ABSTRACT
BACKGROUND AND AIMS: In patients with non-severe acute or chronic autoimmune hepatitis (AIH) without cirrhosis, clinical practice guidelines recommend indistinct use of prednisone or budesonide. However, budesonide is infrequently used in clinical practice. We aimed to describe its use and compare its efficacy and safety with prednisone as first-line options. APPROACH AND RESULTS: This was a retrospective, multicenter study of 105 naive AIH patients treated with budesonide as the first-line drug. The control group included 276 patients treated with prednisone. Efficacy was assessed using logistic regression and validated using inverse probability of treatment weighting propensity score. The median time to biochemical response (BR) was 3.1 months in patients treated with budesonide and 4.9 months in those with prednisone. The BR rate was significantly higher in patients treated with prednisone (87% vs. 49% of patients with budesonide, p < 0.001). The probability of achieving BR, assessed using the inverse probability of treatment weighting propensity score, was significantly lower in the budesonide group (OR = 0.20; 95% CI: 0.11-0.38) at any time during follow-up, and at 6 (OR = 0.51; 95% CI: 0.29-0.89) and 12 months after starting treatment (0.41; 95% CI: 0.23-0.73). In patients with transaminases <2 × upper limit of normal, BR was similar in both treatment groups. Prednisone treatment was significantly associated with a higher risk of adverse events (24.2% vs. 15.9%, p = 0.047). CONCLUSIONS: In the real-life setting, the use of budesonide as first-line treatment is low, and it is generally prescribed to patients with perceived less disease activity. Budesonide was inferior to prednisone as a first-line drug but was associated with fewer side effects.
Subject(s)
Budesonide , Hepatitis, Autoimmune , Humans , Budesonide/adverse effects , Prednisone/therapeutic use , Hepatitis, Autoimmune/drug therapy , Retrospective Studies , Glucocorticoids/adverse effectsABSTRACT
BACKGROUND AND AIMS: Small series suggest that rituximab could be effective as treatment for autoimmune hepatitis (AIH), although data are scarce. We aimed to evaluate the efficacy and safety of rituximab in different cohorts of patients with AIH. METHODS: Multicentre retrospective analysis of the 35 patients with AIH and its variant forms treated with rituximab and included in the ColHai registry between 2015 and 2023. RESULTS: Most patients were female (83%), 10 (29%) had cirrhosis and four (11.4%) variant forms of AIH. Indication for rituximab were as follows: 14(40%) refractory AIH, 19(54%) concomitant autoimmune or haematological disorder, 2(6%) intolerance to prior treatments. In three (9%) subjects with a concomitant disorder, rituximab was the first therapy for AIH. Overall, 31 (89%) patients achieved or maintained complete biochemical response (CBR), including the three in first-line therapy. No difference in CBR was observed according to rituximab indication (refractory AIH 86% vs. concomitant disorders 90%, p = .824) or cirrhosis (80% vs. 92%, p = .319). Rituximab was associated with a significant reduction in corticosteroids (median dose: prior 20 vs. post 5 mg, p < .001) and the discontinuation of ≥1 immunosuppressant in 47% of patients. Flare-free rate at 1st, 2nd and 3rd year was 86%, 73% and 62% respectively. Flares were not associated with the development of liver failure and were successfully managed with repeated doses of rituximab and/or increased corticosteroids. Three (9%) patients experienced infusion-related adverse events (1 anaphylaxis and 2 flu-like symptoms) and five (14%) infections. CONCLUSION: Rituximab is safe and effective in patients with refractory AIH and those treated due to concomitant autoimmune or haematological disorders.
Subject(s)
Hepatitis, Autoimmune , Registries , Rituximab , Humans , Rituximab/therapeutic use , Rituximab/adverse effects , Female , Hepatitis, Autoimmune/drug therapy , Male , Retrospective Studies , Middle Aged , Adult , Aged , Treatment Outcome , Immunologic Factors/therapeutic use , Immunologic Factors/adverse effects , Young AdultABSTRACT
BACKGROUND & AIMS: Few prospective studies have assessed the safety of direct oral anticoagulants (DOACs) in elective endoscopy. Our primary aim was to compare the risks of endoscopy-related gastrointestinal bleeding and thromboembolic events in patients on DOACs or vitamin K antagonists (VKAs) in this setting. Secondarily, we examined the impact of the timing of anticoagulant resumption on the risk of delayed bleeding in high-risk therapeutic procedures. METHODS: We conducted a multicenter, prospective, observational study from January 2018 to March 2020 of 1602 patients on oral anticoagulants (1004 on VKAs and 598 on DOACs) undergoing 1874 elective endoscopic procedures. Our primary outcomes were 90-day thromboembolic events and 30-day endoscopy-related gastrointestinal bleeding. The inverse probability of treatment weighting propensity score method was used for baseline covariate adjustment. RESULTS: The 2 groups had similar risks of endoscopy-related gastrointestinal bleeding (VKAs vs DOACs, 6.2% vs 6.7%; adjusted odds ratio [OR], 1.05; 95% CI, 0.67-1.65) and thromboembolic events (VKAs vs DOACs, 1.3% vs 1.5%; adjusted OR, 0.90; 95% CI, 0.34-2.38). In high bleeding risk procedures (n = 747), delayed anticoagulant resumption (> 48 hours or 24-48 hours vs < 24 hours) did not reduce the risk of postprocedural bleeding (10.3%, 9%, and 5.8%, respectively; adjusted P = .43). Hot and cold snare polypectomy were the most frequent high-risk interventions (41.8% and 39.8%, respectively). CONCLUSION: In a prospective study of patients on DOACs or VKAs undergoing elective endoscopy, endoscopy-related bleeding and thromboembolic events showed similar risk. Our study suggests that early anticoagulant resumption is safe in most patients, but more data are needed for advanced high-risk therapeutic procedures.
Subject(s)
Colonic Polyps , Administration, Oral , Anticoagulants/adverse effects , Colonoscopy , Gastrointestinal Hemorrhage/chemically induced , Gastrointestinal Hemorrhage/epidemiology , Humans , Prospective Studies , Vitamin KABSTRACT
BACKGROUND & AIMS: Management of delayed (within 30 days) postpolypectomy bleeding (DPPB) has not been standardized. Patients often undergo colonoscopies that do not provide any benefit. We aimed to identify factors associated with therapeutic intervention and active bleeding after DPPB. METHODS: We performed a retrospective study of 548 patients with bleeding within 30 days after an index polypectomy (DPPB; 71.9% underwent colonoscopy, 2.6% underwent primary angiographic embolization, and 25.5% were managed without intervention) at 6 tertiary centers in Spain, from January 2010 through September 2018. We collected demographic and medical data from patients. The primary outcomes were the need for therapeutic intervention and the presence of active bleeding during colonoscopy. RESULTS: A need for therapeutic intervention was associated independently with the use of antithrombotic agents, hemoglobin decrease greater than 2 g/dL, hemodynamic instability, and comorbidities (P < .05). The bleeding point during colonoscopy was identified in 344 patients; 74 of these patients (21.5%) had active bleeding. Active use of anticoagulants (odds ratio [OR], 2.6; 95% CI, 1.5-4.5), left-sided polyps (OR, 1.95; 95% CI, 1-3.8), prior use of electrocautery (OR, 2.6; 95% CI, 1.1-6.1), and pedunculated polyp morphology (OR, 1.8, 95% CI, 1-3.2) significantly increased the risk of encountering active bleeding. We developed a visual nomogram to estimate the risk of active bleeding. Overall, 43% of the cohort did not require any hemostatic therapy. Rebleeding (<6%) and transfusion requirements were low in those managed without intervention. CONCLUSIONS: In a study of patients with DPPB, we found that almost half do not warrant any therapeutic intervention. Colonoscopy often is overused for patients with DPPB. We identified independent risk factors for active bleeding that might be used to identify patients most likely to benefit from colonoscopy.
Subject(s)
Colonic Polyps , Cohort Studies , Colonic Polyps/surgery , Colonoscopy , Gastrointestinal Hemorrhage , Humans , Postoperative Hemorrhage , Retrospective StudiesABSTRACT
INTRODUCTION: Obeticholic acid (OCA) and fibrates therapy results in biochemical improvement in placebo-controlled trials in patients with primary biliary cholangitis and insufficient response to ursodeoxycholic acid. There is scarce information outside of clinical trials. Therefore, we have assessed the effectiveness and adverse events of these treatments. METHODS: Data from patients included in the ColHai registry treated with OCA, fibrates, or both were recorded during a year, as well as adverse events and treatment discontinuation. RESULTS: Eighty-six patients were treated with OCA, 250 with fibrates (81% bezafibrate; 19% fenofibrate), and 15 with OCA plus fibrates. OCA group had baseline significantly higher alkaline phosphatase (ALP) (P = 0.01) and lower platelets (P = 0.03) than fibrates. Both treatments significantly decreased ALP, gamma-glutamyl transferase (GGT), and transaminases and improved Globe score. Albumin and immunoglobulin type M improved in the fibrates group. ALP decrease was higher under fibrates, whereas alanine aminotransferase decline was higher under OCA. Although baseline transaminases and GGT were higher in patients with OCA plus fibrates, significant ALP, GGT, alanine aminotransferase, and Globe score improvement were observed during triple therapy. Adverse events were reported in 14.7% of patients (21.3% OCA; 17.6% fenofibrate; 10.7% bezafibrate), mainly pruritus (10.1% with OCA). Discontinuation was more frequent in fenofibrate treatment mainly because of intolerance or adverse events. DISCUSSION: Second-line therapy with OCA or fibrates improves hepatic biochemistry and the GLOBE score in primary biliary cholangitis patients with suboptimal response to ursodeoxycholic acid. Simultaneous treatment with OCA and fibrates improved ALP as well.
Subject(s)
Bezafibrate/therapeutic use , Chenodeoxycholic Acid/analogs & derivatives , Fenofibrate/therapeutic use , Liver Cirrhosis, Biliary/drug therapy , Chenodeoxycholic Acid/therapeutic use , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: Autoimmune hepatitis (AIH) is a chronic liver disease able to progress to acute liver failure, cirrhosis, and liver cancer. A significant proportion of patients fail to first-line therapy or develop severe toxicity. AIMS: To assess safety and effectiveness of tacrolimus as a second-line therapy in AIH patients. METHODS: Multicentric retrospective study of AIH patients treated with tacrolimus for at least 3 months as a second-line therapy. Effectiveness was defined as complete normalization of transaminases and IgG. RESULTS: A total of 23 AIH patients were included in the final analysis. In 13% of patients tacrolimus was initiated because of toxicity to previous first-line treatments and the rest were switched because of previous non-efficacy. Tacrolimus was effective in 18 patients (78%; 95%CI: 55.20-91.92%). The median time receiving tacrolimus was 16 months (IQR 20). There was a sustained response with a significant improvement in all liver enzymes and IgG on last follow-up. Only one patient discontinued tacrolimus at the third month because of severe neuropathy, and ototoxicity. Responders were significantly older at diagnosis of AIH (41 ± 13 vs. 27 ± 10 years old; p = 0.0496). CONCLUSION: Tacrolimus is effective and well tolerated as a second-line therapy in patients with AIH.
Subject(s)
Hepatitis, Autoimmune/drug therapy , Immunosuppressive Agents/therapeutic use , Tacrolimus/therapeutic use , Adult , Chronic Disease , Female , Humans , Immunoglobulin G/blood , Liver/drug effects , Liver/enzymology , Liver/metabolism , Male , Middle Aged , Retrospective StudiesABSTRACT
BACKGROUND AND AIMS: TC-325 (Hemospray, Cook Medical, Winston-Salem, NC) is an inorganic hemostatic powder recently approved by the U.S. Food and Drug Administration. This study aimed to examine the effectiveness, safety, and predictors of TC-325 failure in a large real-life cohort. METHODS: This was a retrospective study conducted at 21 Spanish centers. All patients treated with TC-325 until September 2018 were included. The primary outcome was treatment failure, defined as failed intraprocedural hemostasis or recurrent bleeding within the first 30 postprocedural days. Secondary outcomes included safety and survival. Risk and predictors of failure were assessed via competing-risk models. RESULTS: The cohort comprised 261 patients, of whom 219 (83.9%) presented with upper gastrointestinal bleeding (GIB). The most common causes were peptic ulcer (28%), malignancy (18.4%), and therapeutic endoscopy-related GIB (17.6%). TC-325 was used as rescue therapy in 191 (73.2%) patients. The rate of intraprocedural hemostasis was 93.5% (95% confidence interval [CI], 90%-96%). Risks of TC-325 failure at postprocedural days 3, 7, and 30 were 21.1%, 24.6%, and 27.4%, respectively. On multivariate analysis, spurting bleeding (P = .004), use of vasoactive drugs (P = .02), and hypotension (P = .008) were independent predictors of failure. Overall 30-day survival was 81.9% (95% CI, 76%-86%) and intraprocedural hemostasis was associated with a better prognosis (adjusted hazard ratio, 0.29; P = .006). Two severe adverse events were noted. CONCLUSION: TC-325 was safe and effective for intraprocedural hemostasis in more than 90% of patients, regardless of the cause or site of bleeding and its use as rescue therapy. In this high-risk cohort treated with TC-325, the 30-day failure rate exceeded 25% and was highest with spurting bleeding or hemodynamic instability.
Subject(s)
Gastrointestinal Hemorrhage/drug therapy , Hemostatics/therapeutic use , Minerals/therapeutic use , Postoperative Hemorrhage/drug therapy , Aged , Aged, 80 and over , Endoscopy, Gastrointestinal , Female , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Neoplasms/complications , Hemostasis, Endoscopic , Humans , Male , Middle Aged , Peptic Ulcer Hemorrhage/drug therapy , Recurrence , Retrospective Studies , Treatment FailureABSTRACT
INTRODUCTION: Epistaxis in cirrhotic patients is a common issue. However, the literature published to date is very scarce. MATERIAL AND METHODS: Retrospective case series of patients with cirrhosis who presented with a significant epistaxis, between 2006 and 2016. RESULTS: Data were collected from 39 cirrhotic patients with a mean age of 61.4 (±14) years, 75% of which were males. The main comorbidities were hypertension (33%) and diabetes mellitus (26%). Seven (18%) patients were taking antiplatelet drugs and 3 (8%) anticoagulants. One third of patients had a previous history of epistaxis and 6 had a previous ENT pathology. The main aetiological factor of cirrhosis was alcohol in 46% of cases, with 15 (38%) patients presenting with Child A, 12 (31%) Child B and 12 (31%) Child C class. The median MELD score upon admission was 16 [12-21]. Thirty-five (97%) patients had portal hypertension. At admission, the median platelet count was 89,000 [60,000-163,000] and mean INR was 1.52 (±0.37). Clinically, epistaxis presented as haematemesis or melaena in 8 (21%) patients, simulating gastrointestinal bleeding due to swallowing of blood. In 10 (26%) patients, epistaxis was considered as the probable trigger of an episode of hepatic encephalopathy. Two patients required ICU admission due to bleeding and 8 (21%) died during hospitalisation due to causes not directly related to epistaxis. CONCLUSIONS: Epistaxis is a complication to be taken into account in cirrhotic patients, as it can act as an encephalopathy trigger or simulate an episode of gastrointestinal bleeding.
Subject(s)
Epistaxis/etiology , Liver Cirrhosis/complications , Female , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
BACKGROUND: Helicobacter pylori antibiotic resistance is an increasing problem worldwide. Pylera® may be an option as salvage therapy. AIM: To assess the effectiveness, safety, and tolerance of Pylera® as a third-line in clinical practice. MATERIALS AND METHODS: This was a multicenter, observational, prospective database study in four Spanish hospitals. Consecutive H. pylori-infected individuals treated with Pylera® and a proton-pump inhibitor (PPI) were invited to participate if they had failed to respond to PPI-clarithromycin-amoxicillin as first-line and to levofloxacin-amoxicillin-PPI as second-line therapy. Eradication was tested 4-8 weeks after Pylera® using a C13 -urea breath test. Treatment-related adverse effects (TRAEs) were assessed through a questionnaire and by reviewing databases. A questionnaire on patient satisfaction was completed in the last visit. RESULTS: Of 103 subjects fulfilling the selection criteria, 101 were included in the intention-to-treat (ITT) analysis and 97 in the per-protocol (PP) analysis. A 10 day course was prescribed in all patients. Esomeprazole 40 mg b.i.d. was the most used PPI regimen (ITT=94.1%). Ninety-seven individuals (ITT=96.04%) completed more than 90% of the treatment. Overall eradication rates were ITT=80.2% (95% confidence interval [CI]: 72.3%-88.1%) and PP=84.4% (95% CI: 76.8%-91.8%). One or more TRAEs were experienced by 67.3% (95% CI: 57.7%-75.7%), all mild or moderate. TRAEs and the number of pills were the main complaints. CONCLUSION: In an area of high antibiotic resistance to H. pylori, 10-day Pylera® plus double-dose PPI emerged as an alternative as third-line therapy, although not achieving optimal eradication rates. TRAEs were common but were neither severe nor did they condition compliance.
Subject(s)
Anti-Infective Agents/administration & dosage , Bismuth/administration & dosage , Helicobacter Infections/drug therapy , Helicobacter pylori/isolation & purification , Salvage Therapy/methods , Adult , Aged , Aged, 80 and over , Breath Tests , Drug Therapy, Combination/methods , Female , Hospitals , Humans , Male , Middle Aged , Patient Satisfaction , Prospective Studies , Proton Pump Inhibitors/administration & dosage , Spain , Surveys and Questionnaires , Treatment Outcome , Urea/analysis , Young AdultABSTRACT
INTRODUCTION: Recurrent Clostridium difficile infection (CDI) is common and often difficult to manage. Faecal microbiota transplant (FMT) is an effective therapeutic tool in these cases, although its applicability and effectiveness in Spain is currently unknown. AIM: To analyse the technical aspects, safety and effectiveness of the first consolidated FMT programme in Spain. METHODS: Retrospective descriptive study of all patients with recurrent CDI treated with FMT performed by colonoscopy in a tertiary centre after the implementation of a multidisciplinary protocol between March 2015 and September 2016. RESULTS: A total of 13 FMT were performed in 12 patients (11/12; 91.7% women) with a median age of 84.6 years (range: 38.2-98.2). Recurrence of CDI was the indication for FMT in all cases. Patients had suffered a median of 3 previous episodes of CDI (range: 2-6) and all had failed treatment with fidaxomicin. All procedures were performed by colonoscopy. Effectiveness with one session of FMT was 91.7% (11/12; 95% CI: 64.6 to 98.5%). In the non-responder patient, a second FMT was performed 17 days after the first procedure, with disappearance of symptoms. No side effects related to the endoscopic procedure or the FMT were recorded after a median follow-up of 6.5 months (range: 1-16 months). Two patients died during follow-up due to causes unrelated to FMT. CONCLUSION: FMT by colonoscopy is an effective and safe therapeutic alternative in recurrent CDI. It is a simple procedure that should be implemented in more centres in Spain.
Subject(s)
Clostridium Infections/therapy , Colonoscopy , Fecal Microbiota Transplantation/methods , Adult , Aged , Aged, 80 and over , Fecal Microbiota Transplantation/adverse effects , Female , Humans , Middle Aged , Program Evaluation , Recurrence , Retrospective Studies , Treatment OutcomeABSTRACT
Bacteria can no longer be seen as an enemy. Nowadays, there is enough evidence to place the microbiota as a key element in human homeostasis. Despite initial skepticism, fecal microbiota transplantation (FMT) is a real therapeutic alternative for patients with recurrent Clostridium difficile infection. Moreover, this procedure has shown promising results in ulcerative colitis and other non-gastrointestinal disorders. There is still a lack of knowledge and clinical trials with long- term follow-up. Therefore, the available data should be interpreted with caution. In this document we provide a detailed review of the literature on the intestinal microbiota and FMT.
Subject(s)
Fecal Microbiota Transplantation , Animals , Clinical Trials as Topic , Clostridioides difficile , Enterocolitis, Pseudomembranous/microbiology , Enterocolitis, Pseudomembranous/therapy , Fecal Microbiota Transplantation/adverse effects , Fecal Microbiota Transplantation/methods , Fecal Microbiota Transplantation/standards , Germ-Free Life , Humans , Inflammatory Bowel Diseases/microbiology , Inflammatory Bowel Diseases/therapy , Intestines/immunology , Intestines/microbiology , Metabolic Syndrome/microbiology , Metabolic Syndrome/therapy , MicrobiotaABSTRACT
Syphilis is a chronic systemic infection mainly transmitted through sexual contact that shows a great variety of clinical manifestations. Liver involvement is an unusual complication mainly reported in HIV patients. In this case report we present a case of a 42-year-old immunocompent man with acute cholestatic hepatitis who was finally diagnosed of luetic hepatitis. Liver disease was the only manifestation of syphilis infection difficulty it's diagnostic. We emphasize the importance of including syphilis in the differential diagnosis of abnormal liver function tests in patients at risk of sexually transmitted diseases due to its resolution with appropriate antibiotic treatment.
Subject(s)
Hepatitis/microbiology , Syphilis/complications , Acute Disease , Adult , Hepatitis/diagnosis , Humans , Immunocompetence , Male , Syphilis/diagnosisABSTRACT
INTRODUCTION: Faecal microbiota transplantation (FMT) is a treatment supported by wide scientific evidence and proved to be very effective in the management of Clostridioides difficile infection (CDI). The objective of this study is to analyze its effectiveness and safety in a real clinical practice setting. METHODS: Retrospective, single-center and descriptive observational study in which all FMT performed between May 2016 and December 2020 were included. Technical success was defined as the successful administration of the faecal preparation in the patient's gastrointestinal tract and clinical success the disappearance of diarrhoea in the first 72â¯h after the procedure with no relapse within the following 8 weeks after the therapy was started. RESULTS: 15 FMT were performed in 13 patients. Median age was 79 years (range: 40-98 years); being 60% women and 33.3% depedent persons. The indication for FMT was recurrent CDI in 84.6%. All FMTs were performed by colonoscopy and from related donors. With a first procedure, the FMT was effective in 11 of 13 patients (84.61%; 95% CI; 54.55-98.07). Time until resolution of symptoms was less than 48â¯h in all cases. Post-transplant follow-up was 25.66⯱â¯17.5 months. No significant short or long-term complications were recorded at follow-up. CONCLUSION: TMF is a simple, effective and safe procedure in CD infection, even in elderly patients or those with great comorbidities.
Subject(s)
Clostridioides difficile , Clostridium Infections , Humans , Female , Aged , Male , Fecal Microbiota Transplantation/methods , Retrospective Studies , Treatment Outcome , FecesSubject(s)
Gastrointestinal Hemorrhage/etiology , Pancreatitis, Acute Necrotizing/complications , Abdominal Pain/etiology , Adult , Anticoagulants/adverse effects , Anticoagulants/therapeutic use , Cecal Diseases/etiology , Computed Tomography Angiography , Embolization, Therapeutic , Gastrointestinal Hemorrhage/diagnostic imaging , Hematoma/diagnostic imaging , Hematoma/etiology , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Intestinal Perforation/etiology , Male , Mesenteric Ischemia/diagnostic imaging , Mesenteric Ischemia/drug therapy , Mesenteric Ischemia/etiology , Rupture, Spontaneous , Systemic Inflammatory Response Syndrome/complicationsABSTRACT
BACKGROUND AND AIMS: To assess whether corticosteroids improve prognosis in patients with AS-AIH, and to identify factors at therapy initiation and during therapy predictive of the response to corticosteroids. METHODS: This was a retrospective cohort study including all patients with AS-AIH admitted to 13 tertiary centres from January 2002 to January 2019. The composite primary outcome was death or liver transplantation within 90 days of admission. Kaplan-Meier and Cox regression methods were used for data analysis. RESULTS: Of 242 consecutive patients enrolled (mean age [SD] 49.7 [16.8] years), 203 received corticosteroids. Overall 90-day transplant-free survival was 61.6% (95% confidence interval [CI] 55.4-67.7). Corticosteroids reduced the risk of a poor outcome (adjusted hazard ratio [HR] 0.25; 95% CI 0.2-0.4), but this treatment failed in 30.5%. An internally validated nomogram composed of older age, MELD, encephalopathy and ascites at the initiation of corticosteroids accurately predicted the response (C-index 0.82; [95% CI 0.8-0.9]). In responders, MELD significantly improved from days 3 to 14 but remained unchanged in non-responders. MELD on day 7 with a cut-off of 25 (sensitivity 62.5%[95% CI: 47.0-75.8]; specificity 95.2% [95% CI: 89.9-97.8]) was the best univariate predictor of the response. Prolonging corticosteroids did not increase the overall infection risk (adjusted HR 0.75; 95% CI 0.3-2.1). CONCLUSION: Older patients with high MELD, encephalopathy or ascites at steroid therapy initiation and during treatment are unlikely to show a favourable response and so prolonged therapy in these patients, especially if they are transplantation candidates, should be avoided.
Subject(s)
Brain Diseases , Hepatitis, Autoimmune , Acute Disease , Adolescent , Adrenal Cortex Hormones/therapeutic use , Ascites , Hepatitis, Autoimmune/diagnosis , Hepatitis, Autoimmune/drug therapy , Humans , Prognosis , Retrospective Studies , Severity of Illness IndexSubject(s)
Antineoplastic Agents/therapeutic use , Crohn Disease/complications , Interferon-alpha/therapeutic use , Melanoma/drug therapy , Skin Neoplasms/drug therapy , Adult , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacology , Combined Modality Therapy , Crohn Disease/drug therapy , Female , Follow-Up Studies , Humans , Immunocompromised Host , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Interferon alpha-2 , Interferon-alpha/administration & dosage , Interferon-alpha/pharmacology , Melanoma/complications , Melanoma/surgery , Recombinant Proteins/administration & dosage , Recombinant Proteins/pharmacology , Recombinant Proteins/therapeutic use , Remission Induction , Skin Neoplasms/complications , Skin Neoplasms/surgeryABSTRACT
BACKGROUND & AIMS: Mitochondria are the major organelles for the formation of reactive oxygen species (ROS) in the cell, and mitochondrial dysfunction has been described as a key factor in the pathogenesis of cholestatic liver disease. The methylation-controlled J-protein (MCJ) is a mitochondrial protein that interacts with and represses the function of complex I of the electron transport chain. The relevance of MCJ in the pathology of cholestasis has not yet been explored. METHODS: We studied the relationship between MCJ and cholestasis-induced liver injury in liver biopsies from patients with chronic cholestatic liver diseases, and in livers and primary hepatocytes obtained from WT and MCJ-KO mice. Bile duct ligation (BDL) was used as an animal model of cholestasis, and primary hepatocytes were treated with toxic doses of bile acids. We evaluated the effect of MCJ silencing for the treatment of cholestasis-induced liver injury. RESULTS: Elevated levels of MCJ were detected in the liver tissue of patients with chronic cholestatic liver disease when compared with normal liver tissue. Likewise, in mouse models, the hepatic levels of MCJ were increased. After BDL, MCJ-KO animals showed significantly decreased inflammation and apoptosis. In an in vitro model of bile-acid induced toxicity, we observed that the loss of MCJ protected mouse primary hepatocytes from bile acid-induced mitochondrial ROS overproduction and ATP depletion, enabling higher cell viability. Finally, the in vivo inhibition of the MCJ expression, following BDL, showed reduced liver injury and a mitigation of the main cholestatic characteristics. CONCLUSIONS: We demonstrated that MCJ is involved in the progression of cholestatic liver injury, and our results identified MCJ as a potential therapeutic target to mitigate the liver injury caused by cholestasis. LAY SUMMARY: In this study, we examine the effect of mitochondrial respiratory chain inhibition by MCJ on bile acid-induced liver toxicity. The loss of MCJ protects hepatocytes against apoptosis, mitochondrial ROS overproduction, and ATP depletion as a result of bile acid toxicity. Our results identify MCJ as a potential therapeutic target to mitigate liver injury in cholestatic liver diseases.
ABSTRACT
We report the case of a 37 years old woman who presented to emergency department because of a 3 days history of abdominal disconfort and distension. After physical examination and a CT scan of the abdomen she was diagnosed of Distal Intestinal Obstruction Syndrome (DIOS) in the context of her underlying cystic fibrosis. Conservative management was attempted with no improvement. A colonoscopy was performed and thick solid feces were seen filling the cecum and right colon. An attempt to dissolve the impacted stool was made by instilling one liter of Diet Coca-Cola® through the working channel of the colonoscope. After that, the condition of the resolved in the following 24 h with no more interventions.
Subject(s)
Carbonated Beverages , Cystic Fibrosis/complications , Intestinal Obstruction/etiology , Intestinal Obstruction/therapy , Adult , Colonoscopy , Diagnosis, Differential , Female , Humans , Intestinal Obstruction/diagnostic imaging , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: Patients with hepatocellular carcinoma (HCC) are a growing population of the transplantation waiting list (WL) for orthotopic liver transplantation (OLT). There is no consensus to prioritize these patients while on the WL. AIMS: To assess whether patients with HCC were more prioritized than non-HCC patients based on their WL survival as primary outcome. METHODS: Restrospective cohort study including patients listed for elective OLT from January 2013 to January 2016. RESULTS: 165 patients with cirrhosis were listed for OLT: 64 in the HCC group (38.78%) and 101 in the non-HCC group (61.22%). Outcomes (HCC vs. non-HCC) were: OLT in 75.51% vs. 64.37%; death or dropout due to worsening in 20.41% vs. 27.59%, and delisting because of improvement in 4.08% vs. 8.05%. HCC patients had a significantly higher WL survival rate (HRâ¯=â¯0.45; 95% CI: 0.21-0.96); lower MELD score at transplantation (21 [20-24] vs. 24 [20-30]; pâ¯=â¯0.021); higher delta-MELD - the difference between MELD at transplantation and MELD at listing time - (3 [2-6] vs. 0 [0-5]; pâ¯=â¯0.024) and longer waiting time until OLT (143 [70-233] vs. 67 [21-164] days; pâ¯=â¯0.008). CONCLUSION: Despite having to wait longer, patients with HCC showed higher WL survival than non-HCC patients.
Subject(s)
Carcinoma, Hepatocellular/mortality , Liver Neoplasms/mortality , Liver Transplantation , Waiting Lists/mortality , Carcinoma, Hepatocellular/therapy , Female , Health Care Rationing , Humans , Liver Cirrhosis/mortality , Liver Cirrhosis/therapy , Liver Neoplasms/therapy , Male , Middle Aged , Resource Allocation , Retrospective Studies , Severity of Illness Index , Spain , Survival Analysis , Survival Rate , Tissue and Organ ProcurementABSTRACT
Patients with Crohn's disease often develop perianal disease, successfully managed in most cases. However, its most aggressive form, complex perianal disease, is associated with high morbidity and a significant impairment in patients' quality of life. The aim of this review is to provide an updated approach to this condition, reviewing aspects of its epidemiology, diagnosis and therapeutic alternatives. Emerging treatment options are also discussed. A multidisciplinary assessment of these patients with a coordinated medical and surgical approach is crucial.