Changing clinical and molecular characteristics of hepatitis E virus infection in Mie Prefecture, Japan: Disappearance of indigenous subtype 3e strains.

AIM: To evaluate the clinical and molecular characteristics of hepatitis E virus (HEV) infection in Mie Prefecture, Japan, from 2004 through 2018. METHODS: The clinical information of hepatitis E cases was collected from 21 medical institutions in Mie Prefecture. The nucleotide sequences of infecting HEV strains were determined for cases with available serum samples. The origins or transmission routes were inferred from phylogenetic analyses of the nucleotide sequences. RESULTS: Fifty-three patients were diagnosed with HEV infection. The number of cases increased each year through 2012 and then decreased. Analyses of the clinical characteristics of the cases indicated that even mild cases were detected in the latter 10 years of the study. Nucleotide sequence analyses were undertaken on 38 of the 53 cases. The HEV subtype 3e (HEV-3e) strains identified for 13 cases were closely related to a swine HEV-3e strain that was isolated from the liver of a pig bred in Mie Prefecture. The number of cases infected with the indigenous Mie HEV-3e strains increased until 2012 but have not been reported since 2014. In the latter half of the study, cases involving various HEV strains of different genotypes and subtypes emerged. CONCLUSIONS: The disappearance of indigenous Mie HEV-3e strains appeared to be the primary cause for the decrease in hepatitis E cases in Mie Prefecture. The disappearance might have been associated with improved hygienic conditions on pig farms or the closure of contaminated farms. The results suggest that indigenous HEV strains can be eradicated by appropriate management.

Investigating the origin and global dispersal history of hepatitis E virus genotype 4 using phylogeographical analysis.

BACKGROUND & AIMS: Hepatitis E virus (HEV) genotype 4 has mainly been isolated from sporadic hepatitis cases and swine in Asian countries. We analysed the origin and global dispersal history of genotype 4 using a Bayesian phylogeographical approach. METHODS: The 412-nucleotide sequences of open reading frame 2 of genotype 4 (47 Japanese, 40 Chinese, 1 Indian, 8 Indonesian, 1 Korean, 1 Taiwanese, 2 Danish and 2 Italian), of which sampling date and location were known, were collected. Evolutionary rate, divergence time, demographic growth and phylogeography were co-estimated in the Bayesian statistical inference framework implemented in the BEAST package to model spatial dispersal on a time-scaled genealogy. RESULTS: The most probable origin of genotype 4 was Japan and the time of origin was 1909 (95% highest posterior density, 1871-1940). Seven lineages of genotype 4 migrated from Japan to China. The analysis also showed the migration of genotype 4 from Japan or China to India and Indonesia and from China to Indonesia, Taiwan, Korea and a few European countries. CONCLUSIONS: Swine trade between countries coincided with the migration time and direction of genotype 4 in some cases and was considered the primary cause of dispersal. However, there was no clear cause of dispersal for some cases, for which no records of pig trade were found. Future research should analyse additional nucleotide sequences paired with epidemiological data from various countries to improve our understanding of HEV dispersal.

Hemostasis by esophageal stent placement for management of esophageal tumor bleeding:a case report.

A 67-year-old male was diagnosed with advanced esophageal cancer. A computed tomography scan showed multiple intra-abdominal lymphadenopathies. Because the tumor was thought to be unresectable, we initiated chemotherapy. Twelve months later, the patient was admitted to our hospital because of hematemesis. Gastroduodenoscopy revealed oozing bleeding from the esophageal tumor. Hemostasis was not achieved with conservative treatment, and frequent blood transfusions were required. Endoscopic hemostasis was difficult to achieve because of the malignant esophageal stenosis. To treat the malignant esophageal stricture and esophageal tumor bleeding, we attempted to insert an esophageal covered self-expandable metallic stent. After the procedure, hemostasis was achieved by mechanical tamponade. Here we report a rare case of esophageal tumor bleeding that was managed with mechanical tamponade using an esophageal covered self-expandable metallic stent.

An impacted minor papilla stone in a patient with pancreas divisum that caused acute exacerbation of chronic pancreatitis: a case report.

A 75-year-old woman with epigastric pain was admitted to our emergency department. She was diagnosed with an acute exacerbation of chronic pancreatitis based on the results of blood tests and abdominal computed tomography (CT). The abdominal CT and magnetic resonance cholangiopancreatography revealed pancreas divisum. Abdominal CT also showed a stone in the minor papilla, with impaction of the stone being the most likely cause of the acute episode. Therefore, endoscopic sphincterotomy of the minor papilla and endoscopic naso-pancreatic duct drainage were performed to remove the stone and decrease the internal pressure of the pancreatic duct. These procedures improved the patient's clinical status. The naso-pancreatic drainage tube was removed, and her pancreatitis has not recurred. Herein, we report a rare case of an impacted minor papilla stone in a patient with pancreas divisum that caused an acute exacerbation of chronic pancreatitis.

[Acute obstructive suppurative pancreatic ductitis after endoscopic retrograde cholangiopancreatography in a patient with carcinoma of the pancreatic head:a case report].

An 85-year-old woman with jaundice was referred to our hospital where she was diagnosed with obstructive jaundice due to carcinoma of the pancreatic head based on blood tests and abdominal computed tomography (CT). We performed endoscopic retrograde cholangiopancreatography (ERCP) for biliary drainage, but 5 days after the procedure, she complained of epigastric pain. Laboratory data revealed an elevated white blood cell count and a high serum amylase concentration. Follow-up CT 6 days after the ERCP revealed that the main pancreatic duct diameter had increased since the time of admission. Therefore, ERCP was performed for pancreatic ductal drainage. Purulent pancreatic juice was drained by endoscopic placement of a nasopancreatic drainage tube in the main pancreatic duct, resulting in marked alleviation of clinical symptoms;however, after removal of the tube, the abdominal pain recurred. Subsequent endoscopic placement of a pancreatic stent improved her clinical status once again. Herein, we report this rare case of acute obstructive suppurative pancreatic ductitis in a patient with carcinoma of the pancreatic head.

A case of gastric crystal-storing histiocytosis.

A 54-year-old male patient underwent upper gastrointestinal endoscopy, which revealed a 25-mm brown region in the angular section of the greater curvature of the stomach. The region was histologically determined to be gastric mucosa with an accumulation of histiocytes containing eosinophilic substances in the cytoplasm and chronic inflammatory cell infiltration. Histiocytes were immunohistologically positive for CD68, IgG, and κ. Based on these findings, the patient was diagnosed with gastric crystal-storing histiocytosis comprised of histiocytes phagocytosing IgG-κ-type immunoglobulin. This is a rare disease of which there have been no previous reports that included long-term follow-up. Here, we report the case with a literature review.

[Rupture of a gastroduodenal artery aneurysm caused by duodenal ulcer: a case report].

A 73-year-old man with a history of tarry stools was admitted to our hospital. Gastroduodenoscopy on admission revealed an ulcer with an exposed vessel at the duodenal bulb. During endoscopic clipping for prevention of re-bleeding, a large amount of bleeding from the vessel was observed. Hemostasis was achieved after the procedure. However, 7 days later, the patient passed a large amount of tarry stools and experienced hypovolemic shock. Endoscopic re-examination revealed a pulsatile aneurysmal vessel at the base of the duodenal ulcer. Abdominal contrast-enhanced computed tomography and abdominal angiography demonstrated an aneurysm of the gastroduodenal artery, which was successfully treated with transcatheter arterial embolization. Thus, here we report a rare case of an aneurysm of the gastroduodenal artery caused by a duodenal ulcer.

[Gastric intramucosal cancer spreading to submucosal heterotopic gastric glands].

A 73-year-old man was referred to our hospital for further examination of an intra-abdominal mass. An upper gastrointestinal endoscopy revealed a 0-IIa+IIc lesion on the lesser curvature of the middle body. The lesion was diagnosed as early gastric cancer (tub1, SM), and a partial gastrectomy was performed. Pathological evaluation revealed a well-differentiated intramucosal adenocarcinoma that had partially spread to the submucosa. On immunohistochemical examination, the lesion displayed an intestinal phenotype. The submucosal lesion had poor stromal reaction, and there was smooth muscle tissue surrounding the lesion. As mentioned earlier, we diagnosed the lesion as a gastric intramucosal cancer spreading to the submucosal heterotopic gastric glands.

[A case of polyp-type ampullary carcinoma-in-adenoma within the ampullary channel, displaying an intraductal growth pattern].

A 70-year-old woman with jaundice was referred to our hospital. Obstructive jaundice caused by common bile duct (CBD) stones was diagnosed based on the results of blood tests, abdominal computed tomography, and endoscopic retrograde cholangiopancreatography. We attempted to remove the CBD stones endoscopically. After endoscopic sphincterotomy, a polypoid lesion was exposed at the ampulla of Vater. Histological examination of a biopsy specimen from the ampullary lesion revealed a tubular adenoma, and the patient underwent pylorus-preserving pancreatoduodenectomy. Pathological examination of the resected specimen revealed a polyp-type ampullary carcinoma-in-adenoma arising from the ampullary channel. Herein, we report a rare case of polyp-type ampullary carcinoma-in-adenoma displaying an intraductal growth pattern.

High genomic similarity between European type hepatitis E virus subgenotype 3e strains isolated from an acute hepatitis patient and a wild boar in Mie, Japan.

A 67-year-old male living in Tsu city, Mie prefecture, Japan was referred to our hospital for further examination of acute liver injury and was diagnosed as having clinical hepatitis E virus (HEV) infection in January 2010. The HEV strain (HE-JA11-1701) isolated from the patient belonged to genotype 3 and European-type subgenotype 3e. It was presumed that the patient had been infected from a wild boar (Sus scrofa leucomystax) because he consumed meat/viscera from a wild boar that he had captured himself as a hunter approximately 2 months before disease onset. A specimen of the boar meat/viscera that the patient had ingested was not available. However, the HE-JA11-1701 strain was 99.8% identical within the 412-nucleotide sequence of the open reading frame 2 region to a HEV strain (JBOAR012-Mie08) that had been recovered from a wild boar captured near the patient's hunting area in 2008. A phylogenetic analysis confirmed that the two HEV strains had a close genetic relationship and were segregated into subgenotype 3e, supported by a high bootstrap value of 99%. Of note, the HE-JA11-1701 and JBOAR012-Mie08 strains were remotely related to the 3e strains reported in Japan and European countries, with a nucleotide difference of 7.9-13.9%, reinforcing the uniqueness of the 3e strains obtained in the present study. These results strongly support our speculation that the patient developed acute hepatitis E via consumption of HEV-infected boar meat/viscera. Genetic analyses of HEV strains are useful for tracing infectious sources in sporadic cases of acute hepatitis E.

Characterization of sporadic acute hepatitis E and comparison of hepatitis E virus genomes in acute hepatitis patients and pig liver sold as food in Mie, Japan.

AIM: To characterize hepatitis E in Mie prefecture and to investigate whether raw pig liver sold as food in Mie is contaminated with hepatitis E virus (HEV) strains similar to those recovered from patients. METHODS: Seventeen patients with sporadic acute hepatitis E treated from 2004 to 2012 were studied. A total of 243 packages of raw pig liver from regional grocery stores were tested for the presence of HEV RNA. The partial genomic sequences of human and swine HEV isolates were determined and subjected to the phylogenetic analyses. RESULTS: The HEV isolates recovered from the 17 patients segregated into genotype 3 (n = 15) and genotype 4 (n = 2), and 15 genotype 3 isolates further segregated into 3e (n = 11) and 3b (n = 4). Pig liver specimens from 12 (4.9%) of the 243 packages had detectable HEV RNA. All 12 swine HEV isolates were grouped into genotype 3 (3a or 3b). Although no 3e strains were isolated from pig liver specimens, two 3b swine strains were 99.5-100% identical to two HEV strains recovered from hepatitis patients, within 412-nt partial sequences. CONCLUSION: The 3e HEV was prevalent among hepatitis E patients. HEV RNA was detected in approximately 5% of pig liver sold as food. The presence of identical HEV strains between hepatitis patients and pig liver indicated that pigs play an important role as reservoirs for HEV in humans in Mie. Further studies are needed to clarify the source of 3e HEV in the animal and environmental reservoirs.

[A case of invasive micropapillary carcinoma of the pancreas concomitant with intraductal papillary mucinous neoplasm].

Invasive micropapillary carcinoma (IMPC), a rare subtype of adenocarcinoma, has a high incidence of lymph node metastasis and is associated with a poor prognosis. A 77-year-old woman was admitted to our hospital for the assessment of intraductal papillary mucinous neoplasm (IPMN). We diagnosed her with pancreatic cancer concomitant with IPMN and performed pancreaticoduodenectomy. The lesion was predominantly composed of ductal adenocarcinoma with a micropapillary component. On immunohistochemical analysis, a characteristic " inside-out pattern" was observed in the micropapillary component. This confirmed the diagnosis of pancreatic cancer with a micropapillary component. In the present report, we describe a very rare case of IMPC of the pancreas.

[A case of heterochrony and ectopic recurrence of a gastric signet ring cell carcinoma following partial gastrectomy].

A 53-year-old woman was referred to our hospital with a round, discolored lesion measuring 4mm in diameter that was identified as a minute gastric signet ring cell carcinoma. According to the Japanese classification of gastric carcinoma, it was graded as type 0-IIb. Seven years back, the woman had undergone pylorus-side gastrectomy for a small signet ring cell carcinoma, and the present lesion was assumed to result from heterochrony and ectopic recurrence. Endoscopic submucosal dissection was performed for the minute lesion. Clinicopathological findings revealed gastric mucosal cancer without invading lymph vessels or veins, similar to the previous lesion. We therefore report two very rare lesions in the same case. This case report demonstrates the importance of performing regular follow-up gastroduodenoscopy to detect recurrence in patients with these lesions.

[A case of calcifying fibrous tumor in the abdominal wall, morphologically resembling a gastric submucosal tumor].

We report an extremely rare case of a calcifying fibrous tumor (CFT) occurring in the abdominal wall. A 43-year-old woman was referred to our hospital because of a gastric submucosal tumor. Imaging findings revealed a gastric submucosal tumor with calcification. Endoscopic ultrasound-guided fine-needle aspiration was attempted to obtain a tissue specimen; however, the tumor was not adequately visualized because of calcification. Local excision was performed because of the tumor growth and the risk of progression to gastrointestinal stromal tumor. The tumor was histologically diagnosed as a CFT. We describe the imaging and pathological findings, and discuss the differential diagnosis and histogenesis of CFT.

[A case of advanced gastric cancer with an invasive micropapillary carcinoma component].

A 62-year-old man was admitted for the evaluation of epigastric pain. Upper gastrointestinal endoscopy revealed a type 3 circumferential carcinoma in the gastric antrum. Distal gastrectomy was performed, and the lesion was histopathologically diagnosed as gastric cancer with an invasive micropapillary carcinoma component. Chemotherapy was administered after surgery; however, he died with multiple liver metastases after 39 months. Micropapillary carcinoma is a rare, high-grade, malignant histological subtype of gastric cancer that has not been described in detail till date. Here we describe this rare lesion and present a review of the relevant literature.

The Possibility of Acute Drug-Induced Liver Injury Associated With Prednisolone.

A female patient was referred to our hospital with complaints of liver injury. She had been treated for immunoglobulin (Ig)A nephropathy using prednisolone and other medications. Drug-induced liver injury (DILI) was suspected, as no evidence of viral infection or autoimmune liver disease was apparent. All medications except for prednisolone were discontinued, but liver enzyme levels remained elevated. Percutaneous liver biopsy showed the characteristics of DILI and drug lymphocyte stimulation testing yielded positive results for prednisolone. After stopping administration of prednisolone, liver enzyme levels recovered to near-normal. Prednisolone has immunosuppressive effects and is sometimes used to treat DILI. Some reports have revealed that high-dose corticosteroids can induce liver injury, but liver injuries associated with low-dose corticosteroid therapy have not been described. Prednisolone-induced liver injury is a rare phenomenon. When low-dose corticosteroids are used for treatment, care should be taken regarding the possibility of liver injury.

Bleeding From a Ruptured, Extraluminally Growing Gastric Gastrointestinal Stromal Tumor Treated by Transcatheter Arterial Embolization: A Case Report.

A 49-year-old man with abdominal pain was referred to our hospital. Abdominal computed tomography showed an extraluminal tumor near the gastric anterior wall and intra-abdominal fluid collection. A ruptured intra-abdominal tumor was suspected, and emergency abdominal angiography was performed. Hemorrhage into the abdominal cavity was seen, and transcatheter arterial embolization (TAE) was performed, which stopped the bleeding. The tumor was surgically resected, and a diagnosis of an extraluminally growing gastric gastrointestinal stromal tumor was made. TAE should be considered for rare cases of extraluminally growing tumors with intra-abdominal hemorrhage.

[A case of blastic plasmacytoid dendritic cell neoplasm involving the skin].

A 81 year-old male patient visited our hospital on February, 2011 because he found the subcutaneous tumor on his back. The dermatologist performed skin biopsy and found that large atypical cells diffusely proliferated in the sub-epidermal and subcutaneous tissue. Two month later, we diagnosed him as blastic plasmacytoid dendritic cell tumor, as the blastic cells in the lymph node were CD4+, CD56+, CD3-, CD5-, CD20-, CD138-, MPO-, granzyme B-, TCL1+. None of the gene rearrangements of T-cell receptor and immunoglobulin was negative in the lymph node. The tumor was relapsed after 3 courses of COP therapy and the patient failed to respond to the salvage therapies such as CEPP and FMD therapy. As this tumor is rare and there are no standard regimens, we reviewed the past case series and discussed about the pathogenesis, clinical course and treatment options of this tumor in this article.

Detection of Lymphadenopathy as a Precursor to Autoimmune Liver Diseases Before Clinical Hepatitis Became Apparent: A Report of Two Cases.

Two patients were incidentally diagnosed with intra-abdominal lymphadenopathy on imaging examinations. Although endoscopic ultrasound-guided fine needle aspiration of these areas of lymphadenopathy was performed, their causes remained undetermined. Neither patients had abnormal hepatic enzyme levels at the time lymphadenopathy was detected, but they developed hepatitis 20 months and five months later, respectively. The laboratory data and/or histopathological findings suggested primary biliary cholangitis/cirrhosis (PBC) and autoimmune hepatitis (AIH), respectively. These two patients were each started on appropriate treatment (ursodeoxycholic acid or prednisolone, respectively), their hepatitis ameliorated, and the hepatic enzyme levels recovered to within the normal ranges. These patients' clinical courses suggest that their lymphadenopathy was associated with PBC or AIH and appeared before the causative hepatitis became clinically apparent. We should consider the possibility of latent autoimmune hepatic diseases in cases with cryptogenic intra-abdominal lymphadenopathy even if there is no clinically apparent hepatitis.

Direct­acting antiviral treatment is safe and effective for chronic HCV patients with psychiatric disorders.

Although most patients with hepatitis C virus (HCV) infection have been cured since the introduction of direct-acting antiviral (DAA) treatments, whether patients with psychiatric disorders and chronic HCV infection receive benefits from DAA treatments remain unclear. The efficacy and safety of DAA treatment were compared between patients with and without psychiatric disorders. Data were retrospectively collected from medical records at the Suzuka General Hospital (Japan) between September 2014 and December 2021. The study was an observational, single-center study. Fisher's exact test, Mann-Whitney U test and Friedman's test were used for the comparisons between groups. Patients with HCV infection who had been started on DAA treatments were included. In total, 15 HCV cases with psychiatric disorders (P) and 209 HCV cases with nonpsychiatric disorders (NP) were started on DAA treatments for HCV infection. Patients in group P were younger (55±13.9 years) compared with those in group NP (68±13.0 years). A total of 12 patients (80%) in group P achieved and 188 patients (90%) in group NP achieved sustained virologic response (SVR), with no significant difference between the two groups. The remaining three patients in group P who did not achieve SVR included two drop-out cases. Regarding the laboratory data at the end of DAA treatments and SVR, there were no significant differences between the two groups. There were no cases of discontinuation or reduction of medication due to psychiatric disorders during DAA treatment. DAA treatment for HCV infection is effective, tolerable and safe for psychiatric patients, as well as patients without psychiatric disorders. Psychiatric patients with HCV infection should undergo DAA treatment to prevent progression to liver failure and/or cancer.