Jiro Ikoma

Radiofrequency ablation combined with chemoembolization in hepatocellular carcinoma: treatment response based on tumor size and morphology.

PURPOSE To evaluate local therapeutic efficacy of radiofrequency (RF) ablation after chemoembolization for hepatocellular carcinoma (HCC) based on tumor size and morphology. MATERIALS AND METHODS Sixty-four patients underwent RF ablation under ultrasonographic or real-time computed tomographic (CT) fluoroscopic guidance within 2 weeks after chemoembolization. One hundred eight lesions were treated. Sixty-five lesions were small (<or=3 cm), 32 were intermediate in size (3.1-5 cm), and 11 were large (5.1-12 cm). Seventy-four of the HCCs were nodular lesions and the other 34 were nonnodular (multinodular and infiltrative) lesions. Response to treatment was evaluated by dynamic enhanced CT and magnetic resonance imaging. Tumor necrosis was considered to be complete when no foci of enhancement were seen within the tumor and at its periphery. RESULTS Complete necrosis was achieved in all lesions regardless of tumor size or morphology. There have been no local recurrences in small and intermediate-sized lesions regardless of tumor morphology during a mean follow-up of 12.5 months. In large HCCs, nodular lesions showed no recurrence, but two of six of nonnodular lesions recurred beyond the thermal lesions created around the tumor. The estimated 1-year survival rate was 98.0% in all patients. CONCLUSIONS This combined therapy has a therapeutic effect on small and intermediate-sized HCCs regardless of tumor morphology and is a promising treatment option for large nodular lesions. Control of large nonnodular lesions is still a challenging problem.

A significant reduction in serum alanine aminotransferase levels after 3-month iron reduction therapy for chronic hepatitis C: a multicenter, prospective, randomized, controlled trial in Japan

BackgroundIncreasing evidence indicates that iron cytotoxicity plays an important role in the pathogenesis of chronic hepatitis C (CHC). However, the biochemical effects of iron reduction therapy on CHC remain to be confirmed in a controlled study. This study aimed to test whether iron removal by repeated phlebotomy improves serum alanine aminotransferase (ALT) levels in patients with CHC.MethodsPatients were randomly assigned to an iron reduction therapy or control group. The patients in the treatment group received 3-month iron reduction therapy by biweekly phlebotomy, while the patients in the control group were followed up for 3 months with regular blood tests alone.ResultsThirty-three patients completed the 3-month treatment, while 29 patients received the complete follow-up. The serum ALT levels were reduced from 118 ± 79 to 73 ± 39 IU/L in the treatment group, but did not change in the control group (106 ± 45 versus 107 ± 48 IU/L). Posttreatment enzyme activity was decreased significantly from the baseline. Furthermore, it was significantly lower than the 3-month control level. Although 5 patients withdrew from the study, none was affected by any side effects of repeated phlebotomy that required them to discontinue the treatment.ConclusionsThis short-term controlled trial demonstrated the biochemical efficacy and safety of iron reduction therapy for patients with CHC.

Lactoferrin inhibits hepatitis C virus viremia in chronic hepatitis C patients with high viral loads and HCV genotype 1b

carcinoma have been reported during the past 16 yr. The time interval between fine-needle aspiration/biopsy and recurrence has varied from as early as 3 wk to as late as 4 yr. Needle diameter, number of passes, and the surrounding liver parenchyma are the factors influencing the rate of recurrence (2). The risk of needle tract recurrence of liver tumor should be regarded as significant, especially in patients with small hepatocellular carcinoma for whom long term survival is expected after surgical resection or orthotopic liver transplantation (3). Hence, the role of needle biopsy in confirming hepatocellular carcinoma needs critical evaluation. It should possibly be reserved for cases not amenable to surgical resection or where hepatocellular carcinoma cannot be diagnosed with noninvasive imaging modalities and -fetoprotein levels.

Hepatitis C virus core particle detected by immunoelectron microscopy and optical rotation technique

Hepatitis C Virus (HCV) are 55-65 nm spherical particles, but the internal structure of the virion remains to be clarified. To clarify the morphology of HCV core particles, we performed an immune electron microscopy (IEM) using plasma samples from two blood donors with high HCV RNA titers and a detergent-treated anti-HCV core antibody-free plasma sample with high HCV RNA titer (1.5x10(8) copies/ml). Spherical particles, with 33-40 nm in diameter (an average diameter of 37 nm) were found in 1.22-1.25 g/ml fractions after sucrose density gradient centrifugation by conventional electron microscopy (EM). IEM using rabbit polyclonal antibody (RR8) specific to the putative HCV core protein and goat anti-rabbit IgG colloidal gold particles revealed that these spherical particles specifically reacted with RR8. This finding indicates that the spherical particles are naked HCV core particles. Some of the HCV core particles had an icosahedron-like structure. Optical rotation technique showed that the HCV core particle exhibits six-fold symmetry and that the length of regular hexagon side is approximately 20 nm. These findings showed that HCV core particles are spherical particles of 33-40 nm in diameter and that HCV core particles may possess an icosahedron-like structure and a buoyant density of 1.22-1.25 g/ml.

Pathology of the Liver in “Idiopathic Portal Hypertension” Associated with Autoimmune Disease

The histopathology of the liver in idiopathic portal hypertension (IPH) associated with autoimmune disease (15 cases), was examined and compared with that of IPH without autoimmune disease (31 cases). It was found that hepatic histopathology was heterogeneous in the cases with autoimmune disease. That is, the hepatic histopathology in 7 cases was similar to that of classic IPH without autoimmune disease, and the remaining 8 cases disclosed unusual lesions such as focal non suppurative cholangitis, nodular parenchymal hyperplasia, moderate portal inflammation, and intrahepatic ductopenia. These unusual lesions, which frequently coexisted in the same case, were not typical ones for making other diagnoses such as primary biliary cirrhosis or nodular regenerative hyperplasia of the liver. These findings suggest that unusual histologic lesions in the livers of IPH patients with autoimmune disease may represent an accentuated immunologic reaction inherent in IPH, or that such cases may be an abortive or incomplete form of primary biliary cirrhosis or nodular regenerative hyperplasia of the liver. Acta Pathol Jpn 39: 586‐592, 1989.

Effect of lactoferrin in patients with chronic hepatitis C: Combination therapy with interferon and ribavirin

Objectives:  Lactoferrin has been reported to inhibit hepatitis C virus (HCV) infection in cultured human hepatocytes and HCV viremia in patients with chronic hepatitis C (CHC). The aim of this study was to evaluate the effect of combined triple therapy of lactoferrin, interferon and ribavirin in patients with CHC.

Decrease of regional cerebral blood flow in liver cirrhosis.

Objective Alterations of regional cerebral blood flow (rCBF) in subjects with liver cirrhosis have not been fully evaluated. We evaluated quantitative changes in rCBF using single photon emission computed tomography (SPECT). Methods Twenty‐eight Japanese patients with liver cirrhosis were enrolled in this study. None of them exhibited advanced hepatic encephalopathy at the time of examination. The cause of liver cirrhosis was viral infection in 26 patients; the cause was unknown in two patients. Child ‐ Pugh classification of the patients was as follows: Group A, 12 patients; Group B, 12 patients; and Group C, four patients. The control group consisted of 25 age‐matched healthy subjects. Radionuclide angiography was performed by rapid injection of Tc‐99m ethyl cysteinate dimer (ECD) (740 MBq) via the right cubital vein, and then SPECT brain images were taken. Using the Patlak graphical method, rCBF values (ml/100 g per min) were calculated in the frontal, parietal, temporal and occipital lobes and cerebellum on SPECT images. Results The rCBF values were lower in cirrhotic patients than in controls, i.e. by 15% in the frontal lobe, by 12% in the parietal lobe, by 10% in the temporal and occipital lobes, and by 7% in the cerebellum. They decreased concomitantly with the severity of liver disease. A significant negative correlation was noted between rCBF values and Child‐Pugh score in the frontal (P < 0.01), parietal (P < 0.05) and occipital lobes (P < 0.01). rCBF values of each region were not correlated with age or with results of neuropsychological test. The degree of association between rCBF values and results of laboratory examination was generally poor. Conclusion Patients with liver cirrhosis without advanced encephalopathy showed widespread reduction in rCBF; this reduction was particularly evident in the frontal lobe. Tc‐99m ECD SPECT may be useful for evaluating cerebral functional changes in patients with liver cirrhosis. Eur J Gastroenterol Hepatol 12:1001 ‐ 1006

Evaluating response to nutritional therapy using the branched‐chain amino acid/tyrosine ratio in patients with chronic liver disease

The branched‐chain amino acid (BCAA)/tyrosine (Tyr) ratio (BTR) recently has been reported to be a good indicator of the severity of hepatic parenchymal injury in patients with chronic liver disease. In the present study, sequential changes of BTR after BCAA administration were determined in patients with chronic liver disease to evaluate the value of BTR as a marker of the clinical response to nutritional therapy in these patients. This study comprised 75 patients with chronic hepatitis and 96 with liver cirrhosis. BTR was significantly decreased in patients with cirrhosis and hepatitis compared with healthy subjects. BTR was significantly correlated with the Child‐Pugh score and with other liver function tests. BCAA increased significantly 2 hr after BCAA administration and decreased gradually thereafter. Tyr significantly decreased 4 hr after BCAA administration. BTR significantly increased 2 and 4 hr after BCAA therapy. The increase in BTR 3 hr after BCAA administration was low in patients with decreased basal BTR. The results of this study showed that BTR is a good index of the hepatic parenchymal damage and that it may be a useful marker for monitoring response to nutritional therapy in patients with chronic liver disease. J. Clin. Lab. Anal. 13:31–34, 1999.

Improvement of regional cerebral blood flow after treatment with branched-chain amino acid solutions in patients with cirrhosis

Objective The administration of solutions rich in branched‐chain amino acids leads to mental recovery from acute hepatic encephalopathy in patients with liver cirrhosis. However, the mechanism of action of branchedchain amino acids remains unclear. The purpose of this study was to evaluate the effect of intravenous infusion of branched‐chain amino acids on brain perfusion in patients with liver cirrhosis. Methods Single photon emission computed tomography scans were performed in 14 patients with liver cirrhosis before and after the administration of branched‐chain amino acids in a single‐day split‐dose protocol. The per cent change in regional brain perfusion was calculated in high frontal, parietal, temporal, occipital lobes and cerebellum. Thereafter, statistical parametric mapping was performed to identify brain regions with abnormal cerebral perfusion. Results Intravenous infusion of solutions enriched with branched‐chain amino acids induced a 13‐20% increase in regional cerebral blood flow. Cirrhotic patients had regions of significant hypoperfusion, as determined by statistical parametric mapping, in the left superior parietal and posterior cingulate as compared to the control group. This hypoperfusion of parietal and cingulate regions was not detected after treatment with solutions of branchedchain amino acids. Conclusions The results of the present study suggest that administration of solutions enriched with branched‐chain amino acids improves cerebral perfusion in patients with cirrhosis.

High prevalence of transfusion-transmitted virus among patients with non-B, non-C hepatocellular carcinoma

Many patients with hepatocellular carcinoma are positive for hepatitis B surface antigen (HBsAg) or antibodies to hepatitis C virus (anti‐HCV). Recently, transfusion‐transmitted virus (TTV) DNA was identified in the serum of patients with non‐B, non‐C posttransfusion hepatitis. In this study, the prevalence of TTV DNA in the serum of patients with non‐B, non‐C hepatitis‐associated hepatocellular carcinoma was evaluated.