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Navigating hepatotoxicity of antibody-drug conjugates: from mechanistic insights to clinical and postmarketing evidence.

Antibody-drug conjugates (ADCs) are rapidly developing targeted cancer therapeutic agents that combine specific monoclonal antibodies with cytotoxic agents. Currently, 17 ADCs are approved for the global market for treating hematological and solid tumors with more than 100 ADCs are in phase III clinical trials. ADC-induced hepatotoxicity is a significant concern with unclear mechanisms, and the incidence of hepatic adverse events (AEs) varies across different ADCs. Most hepatic AEs are moderate; however, some ADCs can cause life threatening or fatal AEs. The management of hepatic AEs is limite

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… Anticholestatic therapies, such as ursodeoxycholic acid, may be beneficial in patients presenting with cholestatic injury, while defibrotide, approved for the treatment of SOS, has shown potential benefit when administered early ( Stutz et al., 2022 ; Larue et al., 2025 ). … In these cases, routine prophylactic therapy with low-dose heparin, ursodeoxycholic acid, or defibrotide may be considered. For patients undergoing HSCT, a minimum interval of 2 months between the last ADC dose and transplantation is recommended ( Kantarjian et al., 2019 ). …

Cardiac Amyloidosis: A Rare TTR Mutation Found in an Asian Female.

BACKGROUND: Transthyretin cardiac amyloidosis (ATTR) is a life-threatening, debilitating disease caused by abnormal formation and deposit of transthyretin (TTR) protein in multiple tissues, including myocardial extracellular matrix. It can be challenging to diagnose due to the myriad of presenting signs and symptoms. Additionally, numerous TTR mutations exist in certain ethnicities. Interestingly, our patient was discovered to have a very rare Gly67Ala TTR mutation typically not found in individuals of Asian descent. Recent advances in cardiovascular imaging techniques have allowed for earlier

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… ATTR degraders like doxycycline with TUDCA/UDCA (tauroursodeoxycholic acid/ursodeoxycholic acid) promote the breakdown and clearance of amyloid fibrils. …

Autologous hematopoietic stem cell transplant at a tertiary care centre in India: achieving comparable outcomes with adaptations.

Autologous stem cell transplantation (ASCT) is the standard treatment for many high-risk solid tumors. Patients undergoing ASCT should be managed in a dedicated hematopoietic stem cell transplantation (HSCT) unit with isolation rooms, high-efficiency particulate air (HEPA) filters, and positive pressure. We report the outcomes of the first 20 pediatric patients who underwent ASCT in isolation rooms with no HEPA filters or positive pressure. Moreover, the isolation rooms were not part of a dedicated HSCT unit. Data from 20 patients were analyzed. All patients included in the study underwent ASC

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… All patients received ursodeoxycholic acid as prophylaxis against veno-occlusive disease (VOD). The treatments were terminated on Day +90. Co-triamoxazole was stopped before conditioning and restarted on day +30 after engraftment had been achieved. …

Dual COX-2/TNF-α Inhibitors as Promising Anti-inflammatory and Cancer Chemopreventive Agents: A Review.

Cyclooxygenases (COX) play a pivotal role in inflammation and are responsible for the production of prostaglandins (PGs). Two types of COXs have been identified as key biological targets for drug design: Constitutive COX-1 and inducible COX-2. Nonsteroidal anti-inflammatory drugs (NSAIDs) target COX-1, while selective COX-2 inhibitors are designed for COX-2. These COX isoforms are involved in multiple physiological and pathological pathways throughout the body. Overproduction of tumor necrosis factor-alpha (TNF-α) plays a role in COX-2's inflammatory activity. Tumor necrosis factor-alpha can c

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… Piperine-based triazoles 14 and 15 as selective cyclooxygenases-2 (COX-2)/tumor necrosis factor-alpha (TNF-α) inhibitors With the rise of molecular hybridization as a promising approach in disease therapy, a new series of ursodeoxycholic acid-cinnamic acid hybrids was developed and synthesized. … Design, synthesis and evaluation of ursodeoxycholic acid-cinnamic acid hybrids as potential anti-inflammatory agents by inhibiting Akt/NF-kappaB and MAPK signaling pathways. Eur J Med Chem. 2023;260:115785. doi: 10.1016/j.ejmech.2023.115785. 106. …

Biochemical and Metabolical Pathways Associated with Microbiota-Derived Butyrate in Colorectal Cancer and Omega-3 Fatty Acids Implications: A Narrative Review.

Knowledge regarding the influence of the microbial community in cancer promotion or protection has expanded even more through the study of bacterial metabolic products and how they can modulate cancer risk, which represents an extremely challenging approach for the relationship between intestinal microbiota and colorectal cancer (CRC). This review discusses research progress on the effect of bacterial dysbiosis from a metabolic point of view, particularly on the biochemical mechanisms of butyrate, one of the main short chain fatty acids (SCFAs) with anti-inflammatory and anti-tumor properties

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… On the one hand, there are some microbial metabolites, such as prostaglandin E2 and secondary bile acids, associated with increased risk of CRC and on the other one, some are associated with decreased CRC risk: indole; antioxidants; short-chain fatty acids (SCFAs); and ursodeoxycholic acid [ 22 , 23 …

Targeting the FGFR signaling pathway in cholangiocarcinoma: promise or delusion?

Cholangiocarcinoma (CCA) is a refractory cancer with limited treatment options and poorly understood molecular mechanisms underlying tumor development. The most effective treatment is surgical resection; however, patients are highly prone to recurrence. Moreover, considering that most patients are diagnosed in advanced stages, treatment options are restricted to palliative care, which results in poor prognosis. Due to the limited effect of chemotherapy and radiotherapy, targeted therapy is becoming a hot topic in the field of biliary cancer treatment. The fibroblast growth factor/fibroblast gr

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… Ursodeoxycholic acid and bile-acid mimetics as therapeutic agents for cholestatic liver diseases: an overview of their mechanisms of action . …

Diagnosis and Management of Chronic Pruritus: An Expert Consensus Review.

The aim of this study is to formulate the best clinical practice in the diagnosis and management of chronic pruritus (CP). We searched PubMed, EMBASE, Scopus, Web of Science, and the WHO's regional databases, for studies on "Diagnosis and management of chronic pruritus" from January 1, 2014, to July 31, 2015. We included programmatic reports and hand-searched references of published reviews and articles. Two independent reviewers screened articles and extracted data. We screened 87 of 95 studies that contained qualitative data. Avoid: Dry climate, heat, alcohol compress, ice packs, frequent ba

Обзор заболеваний, связанных с палидомидом и пищеварительной системой.

Талидомид, когда-то обнаруженный и используемый для лечения беременной болезни, вышел из фаворита с скандалами тератогенности, а затем вновь вошёл в общественный глаз с его удивительной эффективностью против проказы и множественной миеломы, и его антиопухоль и антивоспалительные эффекты были постепенно обнаружены. В последние годы талидомид также стал играть все более важную роль в расстройствах пищеварения, особенно в связи с его антиангиогенными последствиями, которые являются эффективными при лечении диспластического желудочно-кишечного кровоизлияния. В ряде клинических испытаний и отчетов

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… A double-blind randomized controlled trial of thalidomide for the treatment of PBC was reported only in 1994 by the British physician P A McCormick ( 41 ), which indicated that apart from ursodeoxycholic acid, which is the only approved drug, drugs such as thalidomide, methotrexate, penciclovir, or colchicine …

History of hematopoietic cell transplantation: challenges and progress.

After more than 60 years of research in allogeneic hematopoietic cell transplantation (HCT), this therapy has advanced from one that was declared dead in the 1960s to a standard treatment of otherwise fatal malignant and non-malignant blood diseases. To date, close to 1.5 million hematopoietic cell transplants have been performed in more than 1,500 transplantation centers worldwide. This review will highlight the enormous efforts by numerous investigators throughout the world who have brought the experimental field of HCT to clinical reality, examine ongoing challenges, and provide insights fo

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… Explanations for the gradual improvements of outcome include use of ursodeoxycholic acid to prevent cholestasis and hyperbilirubinemia and reduce the incidence of liver GvHD, 95 improved GvHD prevention, use of topically active oral glucocorticoids for gut GvHD, 96 more judicious use of systemic glucocorticoid … Ursodeoxycholic acid for the prevention of hepatic complications in allogeneic stem cell transplantation. Blood. 2002;100(6):1977-1983. 96. Hockenbery DM, Cruickshank S, Rodell TC, et al. …

Combination strategies of gut microbiota in cancer therapy through metabolic reprogramming and immune remodeling.

Over the past decade, there has been a qualitative improvement in the understanding of gut microbiota in cancer development and treatment. Gut microbiota regulates metabolic reprogramming that occurs in the competition between tumor cells and immune cells for essential nutrients in the tumor microenvironment (TME). Besides, gut microbiota dysbiosis is one of the key factors leading to the formation of aging environment, which has many similarities with the TME. Accumulating research findings have demonstrated that gut microbiota enhances the efficacy of cancer therapies by activating the immun

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… MCT1, monocarboxylate transporter1; HDACi,histone deacetylase inhibitor; PKM2, pyruvate kinase isozyme type M2; SCFAs, short-chain fatty acids; FFAR2, free fatty acid receptor 2; TAM, tumor-associated macrophage; DCA, deoxycholic acid; UDCA, ursodeoxycholic acid;COX-2, Cyclooxygenase-2; HSC, hepatic … Ursodeoxycholic acid (UDCA), on the other hand, has an anti-inflammatory impact by inhibiting the activity of DCA [ 36 ]. …

Cyclosporine A trough concentrations are associated with acute GvHD after non-myeloablative allogeneic hematopoietic cell transplantation.

Low plasma CsA concentrations (<300-350 ng/mL) early following allogeneic hematopoietic stem cell transplantation (HSCT) is associated with an increased risk of developing acute graft-versus-host disease (aGvHD). Nevertheless, the current optimal target trough concentration for CsA following HSCT is considered to be 200-400 ng/mL. Here, we performed a retrospective analysis of a homogeneous group of 129 patients who received HSCT after non-myeloablative conditioning, and we analyzed the impact of CsA trough concentration measured during the first four weeks (CsA W1-4) on the incidence aGvHD, r

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… Ursodeoxycholic acid was not routinely used in our practice. Definitions As part of routine care at our medical center, CsA concentration was measured 4–5 days after the starting dose, at 12 hrs after the last administration. …

Posterior minimally invasive percutaneous short-segment fixation combined with mini-open anterior L5 corpectomy for metastatic tumor: a case report and literature review.

BACKGROUND: Metastatic tumors of the lumbar spine are a common complication of advanced malignancies. They often present with severe pain, neurological deficits, and spinal instability. Surgical removal of L5 vertebral body metastases is challenging due to the complex anatomy and biomechanical characteristics of the lumbosacral junction. Corpectomy using a combined approach is a common surgical strategy for achieving pain relief, adequate tumor resection, spinal cord and root decompression, and spinal stabilization. However, this approach may be associated with significant surgical trauma and

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… Additionally, the patient received ademetionine 400 mg three times daily and ursodeoxycholic acid 250 mg. Operation The surgery was performed in two stages on the same day. Stage 1. …

Alcohol Consumption and Autoimmune Diseases.

Alcohol is the second-most misused substance after tobacco. It has been identified as a causal factor in more than 200 diseases and 5.3% of all deaths and is associated with significant behavioral, social, and economic difficulties. As alcohol consumption may modulate the immune system's regulatory mechanisms to avoid attacking the body's tissues, it has been proven to play a dichotomic role in autoimmune diseases (ADs) based on the quantity of consumption. In this review, we report updated evidence on the role of alcohol in ADs, with a focus on alcohol addiction and the human biological immun

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… The management of this disease is complex, as it involves the use of ursodeoxycholic acid (UDCA) to improve bile flow and delay disease progression, obeticholic acid (in patients who do not respond adequately to UDCA), antipruritic agents (cholestyramine, rifampicin, or naltrexone), fat-soluble vitamin …

Treatment Approaches for Managing Patients with Hematological Malignancies in the Time of COVID-19 Pandemic.

Background/aimThe COVID-19 pandemic is a unique challenge to the care of patients with hematological malignancies. We aim to provide supportive guidance to clinicians making individual patients decisions during the COVID-19 pandemic, in particular during periods that access to healthcare resources may be limited.ConclusionThis review also provides recommendations, which are convenient in evaluating indications for therapy, reducing therapy-associated immunosuppression, and reducing healthcare utilization in patients with specific hematological malignancies in the COVID-19 era. Specific decisio

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… The use of blinatumomab and inotuzumab (with ursodeoxycholic acid as prophylaxis) should not be deferred as their efficacy in terms of survival has been established in the frontline setting regardless of age [ 6 ]. …

Amyloidosis for the Gastroenterologist: A Comprehensive Systematic Review of Diagnosis and Management of Gastrointestinal Manifestations.

BackgroundAmyloidosis is a rare, multisystem disorder characterized by extracellular deposition of misfolded protein fibrils. Gastrointestinal (GI) amyloidosis is uncommon but under-recognized due to nonspecific symptoms, but early diagnosis is critical to improve quality of life and prognosis. This comprehensive systematic review aimed to summarize current literature on GI and hepatic manifestations of amyloidosis, highlighting diagnostic and management strategies across the major subtypes of amyloidosis, in particular AL (immunoglobulin light chain), ATTR (transthyretin), and AA (serum amylo

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… Fine , “ Clinical Experience With the Use of Doxycycline and Ursodeoxycholic Acid for the Treatment of Transthyretin Cardiac Amyloidosis ,” Journal of Cardiac Failure 25 , no. 3 ( 2019 ): 147 – 153 . 30660664 10.1016/j.cardfail.2019.01.006 89 A. Carroll , P. J. …

Incidence, Risk Factors, and Outcomes of Idiopathic Pneumonia Syndrome after Allogeneic Hematopoietic Cell Transplantation.

Our current knowledge of idiopathic pneumonia syndrome (IPS) predates improved specificity in the diagnosis of IPS and advances in hematopoietic cell transplantation (HCT) and critical care practices. In this study, we describe and update the incidence, risk factors, and outcomes of IPS. We performed a retrospective cohort study of all adults who underwent allogeneic HCT at the Fred Hutchinson Cancer Research Center between 2006 and 2013 (n = 1829). IPS was defined using the National Heart, Lung, and Blood Institute consensus definition: multilobar airspace opacities on chest imaging, absence

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… Ursodeoxycholic acid for the prevention of hepatic complications in allogeneic stem cell transplantation. Blood. 2002;100(6):1977–1983. doi: 10.1182/blood-2001-12-0159. 12. Przepiorka D., Weisdorf D., Martin P. 1994 Consensus conference on acute GVHD grading. …

Emerging insights into the gut microbiota as a key regulator of immunity and response to immunotherapy in hepatocellular carcinoma.

The gut microbiota, a complex microbial ecosystem closely connected to the liver via the portal vein, has emerged as a critical regulator of liver health and disease. Numerous studies have underscored its role in the onset and progression of liver disorders, including alcoholic liver disease, metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). This review provides a comprehensive overview of current insights into the influence of the gut microbiota on HCC progre

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… For example, one study found that ICIs responders had a higher abundance of Lachnoclostridium and a higher ursodeoxycholic acid concentration than non-responders, but a lower abundance of Prevotella_9 . …

Review of Paraneoplastic Syndromes in Children with Malignancy.

A paraneoplastic syndrome (PNS) is a set of symptoms and signs that can accompany the formation of a cancer but is not due to its direct infiltration or metastasis. PNS results from the secretion of peptides or hormones by tumor cells or from an immunological cross-reaction between the tumor antigens and host antigens. In the adult population, PNS affects up to 15% of patients with cancer, but data on pediatric patients remain lacking. The remarkable fact is that PNS can precede an oncology diagnosis, even by months or years. PNS can involve virtually any organ of the human body. In children,

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… In addition, the use of ursodeoxycholic acid as a hepatoprotective element is effective [ 43 ]. In some cases, when the progression of VBDS is advanced and results in hepatic failure, remission of the underlying disease alone is not sufficient, and a liver transplant is required. …

Current Therapies and Future Horizons in Cardiac Amyloidosis Treatment.

Purpose of reviewCardiac amyloidosis (CA) is a condition characterized by misfolding and extracellular deposition of proteins, leading to organ dysfunction. While numerous forms of CA exist, two subtypes dominate clinical prevalence: Transthyretin amyloid (ATTR) and immunoglobulin light chain amyloid.Recent findingsThe current scientific landscape reflects the urgency to advance therapeutic interventions with over 100 ongoing clinical trials. Heart failure treatment is affected by CA phenotype with poor tolerance of otherwise frequently used medications. Treating comorbidities including atrial

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… Clinical Experience With the Use of Doxycycline and Ursodeoxycholic Acid for the Treatment of Transthyretin Cardiac Amyloidosis. J Card Fail. 2019;25:147–53. 10.1016/j.cardfail.2019.01.006. 10.1016/j.cardfail.2019.01.006 79. Kazman P, Absmeier RM, Engelhardt H, Buchner J. …

Defibrotide for prophylaxis of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) in pediatric high-risk patients: consensus guidelines from the European Society for Blood and Marrow Transplantation (EBMT).

SOS/VOD is a life-threatening complication of hematopoietic stem cell transplantation, especially in children, with incidences reaching up to 15-20%. Despite efforts, SOS/VOD remains unpredictable with significant morbidity and mortality. High-risk criteria are clearly defined, and the pediatric EBMT diagnostic criteria have improved sensitivity, reducing treatment delays and enhancing outcomes. A meta-analysis combining retrospective and prospective studies found a risk ratio of 0.30 for SOS/VOD with defibrotide (DF) prophylaxis. Additionally, two prospective trials were conducted: the pediat

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… Specifically, the recommendation for the gene addition approach (Lyfgenia TM ) explicitly states the use of ursodeoxycholic acid or DF. Consequently, bot curative gene-therapeutic approaches were included in the scoring. …