Independent Risk Factors Predicting Eradication Failure of Hybrid Therapy for the First-Line Treatment of Helicobacter pylori Infection.

Hybrid therapy is a recommended first-line anti-H. pylori treatment option in the American College of Gastroenterology guidelines, the Bangkok Consensus Report on H. pylori management, and the Taiwan H. pylori Consensus Report. However, the cure rates of eradication therapy in some countries are suboptimal, and the factors affecting the treatment efficacy of hybrid therapy remain unclear. The aim of this study is to identify the independent risk factors predicting eradication failure of hybrid therapy in the first-line treatment of H. pylori infection. A retrospective cohort study was conducted on 589 H. pylori-infected patients who received 14-day hybrid therapy between September 2008 and December 2021 in ten hospitals in Taiwan. The patients received a hybrid therapy containing a dual regimen with a proton pump inhibitor (PPI) plus amoxicillin for an initial 7 days and a quadruple regimen with a PPI plus amoxicillin, metronidazole and clarithromycin for a final 7 days. Post-treatment H. pylori status was assessed at least 4 weeks after completion of treatment. The relationships between eradication rate and 13 host and bacterial factors were investigated via univariate and multivariate analyses. In total, 589 patients infected with H. pylori infection were included in the study. The eradication rates of hybrid therapy were determined as 93.0% (95% confidence interval (CI): 90.9-95.1%), 94.4% (95% CI: 93.8-97.2%) and 95.5%% (95% CI: 93.8-97.2%) by intention-to-treat, modified intention-to-treat and per-protocol analyses, respectively. Univariate analysis showed that the eradication rate of clarithromycin-resistant strains was lower than that of clarithromcyin-susceptible strains (83.3% (45/54) vs. 97.6%% (280/287); p < 0.001). Subjects with poor drug adherence had a lower cure rate than those with good adherence (73.3% (11/15) vs. 95.5% (534/559); p = 0.005). Other factors such as smoking, alcohol drinking, coffee consumption, tea consumption and type of PPI were not significantly associated with cure rate. Multivariate analysis revealed that clarithromcyin resistance of H. pylori and poor drug adherence were independent risk factors related to eradication failure of hybrid therapy with odds ratios of 4.8 (95% CI: 1.5 to 16.1; p = 0.009) and 8.2 (95% CI: 1.5 to 43.5; p = 0.013), respectively. A 14-day hybrid therapy has a high eradication rate for H. pylori infection in Taiwan, while clarithromycin resistance of H. pylori and poor drug adherence are independent risk factors predicting eradication failure of hybrid therapy.

Differentiation of clinical patterns and survival outcomes of hepatocellular carcinoma on hepatitis B and nonalcoholic fatty liver disease.

BACKGROUND: The main etiologies of hepatocellular carcinoma (HCC) were often hepatitis B virus (HBV) or C and alcohol, rarely autoimmune and biliary diseases. Nonalcoholic fatty liver disease (NAFLD) has been an emerging role that could lead to chronic liver disease, nonalcoholic steatohepatitis, cirrhosis, and eventually HCC in recent years. The aim of our study is to investigate and compare the clinical features of HCC in patients with NAFLD and HBV, including age, gender, cirrhosis, liver function tests, largest tumor size, and cancer stage at the time of diagnosis. The survival outcome was compared between the two groups and the significant predictors of mortality were also analyzed in all patients with HCC. METHODS: Most patients with HCC were recruited from the database of Cancer Registries in Taipei City Hospital, Ren-Ai Branch, from 2011 to 2017; and the other patients consecutively from the HCC multidisciplinary conference between January 2018 and December 2019. NAFLD was defined as nonviral hepatitis B (negative HBsAg and either positive anti-HBs or negative anti-HBc), nonviral hepatitis C (negative antihepatitis C virus [HCV]), nonalcoholic (alcohol consumption of <30 g/d for men and <20 g/d for women) liver disease, or present or past histological or ultrasonographic evidence of fatty liver. Totally, 23 NAFLD-related and 156 HBV-related HCC patients were enrolled in our study for further analysis. RESULTS: NAFLD-related HCC patients were significantly older (median age: 70.0 [61.0-79.0] years vs. 63.0 [56.0-72.0] years, p = 0.012) and heavier (median body mass index [BMI]: 26.6 [24.2-30] kg/m2 vs. 24.8 [22.0-27.1] kg/m2, p = 0.044) than those with HBV-related HCC. They were also more susceptible to diabetes mellitus (DM), and 60.9% (14 of 23) of them had this comorbidity compared with 29.5% (46 of 156) of those with HBV-related HCC (p = 0.003). Only 34.8% (8 of 23) and 71.2% (111 of 156) of patients with NAFLD- and HBV-related HCC were cirrhotic, respectively (p = 0.001). However, gender, tobacco use, international normalized ratio, albumin, creatinine, and cholesterol levels were not significantly different between the two groups. Tumor characteristics such as the Barcelona clinic liver cancer stage, largest tumor size, tumor number, extrahepatic metastasis, and treatment modalities had no significant difference between such groups.According to the Kaplan-Meier method analysis, the overall survival was not significantly different between these two patient groups (log-rank test, p = 0.101). To evaluate which patient group would lead to poor prognosis, we analyzed the survival of all patients through multivariate Cox proportional hazard regression after controlling other factors that may influence the hazard ratio. The analysis revealed that NAFLD and HBV infection as the cause of HCC are not risk factors of poor prognosis. CONCLUSION: In conclusion, our study showed NAFLD-related HCC patients were older, heavier, and more had DM than HBV-related. In addition, more NAFLD-related HCC patients were noncirrhotic than HBV-related. The survival rate was similar between NAFLD and HBV-related HCC patients.

Loss of Tid1/DNAJA3 Co-Chaperone Promotes Progression and Recurrence of Hepatocellular Carcinoma after Surgical Resection: A Novel Model to Stratify Risk of Recurrence.

Tid1, a mitochondrial co-chaperone protein, acts as a tumor suppressor in various cancer types. However, the role of Tid1 in hepatocellular carcinoma (HCC) remains unclear. First, we found that a low endogenous Tid1 protein level was observed in poorly differentiated HCC cell lines. Further, upregulation/downregulation of Tid1 abrogated/promoted the malignancy of human HCC cell lines, respectively. Interestingly, Tid1 negatively modulated the protein level of Nrf2. Tissue assays from 210 surgically resected HCC patients were examined by immunohistochemistry (IHC) analyses. The protein levels of Tid1 in the normal and tumor part of liver tissues were correlated with the clinical outcome of the 210 HCC cases. In multivariate analysis, we discovered that tumor size > 5 cm, multiple tumors, presence of vascular invasion, low Tid1 expression in the non-tumor part, and high Nrf2 expression in the non-tumor part were significant factors associated with worse recurrence-free survival (RFS). A scoring system by integrating the five clinical and pathological factors predicts the RFS among HCC patients after surgical resection. Together, Tid1, serving as a tumor suppressor, has a prognostic role for surgically resected HCC to predict RFS.

Increased monocyte chemoattractant protein-1 and nitrotyrosine are associated with increased body weight in patients with rheumatoid arthritis after etanercept therapy.

OBJECTIVES: Etanercept, a tumor necrosis factor inhibitor, is an effective drug for patients with active rheumatoid arthritis (RA). Monocyte chemoattractant protein-1 (MCP-1) and nitrotyrosine (NT) are pro-inflammatory biomolecules associated with satiety and increased body weight. We evaluated whether MCP-1 and NT are associated with decreased inflammation or increased body mass during etanercept therapy in active RA patients. METHODS: RA patients with moderate to high disease activity were enrolled to receive add-on etanercept (25 mg subcutaneous injection, biweekly) for at least one year, combined with sustained treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). RESULTS: Forty patients received add-on etanercept and 15 received DMARDs alone. At the end of one year, etanercept significantly reduced the disease activity score of 28 joints, C-reactive protein, and erythrocyte sedimentation rate. Moreover, etanercept significantly increased the body weight, body mass index (BMI), as well as MCP-1 and NT levels, compared to that in the csDMARD-only group. CONCLUSIONS: Increased serum MCP-1 and NT levels in RA patients with moderate to high disease activity, who underwent one-year etanercept treatment, might be attributed to increase in body weight and BMI rather than induction of more severe autoimmune inflammation.

Factors predicting outcomes of hepatitis B-related cirrhosis patients with long-term antiviral therapy.

BACKGROUND/PURPOSE: Long-term nucleos(t)ide analog (NA) therapy has been shown to improve the survival in patients with HBV-related cirrhosis. The aim of this study was to evaluate the clinical outcomes and factors associated with survival in HBV-related cirrhotic patients receiving long-term NA treatment. METHODS: A total of 126 HBV-related cirrhosis patients with long-term NA treatment, including 67 compensated cirrhosis and 59 decompensated cirrhosis, were retrospectively enrolled. The effectiveness of treatment, survival and risk factors of mortality were determined. RESULTS: Patients with decompensated cirrhosis had significantly lower baseline serum HBV DNA levels than compensated cirrhotic patients (4.98 ± 1.91 vs. 5.67 ± 1.26 log10 IU/ml, P = 0.031). The mean follow-up duration was 84 and 42 months in compensated cirrhotic and decompensated cirrhotic patients (P < 0.0001), respectively. The 1, 2 and 3-year cumulative survival rates were significantly higher in compensated cirrhotic patients than those with decompensated cirrhosis (100%, 98.5%, 98.5% vs. 81.2%, 75.6%, 69.5%; P < 0.0001). Multivariate analysis for risk factors of mortality in cirrhotic patients showed that older age (hazard ratio: 3.28, 95% CI: 1.25-8.62, P = 0.016) and decompensated cirrhosis (hazard ratio: 8.30, 95% CI: 2.45-28.06, P = 0.0007) were independently associated with liver-related mortality. A total of 31 patients developed HCC during the follow-up. Among them, 70.9% were at the earlier stages of BCLC system, and 83.8% received potentially curative treatment. CONCLUSION: Antiviral therapy improves liver function of HBV-related cirrhotic patients and provides a better chance of curative treatment in those with HCC development. Decompensated cirrhosis is a risk factor for liver-related mortality in this special clinical setting.

Performance of Routine Helicobacter pylori Invasive Tests in Patients with Dyspepsia.

Background. This study was designed to compare the accuracy of three different invasive methods for the detection of Helicobacter pylori (H. pylori) infection in patients with dyspepsia. These tests included culture, histology, and the rapid urease test (CLO test). Methods. H. pylori infection was diagnosed prospectively in 246 untreated dyspeptic patients who underwent upper gastrointestinal endoscopy. The gold standard for H. pylori infection was based on a positive culture or both a positive histological examination and a CLO test. Results. H. pylori was diagnosed in 33.3% of the patients. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were as follows: histology from the antrum (95.12; 95.12; 90.7; 97.5; 95.12%); histology from the antrum and corpus (95.12; 95.12; 90.7; 97.5; 95.12%); histology from the corpus (76.83; 96.95; 92.65; 89.33; 90.24%); culture (91.46; 100; 100; 95.91; 97.15%); a CLO test from the antrum and corpus (85.59; 100; 100; 93.71; 95.52%); a CLO test from the antrum (64.63; 100; 100; 84.97; 88.21%); a CLO test from the corpus (69.51; 100; 100; 96.77; 89.83%), respectively. Conclusions. Antral biopsy histology and culture are the best methods for the diagnosis of H. pylori infection in our cohort of patients with dyspepsia.

More than 9-times increased risk for pancreatic cancer among patients with acute pancreatitis in Chinese population.

OBJECTIVE: This study aimed to assess the risk of pancreatic cancer after acute pancreatitis using a nationwide population-based data set in Taiwan. METHODS: We conducted a retrospective cohort study of 747 patients hospitalized between 2000 and 2003 with a principal diagnosis of acute pancreatitis (the study cohort) and 5976 comparison patients. Stratified Cox proportional hazard regression adjusted for monthly income, urbanization, and geographic location of residence was used to calculate the 5-year hazard ratio (HR) of pancreatic cancer for the study versus comparison cohort. RESULTS: Of the total sample, 21 patients (0.31%) developed pancreatic cancer in the 5 years after index hospitalization: 11 (1.47%) of the study group patients and 10 (0.17%) of the comparison group patients. After adjusting for confounders, acute pancreatitis patients were 9 times as likely as the comparison group to develop pancreatic cancer in the following 5 years (HR = 9.10; 95% confidence interval, 3.81-21.76). Among patients with acute pancreatitis, the adjusted HR of pancreatic cancer was 40.03 and 3.72 times greater, respectively, for those with chronic pancreatitis and for those without than comparison patients. CONCLUSIONS: Patients with acute pancreatitis have more than 9 times the risk of comparison patients to develop pancreatic cancer in the subsequent 5 years among the Hun Chinese ethnic population in Taiwan.

Usefulness of serum des-gamma-carboxy prothrombin in detection of hepatocellular carcinoma.

AIM: Des-gamma-carboxy prothrombin (DCP) has been reported to be more sensitive and specific in diagnosing hepatocellular carcinoma (HCC) when compared with alpha-fetoprotein (AFP). However, its ability to identify small HCC still remains unclear. Thus, we conducted a cross-sectional case control study to evaluate whether DCP is better than AFP for differentiating HCC from nonmalignant liver disease and further evaluate the usefulness of DCP in early diagnosis of small HCC. METHODS: Serum DCP and AFP levels were determined in 127 patients. Among these patients, 32 were with non-cirrhotic chronic hepatitis, 34 were with compensated cirrhosis, and 61 were with HCC. The cut-off value for the DCP and AFP were set as 40 mAU/mL and 20 ng/mL, respectively. To compare the diagnostic value of DCP and AFP in distinguishing HCC from nonmalignant chronic liver disease, receiver operating characteristic (ROC) curves were constructed for each assay. RESULTS: The accuracy, sensitivity and specificity of DCP were higher than AFP in detecting HCC (81.9%, 77% and 86.4% vs 68.5%, 59% and 77.3%, respectively). The area under the ROC (AUROC) curves revealed that DCP had a better accuracy than AFP in diagnosis of HCC (0.85 [95%CI, 0.78-0.91] vs 0.73 [95%CI, 0.65-0.81], P = 0.013). In 39 patients with solitary HCC, the positive rates of DCP were 100% in patients with tumor size larger than 3 cm, 66.7% in patients with tumor size 2-3 cm and 50% in patients with tumor size less than 2 cm. The positive rates of AFP in patients with tumor size larger than 3 cm, 2-3 cm and less than 2 cm were 55.6%, 50%, and 33.3%, respectively. The median level of DCP in HCC patients with tumor size larger than 3 cm was significantly higher than those with tumor size 2-3 cm and those with the size of less than 2 cm. CONCLUSION: Our study indicates that DCP has a better diagnostic value than AFP in differentiating HCC from nonmalignant chronic liver disease. DCP has not only a stronger correlation with HCC than AFP in tumor size but also more effectiveness than AFP in detecting small size of HCC.