Ursodeoxycholic Acid Alone Is Effective and Safe to Treat Cholestatic Checkpoint Inhibitor‐Induced Liver Injury

Liver International, Год журнала: 2025, Номер 45(5)

Опубликована: Апрель 8, 2025

ABSTRACT Introduction Checkpoint Inhibitor‐induced Liver Injury (CHILI) is a frequent complication of immune checkpoint inhibitors (ICIs). Corticosteroids are the standard treatment but have many limitations. Ursodeoxycholic acid (UDCA) offers an alternative for managing cholestatic CHILI, its efficacy remains underexplored. Methods A multicenter retrospective study included 27 patients treated with first‐line UDCA monotherapy. Data were collected from diagnosis to week 52, assessing liver enzyme improvement, recurrence, and outcomes. Results alone achieved improvement in 81.5% patients, average response time 39.3 days. Among 77.8% had severe CHILI (CTCAE grade ≥ 3). Macroscopic bile duct injury was observed 37%, associated higher recurrence rates (75%, p < 0.001). Recurrent led chronic all cases. ICI rechallenge conducted 52% only 23% experiencing relapse. Conclusion monotherapy appears effective presenting viable corticosteroids. Further prospective studies warranted.

Язык: Английский

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Time to use the right classification to predict the severity of checkpoint inhibitor‐induced liver injury, as assessed for causality using the updated RUCAM

Alimentary Pharmacology & Therapeutics, Год журнала: 2024, Номер unknown

Опубликована: Сен. 24, 2024

Summary Background and Aims While immune checkpoint inhibitors (ICIs) are revolutionising cancer therapy, inhibitor‐induced liver injury is a significant immune‐related side effect of this immunotherapy. This study focuses on the severity classifications characteristics patients with hepatitis. Methods A retrospective analysis severe Checkpoint Inhibitor‐induced hepatitis grade 3 4 according to recommended Common Terminology Criteria for Adverse Events (CTCAE) classification was conducted. Data clinicobiological characteristics, treatment outcomes were collected from university hospitals, causality assessed by using updated Roussel Uclaf Causality Assessment Method. The Model End‐stage Liver Disease score, Drug‐Induced Injury Network, International Expert Working Group classifications. Results We retrospectively included 100 presenting various patterns median time onset 20 days after inhibitors. Severity grading varied significantly among used. lower incidence cases observed when instead CCTCAE classification, correlated outcomes. Conclusions challenges efficacy CTCAE in defining suggests that traditional hepatology‐focused scores may be more relevant. inconsistent gives equal weight jaundice elevated transaminases, which leads steroid overtreatment limits rechallenge ICIs.

Язык: Английский

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Immunosuppressant mycophenolate mofetil for patients with steroid-refractory immune-related hepatitis induced by checkpoint inhibitors in oncology

European Journal of Cancer, Год журнала: 2023, Номер 193, С. 113313 - 113313

Опубликована: Авг. 26, 2023

Язык: Английский

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Burning mouth syndrome needs to consider the gut-brain axis from three types of pain: nociceptive, neuropathic, and nociplastic pain

Journal of Gastrointestinal and Liver Diseases, Год журнала: 2023, Номер 32(4), С. 558 - 559

Опубликована: Дек. 22, 2023

Burning mouth syndrome needs to consider the gut-brain axis from three types of pain: nociceptive, neuropathic, and nociplastic painTo Editor,The (GBA) consists bidirectional communication between central nervous system intestinal tract, linking emotional centers brain with peripheral gut function.The GBA may be involved in etiology painful diseases, but relationship is not fully understood.I read great interest article on burning (BMS) by Russo et al. [1].They showed that BMS has a multifactorial etiopathology, including laryngopharyngeal reflux, hormonal salivary changes related aging menopause, oral flora, which induce neurodegeneration orofacial region [1].I agree perspective signals gastrointestinal microbiota, influence unexplained chronic pain.However, there little evidence regarding as BMS.Therefore, I propose organize their LETTERS TO THE EDITORperspectives dimensions for future research: receptor, nerve, circuit (Table I).Burning an intractable pain disorder unknown cause characterized sensation without any organic abnormality mucosa.Pain complaints patients range tingling, stickiness, indescribable pressure-like discomfort.There are nociceptive pain, neuropathic includes all these elements.The review [1] discusses disease such increase transient receptor potential vanilloid1 (TRPV1) receptors neuroinflammation.However, uncomfortable multifocal widespread classified unlike or pain.The mechanisms underlie this type entirely understood, it thought augmented sensory processing altered modulation play prominent roles [2].Nociplastic accompanied symptoms well other origin, fatigue, sleep, memory, mood problems, Table I.Three

Язык: Английский

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Drug induced cholestatic liver diseases

Hepatology, Год журнала: 2024, Номер unknown

Опубликована: Авг. 8, 2024

Cholestatic DILI is an important and frequently challenging differential diagnosis in patients presenting with elevated liver tests predominant elevation alkaline phosphatase. A number of competing etiologies need to be ruled out, such as hepatobiliary malignancy, choledocholithiasis, cholestatic forms viral hepatitis, cholestasis sepsis, primary secondary cholangitis, right-sided cardiac failure name a few. Important advances have occurred the understanding knowledge clinical phenotypes, new etiological agents, risk factors, pathophysiology, genetic determinants drug-induced since last review on was published Hepatology 2011. Secondary sclerosing cholangitis (SSC) due drugs has been well documented for several different drugs. Checkpoint inhibitors are one types shown lead cholangitis. Several herbal dietary supplements recently injury. factors identified decade, pathogenesis behind injury better defined. In this review, focus diagnostic approach description phenotypes vanishing bile duct syndrome. Furthermore, provides overview determinants, pathophysiology transporters leading cholestasis. Management, areas uncertainty, future direction also presented.

Язык: Английский

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Immune checkpoint inhibitors and the liver: balancing therapeutic benefit and adverse events

Gut, Год журнала: 2024, Номер unknown, С. gutjnl - 332125

Опубликована: Дек. 10, 2024

Immune checkpoint inhibitors (ICI) have led to breakthrough improvements in the management of malignancy including hepatocellular (HCC) and biliary tract cancer, improving decades-old standards care increasing patient survival. In both liver tumour types, which commonly arise context inflammation underlying functional impairment, lack validated predictors response underscores need balance predicted gains survival with risk treatment-related hepatoxicity decompensation chronic disease.In addition, is implicated toxicity associated ICI therapy for non-liver cancers, exhibits a high degree variability presentation severity. An accurate assessment mandatory diagnosis ICI-induced injury.In this Recent Advances article, we provide an overview mechanisms efficacy anticancer immunotherapy tumours extrahepatic malignancies.We compare contrast characteristics, strategies outcomes from immune-related injury patients hepatitis/cirrhosis or healthy discuss latest findings on how may impact outlook malignancies offering insights into future directions clinical research practice field.

Язык: Английский

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Histological Characteristics and Management of Hepatitis on Immune Checkpoint Inhibitors: A Retrospective Descriptive Study

Journal of Clinical Medicine, Год журнала: 2023, Номер 12(11), С. 3751 - 3751

Опубликована: Май 29, 2023

the side effects of immune checkpoint inhibitors (ICI) pose a problem for clinical management cancer patients. There is lack knowledge value liver biopsy in patients with ICI-related drug-induced injury (ICI-DILI). The aim this study was to explore impact on and response corticosteroids, according histological findings.We conducted retrospective, single-center evaluate biochemical, data 35 ICI-DILI between 2015 2021 university hospital France.Of (median [interquartile range] age 62 [48-73] years, 40% males) studied, 20 underwent biopsy. no difference terms ICI withdrawal, reduction or rechallenge. According profile, toxic granulomatous profiles had better while cholangitic lesions worst response.In ICI-DILI, must not delay patient care but may be useful identifying profile who have poorer corticosteroids.

Язык: Английский

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Diagnosis and management of immune mediated liver injury from checkpoint inhibitors

Current Opinion in Gastroenterology, Год журнала: 2024, Номер 40(3), С. 164 - 171

Опубликована: Фев. 15, 2024

Purpose of review The aim is to summarize the latest data on incidence, clinical manifestations, and management immune- mediated liver injury from checkpoint inhibitors (ILICI). Recent findings ILICI develops in 10–15% oncology patients receiving immunotherapy with most having asymptomatic serum aminotransferase and/or alkaline phosphatase elevations. Most grade 1–2 improve drug discontinuation short-term oral corticosteroids. In contrast, 2–3% 3/4 hepatotoxicity frequently require or intravenous corticosteroids some are hospitalized initiate further immunosuppression mycophenolate mofetil azathioprine. Liver biopsy generally reserved for atypical features those severe who fail respond treatment. Up 3% a cholestatic profile have MRI evidence intra extrahepatic cholangitis that responds poorly immunosuppression. during follow-up liver-related death very uncommon (<1%). 30% rechallenged develop recurrent shorter latency. Summary increasingly encountered by gastroenterologists evaluating abnormal biochemistries. A stepwise approach exclude viral hepatitis, alcohol, hepatic metastases, pancreaticobiliary disease recommended. majority fully recover ICI second line immunosuppressant.

Язык: Английский

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Review article: Contemporary management of gastrointestinal, pancreatic and hepatic toxicities of immune checkpoint inhibitors

Alimentary Pharmacology & Therapeutics, Год журнала: 2024, Номер 59(11), С. 1350 - 1365

Опубликована: Апрель 8, 2024

Summary Background Immune checkpoint inhibitors (ICIs) are effective oncologic agents which frequently cause immune‐related adverse events (irAEs) can impact multiple organ systems. Onco‐Gastroenterology is a novel and emerging subspecialty within gastroenterology focused on cancer treatment‐related complications. Gastroenterologists must be prepared to identify manage diverse immune‐mediated toxicities including enterocolitis, hepatitis, pancreatitis other ICI‐induced toxicities. Aim To provide narrative review of the epidemiology, diagnostic evaluation management inhibitor‐induced gastrointestinal hepatic Methods We searched Cochrane PubMed databases for articles published through August 2023. Results Gastrointestinal irAEs include most commonly enterocolitis but also pancreatitis, oesophagitis, gastritis, motility disorders (gastroparesis) rarer Guidelines from National Comprehensive Cancer Network, American Society Clinical Oncology European Medical Oncology, in combination with cohort clinical trial data, offer strategies ICI Evaluation severity by formal classification stability, thorough workup alternative etiologies may clinically mimic underlie initial management. Treatments corticosteroids, biologics immunosuppressive plus supportive care; decisions dosing, timing choice steroid adjuncts potential subsequent inhibitor dosing nuanced toxicity‐specific. Conclusions Expanding data have clarified epidemiology characteristics gastrointestinal, pancreatic ICIs. Guidelines, though valuable, remain based principally retrospective data. Quality prospective, controlled studies refine algorithms treatment immunotherapy rechallenge.

Язык: Английский

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Burden of grade 3 or 4 liver injury associated with immune checkpoint inhibitors

JHEP Reports, Год журнала: 2023, Номер 5(12), С. 100880 - 100880

Опубликована: Авг. 12, 2023

There is concern about the burden of liver injury in patients with cancer exposed to immune checkpoints inhibitors (ICIs).In a retrospective cohort study, we evaluated likelihood grade 3/4 injury, cholestatic and failure, as per Common Terminology Criteria for Adverse Events (CTCAE) version 5, following treatment ICIs. We compared these occurrences group who were propensity-matched treated conventional chemotherapy. For all ICI experiencing conducted causality assessment using RUCAM method examined patient outcomes.Among 952 (median [IQR] age 66 [57-73] years, 64% males) between January 1, 2015, December 31, 2019, total 86 (9%) progressed failure was not observed. Anti-PD-(L)1/anti-CTLA-4 antibodies combinations (adjusted hazard ratio 3.36 [95% CI: 1.67-6.79]; p <0.001), chronic hepatitis B 5.48 1.62-18.5]; = 0.006], independent risk factors. Liver attributed 19 (2.0%) patients. Patients toxicity typically presented granulomatous or cholangiocyte inflammation. withdrawal associated progression mortality. Re-introduction recurrent injury. Compared matched conventional, non-ICI-based chemotherapy, anti-PD-(L)1/anti-CTLA-4 (p <0.001) anti-PD-(L)1 monotherapies 0.053) increased respectively.An under observed, whereas no substantial increase occurred even after reintroduction.There (ICIs). investigated ICIs multicentric cancer. Overall, 9% incidence detected ICIs, direct hepatotoxicity demonstrated 2% Anti-PD-(L)1/Anti-CTLA-4 antibody combinations, HBV infection progression.

Язык: Английский

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