Pretreatment with antibiotics is associated with reduced therapeutic response to atezolizumab plus bevacizumab in patients with hepatocellular carcinoma.

Aim: Alterations in microbial composition of gut microbiota due to antibiotics (ATB) may lead to resistance to immune checkpoint inhibitors (ICIs). This study aimed to assess the impact of ATB use on therapeutic response in patients with hepatocellular carcinoma (HCC) receiving atezolizumab plus bevacizumab.

Methods: This study retrospectively analyzed 105 patients with HCC treated with atezolizumab plus bevacizumab as a primary systemic therapy from prospectively-registered, multicenter, cohorts.

Thrombospondin-2 as a Predictive Biomarker for Hepatocellular Carcinoma after Hepatitis C Virus Elimination by Direct-Acting Antiviral.

We evaluated the value of secreted glycoprotein thrombospondin-2 (TSP-2) to predict hepatocellular carcinoma (HCC) occurrence in chronic hepatitis C (CHC) patients after Hepatitis C virus (HCV) elimination by direct-acting antiviral agents (DAAs). A total of 786 CHC patients without an HCC history who achieved a sustained virological response (SVR) with DAAs were randomly assigned 2:1, with 524 patients as the derivation cohort and 262 patients as the validation cohort. Serum TSP-2 levels at the end of treatment were measured by enzyme-linked immunosorbent assay (ELISA).

Fucosylated haptoglobin is a novel predictive marker of hepatocellular carcinoma after hepatitis C virus elimination in patients with advanced liver fibrosis.

Background: Patients with advanced fibrosis are at risk for developing hepatocellular carcinoma (HCC) even after hepatitis C virus (HCV) elimination. We previously reported that serum fucosylated haptoglobin (Fuc-Hp) levels increase as the disease progresses from chronic hepatitis to cirrhosis and then HCC. However, it remains unclear whether serum Fuc-Hp levels can stratify the risk of HCC occurrence after a sustained virological response (SVR) is achieved with direct-acting antivirals (DAAs) in patients with advanced liver fibrosis.

Clinical course of hepatitis C virus-positive patients with decompensated liver cirrhosis in the era of direct-acting antiviral treatment.

Aim: The aim of the present study was to investigate the clinical course in hepatitis C virus (HCV)-positive patients with decompensated liver cirrhosis after direct-acting antivirals (DAAs) have been used for HCV infection.

Methods: This multicenter study prospectively analyzed a registered cohort composed of 73 HCV-positive patients with decompensated cirrhosis who attended our 11 institutions between January 2018 and July 2018. Prognoses, including changes in the liver reserve, hepatocellular carcinoma (HCC), decompensation events, and survival, were analyzed up to July 2020, as was the initiation of DAA treatment.

Prognostic Factors for Patients With a Large Number of Hepatocellular Carcinoma Nodules.

Background: The prognostic factors and treatment strategies for hepatocellular carcinoma (HCC) patients with a large number of tumor nodules have not been fully elucidated. Clinical factors influencing prognosis were investigated in HCC patients with 30 or more tumor nodules.

Methods: Forty-six HCC patients with 30 or more tumor nodules participated in this study.

Chemotherapy-Induced Sclerosing Cholangitis Caused by Systemic Chemotherapy.

A 61-year-old woman diagnosed with cervical cancer received systemic chemotherapy using paclitaxel and bevacizumab. Marked elevation of liver enzyme levels was observed. Ultrasonography and computed tomography showed wall thickening of the extrahepatic and intrahepatic bile ducts accompanied by stricture and dilatation.

Development of a thrombus in the superior mesenteric artery associated with sequential therapy with tyrosine kinase inhibitors for hepatocellular carcinoma.

Tyrosine kinase inhibitors (TKIs) are widely used for systemic chemotherapy of hepatocellular carcinoma (HCC). Arterial thromboembolism (ATE) has been reported to be an adverse event associated with TKI therapy, but its incidence is rare. Here, we report a case of an HCC patient who developed a thrombus in the superior mesenteric artery (SMA) while on TKI therapy.

Two-step progression of varenicline-induced autoimmune hepatitis.

We describe a rare case of drug-induced hepatitis due to the smoking cessation agent varenicline in a 46-year-old Asian woman. The liver injury progressed in two steps. First, the liver injury started in the absence of viral/autoimmune responses, and withdrawal of varenicline lowered the increase in the levels of liver enzymes immediately.

Prospective Comparison of Gd-EOB-DTPA-Enhanced MRI with Dynamic CT for Detecting Recurrence of HCC after Radiofrequency Ablation.

Background: We prospectively compared the efficacy of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) with that of dynamic multidetector computed tomography (MDCT) for detection of recurrent hypervascular hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA).

Methods: Institutional review board approval and written informed consent were obtained for this multicenter study. Ninety-seven HCC patients treated with curative RFA underwent both Gd-EOB-DTPA-enhanced MRI and dynamic MDCT every 3-4 months.

The Effectiveness of a Liver Disease Education Class for Providing Information to Patients and Their Families.

Background: We have been conducting liver disease education classes regularly in our hospital for the purpose of providing health information to patients and their families.

Methods: In order to evaluate the effectiveness of these classes, we conducted a questionnaire survey of patients and family members who attended the classes held three times in 2012. The cumulative total number of participants was 80 (49 patients, 26 family members, and five others).

Subclassification of patients with intermediate-stage (Barcelona Clinic Liver Cancer stage-B) hepatocellular carcinoma using the up-to-seven criteria and serum tumor markers.

Background: Intermediate-stage [Barcelona Clinic Liver Cancer stage-B (BCLC-B)] hepatocellular carcinoma (HCC) comprises of a heterogeneous population of patients with a wide range of tumor burdens. We therefore formulated a subclassification of BCLC-B HCC using the up-to-seven criteria and tumor markers according to the results of a retrospective analysis of these patients.

Methods: This study included 125 patients newly diagnosed with BCLC-B HCC who underwent transarterial chemoembolization.

Quick and stable parallel puncture of hepatic tumors using a double-barreled needle direction system for ultrasound-guided bipolar radiofrequency ablation.

Aim: In bipolar radiofrequency ablation (RFA) therapy, insertion of multiple needles at appropriate points on a target is difficult. The aim of our study was to evaluate a simplified method for multi-electrode insertion using a newly developed double-barreled needle guidance system for percutaneous RFA of hepatic tumors.

Methods: RFA using two bipolar electrodes was performed in 15 consecutive patients (nine men, six women; mean age, 72.

Factors related to shift from hepatic borderline lesion to overt HCC diagnosed by CT.

Background/aims: Factors contributing to the shift from the hepatic borderline lesion to overt hepatocellular carcinoma (HCC) were investigated.

Methodology: Ninety-five borderline nodules from 69 patients were followed-up for 6-55 (median 24) months. The borderline lesion was diagnosed when the CT image demonstrated low density in the portal phase and lacked enhancement in the arterial phase.

Three-dimensional registration of images obtained before and after radiofrequency ablation of hepatocellular carcinoma to assess treatment adequacy.

Objective: The aim of our study was to evaluate the value of 3D registration images reconstructed by fusion of pre- and posttreatment CT or MRI for the assessment of ablative margins after percutaneous radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC).

Materials And Methods: From January 2007 to May 2011, we performed RFA in 84 patients to treat 139 HCC nodules, the margins of which had been assessed by comparing pre- and postablation images side by side. The same nodules were retrospectively assessed again with 3D registration images after classification into four margin grades.

Computed tomography during hepatic arteriography pattern may predict hepatocellular carcinoma recurrence following transarterial chemoembolization.

Aim: This study aimed to determine the role of morphological patterns seen on imaging in predicting hepatocellular carcinoma recurrence following transarterial chemoembolization therapy.

Methods: Forty-seven patients from a single center who underwent transarterial chemoembolization to treat unresectable hepatocellular carcinomas between January 2011 and June 2012 were included in this study. We investigated whether the two pretreatment findings on computed tomography during hepatic arteriography (pattern 1, the single nodule pattern; pattern 2, at least one nodule showing the contiguous multinodular pattern) and other factors (age, sex, etiology, serum total bilirubin, serum albumin, prothrombin time, platelet count, serum level of protein induced by vitamin K absence/antagonist-II, serum α-fetoprotein, number of previous treatments for hepatocellular carcinoma, tumor number and maximum tumor size, presence of hypovascular lesions) could predict post-treatment recurrence.

Association of enhanced activity of indoleamine 2,3-dioxygenase in dendritic cells with the induction of regulatory T cells in chronic hepatitis C infection.

Background: Altered functions of dendritic cells (DCs) and/or increases of regulatory T cells (Tregs) are involved in the pathogenesis of chronic hepatitis C virus (HCV) infection. A tryptophan-catabolizing enzyme, indoleamine 2,3-dioxygenase (IDO), is reported to be an inducer of immune tolerance. Our aim was to clarify whether or not IDO is activated in chronic hepatitis C patients and its role in immune responses.

TIE2-expressing monocytes as a diagnostic marker for hepatocellular carcinoma correlates with angiogenesis.

Unlabelled: Angiogenesis is a critical step in the development and progression of hepatocellular carcinoma (HCC). Myeloid lineage cells, such as macrophages and monocytes, have been reported to regulate angiogenesis in mouse tumor models. TIE2, a receptor of angiopoietins, conveys pro-angiogenic signals and identifies a monocyte/macrophage subset with pro-angiogenic activity.

Clinical trial of the intratumoral administration of labeled DC combined with systemic chemotherapy for esophageal cancer.

Esophageal cancer is a highly aggressive disease, and improved modalities for its treatment are needed. We performed chemoimmunotherapy involving the intratumoral administration of 111In-labeled dendritic cells (DC) in combination with preoperative chemotherapy in 5 esophageal cancer patients. Mature DC were generated and traced by scintigraphy after their administration.

Comparative analyses of regulatory T cell subsets in patients with hepatocellular carcinoma: a crucial role of CD25(-) FOXP3(-) T cells.

Regulatory T cells (Tregs) play pivotal role in cancer-induced immunoediting. Increment of CD25(high+) FOXP3+ natural Tregs has been reported in patients with hepatocellular carcinoma (HCC); however, the involvement of other type of Tregs remain elusive. We aimed to clarify whether FOXP3- Tregs are increased and functionally suppressive or not in patients with HCC.

Dynamics of regulatory T cells and plasmacytoid dendritic cells as immune markers for virological response in pegylated interferon-α and ribavirin therapy for chronic hepatitis C patients.

Background: For the treatment of chronic hepatitis C, a combination of pegylated interferon-α (PEG-IFNα) and ribavirin has been widely used as a standard of care. Enhancement of immune response against hepatitis C virus (HCV) is known to be involved in the efficacy of the combination therapy. Our aim was to elucidate whether or not the frequency or function of blood cells is related to the outcome of the therapy.

[Vaccine therapies against digestive-system cancers].

Cancer vaccine is a promising tool to achieve therapeutic responses in patients by inducing anti-tumor immunity. Several cancer vaccine trials have been performed in patients with digestive-system cancers. Two major candidates are peptide vaccine and dendritic cell (DC) vaccine.

Comprehensive immunological analyses of colorectal cancer patients in the phase I/II study of quickly matured dendritic cell vaccine pulsed with carcinoembryonic antigen peptide.

Dendritic cell (DC) vaccine has been used to treat patients with advanced colorectal cancer (CRC). The results of vaccine-induced clinical responses have not always been satisfactory partially because of DC incompetence. In order to evaluate the feasibility of novel mature DCs for therapeutic adjuvants against CRC, we conducted clinical trials with carcinoembryonic antigen (CEA) peptide-loaded DC quickly generated with a combination of OK432 (Streptococcuspyogenes preparation), prostanoid, and interferon-α (OPA-DC).