 and 8 weeks did not. There was a significant positive correlation between PP and intestinal VEGF levels (r(2) = 0.4, P < 0.005). Plasma VEGF levels were significantly elevated in those rats exposed to 12 weeks of CCl(4) inhalation (63.7 pg/ml, P < 0.01), compared to the controls (8.5 pg/ml). However, no correlation was observed between PP and plasma VEGF levels. It is concluded that portal pressure modulates intestinal VEGF levels during the development of cirrhosis.