Machine-Learning Algorithm for Predicting Fatty Liver Disease in a Taiwanese Population.

The rising incidence of fatty liver disease (FLD) poses a health challenge, and is expected to be the leading global cause of liver-related morbidity and mortality in the near future. Early case identification is crucial for disease intervention. A retrospective cross-sectional study was performed on 31,930 Taiwanese subjects (25,544 training and 6386 testing sets) who had received health check-ups and abdominal ultrasounds in Changhua Christian Hospital from January 2009 to January 2019. Clinical and laboratory factors were included for analysis by different machine-learning algorithms. In addition, the performance of the machine-learning algorithms was compared with that of the fatty liver index (FLI). Totally, 6658/25,544 (26.1%) and 1647/6386 (25.8%) subjects had moderate-to-severe liver disease in the training and testing sets, respectively. Five machine-learning models were examined and demonstrated exemplary performance in predicting FLD. Among these models, the xgBoost model revealed the highest area under the receiver operating characteristic (AUROC) (0.882), accuracy (0.833), F1 score (0.829), sensitivity (0.833), and specificity (0.683) compared with those of neural network, logistic regression, random forest, and support vector machine-learning models. The xgBoost, neural network, and logistic regression models had a significantly higher AUROC than that of FLI. Body mass index was the most important feature to predict FLD according to the feature ranking scores. The xgBoost model had the best overall prediction ability for diagnosing FLD in our study. Machine-learning algorithms provide considerable benefits for screening candidates with FLD.

Pan-Genotypic Direct-Acting Antiviral Agents for Undetermined or Mixed-Genotype Hepatitis C Infection: A Real-World Multi-Center Effectiveness Analysis.

Although the pan-genotypic direct-acting antiviral regimen was approved for treating chronic hepatitis C infection regardless of the hepatitis C virus (HCV) genotype, real-world data on its effectiveness against mixed-genotype or genotype-undetermined HCV infection are scarce. We evaluated the real-world safety and efficacy of two pan-genotypic regimens (Glecaprevir/Pibrentasvir and Sofosbuvir/Velpatasvir) for HCV-infected patients with mixed or undetermined HCV genotypes from the five hospitals in the Changhua Christian Care System that commenced treatment between August 2018 and December 2020. This retrospective study evaluated the efficacy and safety of pan-genotypic direct-acting antiviral (DAA) treatment in adults with HCV infection. The primary endpoint was the sustained virological response (SVR) observed 12 weeks after completing the treatment. Altogether, 2446 HCV-infected patients received the pan-genotypic DAA regimen, 37 (1.5%) patients had mixed-genotype HCV infections and 110 (4.5%) patients had undetermined HCV genotypes. The mean age was 63 years and 55.8% of our participants were males. Nine (6.1%) patients had end-stage renal disease and three (2%) had co-existing hepatomas. We lost one patient to follow-up during treatment and one more patient after treatment. A total of four patients died. However, none of these losses were due to treatment-related side effects. The rates of SVR12 for mixed-genotype and genotype-undetermined infections were 97.1% and 96.2%, respectively, by per-protocol analyses, and 91.9% and 92.7% respectively, by intention-to-treat population analyses. Laboratory adverse events with grades ≥3 included anemia (2.5%), thrombocytopenia (2.5%), and jaundice (0.7%). Pan-genotypic DAAs are effective and well-tolerated for mixed-genotype or genotype-undetermined HCV infection real-world settings.

Real-World Experience of Chronic Hepatitis C-Related Compensated Liver Cirrhosis Treated with Glecaprevir/Pibrentasvir: A Multicenter Retrospective Study.

BACKGROUND: Glecaprevir/pibrentasvir is a protease inhibitor-containing pangenotypic direct-acting antiviral regimen that has been approved for the treatment of chronic hepatitis C. The present study aimed to evaluate the safety and efficacy of glecaprevir/pibrentasvir in patients with compensated cirrhosis in a real-world setting. METHODS: We evaluated the real-world safety and efficacy of glecaprevir/pibrentasvir in patients with compensated cirrhosis from five hospitals in the Changhua Christian Care System, who underwent treatment between August 2018 and October 2020. The primary endpoint was a sustained virological response observed 12 weeks after completion of the treatment. RESULTS: Ninety patients, including 70 patients who received the 12-week therapy and 20 patients who received the 8-week therapy, were enrolled. The mean age of the patients was 65 years, and 57.8% of the patients were males. Sixteen (17.8%) patients had end-stage renal disease, and 15 (16.7%) had co-existing hepatoma. The hepatitis C virus genotypes 1 (40%) and 2 (35.6%) were most common. The common side effects included anorexia (12.2%), pruritus (7.8%), abdominal discomfort (7.8%), and malaise (7.8%). Laboratory adverse grade ≥3 events included anemia (6.3%), thrombocytopenia (5.1%), and jaundice (2.2%). The overall sustained virological response rates were 94.4% and 97.7% in the intention-to-treat and per-protocol analyses, respectively. CONCLUSIONS: the glecaprevir/pibrentasvir treatment regimen was highly effective and well tolerated among patients with compensated cirrhosis in the real-world setting.

Strategy for the Micro-Elimination of Hepatitis C among Patients with Diabetes Mellitus-A Hospital-Based Experience.

Hepatitis C virus (HCV) infection can induce insulin resistance, and patients with diabetes mellitus (DM) have a higher prevalence of HCV infection. Patient outcomes improve after HCV eradication in DM patients. However, HCV micro-elimination targeting this population has not been approached. Little is known about using electronic alert systems for HCV screening among patients with DM in a hospital-based setting. We implemented an electronic reminder system for HCV antibody screening and RNA testing in outpatient departments among patients with DM. The screening rates and treatment rates at different departments before and after system implementation were compared. The results indicated that the total HCV screening rate increased from 49.3% (9505/19,272) to 78.2% (15,073/19,272), and the HCV-RNA testing rate increased from 73.4% to 94.2%. The anti-HCV antibody seropositive rate was 5.7%, and the HCV viremia rate was 62.7% in our patient population. The rate of positive anti-HCV antibodies and HCV viremia increased with patient age. This study demonstrates the feasibility and usefulness of an electronic alert system for HCV screening and treatment among DM patients in a hospital-based setting.

Direct-acting antiviral treatment for Hepatitis C Virus in geriatric patients: a real-world retrospective comparison between early and late elderly patients.

INTRODUCTION: Chronic hepatitis C virus (HCV) infection rates are high in the geriatric population considering that interferon-based therapy is usually intolerable. With the introduction of oral antiviral therapy for HCV, increased treatment tolerability and good treatment responses have been observed. However, treatment data regarding the geriatric population have been limited. Therefore, this retrospective study aimed to evaluate the efficacy and safety of direct-acting antiviral therapy for HCV in the geriatric population. MATERIALS AND METHODS: The primary end point was sustained virologic response (SVR) 12 weeks after treatment completion, whereas the secondary end points were treatment-related side effects and short-term survival rate following treatment. RESULTS: In total, 492 patients (median age, 73 years; 43.9% males), including 278 early elderly patients, were enrolled. Among the included patients, 45% had cirrhosis. HCV genotypes 1 (72.4%) and 2 (25.4%) were the most common. The overall SVR rate was 96.7%, with no difference in SVR rates observed between early and late elderly groups (96.8% vs. 96.7%; p = 0.983). Both groups showed similar side effects, including dizziness (11.4%), and fatigue (8.7%), with three patients discontinuing therapy owing to side effects. Both groups had a similar 3-year survival rate. Significant factors associated with post-treatment survival included cirrhosis, albumin, and creatinine level. CONCLUSIONS: Our real-world data showed that both early and late elderly patients could undergo direct-acting antiviral treatment for HCV with excellent treatment outcomes.

Glecaprevir-pibrentasvir for chronic hepatitis C: Comparing treatment effect in patients with and without end-stage renal disease in a real-world setting.

INTRODUCTION: Chronic hepatitis C virus (HCV) infection is increasingly observed in patients with renal disease. With the introduction of glecaprevir/pibrentasvir (GLE/PIB) as a pan-genotype therapy for HCV, treatment efficacy is expected to rise. MATERIALS AND METHODS: This retrospective study evaluated the efficacy and safety of GLE/PIB treatment in adults with HCV infection and end-stage renal disease (ESRD). The primary end point was sustained virological response (SVR) observed 12 weeks after completed treatment. RESULTS: We enrolled 235 patients, including 44 patients with ESRD. Median age was 60 years, and 48% were males. Twenty-two percent had cirrhosis. HCV genotypes 1 (43%) and 2 (41%) were the most common. The overall SVR rate was 96.6%. Patients with ESRD were older than those without (67.6 years vs 58.3 years, p < 0.001) and trended toward having a higher prevalence of cirrhosis (32% vs 19%, p = 0.071). A significant proportion of patients with ESRD complained of skin itching during treatment (61% vs 26%, p < 0.001), and the SVR rate were similar between these two groups (95.45% vs 96.86%, p = 0.644). CONCLUSIONS: Despite a higher rate of pruritus among patients with ESRD, GLE/PIB-based therapy achieved similarly high SVR rates among patients with and without ESRD.

Association of 3-Dimensional Cartilage and Bone Structure with Articular Cartilage Properties in and Adjacent to Autologous Osteochondral Grafts after 6 and 12 months in a Goat Model.

OBJECTIVE: The articular cartilage of autologous osteochondral grafts is typically different in structure and function from local host cartilage and thereby presents a remodeling challenge. The hypothesis of this study was that properties of the articular cartilage of trochlear autografts and adjacent femoral condyle are associated with the 3-D geometrical match between grafted and contralateral joints at 6 and 12 months after surgery. DESIGN: Autografts were transferred unilaterally from the lateral trochlea (LT) to the medial femoral condyle (MFC) in adult Spanish goats. Operated and contralateral Non-Operated joints were harvested at 6 and 12 months, and analyzed by indentation testing, micro-computed tomography, and histology to compare (1) histological indices of repair, (2) 3-D structure (articular surface deviation, bone-cartilage interface deviation, cartilage thickness), (3) indentation stiffness, and (4) correlations between stiffness and 3-D structure. RESULTS: Cartilage deterioration was present in grafts at 6 months and more severe at 12 months. Cartilage thickness and normalized stiffness of Operated MFC were lower than Non-Operated MFC within the graft and proximal adjacent host regions. Operated MFC articular surfaces were recessed relative to Non-Operated MFC and exhibited lower cartilage stiffness with increasing recession. Sites with large bone-cartilage interface deviations, both proud and recessed, were associated with recessed articular surfaces and low cartilage stiffness. CONCLUSION: The effectiveness of cartilage repair by osteochondral grafting is associated with the match of 3-D cartilage and bone geometry to the native osteochondral structure.

Metabolic transformation of sesamol and ex vivo effect on 2,2'-azo-bis(2-amidinopropane)dihydrochloride-induced hemolysis.

Sesamol (3,4-methylenedioxyphenol), a phenolic constituent in roasted sesame, was reported to exhibit various beneficial activities. To understand the metabolic transformation of sesamol in vivo, rats were given sesamol intravenously and orally. The blood samples were withdrawn via cardiopuncture at specific time points. The serum samples were assayed by high-performance liquid chromatography method before and after hydrolysis with sulfatase and beta-glucuronidase. Our results indicated that following either intravenous or oral administration, sesamol declined rapidly and the sulfate/glucuronide of sesamol emerged instantaneously. The peak serum concentration and systemic exposure of sesamol were markedly lower than sesamol sulfate/glucuronide. Ex vivo evaluation revealed that sesamol exerted profoundly higher capability against 2,2'-azo-bis(2-amidinopropane)dihydrochloride-induced hemolysis than the serum metabolites. In conclusion, sulfate and glucuronide of sesamol were the principle metabolites of sesamol in the bloodstream of rats. The conjugated metabolites of sesamol warrant more bioactivity investigations to understand the in vivo effect of sesamol.

A comparison of elementary schoolchildren's exposure to arsenic and lead.

One hundred fifty seven fifth-grade students (aged 10-12 years) from three elementary schools in three different towns in Taichung County, Taiwan were chosen as study subjects for the present arsenic and lead exposure study. The three towns--Longgang, Shalach, and Shuntain--are known to be highly, moderately, and lightly (control) polluted by As and Pb, respectively. Spot morning urine samples of students were collected and analyzed for arsenic and lead. The levels of As in the urine of Longgang schoolchildren showed the highest value among the three schools, while those of the control group (Shuntain) had the lowest values. In addition, the levels of Pb in the urine of the schoolchildren in Shuntain were significantly lower than those in Longgang and Shalach, while the levels of Pb in the urine of the schoolchildren in Longgang and Shalach showed no significant difference. Results of daily intake of metals from the different exposure pathways (i.e., ingestion from drinking water, household dust and food, and inhalation from airborne particles) showed that the Longgang area had the highest daily intake of As and Pb among the three areas, while the lowest daily intake of As and Pb occurred in the control area (Shuntain). A significant correlation between the doses of daily intake and urinary concentrations of As (p = 0.002) and Pb (p = 0.020) was observed. This correlation suggests that the increase of unit dose of the daily intake for As resulted in an increase of 0.953 microg g(-1) creatinine of As, whereas the increase of unit dose of the daily intake for Pb led to an increase of 0.053 microg g(-1) creatinine of Pb. These data indicate that the level of As in urine increased about 18 times higher than that of Pb for the same amount of increase in daily intake.