Kazuhiro Kasai

Effects of branched-chain amino acid-enriched nutrient for patients with hepatocellular carcinoma following radiofrequency ablation: a one-year prospective trial.

Background and Aim:  This prospective control study examined whether supplementation with branched‐chain amino acid (BCAA)‐enriched nutrients can help maintain and improve residual liver function and nutritional status in cirrhotic patients with hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA).

Therapeutic efficacy of combination therapy with intra-arterial 5-fluorouracil and systemic pegylated interferon α-2b for advanced hepatocellular carcinoma with portal venous invasion.

The prognosis of advanced hepatocellular carcinoma (HCC) remains poor, particularly among patients with portal vein tumor thrombosis (PVTT). This study evaluated the efficacy of combined 5‐fluorouracil and pegylated interferon (PEG‐IFN) α‐2b in patients with advanced HCC.

A novel prostaglandin E receptor subtype agonist, 0N0-4819, attenuates acute experimental liver injury in rats

We evaluated the efficacy of ONO-4819, a newly developed agonist of a prostaglandin receptor subtype (EP4), on experimental model of acute liver injury in rats. Acute liver injury was induced by simultaneous intraperitoneal (i.p.) administration of D-galactosamine (GalN, 1 g/kg body weight) and lipopolysaccharide (LPS, 100 mg/kg body weight). The rats received a single intraperitoneal injection of ONO-4819 (0.2 mg/kg body weight) or physiological saline immediately after GalN/LPS administration. Submassive hepatic necrosis with marked elevation of serum total bilirubin, serum aspartate aminotransferase and serum alanine aminotransferase levels developed 24 h after GalN/LPS administration. The administration of ONO-4819 significantly inhibited the development of submassive hepatic necrosis and inhibited the elevation in levels of biochemical markers that indicate liver function. In addition, the apoptotic index of hepatocytes assessed by the TUNEL method was significantly lower in rats treated with ONO-4819 than in the control. Although serum levels of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and interleukin-8 (IL-8) were markedly elevated after GalN/LPS administration, ONO-4819 significantly inhibited the elevation of those of TNF-alpha and IFN-gamma but not that of IL-8. The beneficial effect of ONO-4819 for acute liver injury was similar at doses of 0.1, 0.05 and 0.01 mg/kg body weight. These results suggest that the EP4 agonist, ONO-4819, may have a protective effect against experimental liver injury in rats through the suppression of inflammatory cytokines.

Changes in liver function parameters after percutaneous radiofrequency ablation therapy in patients with hepatocellular carcinoma

Aim:  To evaluate changes in liver function parameters and risk factors 1 year after percutaneous radiofrequency ablation (RFA) therapy in patients with hepatocellular carcinoma (HCC).

Evaluation of newly developed combination therapy of intra-arterial 5-fluorouracil and systemic pegylated interferon α-2b for advanced hepatocellular carcinoma with portal venous invasion: preliminary results.

Aim:  Prognosis is extremely poor for advanced hepatocellular carcinoma (HCC) in patients with portal invasion. The present study evaluated the efficacy of combined intra‐arterial 5‐fluorouracil (5‐FU) and systemic pegylated interferon (PEG‐IFN)α‐2b in patients with advanced HCC.

Conservative treatment of an aortoesophagial fistula after endovascular stent grafting for a thoracic aortic aneurysm

Summary Background Aortoesophageal fistula (AEF) is an uncommon condition that presents a problem in therapy because of the high rate of morbidity and mortality associated with its surgical management and the uniformly fatal outcome of medical treatment. In this article we describe a case of secondary AEF after endoluminal stent grafting of the thoracic aorta, which was observed by only conservative management and followed up for 14 months with no signs of recurrent hemorrhage or chronic mediastinitis. Case Report A 54-year old man with hepatocellular carcinoma (HCC) was admitted to our hospital because of tarry stool. He had a history of traumatic aneurysm, and undergone segmental replacement with a stent graft three years ago. After admission, Esophagogastroduodenoscopy and computed tomography identified AEF. He was treated conservatively, because his stage of HCC was advanced. Oral intake was prohibited, and the patient received proton pump inhibitors, intravenous hyperalimentation and antibiotics. Afterwards, no signs of hemorrhage were observed. Although oral intake was resumed after that, another bleeding event or development of mediastinitis was not observed. Subsequently, He was received chemotherapy for advanced HCC, and we observed downstaging of his advanced HCC. Conclusions Although we observed 14 months survival in our case under conservative management of secondary AEF, it seems that the treatment of secondary AEF should do the operative management.

Therapeutic efficacy of transarterial chemo-embolization with a fine-powder formulation of cisplatin for hepatocellular carcinoma

AIM To evaluate the efficacy of transarterial chemoembolization (TACE) using a suspension of a fine-powder formulation of cisplatin (DDPH) in lipiodol (LPD) in the treatment of hepatocellular carcinoma (HCC). METHODS The subjects were 262 HCC patients treated with TACE using a DDPH-LPD suspension. The DDPH-LPD suspension was prepared by mixing 50 mg of DDPH into 10 mL of LPD. TACE was repeated when treated lesions relapsed and/or new hepatic lesions were detected. These patients received additional TACE using the same agent. TACE was repeated until complete regression of the tumor was obtained. The primary efficacy endpoint of the current study was the objective early response rate. Secondary efficacy endpoints were progression-free survival (PFS) and overall survival. RESULTS The objective early response rate was 43.6%. Cumulative PFS rates were 56.7% at 6 mo, 23.1% at 12 mo, 13.4% at 18 mo, and 10.5% at 24 mo. The median PFS was 6.6 mo. Cumulative survival rates were 90.6% at 6 mo, 81.9% at 12 mo, 70.5% at 24 mo, and 58.8% at 36 mo. Median survival time was 46.6 mo. All adverse reactions were controllable by temporary suspension of treatment. No serious complications or treatment-related deaths were observed. CONCLUSION TACE using a suspension of DDPH in LPD may be a useful treatment for HCC.

Icteric acute hepatitis E with no response of immunoglobulin M class anti‐hepatitis E virus antibody

A 68‐year‐old Japanese man developed icteric acute hepatitis during periodic care after undergoing gastrectomy due to early gastric cancer. The routine serological markers for hepatitis A, B and C viruses were all negative. Although the liver enzymes spontaneously recovered without any specific therapy, cholestasis was relatively prolonged and successfully treated with prednisolone. Determination of serum hepatitis E virus (HEV) RNA revealed the transient infection of HEV, and both immunoglobulin (Ig)A and IgG class anti‐HEV antibodies were detected after the disease onset, whereas those were negative when measured 3 weeks prior to the onset. In addition, the titer of serum IgA class antibody was associated with the clinical signs of hepatitis. In contrast, no IgM class antibody was detected throughout the course. This case suggests that screening only with IgM class antibody is not sufficient to detect acute HEV infection.

Bimodal peaks of liver stiffness in a case of drug‐induced liver injury

A 69‐year‐old male complained of general fatigue and presented with elevation of liver enzymes without any cause of liver injury. We diagnosed him with hepatocellular drug‐induced liver injury (DILI). Liver stiffness, which was evaluated according to the shear wave velocity (SWV) using virtual touch tissue quantification, was serially observed during hospitalization. A fast SWV was noted on the date of admission, indicating a “hard” degree of liver stiffness. The SWV gradually decreased until the 20th hospital day. However, the patients liver enzymes again became elevated on the 20th hospital day, and the SWV simultaneously increased in association with a rise in the total bilirubin level. The laboratory data for the second peak of the SWV indicated mixed‐type DILI; therefore, the patients pathological state transitioned from the hepatocellular type to the mixed type. A liver biopsy performed before discharge revealed a state of recovery from acute inflammation without fibrotic changes. We conclude that the second peak of the SWV may be affected by the presence of intrahepatic cholestasis. We herein report the occurrence of bimodal peaks of liver stiffness in a patient with DILI. In such cases, each peak of liver stiffness may be the result of a different pathological mechanism, namely acute inflammation versus acute intrahepatic cholestasis. Although the detailed mechanisms underlying the development of liver stiffness due to intrahepatic cholestasis remain unclear, this case presented a limitation of virtual touch tissue quantification for evaluation of liver stiffness as fibrosis marker in the liver with intrahepatic cholestasis.

Contrast-Enhanced Ultrasonography Using Levovist : Usefulness of Diagnosis of Small Focal Nodular Hyperplasia Lesions

Differential diagnosis of focal nodular hyperplasia and hepatocellular carcinoma is clinically important because, while both are hypervascular tumors, they have vastly different prognoses. Because the spoke-wheel appearance is the primary characteristic of focal nodular hyperplasia, we attempted to detect this pattern in nodules smaller than 3 cm in diameter with contrast-enhanced ultrasonography using a contrast agent (Levovist). Four patients were examined with contrast-enhanced US: two of the patients were examined with Coded Harmonic Angio; the other two patients were examined with contrast-enhanced color and power Doppler US without harmonic imaging. Although the hepatic arteriogram showed the spoke-wheel appearance in only one tumor (diameter, 3 cm), contrast-enhanced US clearly demonstrated this characteristic in all four tumors, including three tumors that were less than 2 cm in diameter. Because it is noninvasive and can be carried out in an outpatient clinic, contrast-enhanced US is extremely useful for diagnosing small focal noduler hyperplasia lesions at sites that can be observed with US.