Hiromi Saneto

FDG positron emission tomography/computed tomography for the detection of extrahepatic metastases from hepatocellular carcinoma

Aims:  To compare the efficacy of positron emission tomography (PET) computed tomography (CT), multi‐detector helical computed tomography (MDCT) and bone scintigraphy for the detection of extrahepatic metastases in patients with hepatocellular carcinoma (HCC).

Effectiveness of combination therapy of splenectomy and long-term interferon in patients with hepatitis C virus-related cirrhosis and thrombocytopenia.

Aim:  To elucidate the effectiveness of combination therapy of splenectomy and long‐term interferon (IFN) on survival and hepatocarcinogenesis, we retrospectively analyzed 180 patients with hepatitis C virus (HCV)‐related cirrhosis and thrombocytopenia.

Clinicopathological features of elderly patients with hepatitis C virus-related hepatocellular carcinoma

BackgroundIt is well known that the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) correlates with progression of liver fibrosis. However, there is little information on the impact of aging on hepatocarcinogenesis. The aim of this study was to elucidate the clinicopathological features of elderly patients with HCV-related HCC.MethodsThe study subjects were 693 consecutive patients newly diagnosed with HCC with anti-HCV. First, we divided them into a younger group (<70 years) and an elderly group (≥70 years) and compared clinicopathological features between the two groups. Next, we selected pure HCV-related HCC patients by excluding the patients with other probable factors for hepatocarcinogenesis (anti-HBc, interferon therapy, and alcohol) and compared the two groups again.ResultsHigher platelet count, lower male/female ratio, lower rate of habitual alcohol consumption, and better Child-Pugh class were recognized in the elderly group thant the younger group, statistically. In 133 cases of hepatic resection, fibrosis stage was lower in the elderly than the younger group. After selection of pure HCV-related HCC patients, in a stepwise multi variate analysis, male sex and platelet count <10 × 104/mm3 were significant variables associated with age <70. Regarding the latency period to HCC development, the patients who received a blood transfusion at an older age developed HCC sooner despite their lower grade of fibrosis.ConclusionsThe elderly patients developed HCC more often, despite their lower grade of fibrosis, compared with the younger patients. In addition to fibrosis, aging could be a factor affecting HCV-related hepatocarcinogenesis.

Randomized trial of high-dose interferon-α-2b combined with ribavirin in patients with chronic hepatitis C : correlation between amino acid substitutions in the core/NS5A region and virological response to interferon therapy

The aim of this study was to compare the efficacy of high‐dose interferon (IFN)‐α‐2b with standard dose of IFN‐α‐2b in combination with ribavirin (RBV) for patients with chronic hepatitis C virus (HCV) infection, and to investigate the predictive factors associated with virological response. Two hundred Japanese patients with high HCV viral load (>100 KIU/ml) were randomized to 6 or 10 mega units (MU) of 24‐week IFN‐α‐2b with RBV. Predictive factors were investigated; including pretreatment amino acid (aa) sequences of the core region and the IFN‐sensitive determining region (ISDR). The sustained virological response rate was not different in the two groups (24% vs. 30%) but the incidence of depression was significantly higher in the 10 MU group than 6 MU group (7% vs. 0%, P = 0.02). Younger age (<60) and HCV genotype (2a/b) were significant predictors of sustained virological response. In patients infected with genotype 1b, substitutions of core aa 70 and/or 91 were predictive for non‐virological response (P < 0.001), and substitutions in the ISDR was observed frequently in virological responders. Early viral kinetics study showed that serum HCV core antigen decreased more slowly in both patients with aa 70 and/or 91 substitutions in the core and with absence of substitutions in the ISDR. In conclusion, the use of a higher dose of IFN‐α‐2b in combination with RBV did not improve virological response but resulted in higher incidence of depression. Amino acid substitutions in the core and ISDR are predictive of virological response to the therapy in patients with genotype 1b and high viral load. J. Med. Virol. 81:640–649, 2009

Clinicopathological features, background liver disease, and survival analysis of HCV-positive patients with hepatocellular carcinoma: differences between young and elderly patients

BackgroundThe aim of this retrospective study was to determine the incidence and characteristics of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV) antibody-positive elderly patients with chronic hepatitis without cirrhosis.MethodsThe study included 65 patients who developed HCC at ≥75 years of age and who received their first HCC therapy at Toranomon Hospital between 1985 and 2005. Their clinicopathological and laboratory data were analyzed and compared with those of 33 patients who developed HCC at ≤50 years of age during the same period.ResultsThe ratio of women patients in the elderly group (M: F = 1.1: 1) was higher than in the younger group (M: F = 5.6: 1). Also, patients in the elderly group had better liver function and prothrombin activity (P = 0.001), and lower total bilirubin (P = 0.002) than the young group. Only 11 of 65 elderly patients were diagnosed with liver cirrhosis by biopsy or peritoneoscopy before or at the time of development of HCC. Based on a discriminate score using γ-globulin, hyaluronate level, platelet count, and sex, 27 (41.5%) elderly patients were considered to have chronic hepatitis, compared with six of 33 (18.1%) patients in the young group (P = 0.025). There were no differences in tumor number or size or tumor markers between the two groups. Survival rate was higher in the younger patients (P = 0.002), who were more likely to receive radical treatment.ConclusionsOur results showed distinct differences in HCV-related HCC between elderly and young patients and suggested that elderly patients (especially women) could develop HCC even when liver histology shows chronic hepatitis and lack of cirrhosis.

Amino acid substitutions in core and NS5A regions of the HCV genome can predict virological decrease with pegylated interferon plus ribavirin therapy.

BACKGROUND The current standard therapy for chronic hepatitis C is pegylated interferon (PEG-IFN) plus ribavirin (RBV) combination therapy. Recently, it has been reported that amino acid (aa) substitutions in the core region, as well as the IFN-sensitivity-determining region (ISDR), were predictive of non-virological response (NVR), sustained virological response (SVR) and early virological response. Despite the importance of these two predictive factors for combination therapy, their interaction is poorly understood. METHODS A total of 117 patients who were treated with PEG-IFN-α2b plus RBV combination therapy were selected for participation in this study. We determined the aa sequences in the core region and ISDR by direct sequencing and analysed them along with clinical data to identify predictive factors for therapeutic response. RESULTS The aa sequences in the core region and γ-glutamyl transpeptidase (GTP) levels were associated with SVR and NVR, but aa sequences in the ISDR were not. However, substitutions at both aa 70 and aa 91 in the core region without substitutions in the ISDR and higher levels of γ-GTP were independent predictive factors for NVR. Wild-type aa 70 and aa 91 in the core region, higher platelet counts and lower levels of γ-GTP were independent predictive factors for SVR. CONCLUSIONS These results indicate that analyses of aa substitutions in both the core region and the ISDR are useful for predicting the effectiveness of combination therapy, and could help to avoid therapy exposure for patients who have a low probability of SVR.

Beneficial effects of living-donor liver transplantation on esophageal varices

BackgroundLiver transplantation (LT) is known to improve bleeding esophageal varices (EVs) and portal hypertension. However, many issues related to EVs after LT remain unresolved, such as whether LT reduces blood supply to EVs, improves the diameter of unruptured EVs, or improves or worsens EVs. The aim of this retrospective study was to determine the effects of living-donor liver transplantation (LDLT) in patients with hepatic failure on EVs and inflow vessels to EVs and the factors associated with deterioration of EVs after LDLT.MethodsThe study subjects were 35 patients with cirrhosis who underwent LDLT. Endoscopy and multidetector helical computed tomography (MDCT) were performed before and after LDLT. The diameter of the inflow vessel of EVs was measured by MDCT before and after LDLT, together with the LDLT-related reduction rate of the diameter of the gastric vein (RRGV).ResultsEndoscopic examination showed improvement of EVs in 30 of 35 (86%) patients. RRGV improved in 17/35 (49%) patients, did not change in 13/35 (37%), and deteriorated in 5/35 (14%). The cause of RRGV deterioration seemed to be either the complication of portal vein or graft failure. In patients examined endoscopically at >1 year after LDLT, improvement of EVs was associated with significant changes in the rate of reduction of the major inflow vessel diameter and Child-Pugh score, compared with those who showed no improvement.ConclusionsLDLT results in improvement of EVs. EVs improved in 86% of the patients. Measurement of RRGV with MDCT is a good tool for prediction of EV improvement after LDLT.

Importance of Serum Concentration of Adefovir for Lamivudine-Adefovir Combination Therapy in Patients with Lamivudine-Resistant Chronic Hepatitis B

ABSTRACT Lamivudine (LMV)-adefovir pivoxil (ADV) combination therapy suppresses the replication of LMV-resistant hepatitis B virus (HBV), although its efficacy in suppressing HBV varies among patients. This study analyzed the clinical, virological, and pharmaceutical factors that influence the effect of the combination therapy. Patients negative for hepatitis B virus e antigen (HBeAg) and with low HBV DNA titers immediately prior to the combination therapy effectively cleared serum HBV DNA (P = 0.0348 and P = 0.0310, respectively). The maximum concentration of ADV in serum (ADV Cmax) was higher in patients who showed HBV DNA clearance (P = 0.0392), and the cumulative clearance rates of HBV DNA were significantly higher in patients with ADV Cmax equal to or greater than 24 ng/ml (P = 0.0284). HBeAg negativity and lower HBV DNA at the start of the combination therapy and higher ADV Cmax were found to be independent factors for serum HBV DNA clearance. Serum creatinine increased significantly during the combination therapy, and the ADV Cmax was higher in patients with low creatinine clearance rates. In conclusion, higher serum concentrations of ADV are associated with a good response to therapy based on clearance of HBV DNA in serum. However, care should be taken to prevent worsening of renal function due to high ADV serum concentrations.

The first Japanese case of COACH syndrome

COACH syndrome is a disorder characterized by hypoplasia of cerebellar vermis, oligophrenia, congenital ataxia, coloboma and hepatic fibrosis, and 21 cases have been reported to date. Here we describe the first Japanese case of COACH syndrome, who was diagnosed at the age of 37 years and never progressed to liver failure. The patient was found to have delayed developmental milestones at the age of 5 months and mental retardation at the age of 7 years. She had been treated for hepatopathy of unknown origin from the age of 22 years. She was admitted to Hiroshima University Hospital at the age of 37 years after the identification of esophageal varices on a routine upper endoscopy. Computed tomography of the abdomen revealed portal hypertension and splenomegaly, and liver biopsy showed liver fibrosis. In addition, she had coordination disorder and dysarthria. Brain magnetic resonance images revealed hypoplasia of cerebellar vermis. The final diagnosis was COACH syndrome. She underwent endoscopic injection sclerotherapy for esophageal varices. From that point until her death from ovarian cancer at the age of 41 years, the liver function tests were stable without an episode of hematemesis. Physicians should be aware of COACH syndrome when they examine young patients who present with hepatopathy, portal hypertension of unknown origin and cerebellar ataxia.