Kouji Joko

Complications of radiofrequency ablation for hepatocellular carcinoma in a multicenter study: An analysis of 16 346 treated nodules in 13 283 patients

Aim:  We surveyed multiple centers to identify types and frequency of complications and mortality rate associated with radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC).

Mechanism and therapeutic potential of DNA-based immunization against the envelope proteins of hepatitis B virus in normal and transgenic mice

Two plasmid DNA vectors, pCAGGS(S) encoding the genes of the major envelope protein of hepatitis B virus (HBV), and pCAGGS(S + preS2) encoding the genes of the middle envelope protein were used to study the mechanism and therapeutic potential of DNA‐based immunization. Injection of these plasmids into the regenerating bilateral tibialis anterior muscle (TA) of normal C57BL/6 mice induced hepatitis B surface antigen (HBsAg)‐specific humoral and cellular immune responses. Seventy‐two hours after injection of pCAGGS(S), infiltrating cells including antigen‐presenting dendritic cells (DC) were localized around the injection site and HBsAg was expressed by both muscle cells and infiltrating cells. Spleen DC from the mice were exposed to HBsAg for up to 32 weeks after a single injection of pCAGGS(S), because these DC induced the proliferation of HBsAg‐specific memory lymphocytes in culture without exogenous HBsAg. A single injection of pCAGGS(S) or pCAGGS(S + preS2) resulted in the clearance of HBsAg in 28 out of 30 HBV‐transgenic (Tg) mice. In contrast, more than 7 monthly injections of an HBsAg‐based vaccine were required for the clearance of HBsAg in 6 out of 29 HBV‐Tg mice. Infiltrating DC at the DNA vaccine injection site may have a role in initiating HBsAg‐specific immune response, whereas the persistence of HBsAg exposed spleen DC may contribute to long‐lasting immunity. This study also suggested that DNA‐based vaccines may be a potent tool for treating chronic HBV carriers.

Clinical features associated with radiological response to sorafenib in unresectable hepatocellular carcinoma: a large multicenter study in Japan

There have been no established predictive factors of responders to sorafenib in patients with unresectable hepatocellular carcinoma (HCC). This study aimed to investigate the factors predicting a good response to sorafenib in Japanese patients with HCC.

Albumin-Bilirubin (ALBI) Grade as Part of the Evidence-Based Clinical Practice Guideline for HCC of the Japan Society of Hepatology: A Comparison with the Liver Damage and Child-Pugh Classifications

Aim/Background: The purpose of this study was to evaluate the validity of 3 classifications for assessing liver function, the liver damage and Child-Pugh classifications and the newly proposed albumin-bilirubin (ALBI) grade, in order to examine the feasibility of evaluating hepatic function using ALBI grade with the hepatocellular carcinoma (HCC) treatment algorithm used in Japan. Methods: We analyzed the medical records of 3,495 Japanese HCC patients admitted from 2000 to 2015, which were comprised of 1,580 patients hospitalized in the Ehime Prefecture area and used as a training cohort (Ehime group), and 1,915 others who were used for validation (validation group). ALBI score used for grading (≤-2.60 = grade 1, greater than -2.60 to ≤-1.39 = grade 2, greater than -1.39 = grade 3) as well as clinical features and prognosis (Japan Integrated Staging [JIS], modified JIS, ALBI-TNM [ALBI-T] score) were retrospectively investigated. Results: For prediction of liver damage A, the values for sensitivity and specificity, positive predictive and negative predictive values, and positive and negative likelihood ratios of ALBI-1 and Child-Pugh A were similar among the 2 groups. Akaike information criterion results showed that prognosis based on ALBI grade/ALBI-T score was better than that based on liver damage/modified JIS score and Child-Pugh/JIS score (22,291.8/21,989.4, 22,379.6/22,076.0, 22,392.1/22,075.1, respectively). The cutoff values for ALBI score for indocyanine green retention rate at 15 min (ICG-R15) <10, <20, and <30% were -2.623 (area under the curve [AUC]: 0.798), -2.470 (AUC: 0.791), and -2.222 (AUC: 0.843), respectively. The distribution of ICG-R15 (<10%, 10 to <20%, 20 to <30%, and ≥30%) for ALBI grade 1 was similar to that for liver damage A. There were only small differences with regard to therapeutic selection with the Japanese HCC treatment algorithm between liver damage and ALBI grade. Conclusion: ALBI grade is a useful and easy classification system for assessment of hepatic function for therapeutic decision making.

Risk of hepatocellular carcinoma in cirrhotic hepatitis B virus patients during nucleoside/nucleotide analog therapy

Some patients develop hepatocellular carcinoma (HCC) during nucleoside/nucleotide analog (NA) therapy even if alanine aminotransferase (ALT) or hepatitis B virus (HBV) DNA levels are sufficiently reduced. The aim of this study is to identify the risk factors of development of HCC during NA therapy.

Effects of antiviral therapy for hepatitis C following treatment of hepatocellular carcinoma: survey findings of the Japanese Red Cross Liver Study Group.

To investigate, in a large number of cases at multiple institutions, the effects and limitations of antiviral therapy for hepatitis C following treatment of hepatocellular carcinoma (HCC) in clinical practice.

Does interferon-free direct-acting antiviral therapy for hepatitis C after curative treatment for hepatocellular carcinoma lead to unexpected recurrences of HCC? A multicenter study by the Japanese Red Cross Hospital Liver Study Group

Background and aim This study aimed to elucidate whether interferon (IFN)-free direct-acting antiviral (DAA) therapy for hepatitis C after curative treatment of hepatocellular carcinoma (HCC) promotes HCC recurrence in a real-world large-scale cohort. Methods This multicenter study was conducted by the Japanese Red Cross Hospital Liver Study Group. This retrospective study analyzed 516 patients who underwent antiviral treatment for hepatitis C with either IFN (n = 148) or IFN-free DAA (n = 368) after curative HCC treatment; 78 IFN-treated patients and 347 IFN-free DAA-treated patients achieved sustained virological response (SVR). The recurrence rate of HCC was compared between the antiviral therapies. Logistic analysis and Cox proportional hazards analysis identified factors associated with early recurrence of HCC within 24 weeks of antiviral therapy and recurrence throughout the observation period, respectively. Results AFP at the completion of antiviral therapy, clinical stage of HCC, and non-SVR were independent factors associated with early recurrence of HCC. Among patients who had achieved SVR, the clinical stage of HCC and the level of AFP at completion of antiviral therapy were independent factors associated with early recurrence of HCC. For recurrence throughout the observation period in SVR patients, AFP at completion of antiviral therapy, duration between last HCC treatment to antiviral therapy, and the number of treatments were independent factors. There was no significant difference in the rate of early recurrence of HCC or recurrence throughout the observation period between IFN and IFN-free DAA treated patients. Conclusions There were no differences in the early recurrence rate of HCC between patients who underwent IFN and those who underwent IFN-free DAA as antiviral therapies.

Proposal of Japan Red Cross score for sorafenib therapy in hepatocellular carcinoma

There have been no established predictors of the outcome on sorafenib therapy for hepatocellular carcinoma (HCC) patients. We aimed to establish a new prognostic model suitable for sorafenib in HCC.

Predictors of treatment efficacy and ALT non‐normalization with sofosbuvir/ribavirin therapy for patients with hepatitis C virus genotype 2

The tolerability and efficacy of sofosbuvir and ribavirin in patients infected with hepatitis C virus (HCV) genotype 2 were investigated under actual clinical conditions. A total of 208 patients with chronic HCV genotype 2 infection were treated with sofosbuvir 400 mg and ribavirin (weight‐based dosing) for 12 weeks. Treatment discontinuation and sustained virological response 12 (SVR12) were evaluated. Moreover, factors associated with SVR12, hemoglobin decreasing to less than 10 g/dL during treatment, and alanine aminotransferase (ALT) non‐normalization after treatment were evaluated. In all patients, SVR12 responses were 96.1% (200/208). About 6 of 8 patients (3.8%) who did not achieve SVR12 were re‐treatment patients, and eight patients who did not achieve SVR all had liver cirrhosis. Multivariate analysis also identified body mass index (OR = 0.79; P < 0.001), platelet count (OR = 0.88; P = 0.003), and estimated glomerular filtration rate (eGFR) (OR = 0.96; P = 0.007) as independent contributing factors associated with hemoglobin decreasing to less than 10 g/dL during treatment, and only Mac‐2 Binding Protein Glycosylation isomer (M2BpGi) (OR = 2.46; P = 0.017) as an independent contributing factor associated with ALT non‐normalization after treatment. Cirrhotic patients may have a relatively high rate of treatment failure. In patients whose M2BpGi levels are elevated, their ALT tended to not normalize after treatment completion. These patients who did not achieve normalization of ALT after sofosbuvir plus RBV treatment need more careful observation for emergence of hepatocellular carcinoma even after achievement of SVR.

Efficacy of daclatasvir plus asunaprevir in patients with hepatitis C virus infection undergoing and not undergoing hemodialysis: Daclatasvir plus asunaprevir in non-HD and HD patients

To evaluate the virologic responses and clinical course of daclatasvir plus asunaprevir treatment in non‐hemodialysis (non‐HD) and hemodialysis (HD) patients infected with genotype 1 hepatitis C virus (HCV).