Canadian Journal of Gastroenterology and Hepatology最新文献

Case detection remains a major challenge for hepatitis C virus (HCV) elimination. We have previously published results from a pilot of an emergency department (ED) semiautomated screening program, SEARCH; Screening Emergency Admissions at Risk of Chronic HCV. Several refinements to SEARCH have been developed to streamline and reduce cost. All direct costs of HCV testing until direct-acting antiviral (DAA) therapy initiation were calculated. Cost was assessed in 2018 Australian Dollars. A cost analysis of the initial program and refinements are presented. Sensitivity analysis to understand impact of variation in staff time, laboratory test cost, changes in HCV antibody (Ab) prevalence, RNA positivity percentage, and rate of linkage to care was conducted. Impact of refinements (SEARCH (2)) to cost is presented. The total SEARCH pilot, testing 5000 patients was estimated to cost $110,549.52 (range $92,109.79-$129,581.24) comprising of $68,278.67 for HCV Ab testing, $21,568.99 for follow-up and linkage to care of positive patients and $20,701.86 to prepare HCV RNA positive patients for treatment. Internal program refinements resulted in a 25% cost reduction. Following refinements, the cost of HCV antibody screening was $8.46 per test and the total cost per positive HCV Ab, positive HCV RNA, and per treated patient were $611.77, $2,168.64, and $3,566.11, respectively. Our sensitivity analysis indicates costs per HCV case found are modest so long as HCV Ab prevalence was at least 1%. ED screening is an affordable strategy for HCV case detection and elimination.

Aims: In this report, it was investigated that hepatoma cells can cause downregulation of cytotoxic T lymphocyte (CTL) function and tea polyphenols (TPs) can reverse downregulation of CTL function.

Methods: The expression of GRP78, PD-1, and TIM-3 was detected by western blotting in CTLL-2 cocultured with Hepa1-6 cells. Moreover, perforin (PRF1) and granzyme B (GzmB) protein levels and ER morphology were examined by ELISA and TEM, respectively. After 4-phenylbutyric acid (4-PBA) or tunicamycin (TM) treatment, programmed cell death protein 1 (PD-1), and mucin domain 3 (TIM-3), PRF1, and GzmB were measured by western blotting and ELISA. After sh-CHOP or GSK2656157 (PERK inhibitor) stimulation, the activation of the PERK-CHOP pathway was detected in CTLL-2 cells. Finally, changes in PD-1, TIM-3, PRF1, and GzmB levels were detected to verify the reversal of CTL depletion by TP.

Results: The expression of GRP78, PD-1, and TIM-3 clearly increased, and swelling was observed for the endoplasmic reticulum (ER) in CTLL-2 cells cocultured with hepatoma cells. Concurrently, the levels of PRF1 and GzmB decreased. CTLL-2 depletion was induced after stimulation with TM and differed from 4-PBA stimulation. Treatment with sh-CHOP or GSK2656157 caused a decrease in PD-1 and TIM-3 expression, whereas the expression of PRF1 and GzmB clearly increased. After adding TP, the function of CTLs increased markedly.

Conclusion: Hepatoma cells induced the depletion of CTLs through the ER stress PERK-CHOP pathway, and TP reversed this depletion by downregulating ER stress.

Introduction: This systematic review aimed to summarize evidence to determine the effectiveness of kiwifruit or kiwifruit extracts in the treatment of constipation.

Methods: Electronic databases were searched from inception to May 2022 without any age or language limitations. Eligible studies enrolled participants with constipation who were randomized to receive kiwifruit or kiwifruit extracts vs. any nonkiwifruit control. Standardized mean difference (SMD) and mean difference (MD) with confidence intervals (CI) were determined for the following outcomes: frequency of spontaneous bowel movements (SBM), abdominal pain and straining, as well as stool type as determined by the Bristol Stool Scale (BSS). The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach was used to rate the certainty of evidence. Our review was registered on PROSPERO (CRD42021239397).

Results: Seven RCTs, including 399 participants (82% female; mean age: 42 years (SD 14.6)), were included. Compared with placebo (n = 95), kiwifruit extracts might increase the weekly frequency of SBM (MD: 1.36; 95% CI: -0.44, 3.16) with low certainty of evidence; moreover, it had an uncertain effect on BSS (SMD: 1.54; 95% CI: -1.33, 4.41) with very low certainty of evidence. Additionally, compared with placebo (n = 119), kiwifruit or its extracts reduced abdominal pain (SMD: -1.44, 95% CI -2.83, -1.66) with moderate certainty of the evidence and improved frequency of straining (SMD: -0.29; 95% CI: -1.03, 0.47). Compared with psyllium, kiwifruit may increase the weekly frequency of SBM (MD: 1.01; 95% CI: -0.02, 2.04) with moderate certainty evidence, and may increase the value on the BSS (indicating softer stools) (MD: 0.63; 95% CI: 0.01, 1.25)with low certainty of evidence. Compared to placebo, kiwifruit-encapsulated extracts may result in an increase in minor adverse events (relative risk: 4.58; 95% CI: 0.79, 26.4).

Conclusions: Among individuals with constipation, there is an overall low certainty of evidence indicating that kiwifruit may increase SBM when compared to placebo or psyllium. Although overall results are promising, establishing the role of kiwifruit in constipation requires large, methodologically rigorous trials. Protocol Registration: PROSPERO registration number CRD42021239397.

Background: Genetic variability of Helicobacter pylori is associated with various gastrointestinal diseases; however, little is known about interaction with sociodemographic in the development of premalignant lesions in Colombian patients.

Methods: An analytical study was conducted including cases (patients with gastric atrophy, intestinal metaplasia, and gastric dysplasia) and controls (patients with nonatrophic gastritis). Sociodemographic information was obtained using a questionnaire. Histopathological diagnosis was performed according to the Sydney System. The cagA and vacA genotypes were established using polymerase chain reaction in paraffin blocks. The effect of each variable on the study outcome (premalignant lesion) is presented as odds ratio (OR) and 95% CI. A p value of <0.05 was considered as statistically significant.

Results: The vacA/s1m1 genotype increases the risk of developing premalignant lesions of the stomach (OR: 3.05, 95% IC: 1.57-5.91, p=0.001). Age and educational level showed a positive interaction with the s1m1 genotype (adjusted OR: 3.68, 95% CI: 1.73-7.82, p=0.001). The cagA genotype was not correlated to the development of premalignant lesions of the stomach (OR: 1.32, 95% CI: 0.90-1.94, p=0.151).

Conclusions: The vacA genotype, age, and educational level are indicators of the risk of developing premalignant lesions of the stomach in the study population. Significance Statement. Genetic variability of H. pylori and sociodemographic information could be used to predict the risk of premalignant lesions in stomach in Colombian population.

Background: The goal of this systematic review and meta-analysis was analyzing published studies on the role of neutrophil to lymphocyte ratio (NLR) in infection and spatially spontaneous bacterial peritonitis (SBP) among cirrhotic patients.

Methods: PubMed, Web of Science, and Scopus were searched until May 24, 2022. The Newcastle-Ottawa scale was used for quality assessment.

Results: Of 14 studies included in our study, six studies were on infection with 2786 hospitalized cirrhotic patients, of whom 934 developed an infection. Other studies were on SBP with 1573 cirrhotic patients with ascites, of whom 557 developed SBP. The pooled results showed that there was no difference in NLR levels between hospitalized cirrhotic patients who developed infection compared to those who did not (random-effects model: SMD = 0.63, 95% CI = -0.01-1.27, p=0.054). However, cirrhotic patients with ascites who developed SBP had elevated levels of NLR compared to those who did not (random-effects model: SMD = 1.05, 95% CI = 0.52-1.57,p < 0.001). This difference remained significant in prospective studies (SMD = 0.94, 95% CI = 0.51-1.38,p < 0.001) but not in retrospective studies (SMD = 1.37, 95% CI = -0.56-3.29,p=0.165), in the subgroup analysis according to the study design. The pooled sensitivity of NLR was 92.07% (95% CI = 74.85%-97.84%) and the pooled specificity was 72.58% (95% CI = 57.72%-83.69%). The pooled positive likelihood ratio, negative likelihood ratio, DOR of NLR were 3.35(95%CI = 2.06-5.46), 0.10 (95%CI = 0.03-0.38), and 30.78 (95%CI = 7.01-135.04), respectively.

Conclusion: Our results support NLR to be a valid biomarker that can be readily integrated into clinical settings to help in the prevention and prediction of SBP among cirrhotic patients.

Cirrhosis-induced clinically significant portal hypertension (CSPH) is a fatal disease. Early detection of CSPH is vitally important to reduce the patients' mortality rate. In this study, combined with three-dimensional image construction technology and computational fluid dynamics (CFD), an image-based flow resistance analysis was proposed. The flow resistance analysis was performed for nine cirrhosis patients with CSPH and ten participants without liver diseases, respectively. The results showed that the flow resistance coefficient of the portal vein system in CSPH patients was significantly lower than that in the control group (0.97 ± 0.11 Pa/(mL/s) for CSPH patients; 1.80 ± 0.40 Pa/(mL/s) for the control group; P = 0.028). In contrast, although main portal vein dilation was found in CSPH patients, the cross-sectional area enlargement was not statistically significant (186.01 ± 57.48 mm² for CSPH patients; 166.26 ± 33.74 mm² for the control group; P = 0.39). The research outcomes indicated that the flow resistance analysis was more sensitive than the commonly used vessel size measurement in the detection of CSPH. In summary, we suggest using flow resistance analysis as a supplementary noninvasive method to detect cirrhosis patients with CSPH.

Objective: Intrahepatic cholangiocarcinoma (iCCA) is a primary liver malignancy with a poor prognosis and limited treatment. Cisplatin with gemcitabine is used as the standard first-line chemotherapy regimen; however, there is still no robust evidence for second-line and successive treatments. Although preliminary evidence suggests a vital role of precision therapy or immunotherapy in a subset of patients, the gene alteration rate is relatively low. Herein, we explored the second-line and successive treatments using hepatic arterial infusion chemotherapy (HAIC) based on FOLFIRI after the failure of gemcitabine and platinum combined with target and immunotherapy in refractory CCAs.

Methods: Advanced patients with iCCAs confirmed by diagnostic pathology, who progressed at least on a gemcitabine/platinum doublet and/or other systemic chemotherapy combined with target therapy and immune checkpoint inhibitor, were included. All patients received infusional 5-fluorouracil/leucovorin with irinotecan (FOLFIRI) via HAIC until progression or unacceptable toxicity. The primary objective was the feasibility of treatment, with secondary objectives of disease control rate (DCR) and 6-month survival rate.

Results: A total of 9 iCCA patients treated between Dec 2020 and May 2021 were enrolled; 2 patients suffered from distant metastasis, while 7 had local lymph node metastasis and portal vein or hepatic vein invasion. HAIC was delivered as second-line therapy in 6/9 patients, while a third or successive therapy in 3/9 patients. The patients accepted an average of 2.90 ± 1.69 cycles of HAIC. The objective response rate was 22.2%; the disease control rate was 55.5% (5/9); median progression-free survival was 5 months; and 6-month survival rate was 66.7% (6/9).

Conclusions: Our results provide preliminary evidence that HAIC based on FOLFIRI regimen is efficient and safe in some patients progressing after previous treatment. Therefore, HAIC may be a promising and valuable complementary therapy for advanced CCAs as a second-line and successive therapy. Otherwise, the combination of HAIC with precision medicine may improve clinical benefits (clinical registration number: 2021BAT4857).

Introduction: Autoimmune hepatitis (AIH) is a chronic liver disease with a relevant inflammatory component and an unknown etiology. Evidence for clinical characteristics and risk factors in large cohorts of patients with acute AIH (AAIH) is lacking. We clinically characterized patients with AAIH, the prevalence of a combined adverse outcome (death or liver transplantation (LT)), and its risk factors.

Methods: A retrospective study of adult patients diagnosed with AAIH at three centers (Santiago, Chile; 2000-2018) was conducted. Clinical and laboratory characteristics were obtained. A liver biopsy was performed for all patients. Descriptive statistics and logistic regression models were used.

Results: A total of 126 patients were admitted; 77% were female, 33 (26.2%) had a severe presentation, and 14 (11.1%) had a fulminant presentation. Overall, 24 patients (19.0%) lacked typical autoantibodies, and 26.2% had immunoglobulin G levels in the normal range. The most frequent histological findings were plasma cells (86.5%), interface hepatitis (81.7%), and chronic hepatitis (81.0%). Rosettes were uncommon (35.6%). Advanced fibrosis was present in 27% of patients. Combined adverse outcomes occurred in 7.9% of cases, all fulminant with histological cholestasis. Alkaline phosphatase, bilirubin, and prothrombin less than 50% were independent risk factors for in-hospital death or LT (p value <0.05). Although corticosteroid treatment was associated with better outcomes (OR 0.095, p value = 0.013), more severe patients were less likely to receive this therapy. Discussion. In this large cohort of patients with AAIH, clinical characteristics differ from those reported in patients with chronic AIH. Fulminant hepatitis, histological cholestasis, alkaline phosphatase, bilirubin, and prothrombin were associated with death/LT.

Worldwide, colorectal cancer (CRC) is the second most diagnosed cancer in female and the third in men, arising from the epithelium of the colorectum. It is known that colorectal cancer is common in developed countries than in developing countries which may be due to inaccurate data on the existence of the disease in that region combined with embracing western lifestyle expressed by the current trend of changes in cultural, social, and lifestyle practices playing a major part in the etiology of CRC. The aim of this study was to document epidemiological, pathological characteristics, and prognostics determinants of patients diagnosed with CRC in Rwanda. The data from patients' files and reviewed glass slides for 101 cases all from Kigali University Teaching Hospital (CHUK) were statistically analyzed and patient characteristics were described as mean and frequency accordingly. Comparisons were performed using chi square tests, Fisher's exact test and odds ratio with 95% confidence interval (CI). Survival curves were plotted using the Kaplan-Meier method, and log-rank test was used to assess the statistical differences in the observed survival curves by each categorical variable. A P value < 0.05 was considered statistically significant. Statistical analyses were performed using Statistical Product and Service Solutions (SPSS), GraphPad Prism, and MedCalc, accordingly. Mean age of the participants was 54.26 years, the main symptom was rectal bleeding (46.5%), rectal adenocarcinoma NOS represented 40.6%, conventional adenocarcinoma was 60.4%, most tumors were of Grade II (54.5%), most common stage was pT3N0 (20.8%), resection margins were free at 71.3%, lympho-vascular invasion was 49.5% of cases, a high immune response was in 71.3% of cases and of 101cases, and 55.4% were still alive at the end of the data collection, with 29.3% of patients have overall survival of 5 years. Prognostic determinants also affect the outcome in this study and overall survival period was 3 years for CRC diagnosed in Rwanda.

Based on an experience of more than 50 years in the treatment of portal hypertension (PHT), the authors review and analyze the evolution of the surgical portocaval shunt (PCS). We would like to provide an insight into the past of PCS, in order to compare it with the current state of the treatment of PHT complications. As a landmark of the past, we shall present statistics of more than 500 cases of PHT operated between 1968 and 1983. From this group, 238 patients underwent surgical portocaval shunting during a fifteen-year period. The behavior of the portal hemodynamics following PCS was studied and the postoperative decrease in portal pressure (PP), as well as the residual PP, were recorded. The portal manometric determinations were made by electronic recordings using the Hellige device and direct intraoperative recordings through the catheterization of a ramus in the portal area. The results of PCS are superposable, in terms of hemodynamic efficiency, with those of the intrahepatic shunt (TIPS-transjugular intrahepatic portosystemic shunt). The authors discuss the current place of PCS, in obvious decline in comparison with the situation 50 years ago. The current methods of controlling variceal bleeding represent obvious progress. PCS remains with very limited indications, in specific situations when the other therapeutic methods have failed or are not recommended.