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1.
DEN Open ; 4(1): e334, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38264465

ABSTRACT

We describe a case of gastric cancer treated by photodynamic therapy (PDT) with talaporfin sodium using a novel simultaneous light-emitting method. An 82-year-old man was diagnosed with gastric cancer near the cardia with suspected deep submucosal invasion. Surgical resection was deemed high-risk owing to an underlying pulmonary disease. After ruling out endoscopic procedures due to intense fibrosis resulting from the scarring, PDT with talaporfin sodium was chosen. PDT was successfully conducted using an endoscope with simultaneous light emission. The patient experienced a complete response to the treatment and showed no signs of recurrence during follow-up. This case highlights the potential of PDT with talaporfin sodium as a viable alternative for challenging cases, particularly in patients unsuitable for surgery and endoscopic resection. Furthermore, the novel simultaneous light-emitting method may improve the efficiency of the procedure. This case demonstrates the potential of PDT in gastric cancer treatment, especially for high-risk patients.

2.
Intern Med ; 63(7): 929-935, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-37495533

ABSTRACT

A 29-year-old man with severe ulcerative colitis and gastroduodenitis was initially treated with oral mesalamine and high-dose intravenous steroid therapy; however, his epigastralgia and vomiting did not improve. After initiating infliximab, the patient experienced prompt improvement in symptoms and inflammation. Although steroids were effective for the colon, they proved ineffective for gastroduodenal lesions, highlighting the necessity for molecular-targeted agents, such as infliximab, in these cases. The timing for administering such agents should be carefully considered.


Subject(s)
Colitis, Ulcerative , Duodenitis , Gastritis , Male , Humans , Adult , Infliximab/adverse effects , Colitis, Ulcerative/complications , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/pathology , Duodenitis/drug therapy , Duodenitis/diagnosis , Duodenitis/pathology , Gastritis/complications , Disease Progression
3.
Inflamm Intest Dis ; 8(4): 133-142, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38115911

ABSTRACT

Introduction: Leucine-rich alpha-2-glycoprotein (LRG) is a potential biomarker for disease activity and reflects mucosal healing in patients with ulcerative colitis (UC). However, only a few studies have described a detailed sensitivity analysis of LRG in predicting mucosal healing in patients. This study aimed to evaluate the association between LRG and the endoscopic activity of UC and its predictability for mucosal healing and explore the utility and clinical application of LRG. Methods: The diagnostic accuracy of biomarkers, including LRG, in predicting the endoscopic activity of UC was evaluated. All consecutive patients who underwent total colonoscopy between April 2021 and September 2022 were included. The Mayo endoscopic subscore (MES) was used for assessing endoscopic activity. Furthermore, endoscopic remission was defined as an MES of ≤1. Clinical activity was evaluated based on stool frequency and bloody stool. Receiver operating characteristic curve analysis and binary logistic regression were performed to assess the diagnostic accuracy of the biomarkers. We evaluated LRG trends and treatment response in patients with MES ≥2 who underwent induction therapy. Results: This study comprised 214 patients. The proportions of endoscopically and clinically active patients were 33.6% and 49.1%, respectively. LRG had an area under the curve (AUC) of 0.856, with a higher diagnostic accuracy than other biomarkers, such as C-reactive protein, leukocyte, neutrophil, platelet, and albumin. The cutoff value for LRG was 15.6 µg/mL (sensitivity, 72.2%; specificity, 86.6%). Using the MES, patients with higher scores had higher LRG levels than those with lower scores. The cutoff value, AUC, sensitivity, and specificity varied with a higher AUC for left-sided colitis and pancolitis than for proctitis. Logistic regression analysis showed that LRG was an independent predictor of endoscopic remission using multivariate analysis, even with the factor of clinical activity. The change ratio of LRG pre- and post-treatment was statistically significant in the higher LRG group. Conclusion: LRG reflected endoscopic activity independently, regardless of clinical symptoms. An LRG below the cutoff value could indicate a significantly low probability of endoscopic activity in asymptomatic patients, and follow-up endoscopy (not for cancer screening) may be unnecessary. Furthermore, a higher LRG level might be more useful as an indicator of treatment efficacy.

4.
Intern Med ; 2023 Oct 13.
Article in English | MEDLINE | ID: mdl-37839881

ABSTRACT

We herein report a rare case of idiopathic portal hypertension (IPH)-like disease that developed after allogeneic hematopoietic stem cell transplantation (allo-HSCT). A 53-year-old woman who underwent allo-HSCT for acute myeloid leukemia showed portal hypertension with radiological and histopathological findings consistent with IPH, distinct from veno-occlusive disease (VOD) and graft-versus-host disease (GVHD) of the liver. This case highlights the importance of considering IPH-like disease as a potential cause of portal hypertension after allo-HSCT. Awareness of this complication can aid in the early diagnosis and appropriate management of patients post allo-HSCT.

5.
Hepatol Commun ; 7(9)2023 09 01.
Article in English | MEDLINE | ID: mdl-37655967

ABSTRACT

BACKGROUND: HBV infection causes chronic liver disease and leads to the development of HCC. To identify host factors that support the HBV life cycle, we previously established the HC1 cell line that maintains HBV infection and identified host genes required for HBV persistence. METHODS: The present study focused on endothelial lipase (LIPG), which binds to heparan sulfate proteoglycans (HSPGs) in the cell membrane. RESULTS: We found HBV infection was impaired in humanized liver chimeric mouse-derived hepatocytes that were transduced with lentivirus expressing short hairpin RNA against LIPG. Long-term suppression of LIPG combined with entecavir further suppressed HBV replication. LIPG was shown to be involved in HBV attachment to the cell surface by using 2 sodium taurocholate cotransporting peptide (NTCP)-expressing cell lines, and the direct interaction of LIPG and HBV large surface protein was revealed. Heparin and heparinase almost completely suppressed the LIPG-induced increase of HBV attachment, indicating that LIPG accelerated HBV attachment to HSPGs followed by HBV entry through NTCP. Surprisingly, the attachment of a fluorescently labeled NTCP-binding preS1 probe to NTCP-expressing cells was not impaired by heparin, suggesting the HSPG-independent attachment of the preS1 probe to NTCP. Interestingly, attachment of the preS1 probe was severely impaired in LIPG knockdown or knockout cells. Inhibitors of the lipase activity of LIPG similarly impaired the attachment of the preS1 probe to NTCP-expressing cells. CONCLUSIONS: LIPG participates in HBV infection by upregulating HBV attachment to the cell membrane by means of 2 possible mechanisms: increasing HBV attachment to HSPGs or facilitating HSPG-dependent or HSPG-independent HBV attachment to NTCP by its lipase activity.


Subject(s)
Hepatitis B , Lipase , Animals , Mice , Heparan Sulfate Proteoglycans/genetics , Heparin , Hepatitis B/genetics , Hepatitis B virus , Lipase/genetics
6.
Biochem Biophys Res Commun ; 674: 133-139, 2023 09 24.
Article in English | MEDLINE | ID: mdl-37419034

ABSTRACT

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.


Subject(s)
Aldo-Keto Reductase Family 1 member B10 , Carcinoma, Hepatocellular , Hepatitis B, Chronic , Liver Neoplasms , Humans , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/drug therapy , Liver Neoplasms/pathology , Lamivudine/therapeutic use , Carcinoma, Hepatocellular/pathology , Tenofovir , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Aldo-Keto Reductases
7.
Cell Mol Gastroenterol Hepatol ; 15(3): 533-558, 2023.
Article in English | MEDLINE | ID: mdl-36270602

ABSTRACT

BACKGROUND & AIMS: Hepatitis B virus (HBV) infection is difficult to cure owing to the persistence of covalently closed circular viral DNA (cccDNA). We performed single-cell transcriptome analysis of newly established HBV-positive and HBV-negative hepatocellular carcinoma cell lines and found that dedicator of cytokinesis 11 (DOCK11) was crucially involved in HBV persistence. However, the roles of DOCK11 in the HBV lifecycle have not been clarified. METHODS: The cccDNA levels were measured by Southern blotting and real-time detection polymerase chain reaction in various hepatocytes including PXB cells by using an HBV-infected model. The retrograde trafficking route of HBV capsid was investigated by super-resolution microscopy, proximity ligation assay, and time-lapse analysis. The downstream molecules of DOCK11 and underlying mechanism were examined by liquid chromatography-tandem mass spectrometry, immunoblotting, and enzyme-linked immunosorbent assay. RESULTS: The cccDNA levels were strongly increased by DOCK11 overexpression and repressed by DOCK11 suppression. Interestingly, DOCK11 functionally associated with retrograde trafficking proteins in the trans-Golgi network (TGN), Arf-GAP with GTPase domain, ankyrin repeat, and pleckstrin homology domain-containing protein 2 (AGAP2), and ADP-ribosylation factor 1 (ARF1), together with HBV capsid, to open an alternative retrograde trafficking route for HBV from early endosomes (EEs) to the TGN and then to the endoplasmic reticulum (ER), thereby avoiding lysosomal degradation. Clinically, DOCK11 levels in liver biopsies from patients with chronic hepatitis B were significantly reduced by entecavir treatment, and this reduction correlated with HBV surface antigen levels. CONCLUSIONS: HBV uses a retrograde trafficking route via EEs-TGN-ER for infection that is facilitated by DOCK11 and serves to maintain cccDNA. Therefore, DOCK11 is a potential therapeutic target to prevent persistent HBV infection.


Subject(s)
Hepatitis B, Chronic , Hepatitis B , Humans , Hepatitis B virus/genetics , trans-Golgi Network/metabolism , Hepatitis B/metabolism , Lysosomes/metabolism
8.
Clin J Gastroenterol ; 15(6): 1145-1150, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36053483

ABSTRACT

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) extremely rarely arise in extrahepatic biliary tract. Here, we report a case of bile duct MALT lymphoma diagnosed with direct cholangioscopy. The patient was an 80-year-old female with history of esophageal cancer, and had been occasionally treated with balloon dilatation for anastomotic stricture. She was referred to our hospital for treatment of choledocholithiasis. Since transesophageal endoscope insertion was impossible, stone extraction by transjejunal approach was performed. When gastroduodenoscope was directly inserted to the bile duct (direct cholangioscopy), accidentally two flat lesions with development of large atypical vessels in hilar region were noted. Biopsy revealed diffuse infiltration of CD20 positive small- to medium-sized atypical lymphocytes. A diagnosis of bile duct MALT lymphoma was made. The patient underwent eight courses of chemotherapy with rituximab alone, with no evident complications. Although biliary tract MALT lymphoma is rare, advances in cholangioscopy may promote encounter with such lesions. Accumulation of endoscopic figures of biliary tract MALT lymphoma is required.


Subject(s)
Lymphoma, B-Cell, Marginal Zone , Female , Humans , Aged, 80 and over , Lymphoma, B-Cell, Marginal Zone/diagnosis , Lymphoma, B-Cell, Marginal Zone/surgery , Lymphoma, B-Cell, Marginal Zone/drug therapy , Bile Ducts/pathology , Rituximab/therapeutic use , Catheterization
9.
Can J Gastroenterol Hepatol ; 2021: 3259833, 2021.
Article in English | MEDLINE | ID: mdl-34422709

ABSTRACT

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.


Subject(s)
Hepatitis B, Chronic , Aged , Antiviral Agents/therapeutic use , DNA, Viral , Drug Resistance, Viral/genetics , Female , Guanine/analogs & derivatives , Guanine/therapeutic use , Hepatitis B e Antigens , Hepatitis B virus/genetics , Hepatitis B, Chronic/drug therapy , Humans , Male , Middle Aged , Treatment Outcome
10.
Medicine (Baltimore) ; 100(31): e26835, 2021 Aug 06.
Article in English | MEDLINE | ID: mdl-34397849

ABSTRACT

ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic syndrome, which includes diabetes mellitus and hyperlipidemia. A fraction of NAFLD patients develop nonalcoholic steatohepatitis, leading to cirrhosis associated with various serious complications, including hepatocellular carcinoma, gastroesophageal varices, cardiovascular events, and other organ malignancy. Although the incidence of chronic viral hepatitis with associated complications has gradually decreased as highly effective antiviral therapies have been established, the number of patients with steatohepatitis has been increasing.This retrospective study examined data of 229 patients from 22 hospitals in our region. We examined 155 cases of chronological data and assessed the development of liver fibrosis and evaluated hepatic reserve-related markers such as platelet count, FIB-4 index, prothrombin time, and serum albumin concentration. We analyzed the relationship of these chronological changes and the incidence of NAFLD related serious complications.Data related to liver fibrosis progression, albumin, and prothrombin time were significantly associated with the occurrence of serious complications associated with cirrhosis. We compared 22 event and 133 nonevent cases of chronological changes in the data per year and found that serum albumin concentration was significantly lower in the group that developed serious complications (event cases: -0.21 g/dL/year, nonevent cases: -0.04 g/dL/year (P < .001)). This albumin decline was only the associated factor with the event incidence by multivariate analysis (P < .01).Annual decline in serum albumin concentration in patients with NAFLD is associated with serious events from the outcome of multicenter retrospective study. This highlights its potential utility as a surrogate marker to assess the efficacy of prediction of NAFLD related serious events.


Subject(s)
Liver Cirrhosis , Non-alcoholic Fatty Liver Disease , Serum Albumin/analysis , Aged , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/pathology , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Disease Progression , Esophageal and Gastric Varices/diagnosis , Esophageal and Gastric Varices/epidemiology , Female , Follow-Up Studies , Humans , Japan/epidemiology , Liver Cirrhosis/diagnosis , Liver Cirrhosis/epidemiology , Liver Cirrhosis/etiology , Liver Neoplasms/epidemiology , Liver Neoplasms/pathology , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/blood , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/epidemiology , Predictive Value of Tests , Prognosis , Risk Assessment , Risk Factors
11.
Surg Case Rep ; 7(1): 90, 2021 Apr 13.
Article in English | MEDLINE | ID: mdl-33847839

ABSTRACT

BACKGROUND: Pancreatic acinar cell carcinoma (PACC) is a rare exocrine malignant tumor. Its widespread intraductal extension into the main pancreatic duct (MPD) is also rare. CASE PRESENTATION: We report the case of a 71-year-old man with PACC with MPD extension. The patient was assessed with laboratory and radiographic investigations that facilitated a preoperative diagnosis. Endoscopic ultrasonography (EUS) and dynamic thin-slice multi-detector row computed tomography (MDCT) were useful for determining the resection line of the pancreas. EUS-guided fine needle aspiration (EUS-FNA) was also helpful in determining the tumor biology and treatment strategy. Distal pancreatectomy was performed. The MPD was occupied by the tumor 35 mm downstream and 5 mm upstream. Histopathologically, the pancreatic tail tumor extended continuously into the MPD. The tumor was solid with cells showing eosinophilic and granular cytoplasm, indicating the diagnosis of PACC. This is an interesting case of PACC with intraductal extension into the MPD. We discuss the possible mechanisms of tumor extension in this rare case together with a review of the literature. CONCLUSIONS: We describe a rare pancreatic acinar cell carcinoma that could be adequately treated using preoperative precise imaging and histopathological evaluations. When an intraductal tumor extension in the MPD is encountered, the diagnosis of a rare pancreatic tumor should be considered, as in our case.

12.
Nihon Shokakibyo Gakkai Zasshi ; 118(3): 264-271, 2021.
Article in Japanese | MEDLINE | ID: mdl-33692261

ABSTRACT

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.


Subject(s)
Endoscopic Mucosal Resection , Esophageal Neoplasms , Aged, 80 and over , Biopsy, Fine-Needle , Endoscopic Mucosal Resection/adverse effects , Endoscopic Ultrasound-Guided Fine Needle Aspiration/adverse effects , Esophageal Neoplasms/diagnostic imaging , Esophageal Neoplasms/surgery , Hoarseness/etiology , Humans , Lymph Nodes , Male , Neoplasm Recurrence, Local
13.
Clin J Gastroenterol ; 14(1): 181-186, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33475967

ABSTRACT

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.


Subject(s)
Colitis, Ulcerative , Cytomegalovirus Infections , Pouchitis , Proctocolectomy, Restorative , Adult , Colitis, Ulcerative/complications , Colitis, Ulcerative/surgery , Cytomegalovirus Infections/complications , Cytomegalovirus Infections/drug therapy , Female , Ganciclovir/therapeutic use , Humans , Infliximab/adverse effects , Pouchitis/drug therapy , Pouchitis/etiology , Proctocolectomy, Restorative/adverse effects
14.
Clin J Gastroenterol ; 14(1): 370-374, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33063294

ABSTRACT

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.


Subject(s)
Pancreatic Cyst , Pancreatic Neoplasms , Conservative Treatment , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Endosonography , Humans , Male , Middle Aged , Pancreas/diagnostic imaging , Pancreatic Cyst/diagnostic imaging , Pancreatic Cyst/therapy
15.
Can J Gastroenterol Hepatol ; 2020: 8874620, 2020.
Article in English | MEDLINE | ID: mdl-32908853

ABSTRACT

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.


Subject(s)
Cytomegalovirus Infections , Hepatitis , Immunocompetence , Adult , Cytomegalovirus , Female , Humans , Male , Middle Aged , T-Lymphocytes , Young Adult
16.
Sci Rep ; 9(1): 1621, 2019 02 07.
Article in English | MEDLINE | ID: mdl-30733490

ABSTRACT

Notch1 is regulated by E3 ubiquitin ligases, with proteasomal degradation of the Notch intracellular domain affecting the transcription of target genes. cAMP response element-binding protein (CREB) mediates the transcription of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA). We assessed the relationship between HBV cccDNA and Notch signaling activities. HBV cccDNA levels and relative gene expression were evaluated in HBV-replicating cells treated with Jagged1 shRNA and a γ-secretase inhibitor. The effects of these factors in surgically resected clinical samples were also assessed. Notch inhibition suppressed HBV cccDNA and CREB-related expression but increased ITCH and NUMB levels. Proteasome inhibitor augmented HBV cccDNA, restored Notch and CREB expression, and inhibited ITCH and NUMB function. Increased HBV cccDNA was observed after ITCH and NUMB blockage, even after treatment with the adenylate cyclase activator forskolin; protein kinase A (PKA) inhibitor had the opposite effect. Notch activation and E3 ligase inactivation were observed in HBV-positive cells in clinical liver tissue. Collectively, these findings reveal that Notch signaling activity facilitates HBV cccDNA transcription via CREB to trigger the downstream PKA-phospho-CREB cascade and is regulated by E3 ubiquitin ligase-modulation of the Notch intracellular domain.


Subject(s)
Cyclic AMP Response Element-Binding Protein/metabolism , Hepatitis B virus/genetics , Hepatitis B/metabolism , Receptors, Notch/metabolism , Ubiquitin-Protein Ligases/metabolism , Adult , Aged , DNA, Circular , Female , Hep G2 Cells , Host-Pathogen Interactions , Humans , Jagged-1 Protein/genetics , Jagged-1 Protein/metabolism , Male , Membrane Proteins/genetics , Membrane Proteins/metabolism , Middle Aged , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Peptide Fragments/metabolism , Receptor, Notch1/genetics , Receptor, Notch1/metabolism , Repressor Proteins/genetics , Repressor Proteins/metabolism , Sialoglycoproteins/metabolism , Signal Transduction , Transcription, Genetic , Ubiquitin-Protein Ligases/genetics
17.
Clin J Gastroenterol ; 12(1): 63-70, 2019 Feb.
Article in English | MEDLINE | ID: mdl-29995231

ABSTRACT

We report three cases of genotype 1b hepatitis C virus (HCV) reinfection after liver transplantation. When antiviral treatment was considered, all three patients had renal dysfunction and had been treated with immunosuppressive agents for a long time; one with tacrolimus (TAC) and the others with cyclosporine A (CyA). Therefore, the possible antiviral regimens among direct-acting antivirals (DAA) were limited and so we treated all three patients with ombitasvir/paritaprevir/ritonavir (OBV/PTV/r). Because ritonavir is known to markedly increase the blood concentration of TAC and CyA through drug-drug interactions, close monitoring of blood concentrations of TAC or CyA and dose adjustments of immunosuppressive agents were needed. Sustained virus response was achieved in all the patients treated, and there were no adverse effects or transplant rejection. OBV/PTV/r might be a useful DAA regimen for patients with genotype 1 HCV reinfection in the setting of renal dysfunction.


Subject(s)
Anilides/therapeutic use , Antiviral Agents/therapeutic use , Carbamates/therapeutic use , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/virology , Kidney Failure, Chronic/surgery , Liver Transplantation , Macrocyclic Compounds/therapeutic use , Ritonavir/therapeutic use , Aged , Cyclopropanes , Drug Interactions , Drug Monitoring , Female , Genotype , Hepacivirus/genetics , Hepacivirus/physiology , Humans , Immunosuppressive Agents/therapeutic use , Lactams, Macrocyclic , Male , Middle Aged , Proline/analogs & derivatives , Sulfonamides , Valine , Virus Activation
18.
Endosc Int Open ; 5(1): E47-E53, 2017 Jan.
Article in English | MEDLINE | ID: mdl-28191496

ABSTRACT

Background and study aims It is important to examine the pharynx during upper gastrointestinal endoscopy. Pharyngeal anesthesia using topical lidocaine is generally used as pretreatment. In Japan, lidocaine viscous solution is the anesthetic of choice, but lidocaine spray is applied when the former is considered insufficient. However, the relationship between the extent of pharyngeal anesthesia and accuracy of observation is unclear. We compared the performance of lidocaine spray alone versus lidocaine spray combined with lidocaine viscous solution for pharyngeal observation during transoral endoscopy. Patients and methods In this prospective, double-blinded, randomized clinical trial conducted between January and March 2015, 327 patients were randomly assigned to lidocaine spray alone (spray group, n = 157) or a combination of spray and viscous solution (combination group, n = 170). We compared the number of pharyngeal observable sites (non-inferiority test), pain by visual analogue scale, observation time, and the number of gag reflexes between the two groups. Results The mean number of images of suitable quality taken at the observable pharyngeal sites in the spray group was 8.33 (95 % confidence interval [CI]: 7.94 - 8.72) per patient, and 8.77 (95 % CI: 8.49 - 9.05) per patient in the combination group. The difference in the number of observable pharyngeal sites was - 0.44 (95 % CI: - 0.84 to - 0.03, P = 0.01). There were no differences in pain, observation time, or number of gag reflexes between the 2 groups. Subgroup analysis of the presence of sedation revealed no differences between the two groups for the number of pharyngeal observation sites and the number of gag reflexes. However, the number of gag reflexes was higher in the spray group compared to the combination group in a subgroup analysis that looked at the absence of sedation. Conclusions Lidocaine spray for pharyngeal anesthesia was not inferior to lidocaine spray and viscous solution in terms of pharyngeal observation. It was considered that lidocaine viscous solution was unnecessary for pharyngeal observation. UMIN000016073.

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