Real-world NUDT15 genotyping and thiopurine treatment optimization in inflammatory bowel disease: a multicenter study.

BACKGROUND: This study evaluated the effectiveness of NUDT15 codon 139 genotyping in optimizing thiopurine treatment for inflammatory bowel disease (IBD) in Japan, using real-world data, and aimed to establish genotype-based treatment strategies. METHODS: A retrospective analysis of 4628 IBD patients who underwent NUDT15 codon 139 genotyping was conducted. This study assessed the purpose of the genotyping test and subsequent prescriptions following the obtained results. Outcomes were compared between the Genotyping group (thiopurine with genotyping test) and Non-genotyping group (thiopurine without genotyping test). Risk factors for adverse events (AEs) were analyzed by genotype and prior genotyping status. RESULTS: Genotyping test for medical purposes showed no significant difference in thiopurine induction rates between Arg/Arg and Arg/Cys genotypes, but nine Arg/Cys patients opted out of thiopurine treatment. In the Genotyping group, Arg/Arg patients received higher initial doses than the Non-genotyping group, while Arg/Cys patients received lower ones (median 25 mg/day). Fewer AEs occurred in the Genotyping group because of their lower incidence in Arg/Cys cases. Starting with < 25 mg/day of AZA reduced AEs in Arg/Cys patients, while Arg/Arg patients had better retention rates when maintaining ≥ 75 mg AZA. Nausea and liver injury correlated with thiopurine formulation but not dosage. pH-dependent mesalamine reduced leukopenia risk in mesalamine users. CONCLUSIONS: NUDT15 codon 139 genotyping effectively reduces thiopurine-induced AEs and improves treatment retention rates in IBD patients after genotype-based dose adjustments. This study provides data-driven treatment strategies based on genotype and identifies risk factors for specific AEs, contributing to a refined thiopurine treatment approach.

Aldo-keto reductase family 1 member B10 is regulated by nucleos(t)ide analogues for chronic hepatitis B.

The number of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients persists even under nucleos(t)ide analogues (NAs) treatment. Aldo-keto reductase family 1 member B10 (AKR1B10) expression has been reported in advanced chronic liver diseases as well as cancer tissues. We observed an association between related to HCC incidence and serum AKR1B10 by analyzing patients under treatment with NAs. Serum AKR1B10 levels measured by ELISA were higher in HCC cases under NA treatment compared with non-HCC cases and were associated with lamivudine- and adefovir pivoxil-, but not entecavir- or tenofovir alafenamide-treated cases. The latter drugs did not increase AKR1B10 values even in HCC cases, suggesting that they influence the reduction of AKR1B10 in any cases. This analysis was supported by in-vitro examination, which showed reduced AKR1B10 expression by entecavir and tenofovir via immunofluorescence staining. In conclusion there was a relationship between HBV-related HCC incidence and AKR1B10 under nucleos(t)ide analogues, especially in the use of lamivudine and adefovir pivoxil, but entecavir and tenofovir had suppressive effects of AKR1B10.

Impact of respiratory bacterial infections on mortality in Japanese patients with COVID-19: a retrospective cohort study.

BACKGROUND: Although cases of respiratory bacterial infections associated with coronavirus disease 2019 (COVID-19) have often been reported, their impact on the clinical course remains unclear. Herein, we evaluated and analyzed the complication rates of bacterial infections, causative organisms, patient backgrounds, and clinical outcome in Japanese patients with COVID-19. METHODS: We performed a retrospective cohort study that included inpatients with COVID-19 from multiple centers participating in the Japan COVID-19 Taskforce (April 2020 to May 2021) and obtained demographic, epidemiological, and microbiological results and the clinical course and analyzed the cases of COVID-19 complicated by respiratory bacterial infections. RESULTS: Of the 1,863 patients with COVID-19 included in the analysis, 140 (7.5%) had respiratory bacterial infections. Community-acquired co-infection at COVID-19 diagnosis was uncommon (55/1,863, 3.0%) and was mainly caused by Staphylococcus aureus, Klebsiella pneumoniae and Streptococcus pneumoniae. Hospital-acquired bacterial secondary infections, mostly caused by Staphylococcus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia, were diagnosed in 86 patients (4.6%). Severity-associated comorbidities were frequently observed in hospital-acquired secondary infection cases, including hypertension, diabetes, and chronic kidney disease. The study results suggest that the neutrophil-lymphocyte ratio (> 5.28) may be useful in diagnosing complications of respiratory bacterial infections. COVID-19 patients with community-acquired or hospital-acquired secondary infections had significantly increased mortality. CONCLUSIONS: Respiratory bacterial co-infections and secondary infections are uncommon in patients with COVID-19 but may worsen outcomes. Assessment of bacterial complications is important in hospitalized patients with COVID-19, and the study findings are meaningful for the appropriate use of antimicrobial agents and management strategies.

Diagnostic significance of secondary bacteremia in patients with COVID-19.

OBJECTIVES: We investigated the occurrence of non-respiratory bacterial and fungal secondary infections, causative organisms, impact on clinical outcomes, and association between the secondary pathogens and mortality in hospitalized patients with coronavirus disease 2019 (COVID-19). METHODS: This was a retrospective cohort study that included data from inpatients with COVID-19 from multiple centers participating in the Japan COVID-19 Taskforce (April 2020 to May 2021). We obtained demographic, epidemiological, and microbiological data throughout the course of hospitalization and analyzed the cases of COVID-19 complicated by non-respiratory bacterial infections. RESULTS: Of the 1914 patients included, non-respiratory bacterial infections with COVID-19 were diagnosed in 81 patients (4.2%). Of these, 59 (3.1%) were secondary infections. Bacteremia was the most frequent bacterial infection, occurring in 33 cases (55.9%), followed by urinary tract infections in 16 cases (27.1%). Staphylococcus epidermidis was the most common causative organism of bacteremia. Patients with COVID-19 with non-respiratory secondary bacterial infections had significantly higher mortality, and a multivariate logistic regression analysis demonstrated that those with bacteremia (aOdds Ratio = 15.3 [5.97-39.1]) were at higher risk of death. Multivariate logistic regression analysis showed that age, male sex, use of steroids to treat COVID-19, and intensive care unit admission increased the risk for nosocomial bacteremia. CONCLUSIONS: Secondary bacteremia is an important complication that may lead to poor prognosis in cases with COVID-19. An appropriate medical management strategy must be established, especially for patients with concomitant predisposing factors.

A rare cause of jejunal perforation: Monomorphic epitheliotropic intestinal T-cell lymphoma.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a very rare intestinal T-cell lymphoma which is observed most frequently in the jejunum. MEITL is prone to cause intestinal perforation and the prognosis is very poor when it occurs. Here we report a fatal case of MEITL causing jejunal perforation at the time of diagnosis in a 79-year-old man. The patient underwent emergency surgery for jejunal perforation caused by MEITL but died 3 months after the initial visit due to prolonged peritonitis. It is desirable to establish a method to predict cases with intestinal perforation, and systematize the treatment strategies to avoid perforation.

A study for every second day administration of vonoprazan for maintenance treatment of erosive GERD (ESD von GERD): a multicenter randomized cross-over study.

BACKGROUND: Vonoprazan is a potassium competitive acid blocker used to treat erosive gastroesophageal reflux disease (GERD) with stronger, more stable acid-suppressing effects than proton pump inhibitors (PPIs). This study clarified the usefulness and superiority of vonoprazan administered every second day over PPIs in the maintenance therapy of erosive GERD. METHODS: This is a prospective, multicenter, open-label, two-period randomized cross-over study. Patients were randomized to either the vonoprazan-lansoprazole (VP-LZ) group, who were given vonoprazan 10 mg for the first 4 weeks and then lansoprazole 15 mg for the next 4 weeks both administered once every second day, or the lansoprazole-vonoprazan (LZ-VP) group, who were treated in reverse. GERD symptoms were compared using symptom diaries, the frequency scale for symptoms of GERD (FSSG), and the gastrointestinal symptom rating scale (GSRS). RESULTS: We enrolled 122 patients between December 2017 and May 2019. Symptoms were well controlled in vonoprazan administration and lansoprazole administration were 93.6% and 82.1%, respectively, with a significant difference on McNemar's test (P = 0.003). During the second 4 weeks, 94.4% and 76.7% of patients in the VP-LZ and LZ-VP groups, respectively, were well controlled following for ≥ 6 consecutive days a week (P = 0.009). During the first 4 weeks, 96.7% and 80.0% of patients were well controlled with < 1 weekly in the VP-LZ and LZ-VP groups, respectively, during the first 4 weeks (P = 0.007). GERD symptoms, assessed via FSSG and GSRS, significantly decreased with vonoprazan administration once every second day. CONCLUSIONS: Vonoprazan administered once every second day could be an effective alternative to PPIs in the maintenance treatment of erosive GERD (UMIN000030393).

A nationwide survey concerning the mortality and risk of progressing severity due to arterial and venous thromboembolism in inflammatory bowel disease in Japan.

BACKGROUND: The mortality and risk factors of severe disease and death due to arterial and venous thromboembolism (ATE and VTE, respectively) in patients with inflammatory bowel disease (IBD) remain unclear, especially in Asia. AIMS: This study aimed to reveal the mortality and risk factors of TE in IBD patients in Japan. METHODS: In the primary surveillance, responses to questionnaires regarding the number of cases of severe TE and TE-associated death in IBD patients in a span of over the past 10 years were obtained from 32 institutions in Japan. In the secondary surveillance, detailed data about IBD patients with TE were collected. The characteristics, laboratory data, therapy status, and situation at the time of TE development were retrospectively collected, and the data were compared between the patients with and without severe TE and TE-associated death. RESULTS: The incidence of TE was 1.89% among 31,940 IBD patients. The frequencies of severe TE and TE-associated mortality were 10.7% and 1.0% among the total IBD and TE with IBD patients, respectively. The only risk factor for severe ATE and ATE-associated death was ischemic heart disease. The independent risk factors for severe VTE and VTE-associated death were age (≤ 45 years old), the site of VTE, and disease severity, with anti-TNF therapy as a potential negative risk factor. Patients with severe VTE had a high risk of developing persistent VTE and sequelae. CONCLUSION: Unlike ATE, the incidence of VTE was comparable in Asian and Western countries. Therapeutic and prophylactic strategies for managing IBD-associated TE in Asia are urgently needed.

Clinical Features and Resistance to Entecavir Monotherapy of Patients with Hepatitis B.

Aim: Hepatitis B virus (HBV) infection is a major public health concern worldwide. Entecavir (ETV), a first-line nucleos(t)ide analogue (NA) for HBV, has a low risk of resistance. We evaluated the efficacy of ETV monotherapy, ratio of ETV-resistant, and the clinical features of patients with ETV resistance. Methods: A total of 130 patients (72 males, 58 females; mean age, 61 ± 15 years) were divided into a NA-naïve group (n = 108) and NA-experienced group (n = 22). We examined the clinical outcomes of ETV monotherapy and associated factors. We also assessed the clinical features of 15 patients with resistance to ETV (mean, 51.0 ± 27.4 weeks). Results: Among the 130 patients, 94.1% achieved ALT normalization and 63.6% achieved serum HBV DNA negativity after ETV monotherapy for 96 weeks. Of the patients in the NA-naïve group, 93.1% and 60.4% achieved ALT normalization and HBV DNA negativity, respectively. Of the patients in the NA-experienced group, 100% and 74.9% achieved ALT normalization and HBV DNA negativity, respectively. Compared to patients on ETV continuously, 15 ETV-resistant patients had a higher baseline HBV viral load. There was a significant difference in the time to HBV DNA negativity, but not ALT normalization after ETV monotherapy in these groups. Rescue treatment with other NAs led to ALT normalization in all of these patients, but not HBV DNA negativity. Conclusions: ETV monotherapy has a long-term clinical efficacy. While some patients especially with HBV DNA high viral load developed ETV resistance, rescue treatment led to ALT normalization in these patients.

[Case report of a patient with recurrence after endoscopic submucosal dissection for superficial esophageal cancer, diagnosed with mediastinal lymph node endoscopic ultrasound-fine needle aspiration based on the symptom of hoarseness].

The patient was an 81-year-old man who presented with a complaint of hoarseness. When he was 80 years old, he had developed superficial esophageal cancer and had undergone endoscopic submucosal dissection (ESD) at our hospital. Two months after the ESD, he developed hoarseness. Computed tomography (CT) scan showed no abnormal findings at that time;therefore, he was diagnosed with idiopathic vocal cord paralysis, and followed up with symptom treatment in the Gastroenterology and Otolaryngology Departments. Ten months after the ESD, a CT scan revealed mediastinal lymph node swelling. He was admitted to our hospital for histopathological examination of the lymph node using endoscopic ultrasound-fine needle aspiration (EUS-FNA). The histopathological examination revealed squamous cell carcinoma of the lymph node, similar to the primary esophageal tumor. This result suggests that laryngeal nerve paralysis involving hoarseness is caused by lymph node metastasis of superficial esophageal cancer. We report that histopathological examination with EUS-FNA helps in determining the cause of hoarseness that develops after ESD.

A case of refractory pouchitis complicated by cytomegalovirus infection requiring administration of ganciclovir and infliximab.

Pouchitis is a frequent complication of surgical treatment of ulcerative colitis (UC), and is typically treated using antimicrobials. If pouchitis is refractory to antimicrobials, screening for complications, such as cytomegalovirus (CMV) infection, is necessary. However, the optimal approach to management of pouchitis complicated by CMV infection is unclear. We report the case of a 41-year-old female patient with UC presenting with pouchitis associated with CMV infection; she had received subtotal colectomy/ileal pouch anal anastomosis (IPAA). She was admitted to hospital with persistent fever, epigastric discomfort, and watery diarrhea despite receiving antibiotics. Laboratory findings showed inflammation and reactivation of CMV infection accompanied by liver injury. The endoscopic findings showed inflammation of the pouch and ileal mucosa on the oral side with extensive and deep punched-out ulcers. Immunohistological staining of biopsy specimens from an ulcerated lesion demonstrated CMV infection. Therefore, we diagnosed the patient with pouchitis complicated by CMV infection. The patient was treated with ganciclovir and infliximab, which resolved her symptoms and led to the disappearance of CMV-positive cells. There has been no recurrence of pouchitis. CMV infection should be considered in patients with UC who develop refractory pouchitis.

Risk Factors for Delayed Bleeding after Therapeutic Gastrointestinal Endoscopy in Patients Receiving Oral Anticoagulants: A Multicenter Retrospective Study.

BACKGROUND/AIMS: Delayed bleeding is among the adverse events associated with therapeutic gastrointestinal endoscopy. The aim of this study was to evaluate risk factors for delayed bleeding after gastrointestinal endoscopic resection in patients receiving oral anticoagulants as well as to compare the rates of occurrence of delayed bleeding between the oral anticoagulants used. METHODS: We retrospectively analyzed a total of 772 patients receiving anticoagulants. Of these, 389 and 383 patients were receiving direct oral anticoagulants (DOACs) and warfarin, respectively. Therapeutic endoscopic procedures performed included endoscopic submucosal dissection (ESD), endoscopic mucosal resection, polypectomy, and cold polypectomy. RESULTS: Delayed bleeding occurred in 90 patients (11.7%) with no significant difference between the DOAC and warfarin groups (9.5 and 13.8%, respectively). Delayed bleeding occurred significantly more frequently with apixaban than with rivaroxaban (13.5 vs. 6.4%; p < 0.05). A multivariate analysis identified continued anticoagulant therapy (OR 2.29), anticoagulant withdrawal with heparin bridging therapy (HBT; OR 2.18), anticoagulant therapy combined with 1 antiplatelet drug (OR 1.72), and ESD (OR 3.87) as risk factors for delayed bleeding. CONCLUSION: This study identified continued anticoagulant therapy, anticoagulant withdrawal with HBT, anticoagulant therapy combined with 1 antiplatelet drug, and ESD as risk factors for delayed bleeding after therapeutic endoscopy in patients receiving oral anticoagulants. Delayed bleeding rates were not significantly different between those receiving DOACs and warfarin. It was also suggested that the occurrence of delayed bleeding may vary between different DOACs and that oral anticoagulant withdrawal should be minimized during therapeutic gastrointestinal endoscopy, given the thromboembolic risk involved.

Imaging features and pathological evaluation by EUS-FNA enable conservative management in patient of lymphoepithelial cyst of the pancreas: a case report.

Pancreatic lymphoepithelial cysts (LECs) are rare cystic lesions filled with a keratinous substance and lined by squamous epithelium with underlying lymphoid tissue. Because pancreatic LECs are entirely benign, correct preoperative diagnosis is important to avoid unnecessary surgery. However, the imaging features of pancreatic LECs are not specific and preoperative diagnosis has proven difficult. A pancreatic mass was incidentally detected through abdominal ultrasonography in a 63-year-old male presenting without any symptoms. Computed tomography showed an exophytic cystic lesion in the pancreatic head. The lesion had heterogeneous high signal intensity with partial low intensity on T2-weighted magnetic resonance imaging (MRI) and high signal intensity on diffusion MRI. Endoscopic ultrasound (EUS) examination showed an encapsulated cystic lesion with relatively homogenous and highly echoic contents. EUS-guided fine-needle aspiration (EUS-FNA) revealed caseous appearance and rare fragments of apparently benign squamous epithelium on a background of keratinous debris, cyst contents, and scattered lymphocytes. We diagnosed a pancreatic LEC and opted for conservative management without surgery. Pathological evaluation based on images obtained through EUS-FNA showed macro- and microscopic features that were critical to determining the management strategy. In conclusion, the imaging and pathological features of pancreatic LECs can inform preoperative diagnosis, which may enable conservative management.

Clinical Features and Dynamics of T Cells-Related Markers in Immunocompetent Patients with Cytomegalovirus Hepatitis.

Aim: Cytomegalovirus (CMV) can cause hepatitis, encephalomyelitis, and pneumonitis in immunocompromised patients. In contrast, CMV infection of immunocompetent patients can lead to the development of infectious mononucleosis and is typically self-limiting; severe complications are rare. We evaluated the pathophysiology and immunological aspects of CMV hepatitis in recently immunocompetent adult patients. Methods: We examined the clinical features and outcomes of 47 adult immunocompetent patients with CMV hepatitis (29 men, 18 women; mean age, 34 ± 11 years) from January 2005 to August 2019 treated in our hospital. We also assayed T-cell activation to evaluate the immune responses in these patients. Results: Fever (74.5%), hepatosplenomegaly (74.5%), sore throat (36.2%), headache (31.9%), abdominal pain (27.7%), lymphadenopathy (23.4%), and skin rash (6.4%) were present at admission. Complications included gastrointestinal injury (25.5%), neuropathy (4.3%), thrombocytopenia (2.1%), and splenic infarction (2.1%). All patients had a good clinical course without liver failure or transition to chronic liver injury. The time to recover from liver injury ranged from 12 to 142 days (mean, 43.4 ± 28.7 days). The serum sIL-2R level, which reflects T-cell activation, was transiently elevated and correlated with the extent of hepatic inflammation. Conclusions: CMV hepatitis in immunocompetent individuals has a satisfactory outcome, but occasionally results in complications in other organs. The sIL-2R level has potential as a surrogate marker of hepatic inflammation in immunocompetent patients with CMV hepatitis.

The Serum Mac-2-binding Protein Glycosylation Isomer Dynamics in Acute Liver Injury.

Objective We aimed to examine the dynamics of serum Wisteria floribunda agglutinin-positive human Mac-2-binding protein glycosylation isomer (M2BPGi) in patients with acute liver injury. Methods Serum M2BPGi levels at the time of the diagnosis (n=77) and normalization of the serum alanine aminotransferase (ALT) level (n=26) were examined retrospectively. The difference in the serum M2BPGi level according to the etiology, and the correlations with other laboratory parameters were evaluated. Results The serum M2BPGi level at the time of the diagnosis was increased in 59 of 77 patients [2.3 cutoff index (COI); range, 0.31-11.1 COI] and was significantly decreased at the time of serum ALT normalization (0.68 COI; range, 0.15-1.87 COI; p<0.0001). The serum M2BPGi level was positively correlated with the duration for which serum ALT normalization was achieved (n=46, Spearman rho=0.53, p<0.0001). A multivariate analysis identified total bilirubin (T-bil), albumin, ALT, alkaline phosphatase, and etiology (e.g., drug-induced liver injury or etiology unknown) as independent factors for increased serum M2BPGi. In patients with infectious mononucleosis, the serum M2BPGi level was higher relative to the degree of increase of serum ALT or T-bil levels in comparison to other etiologies. Conclusion The serum M2BPGi level in patients with acute liver injury reflects the magnitude and duration of liver injury. However, it should be noted that the degree of increase of serum M2BPGi in patients with acute liver injury may differ according to the etiology.

Gut-derived Enterococcus faecium from ulcerative colitis patients promotes colitis in a genetically susceptible mouse host.

BACKGROUND: Recent metagenomic analyses have revealed dysbiosis of the gut microbiota of ulcerative colitis (UC) patients. However, the impacts of this dysbiosis are not fully understood, particularly at the strain level. RESULTS: We perform whole-genome shotgun sequencing of fecal DNA extracts from 13 healthy donors and 16 UC and 8 Crohn's disease (CD) patients. The microbiota of UC and CD patients is taxonomically and functionally divergent from that of healthy donors, with E. faecium being the most differentially abundant species between the two microbial communities. Transplantation of feces from UC or CD patients into Il10-/- mice promotes pathological inflammation and cytokine expression in the mouse colon, although distinct cytokine expression profiles are observed between UC and CD. Unlike isolates derived from healthy donors, E. faecium isolates from the feces of UC patients, along with E. faecium strain ATCC 19434, promotes colitis and colonic cytokine expression. Inflammatory E. faecium strains, including ATCC 19434 and a UC-derived strain, cluster separately from commercially available probiotic strains based on whole-genome shotgun sequencing analysis. The presence of E. faecium in fecal samples is associated with large disease extent and the need for multiple medications in UC patients. CONCLUSIONS: E. faecium strains derived from UC patients display an inflammatory genotype that causes colitis.

A case of chronic pancreatitis exacerbation associated with pancreatic arteriovenous malformation: a case report and literature review.

A 60-year-old man with an unruptured cerebral aneurysm and family history of moyamoya disease was admitted to our hospital with epigastric pain since the previous day. Serum levels of pancreatic enzyme were elevated and abdominal contrast-enhanced computed tomography showed localized enlargement of the pancreatic tail in the arterial phase and revealed numerous areas of fine mesh-like vascular hyperplasia consistent with an enlarged pancreatic tail. We diagnosed pancreatic arteriovenous malformation (P-AVM) with acute pancreatitis. Furthermore, in the pancreatic body, endoscopic ultrasonography showed lobularity (honeycombing type) and hyperechoic foci (non-shadowing), which suggests chronic pancreatitis. Acute management was performed with conservative treatment including administration of replacement fluids and proteolytic enzyme inhibitor. Distal pancreatectomy for P-AVM was performed because P-AVM is associated with acute pancreatitis recurrence, development of portal hypertension, progression of chronic pancreatitis, and refractory duodenal bleeding. Histological findings on the resected specimens revealed the anastomosis of abnormal arteries and veins, which suggested P-AVM. In addition, inflammation accompanied by fat necrosis due to ischemic infarction in the pancreatic tail, which suggested acute pancreatitis, and mild fibrosis in the pancreatic body, which suggested chronic pancreatitis, were shown. Although P-AVM is associated with various complications, symptomatic P-AVM should be considered a chronic and progressive disease.

A Young Man with Non-alcoholic Steatohepatitis and Serum Anti-mitochondrial Antibody Positivity.

A 37-year-old obese man who was a social drinker was admitted to our hospital to undergo a detailed examination for liver injury with anti-mitochondrial antibody positivity. Abdominal ultrasonography revealed moderate fatty liver. A histological analysis showed steatosis of approximately 30% of the hepatocytes, focal necrosis, a few ballooning hepatocytes and lobular inflammation suggestive of steatohepatitis, epithelioid granuloma and irregularity of the sequence of the bile duct epithelium accompanied by lymphocyte infiltration suggestive of chronic cholangitis. He was diagnosed with non-alcoholic steatohepatitis complicated with primary biliary cholangitis. His liver injury was improved by weight loss and high-dose ursodeoxycholic acid treatment.

A case of an elderly female with diffuse hepatic hemangiomatosis complicated with multiple organic dysfunction and Kasabach-Merritt syndrome.

Since diffuse hepatic hemangiomatosis (DHH) is an extremely rare disease especially in adults, the etiology and natural course of adult-onset DHH has not been well understood. We report a case of DHH complicated with multiple organic dysfunction and Kasabach-Merritt syndrome (KMS) in an 83-year-old female. She presented with mild abdominal distension and laboratory findings revealed thrombocytopenia and abnormal coagulation, indicating disseminated intravascular coagulation (DIC). Enhanced computed tomography revealed diffuse, hypodense hepatic nodules with delayed enhancement involving the whole liver, and multiple hypodense splenic legions. To obtain a definitive diagnosis, laparoscopic-guided biopsy was performed. Histological findings revealed irregularly dilated non-anastomotic vascular spaces, which were lined with flat endothelial cells without cellular atypia. We diagnosed this as DHH complicated with splenic lesions and KMS. Although the patient was treated with symptomatic treatment, such as anti-coagulation therapy, hemangiomatous lesions, especially in the spleen, progressed rapidly, leading to worsening of DIC. Finally, the patient died of multiple organ failure at 12 months after diagnosis. A postmortem examination demonstrated diffuse hemangiomatosis of not only the liver and spleen, but also the adrenal glands and bone marrow. Despite no malignant histologically, DHH can be fatal if it progresses rapidly within a short period of time.

Comparing macroinvertebrate assemblages at organic-contaminated river sites with different zinc concentrations: Metal-sensitive taxa may already be absent.

We investigated responses of macroinvertebrates to different zinc concentrations in urban rivers contaminated with organic matter in a regional-scale monitoring survey and a smaller-scale field study. The present study was designed to test our prediction that total zinc concentrations of ∼60 µg/L (twice the Japanese environmental quality standard) do not lead to significant reductions in richness or abundance of macroinvertebrates in organic-contaminated rivers (biochemical oxygen demand of >3 mg/L). At the organic-contaminated sites in both surveys, very few species were present, and metal-sensitive heptageniid and ephemerellid mayflies were generally absent. In the regional-scale study, total zinc concentrations of up to 70 µg/L resulted in little reduction in macroinvertebrate richness. In the local-scale study, macroinvertebrate richness and abundance were not greatly reduced at the polluted downstream site with a total zinc concentration of 48 µg/L. Results from both surveys support our prediction. Therefore, an important implication of this study is that macroinvertebrate taxa that are susceptible to metal pollution should be sparse or absent in organic-contaminated rivers, so the impacts of metals such as zinc may be limited owing to the species-poor communities. Further research is required to evaluate the importance of reduced zinc bioavailability associated with increased organic matter and water hardness to the species-poor communities in organic-contaminated rivers.

The Efficacy of Corticosteroid Therapy in a Patient with Non-alcoholic Steatohepatitis Overlapping Autoimmune Hepatitis.

The overlap of multiple liver diseases can cause the disease activity and severity to worsen rapidly in some cases. We rarely see patients with non-alcoholic steatohepatitis (NASH) with overlapping autoimmune hepatitis (AIH). A 64-year-old woman who had been prescribed oral drugs to treat diabetes and hypertension (metformin 500 mg/day and voglibose 0.9 mg/day, and termisartan 40 mg/day and amlodipine 5 mg/day, respectively) was diagnosed with NASH with histological confirmation. At 68 years of age, her liver injury worsened with an IgG of 2,871 mg/dL and a high serum anti-nuclear antibody (ANA) level of 2,560. We repeated the liver biopsy, which revealed NASH and mild interface hepatitis with some lobular focal necrosis consisting of overlapping AIH. Therefore, she was treated with 30 mg of prednisolone daily. The treatment led to an improvement in her IgG levels and ANA in the serum and an improvement in the histology results.