Takahiro Horie

Mutations in a hydrophilic part of the core gene of hepatitis C virus in patients with hepatocellular carcinoma in China

We investigated the association between hepatocellular carcinoma (HCC) and the genomic characteristics of the hepatitis C virus (HCV) isolated from residents of the inshore region of the Yangtze River, an area that has one of the highest incidence of HCC in China. We determined the genomic heterogeneity of HCV, and the sequence divergence of the HCV core gene in individuals with chronic hepatitis and HCC. HCV genotype II was predominant among these isolates, which were homologous to other Chinese and Japanese HCV isolates. The rate of nucleotide substitutions in the core gene was significantly greater for isolates from HCC patients than for those from individuals with chronic hepatitis. The nucleotide substitutions were unevenly scattered along the core gene; a cluster of missense mutations was apparent in the region encoding the second hydrophilic domain of the core protein. The rate of occurrence of missense mutations per nucleotide substitution was significantly greater in this clustering variable region (CVR) of the core gene than in the remaining core gene sequence. These observations suggest that mutations in the CVR may be involved in the pathogenesis of chronic HCV infection during hepatocellular carcinogenesis.

Incidence of hepatitis C virus (HCV) antibodies and HCV-RNA in blood donors and patients with liver diseases in the inshore area of the Yangtze River

The Nantong area is a high risk region for primary hepatocellular carcinoma (PHC) in the inshore area of the Yangtze River. However, no detailed data are available about hepatitis C virus (HCV) infection in this area. We examined the incidences of anti‐HCV and HCV‐RNA in blood donors with hepatitis B surface antigen (HBsAg)‐ and hepatitis B core antibody (HBcAb)‐negative and patients with chronic liver diseases in the Nantong area at Nantong Medical College, Jiangsu Province, the Peoples Republic of China. The incidences of HBV markers (HBsAg and/or HBcAb), anti‐HCV (C100‐3), second generation anti‐HCV, HCV‐RNA and any marker of HCV in the Nantong area were found to be: 0.0, 0.7, 0.4, 0.2 and 0.7% in donor bloods; 16.9, 0.0, 3.4, 15.7 and 16.9% in patients with acute hepatitis; 82.8, 2.7, 4.8, 7.5 and 10.2% in those with chronic hepatitis; 86.4, 4.5, 9.1, 4.5 and 11.4% in those with liver cirrhosis; 87.5, 6.3, 0.0, 0.0 and 6.3% in those with PHC; and 21.8, 1.3, 1.3, 0.0 and 1.3% in patients without liver diseases, respectively. Although the Nantong area is a high risk region for PHC, these data suggest that HCV infection is not an important aetiological factor for PHC in this area.

Colonic pseudolipomatosis, microscopically classified into two groups

Background:  Colonic pseudolipomatosis is rare and the pathogenesis is controversial. The purpose of the present paper was to clarify endoscopic and histological characteristics of colonic pseudolipomatosis and to discuss the etiology.

Mutations of the core gene sequence of hepatitis C virus isolated from liver tissues with hepatocellular carcinoma

Abstract Our preliminary study indicated the presence of a clustering variable region (CVR) in the hepatitis C virus (HCV) core gene sequence in patients with hepatocellular carcinoma (HCC). To compare the sequence divergences of the core gene isolated from cancerous and noncancerous liver tissues in patients with HCC along with those from serum samples in patients with chronic hepatitis (CH), liver cirrhosis (LC), and HCC, we determined nucleotide and deduced amino acid (AA) sequences in a part of the core gene that included the CVR. The sequence diversity in the core gene increased with the progression from CH to LC or HCC and the number of nucleotide substitutions giving rise to changes in AA residues in the CVR was significantly greater in liver tissues than in sera from HCC patients. Moreover, the number of AA residues in the CVR that differed from the representative clone from cancerous liver portions was significantly higher than the number differing from noncancerous portions in each patient. An AA alteration from Gly to Ser at core codon 45 in the CVR was dominant in noncancerous portions rather than in cancerous portions and sera from HCC patients. These findings suggest that a large number of mutations, including biologically important AA sequence changes in the HCV core gene from liver tissue, might be related to hepatocarcinogenesis.

Duodenal lymphangitis carcinomatosa: Endoscopic characteristics and clinical significance

Background and Aim:  Duodenal lymphangitis carcinomatosa has been sporadically described, but so far little attention has been paid to duodenal lymphangitis carcinomatosa.

A Case of Penetration of the Large Intestinal Wall by a Toothpick

A 66‐year‐old man was admitted to hospital with symptoms of acute abdomen. Based on colonoscopic findings, localized peritonitis due to penetration of the sigmoid colon by a toothpick was diagnosed. During colonoscopy, the toothpick was removed using a grasping forceps, meaning that surgery was avoided. In cases where abdominal pain of unknown origin is observed, physicians should proceed with routine medical care while considering the possibility of foreign body ingestion, and work toward an early diagnosis.

Hepatobiliary cystadenocarcinoma without mesenchymal stroma showing a good prognosis

fact that hepatocellular carcinoma (HCC) is the fifth most common cause of cancer, randomized controlled trials studying early detection rate and applicability of curative treatments to support screening are lacking. Screening is limited by patient compliance and operator reliability. Considering randomized controlled trials with intention-to-treat analysis, only chemoembolization has been shown to improve survival in well-selected patients with unresectable HCC. 1

Colonoscopic extiripation of whipworms in patient with acute abdomen-like symptoms

A 25‐year‐old Indonesian male who had been living in Japan for the previous 2 years was hospitalized with sudden severe pain throughout his entire abdomen, but without abdominal guarding. Colonoscopy revealed 15 Trichuris trichiura whipworms in the cecum. These worms were extirpated using biopsy forceps. Immediately after extirpation, the abdominal pain disappeared. In Japan, whipworm infection with acute abdomen‐like symptoms at onset is extremely rare. In the present case, whipworm infection was diagnosed during colonoscopy, and the patient was simultaneously treated by extirpation of worms, thus indicating the utility of colonoscopy.

Virological features of hepatitis C virus infection in patients with liver diseases in the inshore area of the Yangtze River.

The prevalence, genotypes, coinfection and putative core gene sequence of hepatitis C virus (HCV) were investigated in the inshore area of the Yangtze River, where hepatocellular carcinoma (HCC) is thought to be very common. Most patients with liver diseases were infected with hepatitis B virus (HBV), but the incidence of anti-HCV was very low, being 3.4% in patients with acute hepatitis, and approximately 7% in those with chronic liver diseases. The rate of coinfection with HBV and HCV in patients with HCC was 4.5%, which was similar to that in Shanghai (5.6%), but lower than that in Yangzhou (31.2%), Beijing (26.8%) and Zhejiang (28.6%). Of 124 patients with non-A, non-B (NANB) liver disease, 15 (12.1%) were positive for anti-HCV. HCV genotype analysis in 41 HCV-RNA-positive patients with liver diseases showed that genotype II was dominant (85.4%), followed by genotype III (7.3%) and II+III (7.3%). No genotype I or IV was found. The genome sequences of the HCV putative core gene from two patients with chronic hepatitis were more closely similar to those of previous isolates from Japan and China, than to that of an American isolate. These results suggest that HCV infection is not an important etiological factor for liver diseases, and that the HCV isolates in China are from the same subgroup as those in Japan.

Mutations of the core gene sequence of HCV from patients with hepatocellular carcinoma in China

Publisher Summary The association between hepatocellular carcinoma (HCC) and the genomic characteristics of the hepatitis C virus (HCV) isolated from China is investigated in this chapter. The data reveal that nucleotide substitutions are unevenly scattered along the HCV genome, with a cluster of missense mutations in the region encoding the second hydrophilic domain of the core protein, and that the number of mutations in the clustering variable region (CVR) is higher. The sequence divergence of the CVR in HCV isolates from cancerous and noncancerous liver tissues in Japanese patients with HCC. The number of nucleotide substitutions giving rise to changes in amino acid residues in the CVR was greater in liver tissues than in sera from HCC patients. An amino acid alteration from glycine (Gly) to serine (Ser) at core codon 45 in the CVR was dominant in noncancerous portions rather than cancerous portions and sera from HCC patients. These findings suggest that a large number of mutations, including biologically important amino acid sequence changes in the HCV core gene from liver tissue, might be related to hepatocarcinogenesis.