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.

The Acute Disease Quality Initiative advocates multidisciplinary care for the survivors of acute kidney injury (AKI). The bundled care strategy recognizes the role of pharmacists. However, their specific contributions in this context remain underexplored. Methods: This retrospective study examined the efficacy of pharmacist-led post-AKI pharmaceutical care in outpatient settings at a single center. Adults with recent AKI during hospitalization, maintaining an estimated glomerular filtration rate <45 mL/min/1.73 m2 postdischarge, were enrolled in a multidisciplinary team care program from March 2022 to January 2023, with a 6-month follow-up period. Pharmacist-delivered care adhered to international multidisciplinary consensus guidelines. Efficacy was evaluated by analyzing medication-related recommendations, medication adherence, nephrotoxic drug utilization, and renoprotective medication usage before and after the intervention. Results: A total of 40 patients were referred to the pharmacist-managed clinic. Of these, 33 patients (mean age, 63 ± 15 years; 60.6% male) attended the clinic. Nineteen patients completed follow-up visits. The pharmacist provided 14 medication-related recommendations to relevant physicians, with 10 of these recommendations (71.4%) being accepted. There was a significant decrease in the use of modifiable nephrotoxic drugs (p = 0.03). However, no significant improvements were noted in medication adherence or the utilization of renoprotective medications. Conclusion: Our study underscores the potential benefits of pharmacist-led post-AKI bundled care strategy in outpatient settings. We observed a significant reduction in the utilization of modifiable nephrotoxic drugs, indicating the effectiveness of pharmacist interventions in optimizing medication regimens to mitigate renal harm.

Background/Aims: Primary sclerosing cholangitis (PSC) is associated with inflammatory bowel disease (IBD). We aimed to evaluate the prevalence, clinical manifestation, and outcomes of PSC in Taiwanese patients with IBD. Methods: This retrospective study enrolled patients with IBD admitted from January 1, 1996, to December 31, 2018, to National Taiwan University Hospital. A case-matched analysis was performed comparing patients with IBD with and without PSC according to age, sex, and time of admission, with ratios of 1:4 and 1:2 in the adult and pediatric groups, respectively. Results In total, 763 patients with IBD were enrolled, 12 of whom were also diagnosed with PSC (1.57%). All these patients had ulcerative colitis (UC). A greater incidence of IBD with PSC was observed in younger patients than in older patients. Male sex was a risk factor for PSC in pediatric patients with IBD (P=0.015); 75% of these patients were diagnosed with PSC along with or after the diagnosis of UC. There was no significant difference in colitis extent and severity between the groups; however, a higher proportion of rectal sparing was observed in patients with PSC (P=0.001). There was no significant difference in cancer development between the groups (P=0.679). Conclusions: A 1.57% prevalence of PSC was observed in Taiwanese patients with IBD. The majority of patients with IBD and PSC were men and were diagnosed at a younger age. Hence, routine evaluation of biliary enzymes and liver imaging is recommended in young male patients with IBD.

In Taiwan, thyroid fine-needle aspiration cytology is easily accessible and reliable for evaluating thyroid nodules. The sonographic pattern plays a major role and is the deciding factor for aspiration. We conducted a nationwide survey in 2017 and it revealed that 31% of laboratories had adopted The Bethesda System for Reporting Thyroid Cytopathology. There was a relatively high unsatisfactory rate (24.04%) and low rates of indeterminate diagnoses, including atypia of undetermined significance/follicular lesions of undetermined significance: 4.87%, and follicular neoplasm/suspicious for a follicular neoplasm: 0.35%. Moreover, the risks of malignancy in benign, atypia of undetermined significance, and suspicious for a follicular neoplasm were relatively high. These may reflect strict diagnostic criteria for indeterminate categories and better patient selection for surgery. Improvements in specimen sampling and continuing education programs are crucial. Newly-developed thyroid cytology technologies, such as immunocytochemistry, molecular testing, and computerized cytomorphometry, may further facilitate cytology diagnoses.

We studied a family with Gorlin-Goltz syndrome. The novel mutations of our cases were located on the 21st exon of the PTCH1 gene (c.3450C>G). The father, who received a strategic 56-day vismodegib treatment for disease control, was the first patient with Gorlin syndrome treated with the hedgehog inhibitor in Taiwan. The lesions regressed gradually, with scar formation, and were subsequently removed via a wide excision. Further details are provided below.
Basal Cell Nevus Syndrome* ; Cicatrix ; Exons ; Fathers ; Hedgehogs ; Humans ; Taiwan

OBJECTIVE: The malignant transformation (MT) of ovarian mature cystic teratoma (MCT) to squamous cell carcinoma (SCC) is very rare. This study analyzed cases from multiple medical centers in Taiwan to investigate the clinicopathologic characteristics, treatment, and prognostic factors of this disease and reviewed related literature. METHODS: Pathological reports of 16,001 patients with primary ovarian cancer who were treated at Taiwan medical centers from 1990 to 2011 were reviewed. In total, 52 patients with MT of MCT to SCC were identified. RESULTS: Among all ovarian MCTs, the incidence of MT to SCC is 0.2%. The median age of patients was 52 years (range, 29–89 years), and the mean tumor size was 10.5 cm (range, 1–40 cm). We analyzed the patients in our study and those in the literature and determined that early identification and complete surgical resection of the tumor are essential for long-term survival. In addition, adjuvant chemotherapy or concurrent chemoradiotherapy can be used to treat this malignancy. Old age, large tumor size (≥15.0 cm), and solid components in MCTs are suitable indicators predicting the risk of MT of MCT to SCC. CONCLUSION: Similar to general epithelial ovarian cancers, the early detection of MT of MCT to SCC is critical to long-term survival. Therefore, older patients with a large tumor or those with a tumor containing a solid component in a clinically diagnosed MCT should be evaluated to exclude potential MT to SCC.
Carcinoma, Squamous Cell* ; Cell Transformation, Neoplastic ; Chemoradiotherapy ; Chemotherapy, Adjuvant ; Epithelial Cells* ; Humans ; Incidence ; Ovarian Neoplasms ; Taiwan ; Teratoma*

Human diphyllobothriasis is a parasitic disease caused by ingestion of larvae (plerocercoids) in raw or undercooked fish and commonly found in temperate areas. Rare cases were reported in tropical or subtropical areas especially in children. The first documented case of pediatric diphyllobothriasis in Taiwan had been reported 11 years ago. Here, we report another 8-year-old girl case who presented with a live noodle-like worm hanging down from her anus, with no other detectable symptoms. We pulled the worm out and found the strobila being 260 cm in length. Examination of gravid proglottids showed that they were wider than their lengths, containing an ovoid cirrus sac in the anterior side and the rosette-shaped uterus. Eggs extracted from the uterus were ovoid and operculated. Diphyllobothrium latum was confirmed by molecular analysis of the mitochondrial DNA cytochrome c oxidase subunit 1 (cox1) gene. The girl was treated with a single oral dose of praziquantel, and no eggs or proglottids were observed from her stool in the subsequent 3 months. The reemergence of human diphyllobothriasis in non-endemic countries is probably due to prevalent habit of eating imported raw fish from endemic areas. This pediatric case raised our concern that human diphyllobothriasis is likely underestimated because of unremarkable symptoms.
Anal Canal ; Child ; Diphyllobothriasis ; Diphyllobothrium* ; DNA, Mitochondrial ; Eating ; Eggs ; Electron Transport Complex IV ; Female ; Humans ; Larva ; Ovum ; Parasitic Diseases ; Praziquantel ; Taiwan* ; Uterus

Crohn's disease (CD) is a disease with chronic inflammation of unknown etiology involving any part of the gastrointestinal tract. The incidence and prevalence of CD are increasing recently in Asia. Half of the CD patients will have intestinal complications, such as strictures or fistulas, within 20 years after diagnosis. Twenty-five percentage of CD patients have had at least one small bowel stricture and 10% have had at least one colonic stricture and lead to significant complications. Most of these patients will require at least one surgery during their lifetime. Early diagnosis and evaluation with adequate managements for the patients can prevent disability and mortality of these patient. Here, we reviewed the current incidence of CD with stricture, the etiology of stricture, and how to diagnose and manage the stricture.
Asia ; Colon ; Constriction, Pathologic* ; Crohn Disease* ; Diagnosis ; Disease Management ; Early Diagnosis ; Fistula ; Gastrointestinal Tract ; Humans ; Incidence ; Inflammation ; Intestines ; Mortality ; Prevalence