Atsunori Kusakabe

Case–control study for the identification of virological factors associated with fulminant hepatitis B

Background:  Host and viral factors can promote the development of fulminant hepatitis B (FHB), but there have been no case–control studies for figuring out virological parameters that can distinguish FHB.

A weak association between occult HBV infection and non-B non-C hepatocellular carcinoma in Japan

BackgroundIn Japan, approximately 10% of hepatocellular carcinoma (HCC) patients are negative for both hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (anti-HCV), i.e., they constitute the so-called category of non-B non-C (NBNC) HCC. Little is known about the characteristics of NBNC-HCC.MethodsPotential risk factors for carcinogenesis (including occult HBV infection [HBsAg is negative but HBV DNA is positive by polymerase chain reaction (PCR)], obesity, and diabetes) were assessed in 233 HCC patients grouped according to hepatitis virus serological status (152 with HCV-HCC, 36 with HBV-HCC, and 45 with NBNC-HCC).ResultsThe prevalence of patients with obesity or diabetes was significantly higher in the NBNC-HCC group than in the HBV-HCC group. The same trend was observed even when patients with massive alcohol intake were excluded from the analysis. Only 8 patients (18%) in the NBNC-HCC group had detectable serum HBV DNA, and this was at very low levels (HBV/Ce/C2 and HBV/D were determined in 7 and 1 patients, respectively). In the NBNC-HCC group, the determined nucleotide sequences of the enhancer II/core promoter/precore/core region did not contain any HCC-associated mutations, whereas 25 of 30 patients in the HBV-HCC group carried strains with C1653T, T1753V, and/or A1762T/G1764A mutations.ConclusionsA weak association between occult HBV infection and HCC development was observed in the NBNC patients. This study indicates that nonalcoholic steato-hepatitis should be further investigated to assess its contribution to HCC development in this category of patients.

Pitavastatin inhibits hepatic steatosis and fibrosis in non‐alcoholic steatohepatitis model rats

Aim:  Non‐alcoholic steatohepatitis (NASH) may progress to liver cirrhosis, and NASH patients with liver cirrhosis are at risk of developing hepatocellular carcinoma. Statins, 3‐hydroxy‐3‐methyglutaryl‐coenzyme A reductase inhibitors, are well known to reduce low‐density lipoprotein cholesterol and reduce the incidence of coronary heart disease and other major vascular events by anti‐inflammatory and antifibrotic effects, and antiproliferative properties in colorectal cancers have also been reported. Recently, statins have been reported to improve hepatic steatosis; however, the effect on fibrosis is controversial.

Pyogenic granuloma of the stomach successfully treated by endoscopic resection after transarterial embolization of the feeding artery

Pyogenic granulomas represent the aquisition of vasodilative granulation tissue in the skin or mucosa. They are extremely rare in the alimentary tract, other than in the oral cavity. Here, we report a case of pyogenic granuloma arising from the gastric mucosa. An 82-year-old man was admitted to our hospital because of melena of more than 3 months, duration. Esophagogastroduodenoscopy (EGD) revealed a 30-mm-diameter semipedunculated lesion with an irregular surface in the fundus of the stomach. During hospitalization, the patient’s anemia worsened due to loss of blood from the lesion, with the level of hemoglobin declining to 6 g/dl, and a blood transfusion was required. Because radiological and endoscopic findings indicated the lesion was hypervascular, transarterial embolization of the nutritional artery of the lesion was performed before endoscopic resection of the lesion. One week after the embolotherapy, endoscopic mucosal resection was performed, without any complications, such as massive bleeding. Histological studies of the resected specimen revealed many capillaries of various sizes, lined with plump endothelial cells, and accompanied by acute and chronic inflammatory infiltrates. On the basis of these observations, the lesion was diagnosed as a pyogenic granuloma. One year later, the patient was asymptomatic and there was no evidence of tumor recurrence on follow-up EGD.

Clinical Evaluation of Sofosbuvir/Ledipasvir in Chronic Hepatitis C Genotype 1 with and without Prior Daclatasvir/Asnaprevir Therapy.

This study explored treatment outcomes of sofosbuvir (SOF)/ledipasvir (LDV) therapy for chronic hepatitis C patients with and without prior daclatasvir (DCV)/asunaprevir (ASV) therapy.

Clinical evaluation of sofosbuvir/ledipasvir in patients with chronic hepatitis C genotype 1 with and without prior daclatasvir/asunaprevir therapy

This study explored treatment outcomes of sofosbuvir (SOF)/ledipasvir (LDV) therapy for chronic hepatitis C patients with and without prior daclatasvir (DCV)/asunaprevir (ASV) therapy.

Noninvasive evaluation of hepatic fibrosis in hepatitis C virus‐infected patients using ethoxybenzyl‐magnetic resonance imaging

Liver biopsy is the gold standard test to determine the grade of fibrosis, but there are associated problems. Because gadolinium‐ethoxybenzyl‐diethylenetriamine pentaacetic acid is secreted partially in hepatocytes and bile, it is possible that ethoxybenzyl‐magnetic resonance imaging (EOB‐MRI) correlates with liver function and liver fibrosis. The aim of this study was to compare the fibrosis seen in liver biopsy samples to the signal intensity of the hepatobiliary phase measured on EOB‐MRI in hepatitis C virus (HCV)‐infected patients.

Mechanism of the dependence of hepatitis B virus genotype G on co‐infection with other genotypes for viral replication

Hepatitis B virus (HBV) is classified into several genotypes. Genotype G (HBV/G) is characterised by worldwide dispersion, low intragenotypic diversity and a peculiar sequence of the precore and core region (stop codon and 36‐nucleotide insertion). As a rule, HBV/G is detected in co‐infection with another genotype, most frequently HBV/A2. In a previous in vivo study, viral replication of HBV/G was significantly enhanced by co‐infection with HBV/A2. However, the mechanism by which co‐infection with HBV/A2 enhances HBV/G replication is not fully understood. In this study, we employed 1.24‐fold HBV/A2 clones that selectively expressed each viral protein and revealed that the core protein expressing construct significantly enhanced the replication of HBV/G in Huh7 cells. The introduction of the HBV/A2 core promoter or core protein or both genomic regions into the HBV/G genome showed that both the core promoter and core protein are required for efficient HBV/G replication. The effect of genotype on the interaction between foreign core protein and HBV/G showed that HBV/A2 was the strongest enhancer of HBV/G replication. Furthermore, Western blot analysis of Dane particles isolated from cultures of Huh7 cells co‐transfected by HBV/G and a cytomegalovirus (CMV) promoter–driven HBV/A2 core protein expression construct indicated that HBV/G employed HBV/A2 core protein during particle assembly. In conclusion, HBV/G could take advantage of core proteins from other genotypes during co‐infection to replicate efficiently and to effectively package HBV DNA into virions.

Serum interferon‐gamma‐inducible protein‐10 concentrations and IL28B genotype associated with responses to pegylated interferon plus ribavirin with and without telaprevir for chronic hepatitis C

Several studies have shown that high pretreatment concentrations of serum interferon‐γ‐inducible protein‐10 (IP‐10) are correlated with non‐response to pegylated interferon (PEG‐IFN) plus ribavirin (RBV) for chronic hepatitis C (CHC). However, there are few reports on their effect on the Asian population.

Risk of hepatocellular carcinoma in cirrhotic hepatitis B virus patients during nucleoside/nucleotide analog therapy

Some patients develop hepatocellular carcinoma (HCC) during nucleoside/nucleotide analog (NA) therapy even if alanine aminotransferase (ALT) or hepatitis B virus (HBV) DNA levels are sufficiently reduced. The aim of this study is to identify the risk factors of development of HCC during NA therapy.