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.

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.

A Novel Scoring System to Improve the Detection Efficiency of Pancreatic Cystic Lesions in the General Population.

Objective Pancreatic cystic lesions (PCLs) are known risk factors for pancreatic cancer. Therefore, this study explored the predictors identifying PCLs in a general population and developed a scoring system to help more efficiently diagnose these entities during medical checkups. Methods We reviewed 9,369 examinees of abdominal ultrasound (AUS) during medical checkups between January 2013 and November 2019. Predictors of PCLs were identified using a multivariate logistic regression analysis, and we constructed a scoring system based on these predictors. Results PCLs were detected in 118 (1.3%). Age 50-59 years old [odds ratio (OR) 2.52, 95% confidence interval (CI) 1.18-5.35], 60-69 years old (OR 3.91, 95% CI 1.86-8.26), and ≥70 years old (OR 10.5, 95% CI 5.03-21.7) as well as abdominal pain (OR 1.85, 95% CI 1.14-3.00), alcohol consumption (OR 1.72, 95% CI 1.03-2.89), a family history of pancreatic cancer (OR 2.41, 95% CI 1.09-5.34), and pre-diabetes or diabetes (OR 1.78, 95% CI 1.05-3.00) were predictors of PCLs. The following scores were assigned according to regression coefficients: age (50-59 years old, 1 point; 60-69 years old, 1.5 points; ≥70 years old, 2.5 points); abdominal pain, 1 point, alcohol consumption, 1 point; a family history of pancreatic cancer, 1 point; and pre-diabetes, 1 point. The PCL detection rate increased with the total score: 0.2% for total score 0 point, 5.4% for ≥4.0 points. The area under the curve of the scoring system was 0.75 (95% CI 0.70-0.79). Conclusion Our scoring system allows the risk of PCLs to be determined and may help more efficiently diagnose these entities.

Gastric Foveolar-type Adenocarcinoma with Raspberry-like Appearance in a Helicobacter pylori-uninfected Stomach: A Long-term Retrospective Follow-up of 16 Years.

Esophagogastroduodenoscopy in a 58-year-old man revealed a protruding lesion measuring 6 mm in diameter in the fornix. An endoscopic biopsy of the lesion indicated well-differentiated adenocarcinoma. The lesion was resected by polypectomy. According to the Japanese histologic diagnostic criteria, we made a final diagnosis of early gastric cancer (U, Gre, 6×6 mm, Type 0-I, tub1, pT1a (M), pUl0, Ly0, V0, pHM0, pVM0). A retrospective review of the endoscopic images showed that this lesion had already been present in the images taken 16 years ago. The size and morphology of the lesion were the same as those of the first detected lesion.

Ischemic hepatitis with infectious endocarditis: A case report.

A 58-year-old woman was admitted to Suzuka General Hospital with fever. She was diagnosed with infectious endocarditis based on the presence of anterior mitral leaflet vegetation on the echocardiography analysis and isolation of Pseudomonas guariconensis by blood culture. During treatment, the hepatic enzymes levels, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) were increased without any abdominal symptoms. Prolonged prothrombin time (PT) and prothrombin time international normalized ratio were observed, and acute hepatic failure was diagnosed. However, the hepatic injury resolved spontaneously with restoration of the PT value after the hepatic enzymes (AST, ALT, LDH and ALP) peaked. Diffusion-weighted imaging of hepatic magnetic resonance imaging showed diffuse high intensity of the entire liver except for part of the left lobe. The hepatic injury was diagnosed as ischemic hepatitis caused by embolization from the vegetation associated with infectious endocarditis. The recovery from hepatic ischemia was thought to be due to hepatic blood supply from extrahepatic collateral blood. After antibiotic treatment, the patient underwent resection of the vegetation on the anterior mitral valve leaflet. Hepatic artery occlusion is rare, but it may cause severe hepatic complications. During follow-up of infectious endocarditis, clinicians should be aware of the potential for whole organ ischemic damage caused by vessel occlusion, as well as hepatic ischemic damage.

Early stage clear cell adenocarcinoma coexisting with tubular adenoma and adenoma with clear cell change in the colon.

Primary clear cell adenocarcinoma (CCA) of the colorectum is rare. We report a case of a 57-year-old man with early-stage CCA with conventional tubular adenoma and tubular adenoma with clear cell change in the transverse colon, diagnosed with image-enhanced endoscopy. The tumor was then treated with endoscopic submucosal dissection. The endoscopic findings characteristic of clear cell adenoma/adenocarcinoma could not be identified. Therefore, similar diagnostic tools as for conventional colorectal adenoma/cancer were considered. The pathogenesis of the clear cell change was unknown, but it might appear with the progression of the malignancy.

A case of complete atrioventricular block in secondary hemophagocytic syndrome/hemophagocytic lymphohistiocytosis recovered by plasma exchange and cytokine absorbing therapy with AN69ST continuous hemodiafiltration.

We report a case of incipient systemic lupus erythematosus (SLE) that rapidly progressed to complete atrioventricular block (cAVB). A 20-year-old man was admitted with facial erythema, painless oral aphtha, polyarthritis, and myalgia of each extremity. On admission, he developed first-degree atrioventricular block, pericarditis, pleuritis, renal failure, hemophagocytic lymphohistiocytosis, neurophychiatric SLE (left cerebellar infarction), and Staphylococcus aureus bacteremia. He was subsequently diagnosed with SLE based on several positive findings on immunological tests (including positive for antinuclear antibody). Despite immediate glucocorticoid pulse therapy and plasma exchange (PE) along with antibiotic, he developed cAVB that required temporary pacing on day 2. Because it was thought that hypercytokinemia exacerbated pericarditis, which progressed to myocarditis and cAVB, we decided to PE and cytokine-adsorbing therapy with AN69ST-continuous hemodiafiltration (CHDF). Other than renal failure, his organ dysfunctions improved with the multidisciplinary therapy. CAVB improved and temporary pacing was no longer required on day 11. Even a first-degree atrioventricular block can rapidly progress to cAVB; therefore, strict attention to electrocardiogram is necessary in severe SLE cases. When presenting with organ dysfunctions caused by hypercytokinemia such as severe SLE cases or SLE with severe infection cases, use of the combination of PE and AN69ST-CHDF might be beneficial.

The spontaneous clearance of hepatitis E virus (HEV) and emergence of HEV antibodies in a transfusion-transmitted chronic hepatitis E case after completion of chemotherapy for acute myeloid leukemia.

A 64-year-old woman was infected with hepatitis E virus (HEV) during chemotherapy for leukemia. By retrospective analyses of stored serum from the blood products and the patient, the source of the infection was determined to be platelet concentration (PC) transfused during chemotherapy. The partial nucleotide sequence of the HEV strain isolated from the donated PC and that from the patient's sera was identical and was subgenotype 3b. Clinical indicators such as alanine aminotransferase, HEV RNA titer, and anti-HEV antibodies in the serum were investigated from the beginning of the infection until 1 year after the termination of HEV infection. HEV RNA had propagated over 6 months and then cleared spontaneously after the completion of chemotherapy. Anti-HEV antibodies appeared in the serum just before the clearance of HEV RNA. Interestingly, HEV RNA was detected in the patient's urine, spinal fluid, and saliva. The HEV RNA titers in those samples were much lower than in the serum and feces. No renal, neurological, or salivary gland disorders appeared during the follow-up. We observed virological and biochemical progress and cure of transfusion-transmitted chronic hepatitis E in the patient despite an immunosuppressive status during and after chemotherapy against hematological malignancy.

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.

Hepatic Injury without Granulomatous Formation Associated with Intravesical Bacillus Calmette-Guérin Therapy.

A 74-year-old man developed hepatic injury after intravesical Bacillus Calmette-Guérin (BCG) therapy for bladder carcinoma. Although hepatitis-associated disseminated BCG was suspected, granulomatous formations were undetectable. The hepatic injury was considered to have resulted from an allergic reaction to BCG therapy because a histopathological assessment revealed enlarged portal areas with eosinophils and neutrophils. The hepatic injury was resolved by prednisolone. This case suggested that hepatic injury associated with BCG therapy might be due to an allergic mechanism unrelated to disseminated BCG disease. A liver biopsy is needed to confirm the histopathological findings of hepatic injury after BCG therapy in order to differentiate allergic hepatic injury from infectious hepatic injury.

Early stage clear cell adenocarcinoma of the colon examined in detail with image-enhanced endoscopy: a case report.

Primary clear cell adenocarcinoma (CCA) of the colorectum is a rare tumor. We report on a 48-year-old man with early stage CCA in the descending colon who underwent detailed examination with image-enhanced endoscopy, such as magnifying endoscopy with narrow-band imaging and crystal violet staining. The tumor was treated successfully with endoscopic mucosal resection at our hospital.

Gastric adenocarcinoma coexisting with a reddish semipedunculated polyp arising from Helicobacter pylori-negative normal gastric mucosa: a report of two cases.

We experienced two cases of adenocarcinoma coexisting with a hyperplastic polyp arising from Helicobacter pylori-negative normal gastric mucosa. The first case was of a 59-year-old man. Esophagogastroduodenoscopy revealed a protruding lesion measuring 4 mm in diameter on the greater curvature of the middle gastric body. The second case was of a 47-year-old man. Esophagogastroduodenoscopy showed a protruding lesion measuring 5 mm located at the greater curvature of the upper gastric body. The absence of atrophic changes in the entire gastric mucosa was confirmed endoscopically in both cases. Multiple H. pylori tests were all negative. Endoscopically, these protruding lesions appeared as reddish, semipedunculated polyps. Hyperplastic polyps were suspected based on white light endoscopic findings. Magnified endoscopy with narrow band imaging could not predict the coexistence of cancer. However, histopathological examination of the resected specimen revealed focal cancer at the surface of the gastric hyperplastic polyps. Considering the possibility that cancer may be coexisting in polyps, when reddish polyps are detected in H. pylori-negative normal gastric mucosa, it is important to perform a biopsy, or a careful follow-up endoscopy.

Usefulness of Endoscopic Transpapillary Tissue Sampling for Malignant Biliary Strictures and Predictive Factors of Diagnostic Accuracy.

BACKGROUND/AIMS: It is sometimes difficult to distinguish between malignant and benign biliary strictures using imaging studies alone, and pathological diagnosis is necessary. The aim of this study was to determine the usefulness of endoscopic transpapillary tissue sampling and factors predictive of diagnostic accuracy. METHODS: From April 2008 to December 2014, 136 patients underwent endoscopic transpapillary tissue sampling for malignant biliary strictures. The cytological and histological findings were reported as negative, suspicious, or positive. Suspicious and positive findings were defined as pathologically positive. RESULTS: The sensitivity was 65.0% for forceps biopsy, 49.5% for brush cytology, 46.2% for bile aspiration cytology, and 21.9% for endoscopic nasobiliary drainage cytology. The combination of these procedures improved the sensitivity (72.8%). Endoscopic transpapillary tissue sampling was more sensitive for lesions of biliary origin (91.4%) than for extrabiliary lesions (66.3%). In surgical cases, the sensitivity for tumors with an infiltrative growth pattern (53.3%) was significantly lower than for a tumor with an expanding or intermediate growth pattern (87.5%). CONCLUSIONS: Combining procedures can improve diagnostic accuracy. It may be possible to predict the sensitivity of endoscopic transpapillary tissue sampling by evaluating the etiology and tumor growth pattern using preoperative imaging studies.

Hepatitis E virus subtype 3f strains isolated from Japanese hepatitis patients with no history of travel to endemic areas - The origin analyzed by molecular evolution.

Hepatitis E virus subtype 3f (HEV-3f) strains are usually isolated in Europe and Thailand. Recently, HEV-3f strains were detected from six acute hepatitis E patients in Japan, none of whom had a history of travel to endemic areas. We inferred the origin and transmission route of the six HEV-3f strains. A time-scaled phylogenetic tree of the six strains with reference strains was constructed using a Bayesian statistical inference framework. The time-scaled tree indicated that the six strains independently derived from similar European strains between 2008 and 2014. The pattern suggested recent inflow of multiple HEV-3f strains from Europe to Japan. Japan imports a substantial amount of pork from European countries every year. The emergence of acute hepatitis cases caused by HEV-3f strains in Japan, in patients with no history of travel abroad, might be influenced by the increased opportunities to consume pork products imported from European countries.

Full-length genomic sequences of new subtype 1g hepatitis E virus strains obtained from four patients with imported or autochthonous acute hepatitis E in Japan.

Hepatitis E virus (HEV) causes acute or chronic hepatitis in humans worldwide and can be transmitted via the fecal-oral route. Four HEV strains (HE-JA14-2173, HE-JA15-1335, HE-JA15-1920 and HE-JA16-0610) obtained from patients with imported (from Pakistan or India) or autochthonous acute hepatitis E in Japan were most closely related to the Nepalese and Mongolian genotype 1 HEV strains of unassigned subtype within the partial ORF2 sequence. To investigate whether a putative novel subtype (1g) of genotype 1 can be assigned, full-length genomic sequences were determined for the four HEV strains. They shared 95.4-99.2% nucleotide identity over the entire genome, and differed by 6.3-11.7% from the reported HEV strains of subtypes 1a-1f and by only 0.6-4.7% from a Mongolian genotype 1 HEV strain (MNE15-072) of unassigned subtype. A phylogenetic analysis showed that the four HEV strains obtained in the present study formed a cluster with MNE15-072, with a bootstrap value of 100%. Although the p-distance between subtypes 1a and 1f was 0.048-0.083, these five strains showed a higher nucleotide p-distance value of 0.068-0.138 with the genotype 1 HEV strains of subtypes 1a-1f. A BLAST search revealed the presence of candidate members of subtype 1g HEV in at least five other countries, including France, Israel, the Netherlands, Portugal, and the UK, sharing identities of 95.4-99.6% with the HE-JA16-0610 strain within the common sequence of 294-867 nucleotides. These results support the assignment of a new subtype 1g within genotype 1 and suggest a global distribution of subtype 1g strains. Subtype 1g strains found in Europe can be imported from Asia. Further studies are needed to confirm the global distribution of HEV subtype 1g.

A case of diminished pericardial effusion after treatment of a giant hepatic cyst.

A 75-year-old woman was discovered to have a pericardial effusion when she was admitted to our hospital because of a giant hepatic cyst. We could not detect the cause of the effusion and diagnosed idiopathic pericardial effusion. The patient underwent transcutaneous drainage of the hepatic cyst and an injection of antibiotics. There was no communication between the pericardial effusion and the hepatic cyst. Although the hepatic cyst was reduced in size, the pericardial effusion showed no remarkable change immediately after treatment; however, 5 months later, the pericardial effusion was found to be diminished. The pericardial effusion might have been caused by the physical pressure of the giant hepatic cyst and disturbance in the balance between the production and reabsorption of the pericardial fluid. When we experience a huge hepatic cyst, we should take into account its influence against the surrounding organs, including the intrapleural space.

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.