Seropositivity and Titers of Anti-Smooth Muscle Actin Antibody Are Associated with Relapse of Type 1 Autoimmune Hepatitis.

BACKGROUND It is important to avoid relapse in autoimmune hepatitis (AIH) because repeated multiple relapses have been associated with a worse prognosis. However, risk factors for relapse before initiation of treatment are not fully understood. The aim of this study was to find predictive markers for relapse of type 1 AIH. MATERIAL AND METHODS We reviewed the records of 53 patients diagnosed with type 1 AIH based on the revised scoring system proposed by the International Autoimmune Hepatitis Group (IAIHG) between 2009 and 2014 at 4 hospitals belonging to the Saga Study Group of Liver Diseases (SASLD). We analyzed the differences in background characteristics between patients with or without relapse. RESULTS All patients achieved remission after treatment, and 9 (17%) subsequently relapsed. The relapsed patients were significantly younger and had a higher positive rate of anti-smooth muscle antibody (ASMA) than the non-relapsed patients (100% vs. 25%, P=0.0012). Moreover, relapse rate increased with titer of ASMA, while titer of antinuclear antibody was not associated with relapse rate. CONCLUSIONS ASMA is a useful predictive marker for relapse of type 1 AIH during or after withdrawal of medical therapy. More careful attention should be paid to immunosuppressive therapy in patients with high titers of ASMA.

Factors Associated with Post-Progression Survival in Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib.

Sorafenib exerts modest antitumor activity in patients with advanced hepatocellular carcinoma (HCC), and radiological progressive disease (rPD) does not always correspond to so-called clinical progressive disease (cPD). We evaluated 101 patients who initiated sorafenib treatment for HCC and assessed post-progression survival (PPS) using the Cox proportional hazards model. PPS was calculated from the date of the first rPD until the date of death or the last follow-up. Using Cox model analysis of the 76 patients who experienced first rPD, we identified the Child-Pugh class, Eastern Cooperative Oncology Group performance status, the best antitumor response during treatment (using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1) and α-fetoprotein levels as independent factors affecting PPS. When these factors were used to define scores ranging from zero to five with a cutoff value of two, PPS of patients who received best supportive care (BSC) after rPD was not statistically significantly different from that of patients who received post-rPD therapy with scores ≥2 (p = 0.220). In contrast, the PPS for the post-rPD therapy group was significantly longer compared with the BSC patients with scores <2 (p < 0.001). Patients who scored ≥2 at their first rPD were judged cPD and as candidates for BSC.

Skin toxicities and survival in advanced hepatocellular carcinoma patients treated with sorafenib.

AIM: Sorafenib is the first small molecule with significant clinical activity for advanced hepatocellular carcinoma (HCC). However, intolerable adverse events are sometimes observed. On the other hand, it has been reported that some toxicities of molecular targeted drugs, such as skin toxicities and arterial hypertension, are correlated with good clinical outcomes in other cancers. METHODS: We identified the correlations between adverse events and prognosis for sorafenib therapy in all patients with HCC treated at the institutions of the Saga Liver Cancer Study Group. The toxicities were assessed using the Common Terminology Criteria for Adverse Events version 4.0. RESULTS: Ninety-four patients received sorafenib until August 2010. The overall incidence of treatment-related adverse events was 98% of patients. Skin toxicities, including palmar-plantar erythrodysesthesia syndrome, rash, pruritus and alopecia, were the most common adverse events and were observed in 58 patients (62%). Hypertension was observed in 23 patients (24%). The median survival time was 12.5 months among the total patients. The patients with skin toxicities showed significantly longer survival than the patients without these toxicities (hazard ratio, 0.449; 95% confidence interval, 0.256-0.786; P = 0.005). Hypertension had no correlation with survival. Skin toxicities were also significant prognostic factors in a multivariate analysis (hazard ratio, 0.522; 95% confidence interval, 0.274-0.997; P = 0.049), along with Child-Pugh class and α-fetoprotein level. The median development time for skin toxicities was 21 days. CONCLUSION: Skin toxicities occur commonly at the early phase in patients treated with sorafenib, and could be a promising surrogate marker for the treatment outcome.

High-dose vitamins E and C supplementation prevents ribavirin-induced hemolytic anemia in patients with chronic hepatitis C.

AIM: In combination therapy using interferon (IFN) and ribavirin for chronic hepatitis C, reduced doses should be used due to ribavirin-induced hemolytic anemia. The present study aimed to elucidate whether high-dose vitamins E and C supplementation attenuated ribavirin-induced hemolytic anemia. METHODS: Twenty-one consecutive patients with chronic hepatitis C were enrolled in this study between July 2003 and December 2004, and received high-dose vitamins E (2000 mg) and C (2000 mg) supplementation, daily, in addition to IFN alfa-2b and ribavirin combination therapy (vitamins E/C group). Twenty-one sex- and age-matched patients who received a standard regimen of IFN alfa-2b and ribavirin for chronic hepatitis C between January 2001 and June 2003 were evaluated as the control group. RESULTS: Decrease in hemoglobin level was significantly prevented in the vitamins E and C group compared to that in the control group (P = 0.029). Three (14.3%) patients in the control group discontinued treatment because of anemia, while no treated patient dropped out of the study due to anemia. Sustained virological response was not significantly different between the two groups. CONCLUSION: High-dose vitamins E and C supplementation prevented ribavirin-induced hemolytic anemia during combination therapy with ribavirin and IFN alfa-2b in patients with chronic hepatitis C.

Radiofrequency ablation with the real-time virtual sonography system for treating hepatocellular carcinoma difficult to detect by ultrasonography.

Radiofrequency ablation has been applied to treat hepatocellular carcinoma, with favorable therapeutic outcomes. Nevertheless, practitioners have approached radiofrequency ablation with some reluctance due to the difficulty of identifying isoechoic tumors and recurrent tumors. The aim of the present study is to investigate the efficacy of Real-time Virtual Sonography to treat hepatocellular carcinoma difficult to detect by conventional ultrasonography. Real-time Virtual Sonography is a system generating multiplanar reconstruction images in real-time using the Hitachi medico EUB-8500 equipped with a probe. The system included following components: 1) digital imaging and communications in medicine (DICOM) data from dynamic CT, 2) a magnetic field generator to match the multiplanar reconstruction image on the monitor and the actual ultrasonography image, 3) the cross section with the tumor displayed as a multiplanar reconstruction image. Total twenty-five nodules of twenty-one patients underwent radiofrequency ablation monitored by Real-time Virtual Sonography. All nodules difficult to detect via conventional ultrasonography were clearly visualized in real-time. The average nodule diameter was 2.4 +/- 1.6 cm, and punctures and coagulation were performed an average of 2.2 and 3 times per session. Dynamic CT after session confirmed effective coagulation of each nodule. In conclusion, this study demonstrates that the present system is capable of effectively and accurately treating tumors difficult to detect by conventional ultrasonography.