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The long-term outcome of hepatitis B virus (HBV) infection among patients dually infected with HBV and hepatitis C virus (HCV) remains unclear. We aimed to investigate the long-term liver outcomes of HBV/HCV-coinfected patients after antiviral therapy. A total of 11,359 chronically HCV-infected patients with interferon-based therapy were registered in a nationwide Taiwanese Chronic Hepatitis C Cohort. A propensity score matched (PSM) cohort of HCV mono-infected (n = 7020) and HBV/HCV (n = 702) co-infected patients by age, sex, and fibrosis was recruited for outcome analysis. The primary outcome was liver-related complications, including hepatocellular carcinoma (HCC) and liver decompensation during a mean follow-up period of 4.44 years. Among HBV/HCV co-infected patients, patients without HCV-SVR had a significantly higher 10-year cumulative incidence of major liver-related complications than those with HCV-SVR. However, among patients with HCV-SVR in the PSM cohort, the risk of major liver-related complications, both HCC and liver decompensation, did not differ between HBV/HCV co-infected and HCV mono-infected patients. Similar results were observed among those without HCV-SVR. A substantial lower risk of major liver-related complications was found in HBV/HCV co-infected patients with HCV SVR and subsequent anti-HBV nucleot(s)ide analogues treatment. Overall, factors associated with major liver-related complications included age ≥ 65 year-old, BMI ≥ 27 kg/m2, FIB-4 ≥ 3.25, eGFR

Background/aims Direct‐acting antivirals (DAAs) are highly effective in treating chronic hepatitis C virus (HCV)‐infected patients. The real‐world treatment outcome in Taiwanese patients on a nationwide basis is elusive. Methods The Taiwan HCV Registry (TACR) programme is a nationwide registry platform including 48 study sites, which is organized and supervised by the Taiwan Association for the Study of the Liver. The primary endpoint was sustained virological response (SVR12, undetectable HCV RNA 12 weeks after end‐of‐treatment). Results A total of 13 951 registered patients with SVR12 data available were analysed (mean age, 63.0 years; female, 55.9%; HCV genotype‐1 [GT1], 57.9%; cirrhosis, 38.4%; preexisting hepatocellular carcinoma [HCC], 10.6%; and hepatitis B virus coinfection, 7.7%). The overall SVR12 rate was 98.3%, with 98.7%, 98.0%, 98.4% and 97.4% in treatment‐naïve noncirrhotic, treatment‐naïve cirrhotic, treatment‐experienced noncirrhotic and treatment‐experienced cirrhotic patients, respectively. The SVR12 rate was > 95% across all subgroups except treatment‐experienced cirrhotic patients who received sofosbuvir/ribavirin (88.7%), treatment‐naïve noncirrhotic patients (94.8%) and treatment‐experienced cirrhotic (94.8%) patients who received daclatasvir/asunaprevir. The most important factor associated with treatment failure was DAA adherence

Pangenotypic direct-acting antivirals are expected to cure hepatitis C virus (HCV) in more than 95% of treated patients. However, data on the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) in Taiwan are limited. This study aims to characterize the patient population in the nationwide Taiwan Association for the Study of the Liver (TASL) HCV Registry and evaluate treatment outcome in Taiwanese patients receiving SOF/VEL.This study was a retrospective-prospective, observational, multicenter, real-world analysis. Adults with chronic hepatitis C were treated with SOF/VEL 400/100 mg ± ribavirin for 12 weeks. The primary outcome was sustained virologic response 12 weeks after end of therapy (SVR12). Factors associated with not achieving SVR12 were evaluated using logistic regression and covariate analysis. Safety was also assessed.In total, 3480 patients were included: 86.8% genotype 1/2, 2.8% genotype 3, 0.1% genotype 4/5, 9.6% genotype 6; unclassified, 0.8%; 12.2% compensated cirrhosis; 3.3% decompensated cirrhosis; and 15.8% chronic kidney disease. Overall SVR12 rate was 99.4% (genotype 1, 99.5%; genotype 2, 99.4%; genotype 3, 96.9%; genotype 4, 100%; genotype 6, 99.7%). SVR12 rates among patients with compensated cirrhosis, decompensated cirrhosis, and chronic kidney disease stages 4-5 were 99.5%, 100%, and 100%, respectively. There were 21 patients (0.6%) who did not achieve SVR12. Factors associated with failure were treatment adherence below 60%, high viral load, and genotype 3 (p 0.001, p = 0.028, and p = 0.001, respectively). Adverse events occurred in 10% of patients; 0.6% were serious and one was related to treatment. Treatment discontinuation occurred in 0.3% of patients; none were treatment related. The estimated glomerular filtration rate remained stable throughout treatment and follow-up, regardless of baseline values and cirrhosis status.SOF/VEL was highly effective and well tolerated in Taiwanese patients, irrespective of viral genotype, liver disease severity, and comorbidities.

Background/AimsThe study evaluated the real-world treatment outcomes of Glecaprevir/pibrentasvir (GLE/PIB) including effectiveness, safety and healthcare resource utilization based on a nation-wide registry in Taiwan.MethodsThe Taiwan HCV Registry (TACR) is a nation-wide platform organized and supervised by the Taiwan Association for the Study of the Liver. Data were analyzed for patients treated with GLE/PIB, including 3,144 patients who had treatment outcome available. The primary endpoint was sustained virological response (SVR12, undetectable HCV RNA throughout 12 weeks of end-of-treatment). ResultsThe overall SVR12 rate was 98.9% (3110/3144), with 98.8%, 99.4% and 100% in patients receiving 8 weeks, 12 weeks, and 16 weeks of GLE/PIB respectively. The SVR12 rate in the treatment-naïve cirrhotic patients receiving 8 weeks of GLE/PIB was 98.2% (108/110). The most common AEs were fatigue (7.5%), pruritus (6.7%) and dizziness (1.5%). The mean number of outpatient visits during the GLE/PIB was 5.94 visits for patients treated with 8 weeks, significantly different from the patients treated with 12 weeks of GLE/PIB (6.90 visits). ConclusionsThe results support the effectiveness and safety of GLE/PIB treatment in real-world clinical practice, and provide further evidence that the shorter, 8-week GLE/PIB regimen is effective and cost-saving.

Diabetes mellitus (DM) is known to increase the risk of hepatocellular carcinoma (HCC) among individuals with chronic hepatitis C (CHC). We aimed to evaluate whether metformin reduces HCC risk among individuals with DM and CHC after successful antiviral therapy.Individuals with CHC who achieved a sustained virological response (SVR) after interferon-based therapy were enrolled in a large-scale, multicenter cohort in Taiwan (T-COACH). Cases of HCC at least 1 year after SVR were identified through linkage to the catastrophic illness and cancer registry databases.Of 7,249 individuals with CHC enrolled in the study, 781 (10.8%) had diabetes and 647 (82.8%) were metformin users. During a median follow-up of 4.4 years, 227 patients developed new-onset HCC. The 5-year cumulative HCC incidence was 10.9% in non-metformin users and 2.6% in metformin users, compared to 3.0% in individuals without DM (adjusted hazard ratio [aHR] 2.83; 95% CI 1.57-5.08 and aHR 1.46; 95% CI 0.98-2.19, respectively). Cirrhosis was the most important factor significantly associated with higher HCC risk in Cox regression analysis, followed by DM non-metformin use, older age, male sex, and obesity; whereas hyperlipidemia with statin use was associated with a lower HCC risk. Using the two most crucial risk factors, cirrhosis and DM non-metformin use, we constructed a simple risk model that could predict HCC risk among individuals with CHC after SVR. Metformin use was shown to reduce the risk of all liver-related complications.Metformin use greatly reduced HCC risk after successful antiviral therapy in individuals with diabetes and CHC. A simple risk stratification model comprising cirrhosis and DM non-metformin use could predict long-term outcomes in individuals with CHC after SVR.The current study provides evidence that metformin could reduce hepatocellular carcinoma (HCC) incidence after successful antiviral therapy among those with diabetes and chronic hepatitis C in a large-scale nationwide cohort study. Although successful antiviral therapy greatly reduces HCC risk in individuals with chronic hepatitis C, those with cirrhosis, diabetes, obesity, and the elderly remain at high risk of HCC development. We demonstrated that a simple risk model composed of two crucial unfavorable factors, cirrhosis and diabetes without metformin use, predicts the risk of HCC and major liver-related complications after successful antiviral therapy in individuals with chronic hepatitis C. Metformin use is highly recommended for individuals with diabetes and chronic hepatitis C after viral eradication to reduce the risk of HCC.

The Taiwan Association for the Study of the Liver (TASL) HCV Registry (TACR) is a nationwide registry of chronic hepatitis C patients in Taiwan. This study evaluated antiviral effectiveness of ledipasvir (LDV)/sofosbuvir (SOF) in patients in the TACR.Patients enrolled in TACR from 2017-2020 treated with LDV/SOF were eligible. The primary outcome was the proportion of patients with sustained virologic response 12 weeks after end of treatment (SVR12).5644 LDV/SOF ± ribavirin-treated patients were included (mean age: 61.4 years; 54.4% female). Dominant viral genotypes were GT1 (50.8%) and GT2 (39.3%). 1529 (27.1%) patients had liver cirrhosis, including 201 (3.6%) with liver decompensation; 686 (12.2%) had chronic kidney disease. SVR12 was achieved in 98.6% of the overall population and in 98.2% and 98.7% of patients with and without cirrhosis, respectively. SVR12 rates in patients with compensated cirrhosis treated with LDV/SOF without RBV were98%, regardless of prior treatment experience. SVR12 was 98.6%, 98.4%, 100%, 100%, and 98.7% among those with GT1, GT2, GT4, GT5, and GT6 infections, respectively. Although patient numbers were relatively small, SVR12 rates of 100% were reported in patients infected with HCV GT2, GT5, and GT6 with decompensated cirrhosis and 98% in patients with severely compromised renal function. LDV/SOF adherence ≤60% (P 0.001) was the most important factor associated with treatment failure. Incidence of adverse events was 15.8%, with fatigue being the most common.LDV/SOF is effective and well tolerated in routine clinical practice in Taiwan. Cure rates were high across patient populations.

BACKGROUND AND AIM It is currently unknown how hepatitis C virus (HCV) eradication with pegylated interferon and ribavirin (PR) therapy affects the incidence of new-onset liver cirrhosis (LC) in patients without cirrhosis and the incidence of decompensated liver disease (DLD) or hepatocellular carcinoma (HCC) in patients with cirrhosis. METHODS Taiwanese chronic hepatitis C cohort (T-COACH) is a nationwide HCV registry cohort from 23 hospitals in Taiwan recruited between 2003 and 2015. This study enrolled 10 693 patients with chronic hepatitis C (CHC), linked to the Taiwan National Health Insurance Research Database, receiving PR therapy for at least 4 weeks for new-onset LC and liver-related complications (DLD or HCC). RESULTS Of the 10 693 patients, 1372 (12.8%) patients had LC, and the mean age was 54.0 ± 11.4 years. The mean follow-up duration was 4.38 ± 2.79 years, with overall 46 798 person-years. The 10-year cumulative incidence rates of new-onset LC were 5.0% (95% confidence interval [CI]: 3.2-7.7) in patients without cirrhosis with a sustained virologic response (SVR) and 21.9% (95% CI: 13.4-32.4) in those without SVR (hazard ratio [HR]: 0.22, P

Background & Aims Sofosbuvir is approved for chronic hepatitis C (CHC) patients with severe chronic kidney disease (CKD). The impact of sofosbuvir-based therapy on renal function augmentation on a real-world nationwide basis is elusive. Methods The 12,995 CHC patients treated with sofosbuvir-based (n = 6802) or non–sofosbuvir-based (n = 6193) regimens were retrieved from the Taiwan nationwide real-world HCV Registry Program. Serial estimated glomerular filtration rate (eGFR) levels were measured at baseline, end of treatment (EOT), and end of follow-up (EOF) (3 months after EOT). Results The eGFR decreased from baseline (91.4 mL/min/1.73 m2) to EOT (88.4 mL/min/1.73 m2; P 90 mL/min/1.73 m2 was the only factor independently associated with significant slope coefficient differences of eGFR (–1.98 mL/min/1.73 m2; 95% confidence interval, –2.24 to –1.72; P Conclusions Both sofosbuvir and non–sofosbuvir-based regimens restored renal function in CHC patients with CKD, especially in those with significant renal function impairment.

Accumulating evidence suggests that there is a link between the host microbiome and pancreatic carcinogenesis, and that Porphyromonas gingivalis (P. gingivalis) increases the risk of developing pancreatic cancer. The aim of the current study was to clarify the role of P. gingivalis in the pathogenesis of pancreatic cancer and the potential immune modulatory effects of probiotics. The six-week-old LSL-K-rasG12D, Pdx-1-cre (KC) mice smeared P. gingivalis on the gums, causing pancreatic intraepithelial neoplasia (PanIN) after four weeks to be similar to the extent of lesions in untreated KC mice at 24 weeks. The oral inoculation of P. gingivalis of six-week-old LSL-K-rasG12D, Pdx-1-cre (KC) mice caused significantly pancreatic intraepithelial neoplasia (PanIN) after treatment four weeks is similar to the extent of lesions in untreated KC mice at 24 weeks. The pancreas weights of P. gingivalis plus probiotic-treated mice were significantly lower than the mice treated with P. gingivalis alone (P = 0.0028). The histological expressions of Snail-1, ZEB-1, collagen fibers, Galectin-3, and PD-L1 staining in the pancreas were also notably lower. In addition, probiotic administration reduced the histological expression of Smad3 and phosphorylated Smad3 in P. gingivalis treated KC mice. We demonstrated that oral exposure to P. gingivalis can accelerate the development of PanIN lesions. Probiotics are likely to have a beneficial effect by reducing cancer cell proliferation and viability, inhibiting PanIN progression, and cancer cell metastasis (Epithelial&ndash, mesenchymal transition, EMT). The transforming growth factor-&beta, signaling pathway may be involved in the tumor suppressive effects of probiotics.

Rationale & Objective Hemodialysis facilities are high-risk environments for hepatitis C virus (HCV). Eliminating HCV from all dialysis facilities in a community may be achieved more effectively under a collaborative care model. Study Design Quality improvement study of multidisciplinary collaborative care teams including nephrologists, gastroenterologists and public health practitioners. Setting & Participants All dialysis patients in the Changhua county of Taiwan were treated using an inter-disciplinary collaborative care model implemented within a broader Changhua-Integrated Program to Stop HCV Infection (CHIPS-C). Quality Improvement Activities Provision of an HCV care cascade to fill three gaps including screening and testing, diagnosis, and universal direct-acting antiviral (DAA) treatment implemented by collaborating teams of dialysis practitioners and gastroenterologists working under auspices of Changhua Public Health Bureau. Outcomes Outcome measures included quality indicators pertaining to six steps in HCV care ranging from HCV screening to complete treatment and cure from treatment with DAA Analytical Approach A descriptive analysis. Results A total of 3657 patients from 31 dialysis facilities were enrolled. All patients completed HCV screening. The DAA treatment initiation rate and completion rate were 88.9% and 94.0%, respectively. The collaborative care model achieved a cure rate of 96.0% (166/173). No virologic failure occurred. The cumulative treatment ratios for patients with chronic HCV infection increased from 5.3% before interferon-based therapy (2017) to 25.6% after restricted provision of DAA (2017-2018) and then to 89.1% after universal access to DAA (2019). Limitations Unclear impact of this collaborative care program on incident dialysis patients entering dialysis facilities each year and on patients with earlier stages of chronic kidney disease. Conclusions A collaborative care model in Taiwan increased the rates of diagnosis and treatment for HCV in dialysis facilities to levels near those established by the World Health Organization.

Background Chronic hepatitis C (CHC) has been associated with major psychoses, and interferon (IFN)-based therapy may cause psychiatric sequelae. We aimed to evaluate the effects of sustained virological response (SVR) on the incidence of major psychoses in a nationwide Taiwanese CHC cohort. Methods Fifteen thousand eight hundred thirty-six CHC Taiwanese who received IFN-based therapy were enrolled between 2003 and 2015. Of those, 12 723 patients were linked to the National Health Insurance Research Databases for the incidence of major psychoses. Death before major psychoses was considered a competing risk. Results Twenty-four patients developed new-onset major psychoses during 67 554 person-years (3.6 per 10 000 person-years), including 16 affective psychoses, 7 schizophrenia, and 1 organic psychotic condition. The incidence of major psychoses and affective psychoses did not differ between the SVR and non-SVR groups. The 10-year cumulative incidence of schizophrenia were significantly higher in the non-SVR than in SVR patients (0.14% vs 0.04%, P = .036). Cox subdistribution hazards showed that SVR and older age were associated with a significantly lower risk of schizophrenia (hazard ratio = 0.18 and 0.17). Sustained virological response was associated with decreased incidence of schizophrenia and majorly observed among patients with age Conclusions Successful IFN-based therapy might reduce the incidence of schizophrenia among CHC patients, especially among younger patients.

Introduction Chronic hepatitis C virus (HCV) infection is associated with nonhepatocellular carcinoma malignancies. We aimed to evaluate whether achieving a sustained virological response (SVR, defined as HCV RNA seronegativity throughout posttreatment 24-week follow-up) could reduce the risk of non-hepatocellular carcinoma malignancy in a real-world nationwide Taiwanese Chronic Hepatitis C Cohort (T-COACH). Methods A total of 10,714 patients with chronic hepatitis C who had received interferon-based therapy (8,186 SVR and 2,528 non-SVR) enrolled in T-COACH and were linked to the National Cancer Registry database for the development of 12 extrahepatic malignancies, including those with potential associations with HCV and with the top-ranking incidence in Taiwan, over a median follow-up period was 3.79 years (range, 0-16.44 years). Results During the 44,354 person-years of follow-up, 324 (3.02%) patients developed extrahepatic malignancies, without a difference between patients with and without SVR (annual incidence: 0.69% vs 0.87%, respectively). Compared with patients with SVR, patients without SVR had a significantly higher risk of gastric cancer (0.10% vs 0.03% per person-year, P = 0.004) and non-Hodgkin lymphoma (NHL) (0.08% vs 0.03% per person-year, respectively, P = 0.03). When considering death as a competing risk, non-SVR was independently associated with gastric cancer (hazard ratio [HR]/95% confidence intervals [CIs]: 3.29/1.37-7.93, P = 0.008). When patients were stratified by age, the effect of SVR in reducing gastric cancer (HR/CI: 0.30/0.11-0.83) and NHL (HR/CI: 0.28/0.09-0.85) was noted only in patients aged 65 years. Discussion HCV eradication reduced the risk of gastric cancer and NHL, in particular among younger patients, indicating that patients with chronic hepatitis C should be treated as early as possible.

In patients with chronic hepatitis C (CHC), the effects of baseline characteristics, virological profiles, and therapeutic outcome to pegylated interferon plus ribavirin (PR) therapy on autoimmune diseases are unknown. Taiwanese Chronic Hepatitis C Cohort is a nationwide hepatitis C virus registry cohort comprising 23 hospitals of Taiwan. A total of 12,770 CHC patients receiving PR therapy for at least 4 weeks between January 2003 and December 2015 were enrolled and their data were linked to the Taiwan National Health Insurance Research Database for studying the development of 10 autoimmune diseases. The mean follow-up duration was 5.3 ± 2.9 years with a total of 67,930 person-years, and the annual incidence of systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) was 0.03%. Other autoimmune diseases were not assessable due to few events. Body mass index ≥24 kg/m2 was an independent predictor of the low incidence of SLE or RA (hazard ratio 0.40, 95% confidence interval 0.17–0.93, p = 0.034). A sustained virological response (SVR) to PR therapy was not associated with the low incidence of SLE or RA in any subgroup analysis. CHC patients achieving SVR to PR therapy did not exhibit an impact on the incidence of SLE or RA compared with non-SVR patients.

There has been no clear consensus on the optimal consolidation periods following HBeAg seroconversion (SC) in HBeAg-positive chronic hepatitis B (CHB) patients. Our study aimed to prospectively compare relapse rates between 12 months’ and 18 months’ consolidation periods to see whether or not there is beneficial durability of tenofovir disoproxil fumarate (TDF) therapy with longer consolidation periods. We enrolled a total of 137 HBeAg-positive Asian CHB patients treated with TDF monotherapy. Forty-six patients achieved HBeAg SC. Then, they were randomly assigned to consolidation period of either 12 months (group A) or 18 months (group B). After stopping TDF therapy, all patients were followed up for 12 months. Thirteen patients (56.5%) relapsed in group A and 12 patients (52.2%) relapsed in group B after 12 months’ follow-up (P = .958). Pretreatment HBsAg level is the only significant predictor for off-therapy recurrence by univariate analysis (P = .024). Baseline HBeAg >1000 S/CO in group B patients were significantly less likely to relapse than those of group A (P = .046). Baseline alanine aminotransferase (ALT) >133 U/L could significantly predict occurrence of HBeAg SC (P = .008; 95% CI: 0.545–0.763; AUC: 0.654). Overall, a prolonged consolidation period has no positive effect on TDF therapy on sustained viral suppression in HBeAg-positive Asian CHB patients. However, a prolonged consolidation period was beneficial to patients with high baseline semi-quantitative HBeAg levels in terms of off-treatment durability. Baseline ALT > 133 U/L could significantly predict the occurrence of HBeAg SC.

Background/PurposeUltrasonography (US) cannot demonstrate all the etiologies of biliary tract dilatation in patients with jaundice. Thus, we evaluated the etiologic yield of endosonography (EUS) for suspected obstructive jaundice when no definite pathology was found on US. Additionally, we sought to identify the predictors of the most common etiologies.MethodsWe performed a retrospective review of 123 consecutive patients who had undergone EUS for suspected obstructive jaundice when no definite pathology was identified on US.ResultsThe most common diagnoses included no pathological obstruction (n = 43), pancreatobiliary malignancy (n = 41), and choledocholithiasis (n = 28). Pancreatobiliary malignancy was associated with common bile duct (CBD) dilatation, and fever and elevated alanine aminotransferase were predictors of choledocholithiasis (p 0.05).ConclusionMarked CBD dilatation (≥12 mm) should remind us of the high risk of malignancy, and the presence of CBD dilatation and fever is suggestive of choledocholithiasis. Negative EUS findings cannot assure any pathological obstruction in patients with clinically suspected obstructive jaundice.

Cronkhite-Canada Syndrome (CCS) is a rare, non-hereditary disease characterized by gastrointestinal polyposis associated with diarrhea and epidermal manifestations, such as hyperpigmentation, alopecia, and onychodystrophy. The pathogenesis of CCS is still not well understood but it probably involved autoimmune mechanism. Herein, we here report a case of steroid-responsive CCS in a male patient whose polyps presented with IgG-4 positive plasma cells.

Both nonalcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD) are closely related to many metabolic disorders. Multislice computed tomography (MSCT) is a reliable noninvasive method in demonstrating coronary plaque. However, the association between coronary artery calcium (CAC) score and NAFLD remains controversial. The aim of this study is to evaluate the association between CAC score and NAFLD. This retrospective study enrolled 295 consecutive asymptomatic subjects who had both coronary angiography by MSCT and hepatobiliary imaging during self-paid physical check-ups. NAFLD was found in 41% of the enrolled 295 subjects; gall bladder stones were found in 10.8%, and CAC > 100 with moderate-high risk of CAD was found in 12.9% of subjects. Male gender (odds ratios (OR), 3.087; 95% confidence intervals (CI), 1.092–8.729), increased age (OR, 1.108; 95% CI, 1.067–1.151), diabetes mellitus (DM) (OR, 2.968; 95% CI, 1.129–7.803), and NAFLD (OR, 2.462; 95% CI, 1.065–5.691) were the independent factors that increased the risk of CAC > 100 in binary logistic regression. The prevalence of NAFLD also increased with the severity of CAC score (≤100, 38.1%; 101–400, 58.3%; >400, 64.3%; P = 0.03). Besides the traditional risk factors, such as male gender, increased age, and DM, NAFLD was also associated with moderate to high risk of CAD (CAC > 100).

Purpose. To reappraise the accuracy of transabdominal sonography (US), CT, MRI, and endosonography (EUS) in the diagnosis and staging of ampullary tumors. Method. We reviewed the medical records and the images of 41 consecutive patients with ampullary tumors. Tumor detection rate and accuracy of TNM (tumor–node–metastasis) staging of malignant tumors were determined. Imaging findings were correlated with histopathologic findings. Results. The detection rates for ampullary tumors were 97.6% for EUS, 81.3% for MRI, 28.6% for CT, and 12.2% for US (p 0.05 for EUS versus MRI). The accuracy in T staging for ampullary carcinomas was 72.7% for EUS, 53.8% for MRI, and 26.1% for CT (p 0.05 for EUS versus MRI). The accuracy in N staging for ampullary carcinomas was 66.7% for EUS, 76.9% for MRI, and 43.5% for CT with no statistically significant difference between the 3 modalities. The sensitivity in detecting malignant lymph nodes was 46.7% for EUS, 25.0% for MRI, and 0% for CT (p 0.05 for EUS versus MRI; p > 0.05 for MRI versus CT). Transpapillary stenting, advanced tumor extension (>T2), large tumor size (>2 cm), tumor differentiation, and endoscopic appearance of tumor growth did not significantly influence EUS accuracy in T or N staging (p > 0.05). Conclusion. EUS was superior to CT and was equivalent to MRI for tumor detection and T and N staging of ampullary tumors. Neither indwelling stents nor tumor size, differentiation, or endoscopic appearance affected the staging accuracy of EUS. © 2008 Wiley Periodicals, Inc. J Clin Ultrasound, 2009

Background On occasion, it is impossible to perform ERCP with a traditional duodenoscope in patients who have had a Billroth II gastrectomy or hepatojejunostomy, and who now have biliary tract problems. Repeat surgery is not a suitable course of action in these patients. Therefore, finding alternative modalities to resolve these obstructions is of great importance. Objective To report successful endoscopic examination and treatment of difficult biliary obstructions by using double-balloon enteroscopy. Patients Five patients. Design Cases series. Intervention Double-balloon enteroscopy (DBE) for biliary tract examination and treatment. Results We report on 5 patients who underwent Billroth II gastrectomy or biliary tract Roux-en-Y surgery and who later had biliary tract obstruction from various causes. We were unable to perform ERCP with traditional duodenoscopy but successfully completed ERCP with DBE. DBE was originally designed to examine the small intestine. The successful biliary tract cannulation rate when using DBE is lower than with duodenoscope. We performed ERCP by using DBE a total of 5 times, with a successful biliary cannulation rate of 60%. We performed a special-method papillotomy in 2 patients. This method entailed inserting an electric sphincterotome through the percutaneous transhepatic cholangiography and drainage (PTCD) route after performing DBE intubation to the ampulla of Vater. We then successfully completed a papillotomy with an electric sphincterotome under DBE guidance. Conclusions DBE appears to be a promising alternative in the examination and treatment of biliary tract disease in patients after GI operations such as Billroth II gastrectomy and choledochojejunostomy.

The accuracy and clinical significance of sonography (US) in demonstrating fatty liver and hepatic fibrosis in chronic hepatitis C (CHC) are rarely reported. US had sensitivity 71.1%, specificity 72.9%, 58.7% positive predictive value (PPV), and 82.3% negative predictive value (NPV) in demonstrating histological steatosis > or =5%. US had sensitivity 85.7%, specificity 60.4%, 13% PPV, and 98.4% NPV in demonstrating histological steatosis > or =30% with clinical significance in predicting prognosis and therapeutic response in CHC. Subjects with fatty liver on US had a greater prevalence of body mass index (BMI) > or =25 kg/m2, inflammation-necrosis grade >2, and total bilirubin

The prevalence and etiologies of elevated alanine aminotransferase (ALT) have geographic variations and they are rarely reported in Taiwan. Through a population-based screening study, the prevalence and etiologies of elevated ALT in an adult population of Taiwan were assessed.A cross-sectional community study in a rural village of Taiwan was conducted in 3260 Chinese adults (ageor=18 years) undergoing ultrasonography (US), blood tests, and interviews with a structured questionnaire. The diagnostic criteria of non-alcoholic fatty liver disease (NAFLD) included alcohol intake20 g/week for women or30 g/week for men, negative hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, no known etiologies of liver disease, and US consistent with fatty liver.The prevalence of elevated ALT was 11.4% (372/3260). The probable cause of this elevation was excess alcohol consumption in 0.8%, HBV in 28.5%, HCV in 13.2%, both HBV and HCV in 2.2%, NAFLD in 33.6%, and unexplained cause in 21.8%. The etiologic distribution of elevated ALT was similar in both genders, although elevation was more common in men compared to women (17.3%vs 6.1%, P0.05). The prevalence of elevated ALT in NAFLD was 18.1% (125/691), and the positive predictive value was 33.6% (125/372). The development of NAFLD was related to increasing age (age between 40 years and 64 years, odds ratio [OR] 1.59, 95% confidence interval [CI]: 1.25-2.01; ageor= 65 years, OR 1.46, 95%CI: 1.08-1.96), fasting plasma glucose (FPG)or= 126 mg/dL (OR 1.54, 95%CI: 1.11-2.14), body mass index (BMI)or= 25 kg/m(2) (OR 5.01, 95%CI: 4.13-6.26), triglyceridemiaor= 150 mg/dL (OR 1.96, 95%CI: 1.58-2.42), and hyperuricemia (OR 1.50, 95%CI: 1.22-1.84). Elevated ALT was related to male gender, BMIor= 25 kg/m(2), and triglyceridemiaor= 150 mg/dL in subjects without known etiologies of liver disease (all P0.05).Non-alcoholic fatty liver disease appears to be the commonest cause of elevated ALT and presumed liver injury in Taiwan. The development of NAFLD is closely associated with many metabolic disorders. Metabolic disorders are also related to elevated ALT in subjects without known etiologies of liver disease.

Main pancreatic duct dilatation raises concerns about the possibility of pancreatobiliary malignancy. We evaluated the etiologic yield of endosonography (EUS) for main pancreatic duct dilatation without definite pathology on Ultrasonography (US).A retrospective review was conducted in 54 consecutive patients referred for EUS.No pathological finding (37.0%, 20/54), followed by periampullary cancer (35.2%, 19/54), was the most common finding. Elevated alkaline phosphatase (ALK-P) and marked common bile duct (CBD) dilatation (≥ 12 mm) were the predictors of malignancy (p0.05). Among the 37 subjects with available ALK-P and CBD diameter, the probability of malignancy was 84.6% (11/13) for both elevated ALK-P and marked CBD dilatation, 16.7% (1/6) for isolated elevated ALK-P, 18.2% (2/11) for isolated marked CBD dilatation, and none (0/7) was for subjects with neither elevated ALK-P nor marked CBD dilatation, respectively. The overall accuracy of EUS for periampullary carcinomas was 94.7% (18/19) and for choledocholithiasis was 100% (7/7), respectively. EUS had a 100.0% (20/20) sensitivity and a 97.1% (33/34) specificity in the diagnosis of no pathological obstruction.EUS is accurate for main pancreatic duct dilatation without definite pathology on US, and the presence of concomitant elevated ALK-P and CBD dilatation highly suggests malignancy.

A review of the literature pertaining to percutaneous transhepatic cholangioscopic lithotomy (PTCSL) showed that more than 50% of reported patients had undergone earlier biliary surgery.A retrospective study investigated 74 patients undergoing initial PTCSL for hepatolithiasis who had undergone no prior biliary surgery or manipulation. The patients were followed for 1 to 23 years after PTCSL for effective evaluation of the procedure outcome.Complete clearance of hepatolithiasis was achieved for 61 (82%) patients. The incomplete clearance rate was higher for patients with intrahepatic duct stricture (11/37 [30%] vs 2/37 [5%]; p0.05), although it showed no relation to the actual lobar distribution of hepatolithiasis (left: 7/41 [17%] vs right: 2/11 [18%] vs bilateral: 4/22 [18%]; p0.05). The recurrence rate for hepatolithiasis also was higher for patients with intrahepatic duct stricture (18/26 [69%] vs 13/35 [37%]; p0.05), but the recurrence rate showed no relation to the lobar distribution of hepatolithiasis (left: 18/34 [53%] vs right: 4/9 [44%] vs bilateral: 9/18 [50%] p0.05) or the presence of gallbladder stones (5/12 [42%] vs 26/49 [53%]; p0.05). Patients showing the coexistence of retained or recurrent hepatolithiasis demonstrated a higher incidence of recurrent cholangitis (57% [13/23] vs 14% [7/51]; p0.01) or cholangiocarcinoma (17% [4/23]) vs 0% [0/51]; p0.01).The findings show that PTCSL is effective for treating primary hepatolithiasis, and that complete stone clearance is mandatory to diminish the sequelae of hepatolithiasis. Intrahepatic duct stricture was the main factor contributing to incomplete clearance and stone recurrence.

Background and Aim: The relation of helminthic infestation to hepatolithiasis is a subject of dispute. This case–control study was undertaken to evaluate the prevalence of helminthiasis in hepatolithiasis patients and to compare the clinicopathological features of hepatolithiasis between patients with and without helminthiasis. Methods: The prevalence of ascariasis or clonorchiasis was evaluated using ELISA in 131 patients with hepatolithiasis who were treated at Show-Chwan Memorial Hospital and 121 subjects who constituted a control group. The patients’ detailed histories and medical charts were reviewed. Results: The prevalence of positive immunodiagnosis of ascariasis and clonorchiasis was higher in patients with hepatolithiasis than in control subjects (33.6%, 44/131 vs 17.4%, 21/121, odds ratio [OR] = 2.41, 95% confidence interval [CI] = 1.28–4.56, P = 0.005; and 6.9%, 9/131 v 0.8%, 1/121, OR = 8.85, 95% CI = 1.12–188.69, P = 0.02). Patients with helminthiasis rarely had concurrent gallbladder stones (26%, 12/47 vs 55%, 46/84, OR = 0.28, 95% CI = 0.12–0.66, P = 0.002). Prior to the diagnosis of hepatolithiasis in adulthood, most of the patients with helminthiasis tended to have a history of recurrent abdominal pain in their childhood and an asymptomatic ‘lucid interval’ during their teenage years (70.2%, 33/47 vs 39.3%, 33/84, OR = 3.64, 95% CI = 1.59–8.42, P = 0.0005). However, the prevalence of intrahepatic duct stricture (38.3%, 18/47 vs 40.5%, 34/84, OR = 0.91, 95% CI = 0.41–2.02, P > 0.05), secondary biliary cirrhosis (6.4%, 3/47 vs 3.6%, 3/84, OR = 1.84, 95% CI = 0.28–12.03, P > 0.05), cholangiocarcinoma (2.1%, 1/47 vs 0%, 0/84, OR = ∼, P > 0.05), and stone recurrence (54.8%, 24/42 vs 50.0%, 38/76, OR = 1.33, 95% CI = 0.58–3.06, P > 0.05) did not significantly increase. Conclusions: Helminthiasis is a possible risk factor for hepatolithiasis, although it is unlikely to increase the incidence of complications, including bile duct stricture, secondary biliary cirrhosis, and cholangiocarcinoma. Patients with helminthiasis tend to have a history of an asymptomatic ‘lucid interval’ between the periods of recurrent abdominal pain in their childhood and the diagnosis of hepatolithiasis in their adulthood.

Background: Indicators for long-term monitor of the progress of hepatic diseases are of great clinical importance. Since elevated cathepsin was observed in liver diseases, the aim of this study is to investigate the involvement of cystatin C, a very potent inhibitor of cathepsin and a recently introduced marker for renal function, and to see the applicability of serum cystatin C being a convenient marker for the progression of liver diseases. Methods: One hundred eighty consecutive patients with chronic liver disease of various severities and 45 healthy controls were recruited to determine their serum cystatin C concentrations by N Latex Cystatin C kit, as well as certain relevant clinical values, including alanine transaminase (ALT), aspartate transaminase (AST) and AFP. Results: Average serum cystatin C concentration of patients with hepatic diseases was significantly higher than that of control (0.0902±0.0025 mg/dl vs. 0.067±0.007 mg/dl; p

It is essential to manage perianal abscess by clearly delineating the extent of the lesion, damage to the pelvic floor musculature or sphincters, and topographic mapping of the fistulous tract. We present a patient with a ruptured perianal abscess who underwent exploratory laparotomy. Pelvic computed tomography and transrectal endoscopic ultrasound were used to follow the lesion. Endoscopic ultrasound was shown to be accurate and effective in providing detailed images of the perianal abscess.

Objectives Percutaneous transhepatic cholangioscopic lithotomy (PTCSL) for the treatment of hepatolithiasis is particularly suited for those patients who are poor surgical risks or who refuse surgery and those with previous biliary surgery or stones distributed in multiple segments. However, hepatolithiasis is characterized by high rates of treatment failure and recurrence. We examined the long-term results of 245 patients with hepatolithiasis treated by PTCSL. Methods This was a retrospective study of 245 patients who underwent PTCSL for hepatolithiasis; the patients were followed for 1–22 yr to evaluate the immediate and long-term results. Sonography was used to search for stone recurrence every year or whenever the patients presented symptoms suggestive of cholangitis. Cholangiography and/or CT were performed to verify recurrence. Results PTCSL achieved complete clearance of hepatolithiasis in 209 patients (85.3%); the rate of incomplete clearance was higher in patients with intrahepatic duct stricture (29/118, 24.6% vs 7/127, 5.5%; p = 0.002). The rate of major complications was 1.6% (4/245) and included liver laceration (n = 2), intra-abdominal abscess (n = 1), and disruption of the percutaneous transhepatic biliary drainage fistula (n = 1). The overall recurrence rate of hepatolithiasis and/or cholangitis was 63.2%. The absolute rate of stone recurrence was not significantly related to the presence of intrahepatic duct stricture (51/89, 56.2% vs 53/120, 44.4%; p = 0.08), although the median time to recurrence was less in those with stricture (11 vs 18 yr; p = 0.007). In the patients without intrahepatic duct stricture, the rate of complete stone clearance was not related to the presence of dilation (34/38, 89.5% vs 86/89, 96.6%; p = 0.196), but the recurrence rate was higher in those with dilation (20/34, 58.8% vs 33/86, 38.4%; p = 0.042). Among the 209 patients with a successful initial PTCSL, the incidence of recurrent cholangitis or cholangiocarcinoma was significantly higher in those with incompletely removed recurrent hepatolithiasis than in those without coexisting hepatolithiasis (44.3%, 27/61 vs 16.2%, 24/148; p vs 0.7%, 1/148; p = 0.026). Conclusions PTCSL is a relatively safe and effective procedure for treating hepatolithiasis. Long-term follow-up is required because the overall recurrence rate of hepatolithiasis and/or cholangitis is high. The rate of complete stone clearance and the median time to stone recurrence are less in the presence of stricture, but the absolute rate of stone recurrence is not significantly related to stricture. In the absence of stricture, the rate of stone recurrence is higher in patients with dilated intrahepatic duct. Complete stone clearance is necessary, because the incidence of recurrent cholangitis or cholangiocarcinoma is higher in patients with incomplete clearance of recurrent hepatolithiasis.

The efficacy and safety of the boceprevir (BOC)-containing triple therapy in Taiwanese treatment-experienced patients remains elusive. After 4 weeks of peginterferon/ribavirin lead-in therapy, patients with cirrhosis or previous null-response received triple therapy for 44 weeks; whereas others received 32 weeks of triple therapy followed by 12 weeks of peginterferon/ribavirin therapy. Patients with HCV RNA > 100 IU/mL at week 12 or with detectable HCV RNA at week 24 of treatment were viewed as futile. A total of 123 patients received treatment. The rates of sustained virological response (SVR) and relapse were 66.7% and 8.9%, respectively by using intention-to-treat analysis. Multivariate analysis revealed that factors associated with SVR included HCV-1b (odds ratio [OR]/ 95% confidence intervals [CI]: 19.23/1.76–525.15, P = 0.01), BOC adherence (7.69/1.55–48.78, P = 0.01), serum albumin (OR/CI:6.25/1.14–40.07, P = 0.03) levels and HCV RNA levels (OR/CI:0.34/0.12–0.79, P = 0.01). Twenty-six (21.1%) patients experienced severe adverse events (SAEs). Multivariate analysis revealed that APRI > 1.5 was the single factor associated with occurring SAEs (OR/CI: 3.77/ 0.97–14.98, P = 0.05). Merging the cut-off values of HCV RNA > 7 log IU/mL at baseline and HCV RNA > 6 log IU/mL at week 4 provided the earliest and best combing viral kinetics in predicting week 12/24 futility with the PPV of 100% and accuracy of 93.5%. HCV-1 treatment experienced Taiwanese patients treated with boceprevir-containing triple therapy in real world had comparable efficacy and safety profiles with those reported in clinical trials. Early viral kinetics before week 4 of treatment highly predicted futility at week 12 or 24 of treatment.

Purpose The purpose of this retrospective study was to compare the sensitivity of endoscopic sonography (EUS), transabdominal sonography (US), and CT in the detection of, local staging of, and prediction of vascular involvement by or distant metastasis from periampullary tumors. Methods Seventy-four consecutive patients with presumed periampullary tumors were evaluated by EUS, US, and CT during a 3.25-year period. The local staging accuracy of the modalities was assessed in the 36 patients with solid tumors who underwent surgery. The sensitivity of the modalities in predicting vascular involvement and distant metastasis was assessed in the 56 patients with carcinomas. Results EUS was the most sensitive modality in the detection (EUS, 97%; US, 24%; and CT, 39%; p < 0.001 for EUS versus US or CT) and T classification (EUS, 72%; US, 11%; CT, 22%; p < 0.001 for EUS versus US or CT) of periampullary tumors. EUS also had better sensitivity than US in detecting lymph node metastasis from periampullary cancers (EUS, 47%; US, 7%; and CT, 33%; p = 0.02 for EUS versus US; p = 0.7 for EUS versus CT). The accuracy of EUS in determining the T classification (without stent, 81%; with stent, 65%) and N classification (without stent, 80%; with stent, 70%) tended to decrease in the presence of an endobiliary stent, but the differences were not significant. EUS was the most sensitive modality in demonstrating vascular involvement (EUS, 100%; US, 0%; and CT, 33%; p = 0.002 for EUS versus US; p = 0.03 for EUS versus CT) but was not significantly different in detecting distant metastasis (EUS, 11%; US, 44%; and CT, 44%). Conclusions EUS is superior to US and CT in the local assessment of periampullary tumors. The staging accuracy of EUS is minimally but not significantly affected by the presence of an endobiliary stent. © 2001 John Wiley & Sons, Inc. J Clin Ultrasound 29:313–321, 2001.

Objective: The effect of β2-adrenoceptor agonist-induced hypokalaemia on cardiac arrhythmias might be exacerbated during exercise, especially in patients with more compromised airway function. Methods: To evaluate the effect of β2-adrenoceptor agonists on plasma potassium and cardiopulmonary function during exercise, two identical submaximal treadmill exercise tests were performed, at least 48 h apart, by 13 patients with moderate to severe COPD (11 men and 2 women, mean age 66 y, mean FEV1/FVC ratio 48.9 (2.8)%) 30 min after they had received nebulised fenoterol or salbutamol (2 mg). The experiment was done as a randomised, double-blind, crossover trial after an initial baseline study with vehicle (0.45% saline). Plasma potassium concentration, spirometry and the degree of breathlessness (Borg scale) were measured before treatment and immediately after exercise; oxygen saturation, QTc interval and cardiac rhythm were monitored continuously before, during and for 30 min after exercise. Results: After the saline control, exercise caused an increase in Borg rating (of 4.9), a premature ventricular contractions (VPC) (2.8 beats/min), and a fall in oxygen saturation (-6.7%), but no significant change in plasma potassium (+0.04 mEq·dl−1), FEV1 or QTc interval. Inhalation of fenoterol and salbutamol did not affect QTc interval, Borg scale or VPC frequency at rest, but significantly increased the duration of exercise undertaken to reach the submaximal levels (786 s, versus 783 s) compared to the vehicle control. Following exercise, plasma potassium fell after fenoterol by 0.2 mEq·dl−1 and it increased after salbutamol by 0.1 mEq·dl−1 compared to baseline levels. Plasma potassium after exercise was significantly lower after fenoterol (3.2 mEq·dl−1) compared to the saline control (3.7 mEq · dl−1) and salbutamol (3.6 mEq · dl−1). Neither fenoterol nor salbutamol had any significant effect on the change in FEV1, oxygen saturation, Borg scale, frequency of VPCs or QTc interval during or after exercise compared to the saline control. Conclusion: When compared to salbutamol 2 mg, fenoterol 2 mg caused more marked hypokalaemia but no significant difference in cardiopulmonary response in patients with COPD during exercise.