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The patatin-like phospholipase domain-containing protein 3 (PNPLA3) variant is associated with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). However, the role of genetic variations of the peroxisome proliferator-activated receptor gamma coactivator-1-alpha gene (PPARGC1A) and glucokinase regulatory (GCKR) gene on NASH in obese patients remains unclear. We studied the effects and interaction of these genetic polymorphisms on NASH in severely obese Taiwanese patients. The genotypes of PPARGC1A rs8192678, PNPLA3 rs738409, and GCKR rs780094 were determined in 177 severely obese patients who underwent bariatric surgery. NASH was evaluated by liver histopathology. Of 177 patients, 29 (16.4%), 57 (33.2%), and 91 (51.4%) were in the non-NAFLD, steatosis, and NASH groups, respectively. We found that the PPARGC1A and PNPLA3 variants, but not the GCKR variant, were associated with NASH. The PPARGC1A rs8192678 GA/AA genotype was associated with higher steatosis grade and presence of ballooning degeneration. The PNPLA3 rs738409 GG genotype was associated with higher severity in all histologic features except for fibrosis. In multivariate analysis, both the PPARGC1A rs8192678 GA/AA genotype (odds ratio [OR] 2.32; 95% confidence interval [CI] 1.08–4.98; P = 0.031) and the PNPLA3 rs738409 GG genotype (OR 4.05; 95% CI 1.24–13.23; P = 0.021), and also body mass index were independent risk factors for NASH. Further, there was an additive effect of the PPARGC1A rs8192678 GA/AA genotype and the PNPLA3 rs738409 GG genotype on the presence of NASH (OR 6.83; 95% CI 1.61–29.01; P = 0.009). The PPARGC1A rs8192678 GA/AA genotype and the PNPLA3 rs738409 GG genotype had an additive effect on NASH in severely obese Taiwanese patients.

Thyroid disorders, such as the emergence of thyroid autoantibodies (TAs) and thyroid dysfunction (TD), are not uncommon in chronic hepatitis C (CHC) patients. The study aimed to investigate the impact of TAs and dysfunction on the treatment response to pegylated interferon-α plus ribavirin (PegIFN/RBV) combination therapy in CHC patients. The association between interleukin-28B (IL-28B) genetic variants and occurrence of TAs and dysfunction was also analyzed.A total of 449 treatment-naive Taiwanese CHC patients with euthyroid status were consecutively enrolled. They received PegIFN/RBV combination therapy with current recommendation. TAs, TD, and IL-28B genetic variants were measured before treatment. Monitoring of TD was done at 3-month intervals during treatment, at end of treatment, and at end of follow-up (EOF).The development of TAs was detected in 42 (9.4%) patients before treatment, and the incidence of TD during or at EOF was 20%. Of 287 patients with IL-28B rs8099917 TT genotype, 29 (10.1%) had TAs before treatment, whereas the patients with other genotypes did not have TAs (P = 0.04). There was no significant difference of TD incidence during treatment or at EOF between the patients with different IL-28B genotypes. There was also no significant difference of sustained virologic response according to the presence of TAs, TD, or different manifestations of TD.Taiwanese CHC patients with rs8099917 TT genotype had a higher incidence of TAs. The development of TAs and TD did not impact the treatment efficacy of PegIFN/RBV combination therapy.

Aim: Hepatitis C virus (HCV) proteins can activate the PI3K/Akt pathway which is involved in multiple cellular functions such as inflammatory cell activation and liver fibrosis. The aim of the present study was to elucidate the correlation between Akt expression and liver fibrosis staging in chronic hepatitis C (CHC) patients. Methods: Paraffin-embedded liver sections from 133 consecutive treatment-naive CHC patients were recruited. The expression features of Akt were analyzed using immunohistochemical methods and the results were compared with histological, virological and biochemical profiles. Results: The 73 patients with high Akt expression carried higher histological activity index scores (6.52 ± 2.5 vs 5.62 ± 2.4, P = 0.04) and advanced fibrosis (72.7% vs 26.3%, P

Background & Aims Evidence on the efficacy of antiviral treatment in chronic hepatitis C (CHC) patients with hepatocellular carcinoma (HCC) after curative treatment is scarce. We aimed to evaluate the efficacy and safety of pegylated interferon-alpha plus ribavirin (pegIFN/RBV) combination therapy in these patients, compared to cirrhotic patients. Methods This prospective, multicenter, case–control study recruited 82 consecutive CHC patients with HCC after curative management and 87 sex/age-matched cirrhotic patients. All patients received pegIFN-alpha-2a and weight-based RBV according to current treatment recommendations. The primary outcome measurement was sustained virological response (SVR, seronegative of hepatitis C virus RNA throughout the 6-month post-treatment follow-up period). Results The SVR rate was significantly lower in the HCC group compared to the cirrhosis group (48.8% vs 64.4%, p =0.04). However, the significantly lower rate of SVR in the HCC group was observed among genotype-1 patients (33.3% vs 60.7%, p =0.005) but not among genotype-2/3 patients (70.6% vs 71.0%, p =0.88). In patients who achieved 80/80/80 adherence, there was no significant difference of SVR rate between groups (50.7% vs 64.2%, p =0.12) Multivariate logistic regression analysis demonstrated that rapid virological response (viral clearance during the first 4weeks of treatment, odds ratio=22.1, p p =0.05) were predictive factors associated with SVR, whilst previous occurrence of HCC was not associated with SVR (Odds ratio=0.4, p =0.09). The incidence of severe adverse events did not differ between the two groups. Conclusions The study proved the feasibility of pegIFN/RBV therapy with current treatment guidelines in CHC patients after successful eradication of HCC, with careful monitoring.

Whether critically ill neonates needing a surgical intervention should be transferred to an operating room (OR) or receive the intervention in a neonatal intensive care unit (NICU) is controversial. In this study, we report our experience in performing surgical procedures in a NICU including air cleanliness.This was a retrospective study performed at a metropolitan hospital. The charts of all neonates undergoing surgical procedures in the NICU and OR were retrospectively reviewed from January 2007 to June 2017. Data on baseline characteristics, procedure and duration of surgery, ventilator use, hypothermia, instrument dislocations, surgery-related infections and complications, and outcomes were analyzed.Ninety-two neonates were enrolled in this study, including 44 in the NICU group and 48 in the OR group. The air cleanliness was International Organization for Standardization (ISO) 14644-1 class 7 in the NICU and class 5-6 in the OR. The NICU group had a younger gestational age and lower birth body weight than the OR group. The OR group had a higher incidence of hypothermia than in the NICU group (56.3% vs 9.1%, P < .001). However, there were no significant differences in surgical site related infections or mortality between the 2 groups.This study suggests that performing surgical procedures in a NICU with air cleanliness class 7 is as safe as in an OR, as least in part, when performing patent ductus arteriosus ligation and exploratory laparotomy.

Serum high sensitivity C-reactive protein (hs-CRP) is a surrogate marker for cardiovascular disease risks and related mortality. However, the features of hs-CRP in chronic HCV infection (CHC) patients have not been fully addressed. This study aimed to elucidate the characteristics of hs-CRP and its correlation with clinical profiles in CHC patients.Ninety-five CHC patients and 95 age- and sex-matched healthy controls were enrolled for serum hs-CRP level, biochemical, and metabolic profiles examinations. Sequential changes of hs-CRP levels in CHC patients receiving peginterferon/ribavirin combination therapy were also evaluated.The mean hs-CRP level of CHC patients was significantly higher than that of healthy controls (0.97 ± 0.11 vs. 0.24 ± 0.07 mg/L, P 0.001). There was no significant correlation between hs-CRP and both virological and histological factors. CHC patients with a high LDL-C level had significantly higher mean hs-CRP (1.38 ± 0.20 mg/L) than that of patients without (0.59 ± 0.06 mg/L) (P 0.001). Hs-CRP level was significantly decreased in 83 patients after peginterferon/ribavirin combination therapy (0.24 vs. 0.62 mg/L, P 0.001), particularly in 68 patients achieving a sustained virological response (0.25 vs. 0.64 mg/L, P 0.001).CHC patients had a higher hs-CRP level than healthy controls which could be ameliorated after peginterferon/ribavirin combination therapy.

Background and Aim: Cytokines activation is a common feature in chronic hepatitis C (CHC) infection. Visfatin, as a recently-recognized adipocytokine, may correlate with metabolic abnormalities. We aimed to elucidate the characteristics of visfatin in CHC patients. Methods: This retrospective study included 102 treatment-naive CHC patients and 97 sex-/age-matched healthy adults. Serum visfatin levels were examined by an enzyme linked immunosorbent assay test. The correlation between visfatin and hepatitis C virus (HCV) infection in terms of virological, metabolic, and histopathological profiles was analyzed. The impact of visfatin on the treatment response to pegylated interferon plus ribavirin (PEGIFN/RBV) therapy was also assessed. Results: The visfatin level was correlated significantly with fibrosis scores (r = 0.23, P = 0.02) in CHC patients. A significant higher visfatin level was observed in CHC patients with histological activity index scores of mild and more (P = 0.01) and advanced fibrosis (P = 0.04). The mean visfatin level (0.81 ± 0.28 log ng/mL) of 26 CHC patients with metabolic syndrome was significantly lower than their counterparts (0.95 ± 0.30 log ng/mL) (P = 0.03). There was no significant correlation between visfatin and HCV genotypes, viral load, and treatment response to PEGIFN/RBV therapy. Multiple logistic regression analyses demonstrated that metabolic syndrome was the leading negative variable (odds ratio = 0.09, 95% confidence interval = 0.02–0.46, P = 0.004) associated with high visfatin level, followed by advanced fibrosis (odds ratio = 2.88, 95% confidence interval = 1.06–6.78, P = 0.03). Conclusions: Serum visfatin was correlated with disease severity and metabolic syndrome in CHC patients.

Metabolic syndrome (MS) is a complicated disorder associated with a high risk of future development of micro- and macrovascular complications. The extrahepatic manifestations of hepatitis C virus (HCV) infection can include multiple metabolic abnormalities. However, the extent, severity, and characteristics of MS in HCV-infected patients have rarely been investigated in community-based settings. This study aimed to determine the difference in prevalence and distribution of the components of MS between HCV-infected patients and healthy controls. Multipurpose mass screening of adults was conducted in an HCV-endemic area of Southern Taiwan. Clinical profiles in terms of anthropometric data and MS components, as well as viral hepatitis markers, were assessed. Two hundred and thirty-seven adults (94 males; mean age, 55.5 ± 10.8 years) were recruited. The prevalence of anti-HCV seropositivity was 39.2% (93/237). The prevalence of MS was higher in the HCV-infected individuals (24.7%, 23/93) than in the control, uninfected subjects (13.2%, 19/144, p = 0.02). In terms of MS components, HCV-infected subjects had a higher prevalence of high waist circumference (51.6% vs. 25.7%, p < 0.001) and hypertension (58.1% vs. 36.8%, p = 0.001) than controls. Multivariate logistic regression analysis demonstrated that anti-HCV positivity was significantly associated with MS (odds ratio, 6.4; 95% confidence interval, 1.82–22.84; p = 0.004). HCV infection was associated with a higher prevalence of MS. Determination of MS in patients with HCV infection could therefore be indicated.

Diagnosis of abdominal splenosis is often undiagnosed until treatment for splenic rupture or splenectomy. This report describes a patient with splenosis mimicking hepatic tumor. The patient had a history of splenic trauma with splenectomy and chronic hepatitis C. After routine abdominal ultrasound revealed a liver nodule, further imaging studies, including magnetic resonance imaging, computed tomography and angiography, were performed. After the patient eventually underwent surgery, pathology revealed splenic tissue. Despite its distinguishable clinical features, splenosis is difficult to identify by modern imaging modalities. Therefore, accurate and timely diagnosis of this disease requires constant vigilance.

We aimed to investigate whether response-guided therapy (RGT) with peginterferon-alpha plus ribavirin by using hepatitis C virus (HCV) genotype, pretreatment HCV RNA levels, and rapid virological response (RVR, undetectable HCV RNA at treatment week 4) could be applied for active HCV/hepatitis B virus (HBV) dually infected patients, without compromised the treatment efficacy. A total of 203 patients, seropositive of HCV antibody, HCV RNA and HBV surface antigen (HBsAg), and seronegative for HBV e antigen for >6 months, were randomized to receive peginterferon-alpha/ribavirin by either genotype-guided therapy (GGT, n = 102: HCV genotype 1 [HCV-1], 48 weeks; HCV-2/3, 24 weeks) or RGT (n = 101: HCV-1, 48 or 24 weeks if patients with baseline VL

The influence of patatin-like phospholipase domain-containing 3 (PNPLA3) genetic variants in the development of liver steatosis in Asian chronic hepatitis C patients remains elusive. A total of 1018 biopsy-proven chronic hepatitis C patients were enrolled for evaluation. The proportions of PNPLA3 rs738409 GG genotype carriage were 7.8% (44/563), 15.8% (58/367) and 19.3% (17/88) in patients with no (liver fat content 66%) hepatic steatosis, respectively (trend P PNPLA3 rs738409 GG genotype (odds ratio [OR]/95% confidence intervals [CI]:2.34/1.557–3.515, P 2, carriage of the rs738409 GG genotype was the only factor associated with hepatic steatosis (OR/CI:3.44/1.824–6.500, P PNPLA3 genetic variants had minimal effects on hepatic steatosis among overweight or obese patients. Compared to patients with BMI2/non-GG genotype, those with BMI>24 kg/m2/GG genotype were more likely to have hepatic steatosis (OR/CI:3.87/2.292–6.524, P PNPLA3 genetic variants and BMI played important roles in hepatic steatosis among Asian chronic hepatitis C patients. However, the genetic effect was mainly restricted to non-obese patients.

Pegylated interferon-alpha plus ribavirin combination (PegIFN/RBV) therapy possesses positive effect in the secondary prevention of hepatocellular carcinoma (HCC) in chronic hepatitis C (CHC) patients. The current study aimed to assess its efficacy in the tertiary prevention and to validate the performance of the MHC class I polypeptide-related chain A (MICA) level in the prediction of hepatocellular carcinoma (HCC) recurrence.A multi-center study enrolling 105 consecutive HCC patients post curative therapies were prospectively recruited. The primary outcome measurement was recurrence of HCC.The mean observational period was 52.7 months (range = 3.9-121.5 months). Fifty-six (53.3%) patients achieved sustained virological response (SVR). After completion of treatment, 43 (41.0%) patients developed HCC recurrence, and 24 (55.8%) of them had their recurrence within 6 months after completion of therapy. Thirty-three (76.7%) of the patients with HCC recurrence were of de novo pattern. Those responders tended to have a lower cumulative incidence of recurrence than those non-responders (43.2 vs 84.8/100 person-month, log-rank P = 0.13). Those non-responders with a high MICA level (100 pg/mL) carried the lowest cancer-free survival than those non-responders with a low MICA level and those responders (P = 0.002). Cox regression hazard analysis showed high baseline MICA level (Odds ratio [OR] = 4.8, 95% confidence interval [CI] = 1.1-20.8, P = 0.04) and a low platelet count (100 000/mm(3) ) (OR = 5.4, 95% CI = 1.1-27.0, P = 0.04) predicted HCC recurrence.PegIFN/RBV therapy carried a limited effect in the tertiary prevention of HCC. A high MICA level predicted HCC recurrence, particularly among those non-responders.

The optimal therapeutic strategy for hepatitis B virus (HBV) e antigen (HBeAg)-seropositive and hepatitis C virus (HCV) dually infected patients remains unknown. We aimed to elucidate the effectiveness of peginterferon (Peg-IFN)/ribavirin (RBV) with and without lamivudine (LAM) combination therapy in the clinical settings.Nine patients seropositive for HBV surface antigen, HBeAg, antibodies to HCV and HCV RNA for6 months were treated with Peg-IFN/RBV with (n = 5) and without (n = 4) a 12-month LAM add-on therapy at treatment week 12. The treatment duration of Peg-IFN/RBV was 24 weeks (HCV genotype 1 [HCV-1] with rapid virological response [RVR] or HCV-2) or 48 weeks (HCV-1 without RVR). Primary endpoints included HBeAg loss and HCV-sustained virological response (SVR).All of the nine patients had undetectable HCV RNA at treatment weeks 4 and 12 and end-of-Peg-IFN/RBV therapy. However, SVR was achieved in 100% of patients treated with triple therapy, compared with only 50% in those with Peg-IFN/RBV therapy (P = 0.167). The 3-year durability of HCV SVR was 100%. HBeAg loss and HBV DNA2000 IU/mL at 6 months post-LAM treatment were found in 100% and 40% of patients treated with triple therapy, compared with none of the four patients with Peg-IFN/RBV therapy achieved any HBV responses. Of the five patients with triple therapy, four had persistent HBeAg loss during 3-year follow-up period; one developed HBeAg seroreversion 15 months after treatment.For HBeAg-positive HBV/HCV dually infected patients, Peg-IFN/RBV was effective for HCV eradication. Add-on LAM might promote HBeAg loss in the clinical setting.

Intussusception in children may recur after surgical correction. Ileopexy has popularly been used as a procedure to prevent recurrent intussusception, but its effect has not been well evaluated. The present study compared the incidence of recurrent intussusception after several different surgical procedures for intussusception in children. The charts of 278 children undergoing surgical reduction of ileocolic intussusception over 17 years were retrospectively reviewed. The incidence of recurrent intussusception was compared among the three surgical procedures: simple manual reduction, manual reduction plus ileopexy, and segmental resection. Simple manual reduction was performed in 67 (24.1%) of the 278 patients, manual reduction plus ileopexy in 186 (66.9%), and resection of the involved segment in 25 (9.0%). There were four episodes of recurrence in three (4%) patients who had had manual reduction, nine episodes in eight (4%) patients who had undergone ileopexy, and none after segmental resection. There was no statistical difference in recurrent rate among the three groups (reduction vs. ileopexy, P = 0.95; reduction vs. resection, P = 0.28; ileopexy vs. resection, P = 0.29). Ileopexy is not better than simple manual reduction in preventing recurrence of ileocolic intussusception in children.

Choledochal cysts are not rare in East Asia. The classic symptoms of these cysts are intermittent abdominal pain, jaundice, and a right upper quadrant abdominal mass. The authors report the case of an infant with a choledochal cyst presenting with intracranial hemorrhage. This 2-month-old girl with a partial coma presented at the authors' hospital. A brain CT scan revealed right-sided subdural hemorrhage. The routine preoperative survey found coagulopathy. After correcting the bleeding disorder, an emergency craniectomy was performed. Further examination found a choledochal cyst during abdominal ultrasonography and CT. Choledochal cysts are a cause of neonatal cholestasis but rarely produce vitamin K deficiency bleeding.

Rationale: Choledochal cysts are a congenital disorder of the common bile duct that can cause progressive biliary obstruction and biliary cirrhosis. They were classified by Todani into five types. Of these, type VI choledochal cysts are rarely reported in the literature. Patient concerns: A 22-month-old girl presented with intermittent epigastralgia for approximately 10 days and fever for three days. Fasting and total parenteral nutrition were administered after admission. However, sudden onset of severe epigastric pain occurred. An abdominal sonogram showed turbid ascites and peritonitis was impressed. Diagnoses: An emergent exploratory laparotomy was performed, and perforation of the posterior wall of types I and VI choledochal cysts was observed. Interventions: Intraoperative cholangiography revealed concomitant types I and VI choledochal cysts with stricture of the distal common bile duct. Definite surgery for resection of the choledochal cysts and gallbladder was performed with Roux-en-Y choledochojejunostomy. Outcomes: The patient had no evidence of ascending cholangitis at three years after the operation. Lessons: Type VI choledochal cysts are rarely reported in the literature. To our knowledge, this is the first reported pediatric case of concomitant types I and VI choledochal cysts complicated with acute pancreatitis and spontaneous perforation.

Background: For decades, peginterferon and ribavirin (PegIFN/RBV) have been the standard-of-care for chronic hepatitis C virus (CHC) infection. However, the actual cost-effectiveness of this therapy remains unclear. We purposed to explore the real-world cost effectiveness for subgroups of treatment-naïve CHC patients with PegIFN/RBV therapy in a large real-world cohort using a whole population database. Methods: A total of 1809 treatment-naïve chronic hepatitis C virus (HCV) patients (829 HCV genotype 1 [G1] and 980 HCV G2) treated with PegIFN/RBV therapies were linked to the National Health Insurance Research Database, covering the entire population of Taiwan from 1998 to 2013 to collect the total medical-care expenses of outpatient (antiviral agents, nonantiviral agents, laboratory, and consultation costs) and inpatient (medication, logistic, laboratory, and intervention costs) visits. The costs per treatment and the cost per sustained virological response (SVR) achieved were calculated. Results: The average medical-care cost was USD $4823 (±$2984) per treatment and $6105 (±$3778) per SVR achieved. With SVR rates of 68.6% and 87.8%, the cost/SVR was significantly higher in G1 than those in G2 patients, respectively ($8285 vs $4663, P

Background Studies are limited on pegylated interferon (Peg-IFN) therapy for chronic hepatitis B (CHB) patients who failed or relapsed on previous antiviral therapy. Objectives We aimed to investigate the effect of Peg-IFN therapy in treatment-experienced CHB patients. Study Design A total of 57 treatment-experienced CHB patients at two medical centers were enrolled. All of the patients were treated with Peg-IFN α-2a at 180 μg weekly for 24 or 48 weeks. The hepatitis B serological markers and viral loads were tested every 3 months until 1 year after stopping Peg-IFN therapy. The endpoints were HBV DNA 2 log10 IU/mL at 12 weeks of therapy were factors associated with treatment response. In HBeAg-negative patients, 9.1%, 15.2%, and 6.1% of the patients achieved undetectable HBV DNA, HBV DNA

Spontaneous rupture of the kidney is uncommon; here we report a case of spontaneous rupture of the kidney due to a rhabdoid tumor. An 11-year-old boy presented with left flank pain and hematuria, was admitted to a hospital where he was found to have an abnormality of the left kidney on computed tomography (CT) scan. He was referred to our department for further evaluation and treatment on the next day. Spontaneous rupture of left renal tumor was suspected by a drop in hemoglobin level, hemoglobin decreased from 9.2 to 7.6 mg/dl within 72 h. The hemoglobin level continued to drop despite blood transfusion. Urgent trans-abdominal exploration of the left kidney was performed. During the operation, rupture of left renal tumor with massive bleeding was noted. Para-aortic lymph node metastasis is evident. The surgical specimen contained a large peri-renal hemorrhage and tumor rupture into peri-pelvic soft tissue. Histopathological diagnosis was rhabdoid tumor consisting of round nuclei, prominent nucleoli and eosinophic cytoplasm. Two courses of adjuvant chemotherapy with actinomycin D, vincristine and epirubicin and radiotherapy (1,200 cGY) were performed post-operatively. The patient died 5 months after operation due to metastasis of the tumor to the lung and intra-abdominal organs.

The aim of this study is to explore the prevalence of hepatitis C virus (HCV) infection among injection drug users (IDUs) with and without human immunodeficiency virus (HIV) infection in southern Taiwan. For 562 IDUs (265 anti-HIV negative, 297 anti-HIV positive), we analyzed liver function, anti-HIV antibody, anti-HCV antibody, HCV viral loads, and hepatitis B surface antigen (HBsAg). HIV RNA viral loads and CD4 cell count for anti-HIV-seropositive IDUs and the HCV genotype for HCV RNA-seropositive IDUs were measured. The seroprevalence rates of anti-HIV, anti-HCV, and HBsAg were 52.8%, 91.3%, and 15.3%, respectively. All the anti-HIV-seropositive IDUs were positive for HIV RNA. Anti-HCV seropositivity was the most important factor associated with HIV infection (odds ratio [OR], 25.06; 95% confidence intervals [CI], 8.97–74.9), followed by male gender (OR, 6.12; 95% CI, 4.05–9.39) and HBsAg seropositivity (OR, 1.90; 95% CI, 1.11–3.34). Among IDUs positive for anti-HCV, 80.7% had detectable HCV RNA. HCV viremia after HCV exposure was strongly related to HIV infection (OR, 6.262; 95% CI, 1.515–18.28), but negatively correlated to HBsAg seropositivity (OR, 0.161; 95% CI, 0.082–0.317). HCV genotype 6 was the most prevalent genotype among all IDUs (41.0%), followed by genotypes 1 (32.3%), 3 (12.8%), and 2 (5.6%). In conclusion, about half IDUs were infected with HIV and >90% with HCV infection. Male and seropositivity for HBsAg and anti-HCV were factors related to HIV infection among our IDUs. HIV was positively correlated, whereas hepatitis B co-infection was negatively correlated with HCV viremia among IDUs with HCV exposure. Different HCV molecular epidemiology was noted among IDUs.

Backgrounds Chronic hepatitis C virus (HCV) infection has been associated with induction of microRNAs (miRNAs) in peripheral blood mononuclear cells (PBMC). We aimed to evaluate the role of PBMC–miRNAs in the treatment outcome to antiviral therapy for HCV genotype 1 (HCV-1) patients. Methods Treatment-naive chronic HCV-1 patients, including 13 in screening phase and 48 in validation phase, were treated with 48 weeks of peginterferon/ribavirin. The primary end-point was the achievement of a sustained virological response (SVR, HCV RNA undetectable during 24 weeks post-treatment follow-up). Expression profiling of PBMC–miRNAs was performed by quantitative PCR-based array in typical responders and null-responders. Then candidate PBMC–miRNAs were validated by quantitative PCR in an independent validation set. Results PBMC–miR-125b was significantly predictive of an SVR, with expression levels of 5.28-fold lower in sustained responders versus null-responders (p = 0.0163). In multivariate analysis, PBMC–miR-125b was significantly associated with the achievement of SVR (per 2-fold decrease, odds ratio/95% confidence interval (OR/CI): 2.07/1.14-6.31) independent of sex, age and interleukin-28B genotype. In patients who did not achieve a rapid virological response (RVR, undetectable HCV RNA at treatment week 4), PBMC–miR-125b was the only predictive factor of an SVR (per 2-fold decrease, OR/CI: 2.07/1.14-6.31). However, the circulating and hepatic miR-125b did not show significant difference between responders and non-responders. Conclusions PBMC–miR-125b expression levels were inversely related to the achievement of an SVR in HCV-1 patients, independent of interleukin-28B genotype, and was the single predictor of SVR in non-RVR patients.

Background and Aim: Viral hepatitis is a health threat for hemodialysis (HD) patients and it may be transmitted during treatment. Some patients categorized to have viral hepatitis were found to be non-viremic. To clarify the discrepancy between the serological tests in HD patients, we conducted the study. Methods: A total of 1681 HD patients was included. Blood samples were analyzed for hepatitis B surface antigen (HBsAg) and anti-hepatitis C antibody (anti-HCV). Detection of hepatitis B virus (HBV) DNA and hepatitis C virus (HCV) RNA were performed in either HBsAg (+) or anti-HCV (+) samples. HBV DNA/HCV RNA was also measured in a subset of HBsAg (-) and anti-HCV (-) patients. Liver function tests were analyzed and compared with the serological and virological tests. Results: The serological tests showed that 230 patients (13.7%) were HBsAg (+) and 290 (17.3%) were anti-HCV (+). We were unable to detect HBV DNA in 97 of 230 (42.2%) HBsAg (+) patients, and HCV RNA could not be found in 76 of 290 (26.2%) anti-HCV (+) patients. In 167 HBsAg (-) patients, only one showed a trace amount of HBV DNA. None of 151 anti-HCV (-) patients showed detectable HCV RNA. The prevalence rate of viral hepatitis remains high in Taiwanese HD patients: 13.7% for HBV and 17.3% for HCV. However, virological analysis showed 42.2% non-viremic rate for HBsAg and 26.2% non-viremic rate for anti-HCV. Conclusions: The findings might challenge the presently suggested principles of bed and machine dedication and the diagnosis of viral hepatitis in HD patients.

The treatment efficacy of patients with mixed hepatitis C virus (HCV) genotype 1/genotype 2 (HCV-1/2) remains unknown. We aimed to elucidate the sustained virological response (SVR) rate in patients with HCV-1/2 infection.One hundred and ten HCV-1/2 patients treated with response-guided peginterferon/ribavirin therapy (24 weeks for patients with a rapid virological response [RVR] and low viral loads; 48 weeks for patients without a RVR or high viral loads) were allocated. Two hundred HCV-1 patients were selected as a historical control. Interleukin-28B (IL-28B) rs8099917 genotype was tested for the association with an SVR.The rates of RVR, sustained virologic response (SVR), and relapse rate were 71.8%, 87.3%, and 11.1%, respectively. The SVR rate was significantly higher in patients with an abbreviated regimen as compared with those with 48-week regimen (95.5% vs 75.0%, P = 0.002), and both were similar to the HCV-1 historical control. Stepwise logistic regression analysis revealed that lower baseline viral loads were the single factor predictive of an RVR (odds ratio/95% confidence intervals [OR/CI] of 41.62/9.72-178.19, P 0.001). The achievement of an RVR was the single best factor predictive of an SVR (OR/CI: 7.5/1.33-42.27, P = 0.02). Nevertheless, an abbreviated regimen became the single factor associated with an SVR if treatment regimen was taken into consideration (OR/CI: 11.0/1.25-96.79, P = 0.03). The SVR rate did not differ between patients with rs8099917 TT and TG/GG genotype (91.7% vs 87.5%, P = 0.63).The treatment efficacy of patients with HCV-1/2 was satisfactory. The role of IL-28B genetic variants in the population with response-guided therapy was limited.

Hepatitis B virus (HBV) and HCV might cause reciprocal interference. We aimed to elucidate the influence of HCV and interleukin-28B (IL-28B) genetic variants in the HBV DNA and HBsAg levels in uremic HBV carriers. Assessment of HCV and HBV viral loads, HBsAg levels and IL-28B genotype were performed in 229 HBsAg-positive patients from a cohort of 1,681 uremics. Patients with HCV viremia had significantly lower HBV DNA (2.58 ± 0.80 vs. 3.16 ± 1.48 log IU/mL, p = 0.005) and HBsAg levels (1.33 ± 1.35 vs. 2.23 ± 1.31 log IU/mL, p = 0.002) compared with those without. IL-28B rs8099917 genotype had no impact on HBsAg and HBV DNA levels. In multivariate regression analysis, HCV RNA levels had a more significant negative correlation with HBsAg levels [β −0.905; 95 % confidence interval (CI) −1.477, −0.334; p = 0.002] than with HBV DNA levels (β −0.586; 95 % CI −1.206, 0.034; p = 0.06). The serum HBV DNA and HBsAg levels had a positive correlation (r = 0.43, p

Background Measurement of hepatitis B virus (HBV) DNA levels is essential in the clinical management of patients with chronic HBV infection. Performance and accuracy of quantitation for HBV DNA are therefore critical in clinical practice. Objectives We aimed to compare and evaluate the performance characteristics of two HBV DNA quantitative assays: Abbott RealTime HBV (RealTime assay) and Cobas AmpliPrep/Cobas TaqMan HBV assays 2.0 (TaqMan assay). Study design Serum samples from 220 HBV-infected patients were collected. Performance characteristics of the HBV DNA quantitative assays, including sensitivity, linearity, and reproducibility were measured. The assays were compared based on the viral status, including HBeAg, genotype, core promoter and pre-core region mutations. Results The RealTime assay had a sensitivity and specificity of 98.2% and 100%, respectively. The intra-assay coefficients of variation of serum samples ranged from 0.00% to 11.25% for the RealTime assay and 1.22% to 8.22% for TaqMan assay. Paired quantitative results showed excellent correlation by linear regression analysis (R2 = 0.961), good level of agreement with a mean difference of 0.31 log10 IU/mL, and limits of agreement of −0.62 to 1.24 log10 IU/mL, irrespective of HBeAg, genotype, core promoter and pre-core region mutation-specific differences. In this study, a difference of ≥1 log10 IU/mL between the two assays was observed in 8.6% of the samples. Genotype B and average HBV DNA levels of Conclusions The Abbott assay delivered high performance for HBV DNA quantification and correlated extremely well with the TaqMan assay, irrespective of viral status.

Host and viral factors interplay in the spontaneous clearance of hepatitis C virus (HCV) infection. We aimed to explore the roles of IL28B genotypes and hepatitis B virus (HBV) infections in spontaneous HCV seroclearance.IL28B rs8099917 genotypes, HCV and HBV markers were determined in 290 patients who were seropositive for HCV antibodies from 1681 total uremic patients on maintenance hemodialysis.Persistent HCV viremia was observed in 74.6% (214/287) of patients. Logistic regression revealed that the strongest factors associated with spontaneous HCV seroclearance were carriage of rs8099917 TT-type (odds ratio/95% confidence intervals [OR/CI]: 6.22/1.41-27.35, p=0.016), followed by concurrent hepatitis B surface antigen (HBsAg) seropositivity (OR/CI: 2.37/1.06-5.26, p=0.035). The clearance rate was highest among patients with both positive HBsAg/rs8099917 TT-type (44.8%, OR/CI: 20.88/3.5-402.5), followed by positive HBsAg/rs8099917 non-TT-type (28.6%, OR/CI: 8.86/1.8-160.8), and negative HBsAg/rs8099917 TT-type (26.7%, OR/CI: 12.75/1.0-319.4), compared to 4% of negative HBsAg/rs8099917 non-TT-type (trend p=0.0002). HBsAg levels, but not HBV DNA levels, were significantly associated with spontaneous HCV seroclearance. Spontaneous HCV seroclearance rate was 58.3% in patients with HBsAg200IU/ml/rs8099917 TT-type (OR/CI: 42.54/5.7-908.4), 28.0% in patients with HBsAg200IU/ml/rs8099917 TT-type or HBsAg200IU/ml/rs8099917 non-TT-type (OR/CI: 11.12/2.3-201.0), compared to only 3.3% in those with HBsAg200IU/ml/rs8099917 non-TT-type (trend p=0.0004). Five of 214 (2.3%) HCV viremic patients at enrollment had spontaneous HCV seroclearance during one-year follow-up, which was associated with baseline HCV RNA and HBsAg levels.High HBsAg levels and favorable IL28B genotype were additively associated with spontaneous HCV seroclearance in uremic patients.

Chronic hepatitis C virus (HCV) infection has been suggested to be associated with non-insulin-dependent diabetes mellitus and lipid profiles. This study aimed to investigate the possible relationships of insulin resistance (IR) and lipid profiles with chronic hepatitis C (CHC) patients in Taiwan.We enrolled 160 hospital-based CHC patients with liver biopsy and the 480 controlled individuals without CHC and chronic hepatitis B from communities without known history of non-insulin-dependent diabetes mellitus. Fasting plasma glucose, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), alanine aminotransferase, and serum insulin levels, and homeostasis model assessment (HOMA-IR) were tested.When comparing factors between CHC patients, and sex- and age-matched controls who had no HCV infection, patients with HCV infection had a significantly higher alanine aminotransferase level, fasting plasma glucose level, insulin level, and HOMA-IR (P 0.001, P = 0.023, P = 0.017, and P = 0.011, respectively), and significantly lower TG level (P = 0.023), total cholesterol, and HDL-C and LDL-C levels (all P 0.001) than 480 controls. In multivariate logistic regression analyses, a low total cholesterol, a low TGs, and a high HOMA-IR are independent factors significantly associated with chronic HCV infection. In the 160 CHC patients (41 patients with high HOMA-IR [ 2.5]), a high body mass index, TGs, and HCV RNA level are independent factors significantly associated with high HOMA-IR in multivariate logistic analyses.Chronic HCV infection was associated with metabolic characteristics including IR and lipid profile. IR was also associated with virological characteristics.

Host interleukin-28B (IL-28B) genetic variants determine a sustained virological response (SVR) in hepatitis C virus genotype 1 (HCV-1) treatment-naïve patients. Its impact on treatment-experienced Asian patients with peginterferon/ribavirin in is to be elucidated.IL-28B rs8099917 genotype was determined in 70 HCV-1 treatment-experienced patients retreated with 48-week peginterferon/ribavirin.The SVR rate was 60.0% and was significantly higher in previous relapsers than in nonresponders (72.7% and 13.3%, P 0.001). Multivariate analysis revealed that the most important factor predictive of an SVR was previous relapse (Odds ratio [OR]/95% confidence interval [CI]: 14.76/2.72-80.06, P = 0.002), followed by the carriage of rs8099917 TT genotype (OR/95% C.I.: 7.67/1.27-46.49, P = 0.03). Comparing to patients with TG/GG genotype, those with TT genotype had significantly higher rates of rapid virological response (29.3% vs 0%, P = 0.03), end-of-treatment virological response (86.2% vs 50.0%, P = 0.01), SVR (69.0% vs 16.7%, P = 0.002), and lower relapse rate (22.0 % vs 66.7%, P = 0.04). The SVR rate was similarly low between previous nonresponders with different rs8099917 genotypes (12.5% vs 14.3%, P = 1). On the contrary, previous relapsers with rs8099917 TT genotype had a significantly higher SVR rate than those who carried rs8099917 TG/GG genotype (78.0 % vs 20.0%, P = 0.02). Stepwise logistic regression analysis revealed that the only factor predictive of an SVR in previous relapsers was the carriage of rs809997 TT genotype (OR/95% CI:18.50/1.82-188.39, P = 0.014).Host IL-28B genetic variants played a role in Asian relapsers but not nonresponders retreated with peginterferon/ribavirin. Direct antiviral agents might be possibly avoidable in Asian relapsers with favorable IL-28B genotype.

Introduction: Inflammatory myofibroblastic tumors are an uncommon neoplasm, which are very rarely located in the pancreas. Clinically and radiologically, this rare pancreatic tumor presents as an abdominal mass lesion that mimics other pancreatic tumors, and should therefore be considered in the differential diagnosis of pancreatic tumors. Clinical Findings and diagnosis: The 15-year-old boy complained of abdominal pain over the left upper quadrant with intermittent fever for 7 days. Abdominal sonography revealed one cystic lesion with a hyperechoic component in the left upper quadrant of the abdomen. Surgical excision was performed and postoperative findings indicated a pancreatic tail tumor. The pathology indicated inflammatory myofibroblastic tumors. To our knowledge, this patient is a unique case as the tumor was located in the pancreatic tail only, sparing the body. Interventions and outcomes: The patient underwent tumor resection and segmental resection of the transverse colon with simple closure. The patient had no evidence of disease recurrence at 3 years follow-up. Conclusion: Inflammatory myofibroblastic tumors of the pancreas in children are extremely rare. Surgical excision is the standard treatment, and corticosteroids use in children need more large-scale studies.

BACKGROUND/AIMS:The impact of virological factors and interleukin-28B (IL-28B) genetic variants on retreatment of hepatitis C virus genotype 2 (HCV-2) treatment-experienced patients remains unknown. METHODS:On-treatment virological responses and IL-28B rs8099917 genotype were determined in 46 HCV-2 treatment-experienced patients (42 previous relapsers; four previous non-responders) retreated with 24-week peginterferon/ribavirin. RESULTS:Forty (87.0%) patients carried the rs8099917 TT genotype and 6 patients (13.0%) carried the TG/GG genotype. The sustained virological response (SVR; seronegativity of HCV RNA throughout 24 weeks of the post-treatment follow-up period) rate was 71.7%. Compared with previous non-responders, previous relapsers had a significantly higher SVR rate (78.6% vs. 0%, P = 0.004) and a lower relapse rate (17.5% vs. 100%, P = 0.04). All the previous non-responders were with the rs8099917 TT genotype. As for those who relapsed, treatment responses, including the rates of rapid virological response (RVR, 80.6% vs. 66.7%, P = 0.59), early virological response (EVR, 97.2% vs. 83.3%, P = 0.27), end-of-treatment virological response (97.2% vs. 83.3%, P = 0.27) and SVR (80.6% vs. 66.7%, P = 0.59) and relapse rate (17.1% vs. 20.0%, P = 1) did not differ significantly between patients with the rs8099917 TT and those with the non-TT genotype. Multivariate analysis revealed that the most important factor predictive of an SVR in the retreatment of HCV-2 was previous relapse; the only factor predictive of an SVR for previous relapsers was the achievement of an EVR. Compared with the achievement of a RVR, the attainment of an EVR was more accurate in predicting an SVR (88% vs. 74%). CONCLUSIONS:Peginterferon/ribavirin is effective in the retreatment of HCV-2 relapsers, especially among those who achieved an EVR.

To compare the survival outcome between surgical resection (SR) and radiofrequency ablation (RFA) for Barcelona Clinic Liver Cancer (BCLC) early stage hepatocellular carcinoma (HCC). The retrospective study enrolled eighty-two patients with newly diagnosed BCLC early HCC (single nodule, size ≦3 cm, and Child-Pugh class A) treated either surgically (n = 46) or with RFA (n = 36) from year 2004 to 2009. The patients’ survival outcomes were compared. There were no significant differences in overall survival (OS) rates between SR and RFA (p = 0.204). The 3- and 5-year disease-free survival (DFS) rates were 65.8 % and 53.7 % respectively, in the SR group, which were significantly higher than those in the RFA group (34.8 % and 14.9 % respectively) (p = 0.009 and p = 0.001). In subgroup analysis, the DFS was similar between RFA and SR in patients with presentation of lower platelet count (≦100,000/mL) and smaller tumor size (tumor size ≦1 cm). Multivariate analysis showed SR as a procedure type was a significant predictive factor for DFS [HR = 2.26 (CI 1.462–5.227), p = 0.002]. SR yielded similar OS but better DFS when compared to RFA for patients with BCLC early HCC (single nodule, ≦3 cm and Child-Pugh class A). In subgroup patients with lower platelet count (≦100,000/mL) and smaller tumor size (tumor size ≦1 cm), DFS was similar between both treatments.

Cancer patients were generally excluded from the therapeutic guidelines of antiviral therapy. We aimed to evaluate the efficacy and safety of antiviral therapy in patients with hepatitis C virus (HCV) infection concomitant with malignancy other than hepatocellular carcinoma (HCC).Twenty-five HCV patients with curative malignancy other than HCC (group A) and 75 sex- and age-matched controls (group B) were recruited into a prospective and case-control analysis. All patients received peginterferon-alpha-2a (PegIFN-alpha-2a) and weight-based ribavirin according to the current treatment recommendations. The primary outcome measurement was sustained virological response (SVR). The safety issue between groups was also compared.There were 22 (88.0 %) patients of group A and 59 (78.7 %) patients of group B who achieved an SVR (p = 0.39). The SVR rate was comparable between groups both in genotype-1 (HCV-1) (81.8 vs. 72.7 %, p = 0.70) and in genotype-2 (HCV-2) (92.9 vs. 83.3 %, p = 0.66) patients. Multivariate logistic regression analysis demonstrated that the achievement of a RVR (viral clearance during first 4 weeks of treatment) was the strongest predictor of an SVR (odds ratio/95 % confidence intervals [OR/CI]: 6.357/1.50 - 26.99, p = 0.01), followed by lower baseline viral loads (OR/CI: 0.403/0.174 - 0.936, p = 0.034) and higher dose of ribavirin exposure (OR/CI: 1.287/1.092 - 1.517, p = 0.003), whilst previous occurrence of cancer was not associated with SVR. Treatment adherence (76.0 vs. 72.0 %, p = 0.70) and the incidences of grade 3 or more adverse events (28.0 vs. 20.0 %, p = 0.40) were comparable between two groups.Chronic hepatitis C patients with non-HCC malignancies receiving peginterferon/ribavirin combination therapy carried favorable efficacy and safety outcomes.