Takahiro Azakami

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).

Common genetic polymorphism of ITPA gene affects ribavirin‐induced anemia and effect of peg‐interferon plus ribavirin therapy

An association between a single nucleotide polymorphism (SNP) in the inosine triphosphate pyrophosphatase (ITPA) gene and reduction of hemoglobin during peg‐interferon plus ribavirin combination therapy for patients with chronic hepatitis C virus (HCV) infection has been reported. However, the effect of the SNP on outcome of therapy has not been fully elucidated. Factors associated with anemia during combination therapy, including rs1127354 genotype, were analyzed in 1,002 treated patients. The effect of the SNP on outcome of therapy was analyzed in a subset of 830 patients with genotype 1. A rapid initial decrease in hemoglobin levels was observed in patients with rs1127354 genotype CC compared with a slow decrease in non‐CC patients. Cumulative reduction of ribavirin was significantly more frequent in genotype CC patients than non‐CC patients (odds ratio 1.928, P = 8.6 × 10−8). The frequency of patients who received at least the recommended 80% of scheduled ribavirin was significantly lower among genotype CC patients, especially among those who had pretreatment hemoglobin levels between 13.5 and 15 g/dl (P < 0.03), and the sustained viral response rate was significantly lower in this group of patients. Independent predictive factors for sustained virological response included a SNP in the IL28B locus (rs809991), age, fibrosis, ITPA SNP rs1127354 as well as pretreatment hemoglobin levels. Our data suggests that measures to prevent anemia should be considered for patients who have pretreatment hemoglobin levels less than 13.5 g/dl or who have rs1127354 genotype CC and pretreatment hemoglobin levels between 13.5 and 15 g/dl. J. Med. Virol. 83:1048–1057, 2011.

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.

Combination therapy of oral fluoropyrimidine anticancer drug S-1 and interferon alpha for HCC patients with extrahepatic metastases.

Purpose: There is no standard treatment for hepatocellular carcinoma (HCC) patients with extrahepatic metastases. We assessed the efficiency and safety of the oral fluoropyrimidine anticancer drug S-1 combined with interferon alpha (IFN-α) for HCC patients with extrahepatic metastases. Methods: Twenty-nine HCC patients with extrahepatic metastases received S-1/IFN. One cycle of combination therapy represented 2 weeks followed by 2–4 weeks of rest. In each cycle, S-1 was administrated orally at 80–120 mg (depending on body surface area) every day and IFN-α intramuscularly at 5 million units thrice weekly. Results: The overall response of 29 patients was complete response (CR) in 4 (14%), partial response (PR) in 1, stable disease in 4, progressive disease in 12, and dropout in 8 patients. Objective response (CR + PR) was 17%. The time to progression and survival rate were significantly higher in patients with lung metastases (n = 19) than in those with painful bone metastases (n = 7; p = 0.0058 and 0.0015). With regard to NCI-CTC grade 3 adverse reactions, 3 (10%), 3 (10%) and 2 (7%) patients developed anorexia, leukopenia, and neutropenia, respectively. No grade 4 adverse reaction or toxicity-related death occurred. Conclusion: S-1/IFN is a potentially safe and suitable combination therapy for HCC patients with extrahepatic metastases, especially those with lung metastases.

Etiology and outcome of acute liver failure: Retrospective analysis of 50 patients treated at a single center

Background and Aim:  Acute liver failure (ALF) remains a devastating disease carrying considerable mortality. Since deceased donor liver transplantation is rarely performed in Japan, the artificial liver support system (ALS) and living donor liver transplantation (LDLT) are the main modalities used for treatment of ALF. The aim of this study was to analyze the outcome of ALF patients and to evaluate therapies for ALF according to etiology.

Evaluation of portosystemic collaterals by MDCT-MPR imaging for management of hemorrhagic esophageal varices

OBJECTIVE To study the correlation between changes in portosystemic collaterals, evaluated by multidetector-row computed tomography imaging using multiplanar reconstruction (MDCT-MPR), and prognosis in patients with hemorrhagic esophageal varices (EV) after endoscopic treatment. METHODS Forty-nine patients with primary hemostasis for variceal bleeding received radical endoscopic treatment: endoscopic injection sclerotherapy (EIS) or endoscopic variceal ligation (EVL). Patients were classified according to the rate of reduction in feeding vessel diameter on MDCT-MPR images, into the narrowing (n=24) and no-change (n=25) groups. We evaluated changes in portosystemic collaterals by MDCT-MPR before and after treatment, and determined rebleeding and survival rates. RESULTS The left gastric and paraesophageal (PEV) veins were recognized as portosystemic collaterals in 100 and 80%, respectively, of patients with EV on MDCT-MPR images. The rebleeding rates at 1, 2, 3, and 5 years after endoscopic treatment were 10, 15, 23, and 23%, respectively, for the narrowing group, and 17, 24, 35, and 67%, respectively, for the no-change group (P=0.068). Among no-change group, the rebleeding rate in patients with large PEV was significantly lower than that with small PEV (P=0.027). The rebleeding rate in patients with small PEV of the no-change group was significantly higher than that in the narrowing group (P=0.018). There was no significant difference in rebleeding rates between the no-change group with a large PEV and narrowing group (P=0.435). CONCLUSION Changes in portosystemic collaterals evaluated by MDCT-MPR imaging correlate with rebleeding rate. Evaluation of portosystemic collaterals in this manner would provide useful information for the management of hemorrhagic EV.

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.

Clinical outcome of esophageal varices after hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with major portal vein tumor thrombus

Aim:  To analyze the clinical outcome of esophageal varices (EV) after hepatic arterial infusion chemotherapy (HAIC) in patients with advanced hepatocellular carcinoma (HCC) and major portal vein tumor thrombus (Vp3/4).

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.

Eradication of hepatitis C virus genotype 1 after liver transplantation by interferon therapy before surgery: Report of three patients with analysis of interleukin‐28 polymorphism, hepatitis C virus core region and interferon‐sensitivity determining region

The achievement of sustained viral response (SVR) with interferon (IFN) therapy before liver transplantation (LT) is difficult due to liver dysfunction, pancytopenia and frequent side‐effects. Here, we report eradication of hepatitis C virus (HCV) genotype 1 after LT in three patients by IFN therapy before surgery. All three patients achieved virological response (VR), namely, fall in serum HCV RNA titer below the detection limit of real‐time polymerase chain reaction (PCR) during IFN administration. However, HCV RNA rebound after cessation of treatment in all three patients; namely, they could not achieve SVR despite treatment with pegylated (PEG) IFN plus ribavirin. All three patients had wild‐type amino acids (a.a.) at either aa70 or aa91 in the core region. Genotyping of IL‐28 single nucleotide polymorphisms (rs8099917) showed TT genotype in two patients and TG genotype in one. All three patients developed multiple hepatocellular carcinomas during the clinical course, and requested living donor LT using liver grafts from their relatives. The patients were treated with IFN to immediately before LT, at which time they remained negative for HCV RNA in serum by real‐time PCR. The three patients were followed‐up for 14–15 months after LT, during which they remained negative for HCV RNA despite no further IFN therapy. In conclusion, it is possible to eradicate HCV after LT by inducing VR with continuous IFN therapy to before LT in spite of viral and host evidences reflecting low susceptibility to IFN treatment.