Unilateral drainage and chemotherapy prolong the patency of a plastic stent placed above the sphincter of Oddi in patients with malignant hilar biliary obstruction.

Objectives: To evaluate the results of inside stent therapy for unresectable malignant hilar biliary obstruction and identify factors related to stent patency duration. Methods: Of 44 patients who underwent initial inside-stent placement above the sphincter of Oddi from April 2017 to December 2022, 42 with the resolution of jaundice (clinical success rate, 95.5%) were retrospectively analyzed. Univariate and multivariate logistic regression analysis identified factors associated with stent patency duration. Results: Univariate analysis revealed significant differences in the drainage method (406 days for unilateral drainage vs. 305 days for bilateral drainage of the right and left liver lobes, p = 0.022) with or without chemotherapy (406 days with vs. 154 days without, p = 0.038). Multivariate analysis (Cox proportional hazards analysis) revealed similar results, with unilateral drainage (p = 0.031) and chemotherapy (p = 0.048) identified as independent factors associated with prolonged stent patency. Early adverse events were observed in two patients (4.8%; one cholangitis, one pancreatitis). Conclusions: Inside-stent therapy was safely performed in patients with malignant hilar biliary obstruction. Simple unilateral drainage and chemotherapy may prolong stent patency.

Adverse events of self-expandable metal stent placement for malignant distal biliary obstruction: a large multicenter study.

BACKGROUND AND AIMS: Endoscopic placement of self-expandable metal stents (SEMSs) for malignant distal biliary obstruction (MDBO) may be accompanied by several types of adverse events. The present study analyzed the adverse events occurring after SEMS placement for MDBO. METHODS: The present study retrospectively investigated the incidence and types of adverse events in patients who underwent SEMS placement for MDBO between April 2018 and March 2021 at 26 hospitals. Risk factors for acute pancreatitis, cholecystitis, and recurrent biliary obstruction (RBO) were evaluated by univariate and multivariate analyses. RESULTS: Of the 1425 patients implanted with SEMSs for MDBO, 228 (16.0%) and 393 (27.6%) experienced early adverse events and RBO, respectively. Pancreatic duct without tumor involvement (P = .023), intact papilla (P = .025), and SEMS placement across the papilla (P = .037) were independent risk factors for acute pancreatitis. Tumor involvement in the orifice of the cystic duct was an independent risk factor for cholecystitis (P < .001). Use of fully and partially covered SEMSs was an independent risk factor for food impaction and/or sludge. Use of fully covered SEMSs was an independent risk factor for stent migration. Use of uncovered SEMSs and laser-cut SEMSs was an independent risk factor for tumor ingrowth. CONCLUSIONS: Pancreatic duct without tumor involvement, intact papilla, and SEMS placement across the papilla were independent risk factors for acute pancreatitis, and tumor involvement in the orifice of the cystic duct was an independent risk factor for cholecystitis. The risk factors for food impaction and/or sludge, stent migration, and tumor ingrowth differed among types of SEMSs.

Brain-derived neurotrophic factor knock-out mice develop non-alcoholic steatohepatitis.

While brain-derived neurotrophic factor (BDNF), which is a growth factor associated with cognitive improvement and the alleviation of depression symptoms, is known to regulate food intake and body weight, the role of BDNF in peripheral disease is not fully understood. Here, we show that reduced BDNF expression is associated with weight gain and the chronic liver disease non-alcoholic steatohepatitis (NASH). At 10 months of age, BDNF-heterozygous (BDNF+/- ) mice developed symptoms of NASH: centrilobular/perivenular steatosis, lobular inflammation with infiltration of neutrophils, ballooning hepatocytes, and fibrosis of the liver. Obesity and higher serum levels of glucose and insulin - major pathologic features in human NASH - were dramatic. Dying adipocytes were surrounded by macrophages in visceral fat, suggesting that chronic inflammation occurs in peripheral organs. RNA sequencing (RNA-seq) studies of the liver revealed that the most significantly enriched Gene Ontology term involved fatty acid metabolic processes and the modulation of neutrophil aggregation, pathologies that well characterise NASH. Gene expression analysis by RNA-seq also support the notion that BDNF+/- mice are under oxidative stress, as indicated by alterations in the expression of the cytochrome P450 family and a reduction in glutathione S-transferase p, an antioxidant enzyme. Histopathologic phenotypes of NASH were also observed in a knock-in mouse (BDNF+/pro ), in which the precursor BDNF is inefficiently converted into the mature form of BDNF. Lastly, as BDNF reduction causes overeating and subsequent obesity, a food restriction study was conducted in BDNF+/pro mice. Pair-fed BDNF+/pro mice developed hepatocellular damage and showed infiltration of inflammatory cells, including neutrophils in the liver, despite having body weights and blood parameters that were comparable to those of controls. This is the first report demonstrating that reduced BDNF expression plays a role in the pathogenic mechanism of NASH, which is a hepatic manifestation of metabolic syndrome. © 2023 The Pathological Society of Great Britain and Ireland.

Aspartate aminotransferase to platelet ratio index has utility as a biomarker of COVID-19 severity in patients with nonalcoholic fatty liver disease.

AIM: Patients with nonalcoholic fatty liver disease (NAFLD) are reported to have greater coronavirus disease 2019 (COVID-19) severity compared with patients without NAFLD. Previous studies have reported that noninvasive liver fibrosis scores, including the Fibrosis-4 index, NAFLD fibrosis score, and aspartate aminotransferase to platelet ratio index (APRI), have utility in predicting COVID-19 mortality and disease severity in patients without NAFLD. However, the utility of liver fibrosis scores in predicting COVID-19 mortality and disease severity among patients with NAFLD infected with SARS-CoV-2 has yet to be evaluated. METHODS: This retrospective observational study comprised 126 patients with NAFLD and active SARS-CoV-2 infection. Patients were classified into low COVID-19 severity (mild or moderate I disease) and high COVID-19 severity (moderate II or severe disease) groups based on the therapeutic guideline implemented by the Ministry of Health, Labor, and Welfare of Japan. RESULTS: Of the 126 patients, only one had been diagnosed with NAFLD before admission. Age; levels of serum aspartate aminotransferase, γ-glutamyl transpeptidase, lactate dehydrogenase, blood urea nitrogen, and serum C-reactive protein; Fibrosis-4 index; NAFLD fibrosis score; and APRI levels on admission were higher in the high COVID-19 severity group compared with the low COVID-19 severity group. Serum albumin levels, platelet counts, and lymphocyte counts on admission were lower in the high COVID-19 severity group compared with the low COVID-19 severity group. Univariate and multivariate analysis revealed that APRI values were significantly associated with COVID-19 severity and hospitalization duration for COVID-19. CONCLUSIONS: APRI was independently associated with COVID-19 severity and hospitalization duration for COVID-19 in patients with NAFLD.

Liver Biopsy-confirmed Primary Hepatic Amyloidosis with Only Jaundice As the Initial Symptom: An Autopsy Case Report.

Amyloidosis causes various symptoms in many organs of the body, but amyloidosis that presents with liver damage alone has never been reported. We treated an 83-year-old man with amyloidosis who presented with liver damage alone. The liver damage in this patient was histologically proven to be liver amyloidosis. The administration of bortezomib and dexamethasone was not effective, so he rapidly died of liver failure. An aggressive liver biopsy should be considered when unexplained jaundice is observed.

Small intestinal follicular lymphoma induced by methotrexate: a case report.

BACKGROUND: Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is a rare but critical complication that develops in patients treated with MTX. Although MTX-LPD has been recently reported, the incidence of follicular lymphoma in the intestine is very low. CASE PRESENTATION: A 73-year-old woman who had been receiving MTX for over 10 years visited our hospital complaining of postprandial abdominal pain and nausea. Upper and lower digestive tract endoscopies did not show any abnormal findings. A patency capsule was stagnated at the proximal part of the ileum with a mild dilation on the oral side. An oral balloon endoscopy revealed shallow ulcerative lesions in the jejunum. She was diagnosed with MTX-LPD based on histopathological findings. The symptoms did not improve with the discontinuation of MTX, and the patient required partial resection of the small intestine. The test result for Epstein-Barr virus-encoded small RNA was negative. She was diagnosed with follicular lymphoma based on the histology findings of a surgical specimen. Postoperative positron emission tomography-computed tomography and bone marrow aspiration did not show any findings of lymphoma. On follow-up, no recurrence was noted four years after the surgery. CONCLUSIONS: Herein, we report the first case of follicular lymphoma that occurred in the small intestine, negative for Epstein-Barr virus-encoded small RNA. If intestinal symptoms occur during MTX administration, it is important to directly observe by endoscopy and perform histological examination.