Tatsuo Kanda

Early occurrence and recurrence of hepatocellular carcinoma in hepatitis C virus-infected patients after sustained virological response

Chronic hepatitis C virus (HCV) infection is one of the major causes of liver cirrhosis and hepatocellular carcinoma (HCC). Recently, the interferon-free combination of direct-acting antiviral agents (DAAs) against HCV could result in higher sustained virological response (SVR) rates (* 95%) [1]. In the interferon era, long-term eradication of HCV could lead to the reduction of liver-related complications, including HCC [2]. In the DAA era, achievement of SVR and long-term eradication of HCV can be expected to prevent liver-related complications, including HCC.

Rapid hepatitis C virus clearance by antivirals correlates with immune status of infected patients: SASAKI et al.

Altered immune parameters associated with hepatitis C virus (HCV) genotype 1b infection and their correlation with virus eradication in direct‐acting antivirals (DAA)‐treated patients were examined. Thirty‐one HCV‐infected patients were treated with DAAs for 12 weeks. Pre‐DAA‐treatment and post‐DAA‐treatment sera were analyzed for cytokines/chemokines using MILLIPLEX MAP. Serum complement level and antibody neutralization activity were measured separately. Sera from 11 spontaneously cleared HCV subjects were included for comparison. Rapid virological responders (RVR) or end‐of‐treatment responders (EOTR) were defined as patients with HCV RNA negative at week 4 or positive at week 4 and negative at week 12, respectively. HCV RNA eradication and a decrease in liver fibrosis‐related cytokines after treatment were observed when compared with pretreatment sera from RVR and EOTR. In pretreatment sera, interferons and T‐helper 1 or 2 cell‐associated cytokines/chemokines were significantly higher among RVR as compared with EOTR. Furthermore, serum complement and virus neutralizing antibody levels were higher in pretreatment RVR sera. Eradication of HCV RNA by DAA decreased liver fibrosis‐related cytokines. Pretreatment sera from RVR displayed an enhanced cytokine/chemokine, complement and virus neutralizing antibody response as compared with EOTR sera. Our results suggested that enhanced host immune status may play an additive role on HCV RNA clearance by DAA.

Hepatitis C virus genotype 4-infection and interferon-free treatment in Egypt

In interferon-free treatment era, therapeutic regimens and sustained virological response (SVR) rates differ among different hepatitis C virus (HCV) genotypes (GTs) with either interferon-including or interferon-free treatments. The estimated rates of HCV infection in Egypt is around 14.7%, and the predominant HCV GT is GT4, where GT4a, GT4b, GT1 and GT3 represent 63, 30, 6 and 1% of cases, respectively [1]. Recently, the results of treatment with combinations of direct-acting antivirals (DAAs) for HCV GT4 Egyptian patients have been reported [2–6]. Almost all of these regimens could lead to more than 95% or more than 90% SVR rates, respectively, in the following patients: ‘‘easy-to-treat’’ patients who were treatment-naı̈ve and did not have cirrhosis but had compensated liver biochemical parameters or ‘‘difficult-to-treat’’ patients who had previously failed interferon therapy with or without DAAs or an interferon-free combination, regardless of fibrosis stage, and had cirrhosis. Daclatasvir (DCV) is a pangenotypic nonstructural protein 5A (NS5A) inhibitor [7]. Sofosbuvir (SOF) is a nucleoside inhibitor of HCV NS5B with pangenotypic potency [8]. The combination of SOF/DCV with or without ribavirin makes up one of the pangenotypic regimens. Shiha et al. [2] investigated the efficacy and safety of 12 or 24 weeks of 400 mg/day SOF plus 60 mg/day DCV, with or without 800–1000 mg/day ribavirin, in HCV GT4 Egyptian patients. Although this was an open-label observational study, it includes a total 1168 patients: 385 patients with cirrhosis and 1063 treatment-naı̈ve patients [2]. The authors observed rates of 96 and 93% SVR at 12 weeks (SVR12), respectively, with 12and 24-week combinations of SOF/DCV with or without ribavirin, both in naı̈ve and treatment-experienced patients with or without cirrhosis. Shiha et al. [2] demonstrated that combinations of SOF/ DCV with or without ribavirin for 12 or 24 weeks was effective and safe for chronic HCV GT4 ‘‘real-world’’ patients. SVR rates were higher for patients with no cirrhosis although APASL, AASLD or EASL HCV guidelines do not recommend SOF/DCV for HCV GT4 patients without cirrhosis [8–10]. SVR rates for the combination of SOF/DCV were almost similar to those for the combination of the HCV NS5A inhibitor ledipasvir (LDV)/SOF with or without ribavirin for HCV GT4 [2], demonstrating a SVR12 of 98% in treatment-naı̈ve patients and 94–98% in treatment-experienced patients [5]. The presence of cirrhosis was associated with lower SVR12 rates in all treatment groups [2]. The authors also observed that the addition of ribavirin to the 24-week combination of SOF/ DCV was associated with a significant increase in the SVR12 rate in the treatment-experienced group [2], supporting APASL recommendation [8], although the mechanism of action of ribavirin remain unknown [11]. During SOF/DCV treatment, the most common adverse events were insomnia, fatigue, headache, anemia and cough, and no treatment-related serious adverse events were observed [2]. Abdel-Moneim et al. [3] also analyzed data from a large cohort of 946 HCV GT4 Egyptian patients treated with a 12-week combination of SOF/DCV with or without & Tatsuo Kanda kanda.tatsuo@nihon-u.ac.jp

Prediction of the very early occurrence of HCC right after DAA therapy for HCV infection

BackgroundAlthough direct-acting antiviral (DAA) developments make most of hepatitis C virus (HCV) infection curable, some HCV patients develop hepatocellular carcinoma (HCC) after curative treatment of HCV. There is much dispute whether the rapid clearance of the virus enhances the HCC development. In advance of the dispute, we should make clear the characteristics of the patients with very early occurrence and recurrence of HCC after DAA therapy because it was still unclear.MethodsWe prospectively followed consecutive patients with HCV who had received sofosbuvir (SOF)-based treatment at two hospitals. The baseline characteristics, laboratory data, and liver imaging findings were acquired. We evaluated the rate of HCC occurrence and recurrence within 1-year after DAA therapy and analyzed the associated factors of very early HCC occurrence and recurrence right after SOF therapy.ResultsBetween July 2013 and October 2016, we studied two cohorts with HCV infection that received SOF therapy. 402 and 462 patients in Yamanashi Central Hospital and Chiba University Hospital were included in this analysis, respectively. The SVR12 rates of genotypes 1 and 2 were 98.9% (561/567) and 96.0% (285/297), respectively. 41 patients developed HCC within 1xa0year after SOF therapy. The cumulative HCC occurrence and recurrence rate after SOF therapy was 5.0%. The common associated factor of 1-year HCC occurrence and recurrence in all cohorts was the existence of imaging “dysplastic nodule”.ConclusionsSOF regimens for HCV also have very high rates of SVR 12 in the post-market distribution. The appearance of imaging “dysplastic nodule” was an associated factor of 1-year HCC occurrence and recurrence. To investigate existence of “dysplastic nodule” by imaging surveillance before DAA treatment is useful to detect high-risk patients of very early HCC occurrence and recurrence and it should be performed.

Determination of serum carbohydrate-deficient transferrin by a nephelometric immunoassay for differential diagnosis of alcoholic and non-alcoholic liver diseases

BACKGROUNDnCarbohydrate-deficient transferrin is a biological marker of excessive drinking. The aim of this study was to evaluate the diagnostic value of a direct nephelometric immunoassay for the differential diagnosis of alcoholic and non-alcoholic liver diseases in comparison with gamma glutamyl transferase.nnnMETHODSnSerum samples were obtained from 305 subjects, including 122 patients with alcoholic and 102 cases with non-alcoholic liver diseases. Serum levels of carbohydrate-deficient transferrin were expressed as a percentage of total transferrin.nnnRESULTSnSerum % carbohydrate-deficient transferrin levels were significantly higher in patients with alcoholic than with non-alcoholic liver diseases. Carbohydrate-deficient transferrin had better specificity than gamma glutamyl transferase to differentiate between alcoholic and non-alcoholic liver diseases.There were 8 alcoholic liver disease patients with normal gamma glutamyl transferase levels, and carbohydrate-deficient transferrin was significantly elevated in 6 of them. On the other hand, there were 25 non-alcoholic liver disease patients with elevated gamma glutamyl transferase levels; their carbohydrate-deficient transferrin levels were within the reference intervals in all cases.nnnCONCLUSIONnThis simple carbohydrate-deficient transferrin immunoassay is useful to detect so-called gamma glutamyl transferase non-responding drinkers and also to exclude the possible role of excessive drinking in apparently non-alcoholic liver diseases. A large-scale prospective study is needed to further confirm the diagnostic utility of carbohydrate-deficient transferrin.

The Effect on Gastric Emptying of Telaprevir-Based Triple Therapy for Chronic Hepatitis C Patients

Aim: We evaluated food intake in telaprevir-based triple therapy (telaprevir, pegylated-interferon, and ribavirin) and its relation to Gastric Emptying (GE).