Search Results (488)

Obesity, a heterogeneous metabolic disease, is linked with severe comorbidities, prominently increasing morbidity and mortality. A weight loss between 5% and 10% is already sufficient to induce clinically relevant improvements in human health. Activation of energy expenditure through an impact on the brown and beige adipose tissues has recently become an interesting new target in obesity treatment. Obeticholic acid (OCA) is a semisynthetic derivative of the primary human bile acid, chenodeoxycholic acid. The compound is an agonist of farnesoid X receptor (FXR) and Takeda G protein-coupled receptor (TGR5), activating the cellular pathways such as fibroblast growth factor-19, tissue-specific uncoupling protein 1, or type 2 iodothyronine deiodinase associated with energy expenditure and brown adipose tissue activity. So far, OCA has been approved to treat primary biliary cholangitis. Interestingly, the drug demonstrated therapeutic effects in animal models of obesity. Preliminary results from the human studies show that OCA administration holds potential as a treatment option in obesity, although some adverse effects may occur. Long-term administration of OCA might constitute an attractive therapeutic add-on approach, complementary to the currently approved treatments. The design of OCA derivatives targeting similar mechanisms, yet with a better pharmacological profile, seems to be an exciting pathway in the search of novel anti-obesity drugs. Further clinical trials involving larger cohorts of patients, with and without comorbidities, are warranted to confirm the benefits and safety of OCA administration. Full article

A 47-year-old woman with metastatic pancreatic adenocarcinoma, diagnosed five months earlier and treated with palliative chemotherapy, was admitted with fever, jaundice, and right upper quadrant pain consistent with ascending cholangitis. Treatment with antibiotics was initiated and an endoscopic retrograde cholangiography was performed, whereby a biliary stent was placed to relieve malignant biliary obstruction. Physical examination revealed moderate ascites. Careful inspection of the umbilicus revealed a small nodular lesion located within the umbilical fold that became visible only after eversion of the umbilicus. The lesion had developed gradually over several weeks. Computed tomography confirmed the known pancreatic malignancy with metastatic disease and ascites. On re-review of the images, a small soft tissue nodule replacing the umbilicus was also visible. The lesion was clinically consistent with a Sister Mary Joseph nodule, an umbilical metastasis most commonly associated with advanced gastrointestinal or gynecologic malignancies. These lesions may arise through lymphatic or hematogenous spread or through direct extension into the umbilicus. This case highlights that umbilical metastases may be subtle and located within the umbilical fold, requiring careful physical examination to be detected. Full article

Background: Isolated gallbladder injuries are rare, especially when initial imaging is normal. Advanced imaging is required to detect delayed complications. Moreover, it is necessary to make an appropriate diagnosis while selecting the most suitable treatment option. Case Presentation: A 49-year-old man fell while cycling and developed worsening abdominal pain. Initial contrast-enhanced computed tomography (CT) scans showed no abnormalities. However, the patient later developed cholangitis and cholecystitis caused by biliary obstruction from a delayed gallbladder hematoma. Magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography (MRCP) were used to diagnose this condition. The patient was initially managed conservatively with antibiotics, which led to temporary symptomatic improvement. Notably, the patient developed a delayed recurrence of suspected acute cholangitis (Grade I) on Day 12 due to hematoma migration. After recurrence, endoscopic nasobiliary drainage was performed as a step-up approach, in accordance with the Tokyo Guidelines 2018 management bundle, to achieve biliary decompression, followed by elective laparoscopic cholecystectomy. Pathological examination revealed chronic cholecystitis with hematoma. Conclusions: Isolated gallbladder injuries should be considered in patients with blunt abdominal trauma. Delayed hematoma formation can lead to biliary obstruction, even without initial CT findings. In such cases, early implementation of MRI and MRCP, along with close clinical monitoring for delayed recurrence, is essential. A strategic “step-up approach” incorporating endoscopic drainage is a safe and effective management option prior to definitive surgery. Full article

Background and goals: The outcomes of patients with primary sclerosing cholangitis (PSC) in central Missouri are unknown. The University of Missouri–Columbia services 600,000 individuals in central Missouri. Our aims were (a) to examine the outcomes of PSC patients receiving care at our academic institution, and (b) to identify the predictors of PSC-related serious adverse events. Methods: A retrospective study of patients with PSC in a non-transplant center. The primary outcome was the development of ≥1 of PSC-related serious adverse event for (1) progression to cirrhosis, or (2) development of cholangiocarcinoma. Results: From 2000 to 2018, 42 patients fulfilled the criteria for the diagnosis of PSC. A total of 55% of the patients were male, and 79% had associated inflammatory bowel disease (IBD). The median follow-up from time of diagnosis of PSC until the last follow-up or death was 5.5 years. A total of 57% of the patients developed ≥ 1 PSC-related adverse event; 36% (8/22) of those who progressed to decompensation underwent liver transplantation. The median time from diagnosis of PSC until progression to decompensation was 6.3 years; the median time from decompensation to transplantation was 10.8 years. A total of 12% of the patients developed ≥ 1 cancer (cholangiocarcinoma = 2; gallbladder cancer = 2; colon cancer = 1; and hepatocellular carcinoma = 1). The overall mortality was 9.5%. The median time from PSC diagnosis until death was 10.2 years. A Cox hazards regression analysis showed only age (HR = 1.16; p = 0.032; 95% CI, 1.01–1.13) and serum bilirubin (HR = 1.42; p = 0.036; 95% CI, 1.03–2.69) at the time of PSC diagnosis were independently associated with PSC-related serious events. Conclusions: Age and bilirubin are important predictors of PSC-related outcomes. Full article

Background. Autoimmune sclerosing cholangitis (ASC) is a rare clinical entity characterized by overlapping features of autoimmune hepatitis and primary sclerosing cholangitis. It predominantly affects pediatric patients. Therapeutic management is often complex, requiring a multidisciplinary and individualized approach, especially in the context of associated autoimmune diseases. Case presentation. We present the case of a female patient diagnosed at the age of 10 with ASC, for which immunosuppressive therapy with prednisone, azathioprine (AZA), and ursodeoxycholic acid (UDCA) was initiated, with an initially favorable course. One year later, following a Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection, the patient experienced reactivation of liver disease and subsequently developed ulcerative pancolitis (UC), for which 5-aminosalicylic acid (5-ASA) therapy was initiated. Due to repeated hepatic flares and/or colitis relapses, therapy was escalated successively to mycophenolate mofetil, tacrolimus, and eventually infliximab (IFX). Despite treatment, the liver disease progressed, culminating in liver cirrhosis. Our patient developed portal hypertension and esophageal varices, with two episodes of upper gastrointestinal bleeding requiring endoscopic band ligation. At the age of 14, the patient developed recurrent episodes of non-infectious ulcerative stomatitis. Biopsy of the lesions revealed non-specific chronic inflammation, unrelated to colitis activity (confirmed microscopic remission of UC). By exclusion, an adverse drug reaction was suspected, with AZA being the most likely cause. Following its discontinuation, the lesions resolved. Beyond the physiological and therapeutic aspects, the patient displays marked emotional fragility due to prolonged and repeated hospitalizations (18 out of 60 months), which have impacted treatment adherence. Conclusions. This case highlights the complexity of managing pediatric patients with multiple autoimmune diseases. The necessary combination of immunosuppressive therapies may lead to significant adverse effects and further complicate disease progression. Moreover, psychological components play a crucial role in treatment compliance and therapeutic success, emphasizing the need for an integrated approach that includes specialized psychological support. Full article

Background: Acute calculous cholangitis is commonly associated with biliary tract infections and is predominantly caused by enteric bacteria. Increasing antimicrobial resistance, particularly among extended-spectrum β-lactamase (ESBL)-producing Gram-negative organisms, has become a major concern in Southeast Asia, including Vietnam. Updated local microbiological data are essential to guide appropriate empirical antibiotic therapy. Methods: This retrospective multicenter study analyzed clinical and microbiological data from patients diagnosed with acute calculous cholangitis. Bacterial culture results were collected from Hanoi Medical University Hospital, Thanh Nhan Hospital, and E Hospital between June 2022 and December 2024. Results: Gram-negative bacteria were predominant (286/366, 78.14%), while Gram-positive bacteria accounted for 80/366 (21.86%). Escherichia coli was the most frequently isolated organism (133/366, 36.34%), of which 77/133 (57.89%) were ESBL producing. Klebsiella spp. accounted for 60/366 (16.39%), with 17/60 (28.33%) ESBL-producing isolates. Enterococcus spp. (n = 80) exhibited high susceptibility to vancomycin (69/80, 86.15%) and complete susceptibility to linezolid (80/80, 100%). Conclusions: This multicenter study highlights evolving pathogen distributions and antimicrobial resistance patterns in acute calculous cholangitis in Vietnam. These findings provide valuable evidence to support the optimization of empirical antibiotic regimens in clinical practice. Full article

Background: We aimed to describe the clinical and microbiological characteristics of biliary-source bloodstream infections (bBSIs) in patients with malignancies and identify risk factors for recurrence. Methods: All bBSI episodes in patients with active solid tumors during 2021–2025 were retrospectively reviewed. Independent risk factors for recurrent bBSI and mortality were identified. A previously published recurrence risk score was externally validated. Results: Overall, 136 patients experienced 199 bBSI episodes. Pancreatic (36.7%) and biliary tract (33.2%) were the most common cancers, and 60.8% had metastatic disease. The main pathogens were Escherichia coli (43.2%), Klebsiella pneumoniae (24.1%), and Enterococcus faecium (19.1%), and multidrug-resistant organisms accounted for 19.1%. Inappropriate empirical antibiotic treatment (IEAT) occurred in 37.2% and was independently associated with increased 30-day mortality, together with metastatic disease and septic shock. Thirty-day mortality was 24.6%. Recurrent bBSI occurred in 35.7% and was independently associated with biliary tract cancer, previous multidrug-resistant isolation, and prior hospitalization for suspected biliary infection. The externally validated recurrence score showed excellent discrimination (AUC 0.815). Conclusions: bBSI in oncology patients is associated with high rates of MDR pathogens, IEAT, recurrence, and mortality. A simple clinical score may identify patients at high risk of recurrence and guide preventive strategies. Full article

Multicentric reticulohistiocytosis (MRH) is a rare systemic histiocytic disorder of uncertain etiology characterized by papulonodular cutaneous lesions and potentially destructive polyarthritis, with variable multisystem involvement. Owing to its low prevalence, evidence for optimal management remains limited, and treatment responses are heterogeneous. Emerging reports suggest that Janus kinase (JAK) inhibition may provide benefit in refractory disease. We report a 60-year-old woman with MRH presenting with papulonodular skin lesions, symmetric polyarthritis, constitutional symptoms, and interstitial lung disease (nonspecific interstitial pneumonia pattern) in the context of co-existing primary biliary cholangitis and no evidence of malignancy. Prior therapies (glucocorticoids, methotrexate, leflunomide) achieved suboptimal control. Upadacitinib, a selective JAK1 inhibitor, induced rapid and complete remission of cutaneous and articular disease with improvement of pulmonary involvement. Secondary weight gain and incident diabetes were managed with tirzepatide. This case adds to the limited literature supporting JAK inhibition as a targeted option for refractory MRH, including multisystem disease with pulmonary involvement. Systematic evaluation of efficacy, durability, and safety is warranted. Full article

Background/Objectives: Primary biliary cholangitis (PBC) is a chronic immune-mediated cholestatic liver disease with increasing global prevalence. However, data on this disease from Central Asia are lacking. We aimed to describe the clinical, serological, and treatment characteristics of PBC patients in Kazakhstan. Methods: This study was a multicenter, retrospective, observational study including adults diagnosed with PBC between 2014 and 2022 across seven hepatology centers in Kazakhstan. Clinical presentation, laboratory parameters, autoimmune comorbidities, liver disease severity, and ursodeoxycholic acid (UDCA) treatment response were assessed. Biochemical response at 1 year was evaluated using Paris-1 and Barcelona criteria. Results: A total of 230 patients were included; 93.9% were female and 91.3% were of Asian ethnicity, with a median age at diagnosis of 53 years. Cirrhosis was present at diagnosis in 50.2% of the patients. PBC with autoimmune hepatitis (AIH) features was identified in 56.1% of the patients and was associated with higher rates of cirrhosis, portal hypertension complications, antinuclear antibody (ANA) positivity, and higher elastography indices compared with isolated PBC. Overall, approximately 55% of the patients achieved a biochemical response to UDCA at 1 year, with similar response rates between patients with PBC and those with PBC with AIH features. Conclusions: This first comprehensive study of PBC in Kazakhstan demonstrates late disease presentation with a high burden of cirrhosis and frequent AIH features. Despite advanced disease, about half of the patients achieved biochemical remission on UDCA. These findings underscore the need for earlier diagnosis and optimized management strategies for PBC in Kazakhstan and similar settings in Central Asia. Full article

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by cholestasis, which can progress to end-stage liver disease and even hepatocellular carcinoma. Its onset is typically triggered by complex interactions between genetic and environmental factors. In recent years, epidemiological and mechanistic studies have highlighted bacterial and fungal infections as potential key environmental factors in PBC pathogenesis. Bacteria may be associated with PBC autoimmunity through mechanisms such as molecular mimicry. Gut microbiota dysbiosis has been linked to aberrant immune recognition, altered metabolites, and intestinal barrier disruption, which may contribute to the aggravation of liver injury. Case reports of fungal infections suggest an association with poor prognosis in PBC, although the underlying mechanisms remain to be elucidated. This review systematically summarizes existing clinical epidemiological data, microbiome association studies, and mechanistic evidence; synthesizes the possible molecular mechanisms linking bacterial infections to PBC development and progression; discusses the potential role of the gut microbiota in PBC progression; and analyzes the possible molecular mechanisms underlying the poor prognosis associated with fungal infections in PBC. This study aims to provide valuable insights for developing optimal prevention, diagnosis, and treatment strategies targeting bacterial and fungal infections in PBC. Full article

Background/Objectives: The COVID-19 pandemic has brought about significant clinical challenges in regard to digestive systems, as well as causing complications such as pancreatitis and biliary infections. Whether diabetes mellitus (DM) contributes to both an increased risk for these complications and mortality amongst COVID-19 patients remains to be investigated. This study aimed to illuminate any possible outcomes, including pancreatitis, cholangitis, cholecystitis and all-cause mortality, among COVID-19 patients with and without pre-existing type 2 diabetes mellitus (T2DM), using real-world data taken from a multinational electronic health record database. Methods: A retrospective cohort study based upon data taken from the database of the TriNetX Global Collaborative Network was conducted. We included patients from the database who had been diagnosed with COVID-19 from January 2020 to December 2023. Enrolled subjects were divided into two cohorts: COVID-19 patients with pre-existing T2DM who had had at least two medical visits, and those without T2DM. Propensity score matching was performed using 68 baseline variables. Outcomes were evaluated within 90 days following COVID-19 diagnosis, with patients with prior relevant diagnoses being excluded. Risk analyses, Kaplan–Meier survival estimates, and hazard ratios were calculated as the outcomes. Results: The incidence of acute pancreatitis was significantly higher in the DM+ group when compared to the DM– group (Hazard ratio (HR) = 1.307; 95% confidence interval (CI) 1.048–1.630, p = 0.017) and mortality (HR = 1.141; 95% CI 1.102–1.181, p < 0.05) by Kaplan–Meier analysis. Risk of cholecystitis (HR = 1.264; 95% CI 1.042–1.533, p = 0.017) was borderline increased, and cholangitis was not significant (HR 0.847, 95% CI 0.583–1.230) Conclusions: In COVID-19 patients, pre-existing T2DM is independently associated with increased risks of acute pancreatitis and mortality. Full article

Primary biliary cholangitis (PBC) is an autoimmune-mediated disease characterized by chronic, non-suppurative, small-duct lymphocytic cholangitis. The prognosis largely depends on early disease recognition and treatment. Suboptimal response to first-line therapy (ursodeoxycholic acid) is associated with risk for disease progression. Reliable biomarkers are also required to enhance risk stratification. The traditional gold standard for assessing fibrosis is liver biopsy, but it is invasive and unsuitable for serial evaluations. Hence, trends are towards non-invasive surrogate biomarkers (blood-based and imaging biomarkers respectively) which have a much better safety profile. Blood-based biomarkers include: (i) Fibrosis-4 [Fib-4], (ii) Aspartate Aminotransferase to Platelet Ratio Index [APRI], (iii) Enhanced Liver Fibrosis score [ELF], and (iv) total bile acid to platelet ratio [TPR]. They show much potential but are not particularly sensitive tests. Ultrasound-based imaging biomarkers are increasingly being utilized for liver stiffness measurement (LSM), with vibration-controlled transient elastography (VCTE) emerging as the preferred technique. However, despite its growing popularity, VCTE is limited by technical issues. Hence, currently, none of the non-invasive tests fulfill the prerequisites to be the new gold standard as defined by the FDA. Nonetheless, there may be value to combining LSM with various serum biomarkers such as Fib-4, APRI, as aforementioned. The hope is to create nomograms for predicting liver-related events and decision tree algorithms. Newer studies are investigating microbiota in the gut-liver axis, biomolecules such as nanovesicles/nanofibers, and metabolic reprogramming as it pertains to e.g., proteomics and lipidomics. These approaches hold much promise, and if validated, could significantly change the management of PBC. Full article

Candida species are frequently detected in bile cultures during endoscopic retrograde cholangiopancreatography (ERCP), but their clinical significance and the value of antifungal treatment remain unclear. We performed a retrospective single-center cohort study of adults with growth of Candida species from bile cultures collected by ERCP performed between 2010 and 2023. We compared inpatients who received vs. those who did not receive antifungals within one week of ERCP and a subgroup with acute cholangitis. The primary outcome was a composite of death and invasive candidiasis within one year. Secondary outcomes included death, invasive candidiasis, and rehospitalization. Inverse probability of treatment weighting (IPTW) was performed using baseline characteristics. Adjusted hazard ratios and odds ratios were calculated. Among 197 inpatients, 51 (25.9%) received antifungals. At one year, the primary outcome occurred in 23 of 51 patients (45.1%) receiving antifungal therapy and in 67 of 146 patients (45.9%) who did not; the IPTW-adjusted hazard ratio was 0.93 (95% confidence interval 0.69–1.27; p = 0.66). No significant differences were seen in the acute cholangitis subgroup (n = 117). In this study, antifungal therapy was not associated with improved survival, lower rates of invasive candidiasis, or fewer readmissions. Findings support a conservative, stewardship-oriented approach to managing Candida-positive bile cultures in the absence of invasive disease. Full article

Primary Biliary Cholangitis (PBC) is a chronic, immune-mediated cholestatic liver disease characterized by progressive intrahepatic bile duct destruction, leading to pruritus, fatigue, cirrhosis, and eventually hepatocellular carcinoma. Early diagnosis has improved with the development of sensitive serologic assays (e.g., antimitochondrial antibodies, antinuclear antibodies) and the introduction of newer biomarkers. Risk stratification has become standardized with the help of GLOBE and UK-PBC scores, alongside non-invasive tools such as vibration-controlled transient elastography, enabling earlier intervention. Ursodeoxycholic acid (UDCA) is the first-line therapy; however, 30–40% of patients show an incomplete response, increasing their risk of liver failure and mortality. Second-line therapies have emerged which provide viable treatment avenues for those who do not respond to UDCA or are unable to tolerate it. However, in certain situations, such as decompensated cirrhosis, carcinoma, or refractory pruritus, liver transplantation constitutes the only curative therapy. While PBC has excellent post-liver transplant (post-LT) outcomes, patients with PBC face higher waitlist mortality as they tend to have lower MELD scores. Management post-LT includes the use of UDCA, immunosuppressants, and surveillance for recurrent PBC. Our review highlights the recent advances in medical management and transplant risk stratification of patients at risk of decompensation, as well as the perioperative transplant period outcomes and long-term post-transplant management strategies in patients with PBC. Full article

Liver disease encompasses a wide range of conditions, each requiring tailored therapeutic approaches. This review describes and critically discusses treatments with robust evidence for improving liver health. Ursodeoxycholic acid (UDCA) is a drug approved by the Food and Drug Administration of the USA to treat primary biliary cholangitis (PBC). In addition, UDCA has been demonstrated to protect against metabolic dysfunction-associated steatohepatitis, fibrosis, and drug-induced liver injury (DILI). The mechanism of action of UDCA has been attributed not only to decreasing the effects of toxic bile acids but also to protecting mitochondrial integrity and function, as well as to antioxidant, anti-inflammatory, and anti-apoptotic activities. UDCA can scavenge reactive oxygen species (ROS) and activate the nuclear factor-E2-related factor-2 (Nrf2) pathway, thereby exerting antioxidant activity. The anti-inflammatory activity of UDCA is associated with its ability to inhibit the nuclear factor-κB pathway. Pirfenidone is a well-recognized antifibrotic drug for the treatment of idiopathic pulmonary fibrosis; its effects on liver fibrosis have also been demonstrated. Pirfenidone exerts anti-inflammatory effects by attenuating the nucleotide-binding oligomerization domain-like receptor 3 inflammasome signaling pathway. The antioxidant actions of pirfenidone are associated with its ability to upregulate the Nrf2 pathway. Both the anti-inflammatory and antioxidant properties of pirfenidone act together to attenuate lung and liver fibrosis, decreasing transforming growth factor-β levels, inhibiting profibrogenic hepatic stellate cell activation, and increasing extracellular matrix degradation. Methyltransferases utilize S-adenosyl-L-methionine (SAM) as a methyl donor for most transmethylation reactions in the body. SAM increases reduced glutathione (GSH) levels, exerting important antioxidant effects. Evidence indicates that SAM prevents fibrosis and attenuates hepatocellular carcinoma development, improving patient survival. N-acetylcysteine (NAC) is a precursor to L-cysteine and GSH and is used in clinical settings to treat cancer, nephropathy, heart disease, pulmonary fibrosis, polycystic ovary syndrome, and influenza. Regarding the liver, NAC is the most accepted treatment for DILI, especially after paracetamol overdose. Owing to its antioxidant and anti-inflammatory actions, NAC has been successfully used to treat chronic liver injuries, including hepatosteatosis and fibrosis. Therefore, ursodeoxycholic acid, pirfenidone, S-adenosyl-L-methionine, and N-acetylcysteine could represent therapeutic strategies for the treatment of liver pathologies. Full article