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Objective The treatment outcome of direct-acting antivirals (DAAs) in chronic hepatitis C patients with hepatocellular carcinoma (HCC) is controversial. The current study aimed to address the treatment efficacy and safety of DAAs in patients with curative or active HCC, compared with those of patients without HCC. Design A prospective cohort study Setting A medical centre and two regional hospitals in Taiwan Participants A total of 713 Taiwanese patients (601 non-HCC, 74 curative HCC and 38 active HCC patients) who received standard-of-care DAAs were consecutively enrolled in the study. Main outcome measurement The primary objective was to determine treatment efficacy, defined as undetectable hepatitis C virus RNA throughout 12 weeks of the posttreatment follow-up period (sustained virological response 12 [SVR12]). Results The overall SVR12 rate was 96.9%. The SVR12 rate was similar between the patients with HCC and those without HCC (95.5% vs 97.2%, p=0.37). The HCC patients were divided into two groups, those with curative HCC and those with viable HCC; a substantially but not significantly lower SVR rate, 92.1% (35/38), was observed in the patients with viable HCC compared with the SVR rate, 97.3% (72/74), in those with curative HCC (p=0.33). Compared with the patients with curative HCC, the patients with viable HCC had a significantly higher proportion of serious adverse events (10.5% vs 1.0%, p=0.002), early treatment discontinuation (10.5% vs 2.8%, p=0.03) and mortality (5.3% vs 0.1%, p=0.008). Conclusions An equivalently high SVR rate was observed in patients with either past or active HCC compared with those without HCC. The safety concerns in the HCC patients did not compromise treatment efficacy. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) is a small-enveloped RNA virus belonging to the Flaviviridae family. Since first identified in 1989, HCV has been estimated to infect 170 million people worldwide. Mostly chronic hepatitis C virus has a uniform natural history, from liver cirrhosis to the development of hepatocellular carcinoma. The current therapy for HCV infection consists of a combination of Pegylated interferon and ribavirin. On the other hand, HCV-related liver disease is also the leading indication for liver transplantation. However, posttransplant HCV re-infection of the graft has been reported to be universal. Furthermore, the graft after HCV re-infection often results in accelerated progression to liver failure. In addition, treatment of recurrent HCV infection after liver transplantation is often compromised by enhanced adverse effects and limited efficacy of interferon-based therapies. Taken together, poor outcome after HCV re-infection, regardless of grafts or recipients, poses a major issue for the hepatologists and transplant surgeons. The aim of this paper is to review several specific aspects regarding HCV re-infection after transplant: risk factors, current therapeutics for HCV in different stages of liver transplantation, cellular function of HCV proteins, and molecular mechanisms of HCV entry. Hopefully, this paper will inspire new strategies and novel inhibitors against recurrent HCV infection after liver transplantation and greatly improve its overall outcome. [ABSTRACT FROM AUTHOR]

Background/Aims: Pretreatment insulin resistance (IR) is associated with treatment response to peginterferon plus ribavirin (PegIFN/RBV) combination therapy in chronic hepatitis C (CHC) infection. However, the impact of PegIFN/RBV therapy on both IR and β-cell function in CHC patients has rarely been investigated. Methods: A total of 277 non-diabetic patients treated with PegIFN-α and weight-based RBV, with 80/80/80 adherence, were recruited. Their IR and β-cell function by homeostasis model assessment model (HOMA-IR and HOMA-%B) before treatment and at 24 week after treatment [end of follow-up (EOF)] was measured. Results: A sustained virological response (SVR) was achieved by 79.4% (220/277) of all patients: 63.6% (75/118) of genotype-1 and 91.2% (145/159) of genotype-non-1 patients. There was no significant change of HOMA-IR post-therapy (2.25 ± 2.46 vs 2.04 ± 2.12, P=0.42). By contrast, there was a significant reduction of HOMA-%B of all patients at EOF (122.9 ± 145.2 vs 92.4 ± 73.2, P=0.001), particularly in those responders (119.1 ± 142.1 vs 89.6 ± 70.3, P=0.002). In 80 patients with high baseline HOMA-IR, both HOMA-IR and HOMA-%B decreased significantly at EOF, irrespective of SVR achievement. Conclusion: This study demonstrated pancreatic β-cell function was ameliorated by PegIFN/RBV therapy in CHC patients, particularly in those responders. [ABSTRACT FROM AUTHOR]

Background: Interferon-a/ribavirin combination therapy might promote hepatitis B surface antigen (HBsAg) seroclearance in patients dually infected with hepatitis B and C viruses (HBV/HCV), but the long-term effect remains unclear. We aimed to investigate the rate of and the factors associated with HBsAg seroclearance during long-term follow-up after interferon-a/ ribavirin combination therapy in HBV/HCV dually-infected patients. Methodology/Principal Findings: Eighty-one patients who received interferon-a/ribavirin combination therapy for 24 weeks with a follow-up period of >24 weeks were enrolled. HBV serological markers and HBV DNA were determined every 6 months. Early and late HBsAg seroclearance were defined as HBsAg loss in less or more than 6 months after end-oftreatment, respectively. Fifteen (18.5%) patients had HBsAg seroclearance during a mean follow-up period of 3.4 (0.5-5.1) years. The 5-year cumulative incidence was 25.6%. Baseline cirrhosis and HBV DNA negativity 1 year after end-of-treatment were independently predictive of HBsAg seroclearance with an odds ratio (OR), 95% confidence intervals (CI) of 16.6, 1.8- 153 and 9.2, 1.4-62.1, respectively, by Cox regression hazard analysis. Four patients developed early and 11 developed late HBsAg seroclearance, respectively. Cox regression hazard analysis showed no factor was associated with early HBsAg seroclearance, whilst HBV DNA negativity 1 year after end-of-treatment was the only significant factor predicting late HBsAg loss (OR, 43.0; CI, 2.5-745). Five patients had HBsAg seroconversion with a 5-year cumulative incidence of 8.3%. HBV DNA negativity at baseline and one year after EOT had a trend for HBsAg seroconversion. HCV response did not correlate to HBsAg loss. Conclusions: We demonstrated that interferon-a/ribavirin had long-term effect on HBsAg seroclearance in dually HBV/HCVinfected patients. Baseline cirrhosis and seroclearance of HBV DNA 1 year after end-of-treatment were significant factors associated with HBsAg seroclearance. [ABSTRACT FROM AUTHOR]

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. This retrospective study included 102 treatment-naïve 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. 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). Serum visfatin was correlated with disease severity and metabolic syndrome in CHC patients. [ABSTRACT FROM AUTHOR]

Abstract From October 1996 to July 2001, 61 patients received primary laparoscopy-assisted endorectal pull-through (LAERPT) for biopsy-proven Hirschsprung’s disease (HD) at Mackay Memorial Hospital. The patients’ ages at operation ranged from 7 days to 8 years. The patients were followed up for an average of 3.8 years (range 1–5.5 years). Major complications occurred in five (8.1%) patients, of whom four had surgical complications (two instances of anastomotic leakage, one colon perforation, and one delayed formation of colovesical fistula) and one had postoperative Salmonella infection-induced colonic stricture. The five patients required a diverting colostomy and a redo-pull-through procedure. Postoperative enterocolitis developed in 13 (21%) infants. All of them had enterocolitis before the diagnosis of HD was established. The majority of the episodes of postoperative enterocolitis were mild and resolved spontaneously, but four neonates were hospitalized with significant systemic manifestations, and two of them needed a second operation to solve the problem. After primary LAERPT, stooling frequency in young infants declined rapidly from 10.5±3.2 to 4.4±1.6 bowel movements per day in the first 3 months and more slowly thereafter. Most of these infants had regular bowel movements one to two times per day 1 year after operation. Continence evaluation of the 43 patients over 3 years of age was graded as normal in 24 (56%) patients and good in 19 (44%) patients. Of the 13 patients between 1 and 3 years of age, 11 (85%) had regular normal stools, and two (15%) had occasional soiling. From the current study, the authors concluded that primary LAERPT is a safe and effective method of managing HD with excellent continence results. Considering the complications of surgery and postoperative enterocolitis, patients with long segment aganglionosis, severe enterocolitis, or prominently dilated colon are not good candidates for primary LAERPT. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article regarding glucose abnormalities in patients with chronic hepatitis C infection.