Noritaka Wakui

Long-term follow-up of chronic hepatitis C patients treated with oral lactoferrin for 12 months.

BACKGROUND/AIMS: Bovine lactoferrin (bLF) has been shown to prevent the infection of cultured hepatocytes by hepatitis C virus (HCV). The present study attempted to clarify the effects of long-term administration of bLF on serum parameters, including immunomodulatory cytokines, in patients with chronic hepatitis C (CHC). METHODS: Sixty-three CHC patients were randomly assigned into 2 groups. At an oral dose of 600 mg/day, bLF was administered for 12 months to 36 patients (bLF group), while no bLF was given to the remaining 27 patients (control group. Serum levels of alanine aminotransferase, HCV-RNA, IL-10, and IL-18 were evaluated, as well as CD4-positive T cell subsets in the peripheral blood. RESULTS: The serum IL-18 level was increased by bLF administration, but not in the control group. After 3 months of bLF treatment, it was significantly higher than before bLF administration, but it decreased gradually thereafter. The percentage of interferon (IFN)-gamma+ and IL-4- (Th1) cells in the peripheral blood increased along with the serum IL-18 level, although the change was not statistically significant. The other parameters did not change significantly during the study period in both groups. CONCLUSIONS: These results suggest that oral administration of bLF to CHC patients for up to 3 months can produce a Th1-cytokine dominant environment in the peripheral blood that favors the eradication of HCV by IFN therapy.

Evaluation of local recurrence after treatment for hepatocellular carcinoma by contrast‐enhanced ultrasonography using Sonazoid: Comparison with dynamic computed tomography

To evaluate the effectiveness of contrast‐enhanced ultrasonography (CEUS) using Sonazoid for the diagnosis of the local recurrence after treatment for hepatocellular carcinoma (HCC) by comparing it with dynamic CT.

Usefulness of Arrival Time Parametric Imaging in Evaluating the Degree of Liver Disease Progression in Chronic Hepatitis C Infection

To determine whether the degree of liver disease progression in chronic hepatitis C infection can be evaluated by arrival time parametric imaging using contrast‐enhanced sonography with Sonazoid (perfluorobutane; GE Healthcare, Oslo, Norway).

Sorafenib Prevents Escape from Host Immunity in Liver Cirrhosis Patients with Advanced Hepatocellular Carcinoma

Purpose. It has been reported that Th2 cytokines downregulate antitumor immunity, while activation of type T cells promotes antitumor immunity. The aim of this paper was to evaluate host immunity in liver cirrhosis (LC) patients with advanced hepatocellular carcinoma (aHCC) receiving sorafenib therapy. Methods. Forty-five adult Japanese LC patients received sorafenib for aHCC between 2009 and 2011 at our hospital. Sorafenib was administered at a dose of 200–800 mg/day for 4 weeks. Blood samples were collected before and after treatment. Results. Eleven patients were treated with sorafenib at 200 mg/day (200 group), 27 patients received sorafenib at 400 mg/day (400 group), and 7 patients were given sorafenib at 800 mg/day (800 group). There was no significant change in the percentage of Th1 cells after treatment in any group. However, the percentages of Th2 cells and regulatory T cells were significantly decreased after treatment in the 400 group and 800 group compared with before treatment, although there was no significant change after treatment in the 200 group. Conclusions. These results indicate that treatment with sorafenib might induce Th1 dominance and prevent the escape of tumor cells from the host immune system in LC patients with aHCC.

Risk factors for the local recurrence of hepatocellular carcinoma after single-session percutaneous radiofrequency ablation with a single electrode insertion

Radiofrequency ablation (RFA) is a new local therapy for hepatocellular carcinoma (HCC). In this study, we investigated the risk factors associated with local recurrence of HCC after single-session RFA with a single electrode insertion. From April 2003 to December 2007, we treated 138 HCC lesions by single-session RFA with a single electrode insertion using the Cool-tip RFA, RTC 2000 and RTC 3000 Systems. Risk factors for the local recurrence of these lesions and complications after RFA were analyzed. The mean size of the 138 lesions was 16.9±5.4 mm in diameter (range 7-33 mm). Local recurrence rates were 6.6 and 22.0% at 1 and 2 years, respectively, during the mean follow-up period of 16.4 months. Univariate analysis showed that tumor diameter (≥20 mm), tumor location, pre-treatment AFP-L3 fraction level and ablation pattern were significant variables. Multivariate analysis of these four variables identified only the tumor diameter as an independent risk factor for local recurrence. Complications occurred in 2.2% of the lesions (3/138). Single-session RFA is an effective treatment for HCC in that it reduces serious complications. This study demonstrated that a tumor size ≥20 mm influenced the local recurrence of single-session RFA with a single electrode insertion.

Postprandial middle cerebral arterial vasoconstriction in cirrhotic patients. A placebo, controlled evaluation

BACKGROUND/AIMS The objective of this study was to determine whether cerebral arterial vasoconstriction occurs in relation to postprandial splanchnic blood pooling in cirrhotic patients. METHODS The pulsatility and the resistive indexes and blood flow in the middle cerebral artery were measured by magnetic resonance imaging in 21 cirrhotics and 14 controls. These measurements were repeated 30 min after ingestion of a 400 kcal liquid meal or placebo. Seven controls and 14 patients received the meal, and seven controls and seven patients received placebo. RESULTS In the fasting conditions, cirrhotics had a greater pulsatility index (0.81 +/- 0.10 vs. 0.67 +/- 0.05, P < 0.001) and a greater resistive index (0.61 +/- 0.04 vs. 0.53 +/- 0.04, P < 0.001) and a lower blood flow (127 +/- 42 ml/min vs. 167 +/- 37 ml/min, P < 0.03) in the middle cerebral artery compared with controls. Meal ingestion significantly increased the pulsatility index (P < 0.03) and the resistive index (P < 0.01) and decreased blood flow (P < 0.03) in the middle cerebral artery in cirrhotics but not in controls. In contrast, placebo ingestion had no effect on the hemodynamic parameters in the middle cerebral artery in the two groups. CONCLUSIONS Results support the hypothesis that middle cerebral arterial vasoconstriction seen in cirrhotic patients is one of the cerebral arterys homeostatic responses to underfilling of the splanchnic arterial circulation.

Drinking status of heavy drinkers detected by arrival time parametric imaging using sonazoid-enhanced ultrasonography: study of two cases.

Chronic heavy consumption of alcohol is associated with increased risks of developing liver cirrhosis, hepatocellular carcinoma, and esophageal varices. Cessation of alcohol consumption is the most important requirement in treating these diseases. However, judging whether patients have actually maintained abstinence from alcohol requires reliance on their reports, which vary substantially across individuals using the test methods currently available. Arrival time parametric imaging (At-PI) using Sonazoid-enhanced ultrasonography is regarded as a useful approach for assessing the progression of lesions that have developed in liver parenchyma. In this study, we report two cases for whom this approach was successfully applied to indicate the drinking status of a heavy drinker. At-PI enables approximate and objective assessment of the drinking status of patients, independent of their reports; therefore, it is a promising method for providing information about drinking status.

Analysis of patients with tumor seeding after percutaneous radiofrequency ablation of hepatocellular carcinoma

To determine the incidence and risk factors associated with tumor seeding after radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC), 781 lesions from 352 patients who had undergone ultrasound (US)-guided RFA at our hospital between April 1999 and December 2005 were examined. Of these patients, 6 presented HCC lesions (6 lesions in total) and tumor seeding (7 seedings in total), which were analyzed. RFA using RITA 500 PA, the Cool-tip RFA System or the RTC 2000 System was performed. RFA sessions were repeated until complete necrosis was confirmed by imaging. Subsequently, follow-up was performed every 3-4 months by means of computed tomography (CT) and US scans. The 6 patients were retrospectively analyzed for patient characteristics, CT and histopathological findings, RFA method and complications, and clinical and imaging progress and outcome. Of the 6 lesions, 2 were in a subcapsular location at S7. Mean tumor diameter was 23.3±9 mm. Tumor biopsies indicated that 1 of the 6 lesions was well-differentiated, 4 were moderately-differentiated, and 1 was undifferentiated. The RITA 500 PA was used in 2 cases, and the Cool-tip RFA System in 4. Seeding was identified 14.6±13 months after RFA. Four of the cases with seeding were located on the abdominal wall, 2 on the thoracic wall and 1 in the Douglas pouch. Four of the patients underwent surgical resection, 1 radiation, and 1 conservative treatment for seeding. Five of the 6 patients died 12.6±9 months after seeding was detected, with the exception having undergone surgical treatment. The seeding risks identified in this study include treatment of subcapsular lesions and patient treatment over multiple sessions. The selection of the proper RFA system to avoid multiple sessions and the use of ablation technique are important for the prevention of seeding. Additionally, long-term follow-up after RFA by extensive imaging of the pelvic cavity and the thoracoabdominal wall is needed.

Disappearance of HCV after cessation of immunosuppression in a patient with ulcerative colitis and renal transplantation

We report a patient, a 45-year-old Japanese woman, who underwent living-related donor renal transplantation in 1986 and 1988, with the second procedure being successful. Ulcerative colitis (UC) was diagnosed in 1987 while she was receiving immunosuppressive therapy after the renal transplantation. She became positive for serum anti-hepatitis C virus (HCV) in November 1990, although her serum aminotransferase levels were normal. In June 2001, she had frequent episodes of melena with abdominal pain, as control of her UC deteriorated. In July 2001, she was admitted to the Department of Surgery at our hospital, and her daily dose of prednisolone was increased from 40 mg to 80 mg. After 2 weeks of high-dose prednisolone therapy, there was a significant increase of serum aminotransferases, and serum HCV-RNA rose above 850 KIU/ml (by reverse transcription-polymerase chain reaction [RT-PCR]). Control of UC was still poor, so cyclosporine A (CyA) was added at a dose that maintained a high serum concentration. The daily dose of prednisolone was tapered and leukapheresis was performed three times weekly. As result, serum aminotransferases decreased to the normal range. However, total colectomy and colostomy were required because the UC could not be controlled by these therapies. Serum aminotransferase levels increased transiently 2 months after the cessation of immunosuppressive therapy (prednisolone, azathioprine [AZP], and CyA). Subsequently, serum aminotransferases rapidly declined below normal, and the serum level of HCV-RNA (by RT-PCR) fell from 480 KIU/ml to less than 0.5 KIU/ml. She was discharged on April 25, 2002. During follow-up as an outpatient, serum HCV-RNA became negative and remained negative for 7 months. To confirm clearance of HCV, liver biopsy was performed, and no HCV-RNA was detected in the liver tissue by RT-PCR. These findings suggested that HCV was cleared by the cessation of immunosuppressive therapy, as a rebound effect.

Spontaneous complete necrosis of hepatocellular carcinoma: A case report and review of the literature

The present study reports the case of a 68-year-old male patient who presented to Tokyo Rosai Hospital for the treatment of alcoholic liver disease. A high density was observed in liver segment S2, while a tumor, 30 mm in size, exhibiting a low density was observed in the delayed phase upon contrast-enhanced computed tomography (CT), which was performed prior to admission. The tumor appeared slightly poorly defined upon abdominal ultrasound and was observed as a 30 mm low-echoic nodule that was internally heterogeneous. A 5-mm thick contrast enhancement effect was observed in the tumor border in the vascular phase on Sonazoid contrast-enhanced ultrasonography, while a defect in the entire tumor was observed in the post-vascular phase. Dysphagia had commenced three months prior to presentation and a weight loss of ~3 kg was observed. Therefore, the patient was admitted to Tokyo Rosai Hospital due to the presence of a hepatic tumor, and to undergo a close inspection of the cause of the tumor. Upon close inspection, it was determined that the weight loss and aphagia were caused by progressive bulbar paralysis. A contrast-enhanced CT was performed on post-admission day 29 as a follow-up regarding the hepatic tumor. As a result, although no change in the tumor size was observed, the contrast enhancement in the tumor borderline had disappeared. Necrosis of the tumor was considered. However, as viable persistence of the malignant tumor could not be excluded, a hepatic left lobe excision was performed. The patient was diagnosed with hepatocellular carcinoma (HCC) based on the morphology of the cellular necrosis. In addition, occlusion due to thrombus was observed within the blood vessels passing inside the fibrous capsule. It was hypothesized that the formation of a thick fibrous capsule and occlusion due to thrombus in the feeding vessel were possibly involved as the cause of complete spontaneous necrosis. Written informed consent was obtained from the patient.