Juichi Takada

Higher discontinuation and lower survival rates are likely in elderly Japanese patients with advanced hepatocellular carcinoma receiving sorafenib

Aim:  Sorafenib is approved for the treatment of advanced hepatocellular carcinoma (HCC) in Japan; however, its tolerability and efficacy in elderly patients with HCC have not been clarified. We aimed to evaluate the tolerability and efficacy of sorafenib with increasing age.

Early increase in α-fetoprotein for predicting unfavorable clinical outcomes in patients with advanced hepatocellular carcinoma treated with sorafenib.

Background To determine the value of early alterations of the tumor markers &agr;-fetoprotein (AFP) and des-&ggr;-carboxy prothrombin (DCP) for predicting the outcomes of patients with advanced hepatocellular carcinoma (HCC) who receive sorafenib. Materials and methods Tumor response, overall survival (OS), and progression-free survival (PFS) were retrospectively analyzed in 59 patients with advanced HCC. Serum AFP and DCP were examined for early elevation within 4 weeks after the initiation of sorafenib. An increase in AFP was defined as AFP of more than 20%, and an increase in DCP was defined as more than two-fold higher level than the baseline. The relationship of the clinical characteristics, laboratory data at baseline, and early elevations of AFP and DCP with disease progression was analyzed. Results The median OS and PFS were 11 and 3.3 months, respectively. The rate of progressive disease (PD) was 54%, and an early increase in AFP was significantly related to PD (P=0.006) and was a significant independent predictor of both poorer OS and PFS (P<0.001, hazard ratio, 4.14; 95% confidence interval, 1.946–8.811; and P=0.001, hazard ratio, 2.852; 95% confidence interval, 1.524–5.337, respectively). There was no association between early increase in DCP and clinical outcomes. Conclusion Early increase in AFP predicted PD and poorer survival and may thus be a useful biomarker in patients with advanced HCC who receive sorafenib.

Entecavir is an optional agent to prevent hepatitis B virus (HBV) reactivation: A review of 16 patients

BACKGROUND Hepatitis B virus (HBV) reactivation is a fatal complication in patients who receive chemotherapy or immunosuppressive therapy. We examined the effect of preventive entecavir (ETV), a new nucleoside analogue on HBV reactivation during chemotherapy or immunosuppressive therapy. METHODS Between February 2007 and September 2009, sixteen nucleoside analogue treatment-naive patients with chronic HBV infection (HB surface antigen [HBsAg] positive) who required chemotherapy or immunosuppressive therapy were enrolled. Referring to some guidelines, the patients received preventive ETV to reduce incidence of HBV reactivation, and were closely monitored for HBV markers. RESULTS HBV reactivation did not occur in any of the 16 patients and the indispensable treatments for their underlying diseases could be continued. However, HBV relapsed after preventive ETV was discontinued in 2 patients. CONCLUSIONS This study suggests that ETV is a useful option for preventing HBV reactivation in patients with chronic HBV infection.

Repeat Radiofrequency Ablation Provides Survival Benefit in Patients With Intrahepatic Distant Recurrence of Hepatocellular Carcinoma

OBJECTIVES:Intrahepatic distant recurrence (IDR) of hepatocellular carcinoma (HCC) after curative treatment occurs frequently and influences the prognoses. The aim of this study was to determine prognostic factors affecting survival after IDR and the optimum therapy for IDR.METHODS:A total of 115 patients with a single small primary HCC who had complete radiofrequency (RF) ablation were enrolled in this study. The prognostic factors and the optimum therapy affecting survival were statistically analyzed among patients with IDRs.RESULTS:IDRs were observed in 59 (51.3%) patients with the median observation period of 19.6 months. The cumulative rates of IDRs were 11.8, 53.9, and 75.8% at 1, 3, and 5 years, respectively. IDR nodules were present as a single nodule in 38 patients and as multiple nodules in 21 patients. In all, 23 patients died during the follow-up. A total of 30 patients were treated with RF ablation, and 27 were treated with transcatheter arterial chemoembolization (TACE). The overall cumulative survival rates after IDRs were 92.7, 55.4, and 43.7% at 1, 3, and 5 years, respectively. A multivariate analysis showed that treatment with RF ablation for IDR was a significant favorable prognostic factor after IDR (hazard ratio: 0.167, 95% confidence interval: 0.048−0.584, P=0.005). In a comparison of survival after IDR between patients treated with RF ablation and TACE, who were comparable with clinical and tumoral characteristics, the cumulative survival rate of patients treated with RF ablation was significantly higher than that of those treated with TACE (77.2 vs 28.5% at 3 years). The cumulative survival rates obtained from the initial RF ablation of the patients with IDRs treated with repeat RF ablation were similar to those of recurrence-free patients.CONCLUSIONS:Repeat RF ablation should be attempted for IDR as much as possible despite tumor multiplicity for survival benefit; by reducing the need, it will help solve the problem of the current shortage of donors for liver transplantations.

Re-appearance of hepatitis B virus following therapy with rituximab for lymphoma is not rare in Japanese patients with past hepatitis B virus infection.

Background and aim: De novo hepatitis B virus (HBV)‐related hepatitis is a well‐known fatal complication following chemo‐immunosuppressive therapy in patients with past HBV infection (HB surface antigen and serum HBV DNA negative, but HB core antibody and/or HB surface antibody positive). This research was conducted to evaluate the incidence of and clinical features associated with re‐appearance of serum HBV DNA following chemo‐immunosuppressive therapy in Japanese patients with past HBV infection.

Radiotherapy for patients with unresectable advanced hepatocellular carcinoma with invasion to intrahepatic large vessels: Efficacy and outcomes

To examine the efficacy and outcomes of radiotherapy (RT) in patients who have hepatocellular carcinoma with invasion to intrahepatic large vessels (IHLVs).

Therapeutic benefits of partial splenic embolization for thrombocytopenia in hepatocellular carcinoma patients treated with radiofrequency ablation

Aim:  Partial splenic embolization (PSE) is a non‐surgical procedure developed to treat hypersplenism. The purpose of this study is to evaluate therapeutic benefits of PSE with follow‐up radiofrequency ablation (RFA) treatment in hepatocellular carcinoma (HCC) patients with thrombocytopenia.

Reliability and validity of splenic volume measurement by 3‐D ultrasound

Aim:  We prospectively evaluated the reliability and validity of splenic volume with 3‐D ultrasound measurement and clarified its clinical usefulness.

Branch retinal artery occlusion and central retinal vein occlusion associated with pegylated interferon plus ribavirin combination therapy for chronic hepatitis C

A 62-year-old male treated with pegylated interferon α-2b plus ribavirin for chronic hepatitis C complained of sudden painless decreased visual acuity. This patient was diagnosed as having simultaneous occlusions of the branch retinal artery and central retinal vein, although he had no history of major risk factors for retinal vessel (artery and vein) occlusion. Unfortunately, visual acuity did not completely recover. Furthermore, the patient was heterozygous for interleukin (IL) 28B genetic polymorphisms. The etiology of interferon-associated retinal vessel occlusion is not yet clear. However, a review based on previous case reports suggested that some factors including ribavirin might act as a risk or cause of retinal vessel occlusion.

Viral level is an indicator of long‐term outcome of hepatitis B virus e antigen‐negative carriers with persistently normal serum alanine aminotransferase levels

Summary.  The association between viral level and the long‐term outcomes of hepatitis B virus (HBV) carriers who test negative for hepatitis B virus e antigen (HBeAg) but have persistently normal serum alanine aminotransferase levels (PNALT) remains unclear. We examined hepatocarcinogenesis, hepatitis reactivation, predictive factors and the time course of HBV DNA levels during follow‐up in 104 HBeAg‐negative Japanese carriers with PNALT. During a mean follow‐up period of 6.4 ± 3.4 years, 5 patients (4.8%) had hepatocarcinogenesis and 14 (13.5%) had hepatitis reactivation. At 5 and 10 years, the cumulative rates of hepatocarcinogenesis were 2.4% and 9.9%, while those of hepatitis activation were 13.7% and 15.5%, respectively. An HBV DNA level of ≥5 log10 copies/mL was the sole predictor of hepatocarcinogenesis with a univariate analysis. An HBV DNA level of ≥5 log10 copies/mL and an alanine aminotransferase (ALT) level of >20 to ≤40 IU/L were independent predictors of hepatitis reactivation in a Cox model. Because there was no association between hepatocarcinogenesis and ALT activity, the HBV DNA level was considered an essential predictor. In addition, the baseline HBV DNA level was related to the future level and was not subject to wide fluctuations. Our results showed that an HBV DNA level of ≥5 log10 copies/mL predicts subsequent hepatocarcinogenesis and hepatitis reactivation in HBeAg‐negative carriers with PNALT. As the baseline HBV DNA level reflects the future level, appropriate clinical management according to the viral level is expected to decrease future risk.