Canadian Journal of Gastroenterology and Hepatology

Introduction. Hepatocellular carcinoma (HCC) accounts for approximately 90% of primary liver malignancies and is currently the fourth most common cause of cancer-related death worldwide. Due to varying underlying etiologies, the prognosis of HCC differs greatly among patients. It is important to develop ways to help stratify patients upon initial diagnosis to provide optimal treatment modalities and follow-up plans. The current study uses Artificial Neural Network (ANN) and Classification Tree Analysis (CTA) to create a gene signature score that can help predict survival in patients with HCC. Methods. The Cancer Genome Atlas (TCGA-LIHC) was analyzed for differentially expressed genes. Clinicopathological data were obtained from cBioPortal. ANN analysis of the 75 most significant genes predicting disease-free survival (DFS) was performed. Next, CTA results were used for creation of the scoring system. Cox regression was performed to identify the prognostic value of the scoring system. Results. 363 patients diagnosed with HCC were analyzed in this study. ANN provided 15 genes with normalized importance >50%. CTA resulted in a set of three genes (NRM, STAG3, and SNHG20). Patients were then divided in to 4 groups based on the CTA tree cutoff values. The Kaplan–Meier analysis showed significantly reduced DFS in groups 1, 2, and 3 (median DFS: 29.7 months, 16.1 months, and 11.7 months, p < 0.01) compared to group 0 (median not reached). Similar results were observed when overall survival (OS) was analyzed. On multivariate Cox regression, higher scores were associated with significantly shorter DFS (1 point: HR 2.57 (1.38–4.80), 2 points: 3.91 (2.11–7.24), and 3 points: 5.09 (2.70–9.58), p < 0.01). Conclusion. Long-term outcomes of patients with HCC can be predicted using a simplified scoring system based on tumor mRNA gene expression levels. This tool could assist clinicians and researchers in identifying patients at increased risks for recurrence to tailor specific treatment and follow-up strategies for individual patients.

Background and Aims. The impact of COVID-19 has been of great concern in patients with inflammatory bowel disease (IBD) worldwide, including an increased risk of severe outcomes and/or possible flare of IBD. This study aims to evaluate prevalence, outcomes, the impact of COVID-19 in patients with IBD, and risk factors associated with severe COVID-19 or flare of IBD activity. Methods. A consecutive cohort of IBD patients who were diagnosed with COVID-19 infection and followed up at the McGill University Health Care Centre was obtained between March 1, 2020, and April 30, 2021. Demographics, comorbidities, IBD (type, treatments, pre- and post-COVID-19 clinical activity, biomarkers, and endoscopic activity), and COVID-19-related outcomes (pneumonia, hospitalization, death, and flare of IBD disease) were analyzed. Results. A cohort of 3,516 IBD patients was included. 82 patients (2.3%) were diagnosed with COVID-19 infection (median age: 39.0 (IQR 27.8–48.0), 77% with Crohn’s disease, 50% were female). The prevalence of COVID-19 infection in IBD patients was significantly lower compared to the general population in Canada and Quebec (3.5% versus 4.3%, ). Severe COVID-19 occurred in 6 patients (7.3%); 2 patients (2.4%) died. A flare of IBD post-COVID-19 infection was reported in 8 patients (9.8%) within 3 months. Biologic therapy was held during active COVID-19 infection in 37% of patients. Age ≥55 years (odds ratio (OR): 11.1, 95% CI: 1.8–68.0), systemic corticosteroid use (OR: 4.6, 95% CI: 0.7–30.1), active IBD (OR: 3.8, 95% CI: 0.7–20.8), and comorbidity (OR: 4.9, 95% CI: 0.8–28.6) were factors associated with severe COVID-19. After initial infection, 61% of IBD patients received COVID-19 vaccinations. Conclusion. The prevalence of COVID-19 infection among patients with IBD was lower than that in the general population in Canada. Severe COVID-19, mortality, and flare of IBD were relatively rare, while a large proportion of patients received COVID-19 vaccination. Older age, comorbidities, active IBD disease, and systemic corticosteroid, but not immunosuppressive or biological therapy, were associated with severe COVID-19 infection.

Background. Women with inflammatory bowel disease (IBD) are at risk of certain pregnancy outcomes such as preterm delivery, infants small for gestational age (SGA), and Cesarean delivery. Whether regional variation in these outcomes exists remains unknown. We aimed to assess the geographical variation in these pregnancy outcomes in women with IBD. Methods. All pregnancies in women with and without IBD (2002-2013) were identified using Ontario health administrative datasets. Geographical variation in preterm delivery, infants SGA, and Cesarean delivery was assessed using age-adjusted odds ratios (aOR) with 95% confidence intervals (CI) comparing women with and without IBD, stratified by Ontario’s 14 health-service regions, known as Local Health Integration Networks (LHINs). Results. 1621 women with IBD (2466 pregnancies) and 855,425 women without IBD (1,280,493 pregnancies) were included. Women with IBD were more likely to have preterm delivery (aOR 1.56, 95% CI, 1.35–1.79), infants SGA (aOR 1.52, 95% CI, 1.23–1.88), and Cesarean section (aOR 1.34, 95% CI, 1.22–1.49). Significant geographical variation in these outcomes was detected, with the highest rates observed in the most northern rural areas (aOR for preterm delivery 2.78 (95% CI, 1.03–7.46), aOR for SGA 5.66 (95% CI, 1.67–19.14), and aOR for Cesarean delivery 2.48 (95% CI, 1.11–5.55)). There were no differences in these outcomes in women with and without IBD in more central urban LHINs. Conclusion. Significant regional variation was detected in rates of adverse pregnancy outcomes and Cesarean delivery in women with IBD. Further study is required to determine specific reasons for this variation.

Background. In Ethiopia, chronic liver disease (CLD) is the 7th leading cause of death, accounting for about 24 deaths per 100000 populations in 2019. Despite its burden, there is a lack of compiled pieces of evidence on CLD in the country. Thus, this systematic review and meta-analysis is intended to provide the pooled estimates of CLD etiologies and mortality rate in CLD patients in Ethiopia. Method. PubMed, Google Scholar, ScienceDirect, institutional repositories, national digital library, and the bibliography of the eligible articles information were the source of data for the present review. The keywords “hepatitis, chronic” [Mesh], “end-Stage Liver Disease” [Mesh], “chronic liver disease”, “liver cirrhosis” [Mesh], and “Ethiopia” were used for the searches. Overall, we retrieved 199 records and 12 were included in this review. We used the DerSimonian-Laird random-effects models to perform the meta-analysis. We conducted subgroup and meta-regression analyses to account for the heterogeneity of the estimates. Result. Hepatitis B virus, alcohol, and hepatitis C virus are the three most common etiologies of CLD in Ethiopia accounting for a pooled estimate of 40.0% [95% CI: 29.0, 51.0, I² = 96.3, ], 17.0% [95% CI: 9.0, 25.0, I² = 96.7, ], and 15.0% [95% CI: 9.0, 21.0, I² = 95.8, ], respectively. Unidentified etiology report has a substantial contribution accounting for an estimated pooled proportion of 45% [95% CI: 34.0, 56.0%, Q = 32.08, , I² = 87.53] of the CLD cases in the country. On the other hand, the overall hospital mortality rate in CLD patients is 25.0% [95% CI: 2.0, 47.0, I² = 94.6, ] in Ethiopia. Conclusion. Hepatitis B virus, hepatitis C virus, and alcohol are the three most common contributors to CLD cases in Ethiopia. The authors warrant routine screening and strengthening of preventive and treatment programs for viral hepatitis B and C, further enhancing the alcohol policy of the country.

Aims. This meta-analysis of randomized placebo-controlled clinical trials assessed the effect of glucose-like peptide-1-receptor agonists (GLP-1RA) on the lipid profile and liver enzymes in patients with nonalcoholic fatty liver disease (NAFLD). Materials and Methods. Randomized placebo-controlled trials investigating GLP-1RA on the lipid profile and liver enzymes in patients with NAFLD were searched in PubMed-Medline, Scopus, Web of Science, and Google Scholar databases (from inception to January 2020). A random-effects model and a generic inverse variance method were used for quantitative data synthesis. Sensitivity analysis was conducted. Weighted random-effects meta-regression was performed on potential confounders on lipid profile and liver enzyme concentrations. Results. 12 studies were identified (12 GLP-1RA arms; 677 subjects) that showed treatment with GLP-1RA reduced alanine transaminase (ALT) concentrations (WMD = −10.14, 95%CI = [−15.84, −0.44], ), gamma-glutamyl transferase (GGT) (WMD = −11.53, 95%CI = [−15.21,−7.85], ), and alaline phosphatase (ALP) (WMD = −8.29, 95%CI = [−11.34, −5.24], ). Aspartate aminotransferase (AST) (WMD = −2.95, 95% CI = [−7.26, 1.37], ) was unchanged. GLP-1 therapy did not alter triglycerides (TC) (WMD = −7.07, 95%CI = [−17.51, 3.37], ), total cholesterol (TC) (WMD = −1.17 (−5.25, 2.91), ), high-density lipoprotein (HDL-C) (WMD = 0.97, 95%CI = [−1.63, 3.58], ), or low-density lipoprotein (LDL-C) (WMD = −1.67, 95%CI = [−10.08, 6.74], ) in comparison with controls. Conclusion. The results of this meta-analysis suggest that GLP-1RA treatment significantly reduces liver enzymes in patients with NAFLD, but the lipid profile is unaffected.

Objective. To identify markers that predict the progression to hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF). Methods. We recruited 125 patients with chronic hepatitis B (CHB) between September 2013 and March 2017. During hospitalization, 25 patients progressed to LF and were classified as the LF group, while the remaining 100 patients were classified as the non-LF (NLF) group. We compared the kinetic changes in clinical and immune indicators including age, total bilirubin level, prothrombin time, model for end-stage liver disease score, interleukin (IL)-6, IL-8, and IL-10 cytokine levels, and number of T helper 17 and regulatory T cells between groups to determine their association with progression to HBV-ACLF. The prognostic value of clinical and immune indicators was determined using the area under the receiver operating characteristic curve (AUC) value. Results. Cox regression analysis suggested that the plasma IL-6 level could predict CHB progression to HBV-ACLF (relative risk = 1.082, 95% confidence interval: 1.006–1.164; ). The AUC value, sensitivity, and specificity of baseline IL-6 level for predicting HBV-ACLF were 82.63%, 83.3%, and 82.9%, respectively (). Conclusion. A high plasma IL-6 level in CHB patients could be an early biomarker for HBV-ACLF.