Kei Morio

Development of hepatocellular carcinoma in patients with hepatitis C virus infection who achieved sustained virological response following interferon therapy: A large‐scale, long‐term cohort study

We assessed the risk factors for the development of hepatocellular carcinoma (HCC) following successful eradication of hepatitis C virus (HCV) with interferon (IFN) therapy in a long‐term, large‐scale cohort study.

Improvement of renal dysfunction in a patient with hepatitis C virus‐related liver cirrhosis by daclatasvir and asunaprevir combination therapy: A case report

Recently, treatments for chronic hepatitis C virus (HCV) infection have been drastically improved by the development of direct‐acting antiviral agents. In September 2014, dual oral therapy using daclatasvir (DCV) and asunaprevir (ASV) was approved for the treatment of chronic HCV infection in Japan. We treated a patient with HCV‐related liver cirrhosis with severe leg edema due to chronic renal dysfunction using this dual oral therapy. Although serum alanine aminotransferase increased rapidly during the first week of treatment, the antiviral therapy was able to continue, and liver function recovered spontaneously. After 1 month of treatment, serum HCV RNA became continuously undetectable, and serum albumin level gradually increased. Throughout the therapy, serum creatinine level nearly normalized, and leg edema gradually improved. These improvements continued after the combination therapy was completed. HCV RNA remained undetectable following the end of therapy, and sustained virological response at 12 weeks was achieved. It has been reported that chronic HCV infection is associated with renal dysfunction and that HCV eradication can improve it. DCV and ASV combination therapy is safe for patients who have renal dysfunction and may be a suitable therapy for chronic hepatitis C patients with renal dysfunction.

Preoperative Fluorine 18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography for Prediction of Microvascular Invasion in Small Hepatocellular Carcinoma.

Objectives This study aimed to assess the value of preoperative fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET-CT) for predicting microvascular invasion (MVI) in small hepatocellular carcinoma (HCC). Methods We retrospectively examined 60 patients who received 18F-FDG PET-CT prior to hepatic resection for small HCC (⩽30 mm) with subsequent MVI confirmation by histopathology. The associations between PET-positive status and tumor factors were assessed. Furthermore, independent predictors for MVI and diagnostic utility of each MVI predictor were assessed. Results Multivariate analysis revealed the presence of MVI as an independent predictor of PET-positive status (P = 0.023). Maximum standardized uptake value (SUVmax) of 3.2 or greater (P = 0.017) and lens culinaris agglutinin a-reactive &agr;-fetoprotein (AFP-L3) 19% or greater (P = 0.010) were independent predictors of MVI. Areas under the receiver operating characteristic curves for SUVmax of 3.2 or greater, AFP-L3 19% or greater, and both factors combined for predicting MVI were 0.712 (0.493-0.932), 0.755 (0.563-0.947), and 0.856 (0.721-0.991), respectively. The sensitivity and specificity for predicting MVI were 77.8% and 74.5% for SUVmax of 3.2 or greater, 66.7% and 84.3% for AFP-L3 19% or greater, and 88.9% and 82.4% for the combination. Conclusions 18F-FDG PET-CT and AFP-L3 may be useful for predicting MVI in small HCC, and the combination of the 2 factors provided reliable assessment for selection of suitable hepatic resection and liver transplantation candidates.

Comparison of hepatic arterial infusion chemotherapy versus sorafenib monotherapy in patients with advanced hepatocellular carcinoma

Sorafenib is the standard treatment for advanced hepatocellular carcinoma (HCC) with distant metastasis, unresectable HCC, and those refractory to transcatheter arterial chemoembolization (TACE) or with macroscopic vascular invasion (MVI). The application of sorafenib has been approved by the Japanese Government‐sponsored Medicare for unresectable HCC. In this retrospective cohort study we aimed to compare various aspects of HAIC with sorafenib in the treatment of Child–Pugh A patients with advanced HCC who were otherwise free of extrahepatic metastasis.

The risks of hepatocellular carcinoma development after HCV eradication are similar between patients treated with peg-interferon plus ribavirin and direct-acting antiviral therapy

The risk of hepatocellular carcinoma (HCC) development is reduced following viral elimination by interferon therapy in chronic hepatitis C patients. However, the risk in patients treated with interferon-free direct-acting antivirals (DAAs) is unknown. We evaluated chronic hepatitis C patients who achieved viral eradication by pegylated-interferon plus ribavirin (PEG-IFN/RBV, n = 244) or daclatasvir plus asunaprevir (DCV/ASV, n = 154) therapy. None of the patients had prior history of HCC or antiviral therapy. The median observation period after the end of treatment for the PEG-IFN/RBV and DCV/ASV groups were 96 (range 10–196) and 23 (range 4–78) months, respectively. During the observation period, HCC developed in 13 (5.3%) and 7 (4.5%) patients in the PEG-IFN/RBV and DCV/ASV groups, respectively. The cumulative HCC development rate after 1-, 3- and 5-years (0.4%, 3% and 5% for the PEG-IFN/RBV group and 0.6%, 9% and 9% for the DAA group, respectively) were similar between the two groups. Propensity score matching analysis also showed no significant difference in HCC development rates between the two groups. Serum AFP levels decreased to similar levels between PEG-IFN/RBV and DCV/ASV groups following the achievement of viral eradication. The risk for HCC development following viral eradication by IFN-free DAA therapy may be similar to that in IFN-based therapy.

Real-World Efficacy and Safety of Daclatasvir and Asunaprevir Therapy for Hepatitis C Virus-Infected Cirrhosis Patients.

Daclatasvir and asunaprevir combination therapy has shown a high virological response for chronic genotype 1 hepatitis C virus (HCV) infected‐patients. However, the real‐world efficacy and safety of the therapy for patients with cirrhosis are unknown.

Efficacy and safety of daclatasvir plus asunaprevir therapy for chronic hepatitis C patients with renal dysfunction.

Chronic hepatitis C virus (HCV) infection is associated with renal dysfunction. Daclatasvir and asunaprevir combination therapy showed a high virological response for genotype 1 chronic HCV‐infected patients with renal dysfunction on hemodialysis. However, the safety and efficacy of the therapy for patients with renal dysfunction who are not on hemodialysis are not well‐known. In total, 147 patients with chronic HCV genotype 1 infection were treated with 24 weeks of daclatasvir plus asunaprevir therapy. Among these patients, 126 had normal renal function (estimated glomerular filtration rate [eGFR] ≥ 50 ml/min/1.73 m2) and 21 had renal dysfunction (eGFR < 50 ml/min/1.73 m2). Plasma concentrations of daclatasvir and asunaprevir after 5 days of treatment were the same in the normal renal function and renal dysfunction groups. Early virological response (4, 8, 48, 96, and 168 hr after the start of the therapy) was similar between the two groups. End‐of‐treatment response was achieved in 122 (96.8%) and 20 (95.2%) patients with normal renal function and with renal dysfunction, respectively, and sustained virological response was achieved in 119 (94.4%) and 20 (95.2%) patients. The frequency of adverse events was also comparable between the two groups. Treatment discontinuation due to adverse events was required for only one patient in each group. Renal function did not change either during or after treatment in both groups. In conclusion, renal function is unlikely to have a significant impact on blood kinetics of daclatasvir and asunaprevir. This combination therapy was effective and safe for patients without hemodialysis. J. Med. Virol. 89:665–671, 2017.

Three patients treated with daclatasvir and asunaprevir for recurrent hepatitis C after liver transplantation: Case report

We previously reported our data on telaprevir or simeprevir used in combination with pegylated interferon (PEG IFN) and ribavirin (RBV) for the treatment of recurrent hepatitis C virus (HCV) genotype 1 infection after liver transplantation (LT). Here, we report three patients who achieved viral responses with no effect on the blood concentrations of immunosuppressive agents following daclatasvir and asunaprevir treatment. The first patient was a 57‐year‐old man with HCV‐related liver cirrhosis who failed to respond to PEG IFN/RBV after living donor LT. He had been treated with 1 mg/day of tacrolimus. The second was a 63‐year‐old man with HCV‐related liver cirrhosis and hepatocellular carcinoma who failed to respond to PEG IFN/RBV after living donor LT. He had been treated with 1 mg/day of tacrolimus. The third was a 61‐year‐old man with HCV‐related liver cirrhosis. He had been treated with mycophenolate mofetil (MMF). Serum HCV RNA became undetectable by TaqMan polymerase chain reaction test after 4 weeks of daclatasvir and asunaprevir treatment in all patients, and no remarkable fluctuations in blood concentration were observed either in tacrolimus or in MMF during 24 weeks of therapy. No adverse events were observed, and all patients received the full dose of daclatasvir and asunaprevir over 24 weeks. Serum HCV RNA remained negative at 12 weeks after the end of treatment in all patients. The daclatasvir and asunaprevir treatment showed a remarkable viral response with little effect on blood levels of immunosuppressive agents for recurrent HCV genotype 1 infection after LT.

Efficacy and safety of edoxaban for treatment of portal vein thrombosis following danaparoid sodium in patients with liver cirrhosis

To compare the efficacy and safety of edoxaban and warfarin for treatment of portal vein thrombosis (PVT) following danaparoid sodium in patients with liver cirrhosis.

Impact of Hepatitis C Virus Eradication on the Clinical Outcome of Patients with Hepatitis C Virus-Related Advanced Hepatocellular Carcinoma Treated with Sorafenib

Objective: To evaluate the impact of hepatitis C virus (HCV) eradication on the clinical outcome of patients with HCV-related advanced hepatocellular carcinoma (HCC) treated with sorafenib. Methods: A total of 58 HCV-related advanced HCC patients with Child-Pugh grade A disease who were treated with sorafenib were enrolled in this retrospective cohort study. Of these, 27 patients were HCV RNA negative as a result of previous antiviral therapy (sustained viral response [SVR] group), while the remaining 31 were HCV RNA positive (non-SVR group). Results: The response rate, disease control rate and median time to progression in the SVR group (6, 46.0%, and 3.8 months, respectively) were similar to those in the non-SVR group (3, 51.5%, and 2.7 months, respectively). On the other hand, the median time to treatment failure (TTTF), post-progression survival (PPS), and overall survival (OS) were significantly longer in the SVR group than in the non-SVR group (9.7, 8.5, and 15 months vs. 5.9, 5.2, and 9.3 months; p = 0.023, 0.02, and 0.014, respectively). On multivariate analysis, SVR was identified as a significant and independent determinant of PPS (p = 0.009), TTTF (p = 0.028), and OS (p = 0.01). Conclusion: HCV eradication before sorafenib treatment for HCV-related advanced HCC could prolong PPS and TTTF and improve OS.