Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Background/Aims: Steatotic liver disease (SLD) is a common manifestation in chronic hepatitis C (CHC). Metabolic alterations in CHC are associated with metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to elucidate whether hepatitis C virus (HCV) eradication mitigates MASLD occurrence or resolution. Methods: We enrolled 5,840 CHC patients whose HCV was eradicated by direct-acting antivirals in a nationwide HCV registry. MASLD and the associated cardiometabolic risk factors (CMRFs) were evaluated at baseline and 6 months after HCV cure. Results: There were 2,147 (36.8%) patients with SLD, and 1,986 (34.0%) of them met the MASLD criteria before treatment. After treatment, HbA1c (6.0% vs. 5.9%, p<0.001) and BMI (24.8 kg/m2 vs. 24.7 kg/m2, p<0.001) decreased, whereas HDL-C (49.1 mg/dL vs. 51.9 mg/dL, p<0.001) and triglycerides (102.8 mg/dL vs. 111.9 mg/dL, p<0.001) increased significantly. The proportion of patients with SLD was 37.5% after HCV eradication, which did not change significantly compared with the pretreatment status. The percentage of the patients who had post-treatment MASLD was 34.8%, which did not differ significantly from the pretreatment status (p=0.17). Body mass index (BMI) (odds ratio [OR] 0.89; 95% confidence intervals [CI] 0.85–0.92; p<0.001) was the only factor associated with MASLD resolution. In contrast, unfavorable CMRFs, including BMI (OR 1.10; 95% CI 1.06–1.14; p<0.001) and HbA1c (OR 1.19; 95% CI 1.04–1.35; p=0.01), were independently associated with MASLD development after HCV cure. Conclusions HCV eradication mitigates MASLD in CHC patients. CMRF surveillance is mandatory for CHC patients with metabolic alterations, which are altered after HCV eradication and predict the evolution of MASLD.

Ulcerative colitis (UC) is a chronic inflammation of the gastrointestinal tract and is characterized by alternating periods of inflammation and remission. Although UC incidence is lower in Taiwan than in Western countries, its impact remains considerable, demanding updated guidelines for addressing local healthcare challenges and patient needs. The revised guidelines employ international standards and recent research, emphasizing practical implementation within the Taiwanese healthcare system. Since the inception of the guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease has acknowledged the need for ongoing revisions to incorporate emerging therapeutic options and evolving disease management practices. This updated guideline aims to align UC management with local contexts, ensuring comprehensive and context-specific recommendations, thereby raising the standard of care for UC patients in Taiwan. By adapting and optimizing international protocols for local relevance, these efforts seek to enhance health outcomes for patients with UC.

Crohn’s disease (CD) is a chronic, fluctuating inflammatory condition that primarily affects the gastrointestinal tract. Although the incidence of CD in Taiwan is lower than that in Western countries, the severity of CD presentation appears to be similar between Asia and the West. This observation indicates the urgency for devising revised guidelines tailored to the unique reimbursement system, and patient requirements in Taiwan. The core objectives of these updated guidelines include the updated treatment choices and the integration of the treat-to-target strategy into CD management, promoting the achievement of deep remission to mitigate complications and enhance the overall quality of life. Given the diversity in disease prevalence, severity, insurance policies, and access to medical treatments in Taiwan, a customized approach is imperative for formulating these guidelines. Such tailored strategies ensure that international standards are not only adapted but also optimized to local contexts. Since the inception of its initial guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease (TSIBD) has acknowledged the importance of continuous revisions for incorporating new therapeutic options and evolving disease management practices. The latest update leverages international standards and recent research findings focused on practical implementation within the Taiwanese healthcare system.

Objectives: . Type 2 diabetes mellitus (T2DM) is a risk factor for deep neck infection (DNI) and leads to complications and poor outcomes. Our study aimed to investigate the risk, prognosis, and complications of peritonsillar abscess (PTA) in patients with T2DM. Methods: . We extracted data of patients newly diagnosed as having T2DM between January 2000 and December 2011 from Taiwan’s National Health Insurance Research Database. These patients were matched with patients without T2DM, and PTA incidence was compared between both cohorts. Results: . In total, 67,852 patients with and 135,704 patients without T2DM were enrolled. PTA incidence was significantly higher in patients with T2DM (incidence rate ratio, 1.91; P<0.001); moreover, PTA incidence was higher at 1 to 5 years after T2DM diagnosis than at <1 and >5 years after T2DM diagnosis. Cox regression analysis showed that patients with T2DM had an approximately 2-fold higher PTA risk (adjusted hazard ratio [aHR]: 1.89, P<0.001). Patients with a higher adapted Diabetes Complications Severity Index (aDCSI) had higher PTA risk than those with a lower aDCSI (aHRs: 2.17 for aDCSI ≥1, P=0.006 and 1.81 for aDCSI=0, P=0.002). T2DM patients with a high aDCSI (≥1) had a nonsignificantly longer hospitalization duration and a higher rate of DNI complications than did those with a low aDCSI (=0). Conclusion . In patients with T2DM, PTA incidence was relatively high, and it increased with T2DM severity. Moreover, T2DM patients should be particularly careful about PTA within 1 to 5 years after the diagnosis, and physicians should keep in mind that the prognosis of PTA was correlated with T2DM severity.

Background/Aims: Growth hormone (GH) is the main regulator of somatic growth, metabolism, and gender dimorphism in the liver. GH receptor (GHR) signaling in cancer is derived from a large body of evidence, although the GHR signaling pathway involved in the prognosis of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related HCC, remains unclear. We aimed to explore the expression of GHR and analyze its association with clinicopathologic features and prognosis of patients with chronic hepatitis C and HCC. Methods: The expression of GHR mRNA was investigated by quantitative real-time polymerase chain reaction in paired tumors and adjacent non-tumorous (ANT) liver tissues of 200 patients with chronic hepatitis C and HCC. Western blotting and immunofluorescence assays using the HCV-infected Huh7.5.1 cell model was performed. Results: GHR mRNA was significantly lower in HCV-HCC tissues than in corresponding ANT liver tissues. GHR mRNA and protein levels also decreased in the HCV-infected Huh7.5.1 cell model. Notably, lower GHR expression was associated with age of >60 years (P=0.0111) and worse clinicopathologic characteristics, including alpha-fetoprotein >100 ng/mL (P=0.0403), cirrhosis (P=0.0075), vascular invasion (P=0.0052), pathological stage II–IV (P=0.0002), and albumin ≤4.0 g/dL (P=0.0055), which were linked with poor prognosis of HCC. Most importantly, the high incidence of recurrence and poor survival rates in patients with a low ratio of tumor/ANT GHR (≤0.1) were observed, indicating that low expression levels of GHR had great risk for development of HCC in patients with chronic hepatitis C. Conclusions Our study demonstrates a significant down-regulation of GHR expression as a new unfavorable independent prognostic factor in patients with chronic hepatitis C and HCC.

Objectives: . Type 2 diabetes mellitus (T2DM) is a risk factor for deep neck infection (DNI) and leads to complications and poor outcomes. Our study aimed to investigate the risk, prognosis, and complications of peritonsillar abscess (PTA) in patients with T2DM. Methods: . We extracted data of patients newly diagnosed as having T2DM between January 2000 and December 2011 from Taiwan’s National Health Insurance Research Database. These patients were matched with patients without T2DM, and PTA incidence was compared between both cohorts. Results: . In total, 67,852 patients with and 135,704 patients without T2DM were enrolled. PTA incidence was significantly higher in patients with T2DM (incidence rate ratio, 1.91; P<0.001); moreover, PTA incidence was higher at 1 to 5 years after T2DM diagnosis than at <1 and >5 years after T2DM diagnosis. Cox regression analysis showed that patients with T2DM had an approximately 2-fold higher PTA risk (adjusted hazard ratio [aHR]: 1.89, P<0.001). Patients with a higher adapted Diabetes Complications Severity Index (aDCSI) had higher PTA risk than those with a lower aDCSI (aHRs: 2.17 for aDCSI ≥1, P=0.006 and 1.81 for aDCSI=0, P=0.002). T2DM patients with a high aDCSI (≥1) had a nonsignificantly longer hospitalization duration and a higher rate of DNI complications than did those with a low aDCSI (=0). Conclusion . In patients with T2DM, PTA incidence was relatively high, and it increased with T2DM severity. Moreover, T2DM patients should be particularly careful about PTA within 1 to 5 years after the diagnosis, and physicians should keep in mind that the prognosis of PTA was correlated with T2DM severity.

Background/Aims: Growth hormone (GH) is the main regulator of somatic growth, metabolism, and gender dimorphism in the liver. GH receptor (GHR) signaling in cancer is derived from a large body of evidence, although the GHR signaling pathway involved in the prognosis of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related HCC, remains unclear. We aimed to explore the expression of GHR and analyze its association with clinicopathologic features and prognosis of patients with chronic hepatitis C and HCC. Methods: The expression of GHR mRNA was investigated by quantitative real-time polymerase chain reaction in paired tumors and adjacent non-tumorous (ANT) liver tissues of 200 patients with chronic hepatitis C and HCC. Western blotting and immunofluorescence assays using the HCV-infected Huh7.5.1 cell model was performed. Results: GHR mRNA was significantly lower in HCV-HCC tissues than in corresponding ANT liver tissues. GHR mRNA and protein levels also decreased in the HCV-infected Huh7.5.1 cell model. Notably, lower GHR expression was associated with age of >60 years (P=0.0111) and worse clinicopathologic characteristics, including alpha-fetoprotein >100 ng/mL (P=0.0403), cirrhosis (P=0.0075), vascular invasion (P=0.0052), pathological stage II–IV (P=0.0002), and albumin ≤4.0 g/dL (P=0.0055), which were linked with poor prognosis of HCC. Most importantly, the high incidence of recurrence and poor survival rates in patients with a low ratio of tumor/ANT GHR (≤0.1) were observed, indicating that low expression levels of GHR had great risk for development of HCC in patients with chronic hepatitis C. Conclusions Our study demonstrates a significant down-regulation of GHR expression as a new unfavorable independent prognostic factor in patients with chronic hepatitis C and HCC.

OBJECTIVE: To investigate the efficacy of frankincense and myrrha in the treatment of acute interstitial cystitis/painful bladder syndrome (IC/PBS). METHODS: The effects of frankincense and myrrha on the proliferation and migration of primary human urothelial cells (HUCs) were assessed in vitro. In the animal study, 48 virgin female rats were randomized into 4 groups (12 in each group): (1) control group (saline-injected control); (2) cyclophosphamide (CYP) group (intraperitoneal injected 150 mg/kg CYP); (3) CYP + pentosan polysulfate sodium group (orally received 50 mg/kg pentosan polysulfate sodium); and (4) CYP + frankincense and myrrha group [orally received frankincense (200 mg/kg) and myrrha (200 mg/kg)]. Rats orally received pentosan polysulfate sodium or frankincense and myrrha on day 1, 2, and 3. The experiments were performed on day 4. Pain and cystometry assessment behavior test were performed. Voiding interval values were assessed in rats under anesthesia. Finally, immunohistochemistry and Western blot were used to confirm the location and level, respectively, of cell junction-associated protein zonula occludens-2 (ZO-2) expression. RESULTS: Low dose frankincense and myrrha increased cell proliferation and migration in HUCs compared with control (P<0.05). Rats with acute IC/PBS rats exhibited lower voiding interval values, pain tolerance, and ZO-2 expression (P<0.05). Voiding interval values and pain tolerance were higher in the frankincense and myrrha group than CYP group (P<0.05). ZO-2 expression in the bladder was increased in the CYP + pentosan polysulfate and frankincense + myrrha groups compared with the CYP-induced acute IC/PBS group (P<0.05). CONCLUSION frankincense and myrrha modulate urothelial wound healing, which ameliorates typical features of acute IC/PBS in rats.