Immune-mediated hepatitis: Basic concepts and treatment.

Immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized advanced cancer management. Nevertheless, the generalized use of these medications has led to an increase in the incidence of adverse immune-mediated events and the liver is one of the most frequently affected organs. Liver involvement associated with the administration of immunotherapy is known as immune-mediated hepatitis (IMH), whose incidence and clinical characteristics have been described by different authors. It often presents as mild elevations of amino transferase levels, seen in routine blood tests, that spontaneously return to normal, but it can also manifest as severe transaminitis, possibly leading to the permanent discontinuation of treatment. The aim of the following review was to describe the most up-to-date concepts regarding the epidemiology, diagnosis, risk factors, and progression of IMH, as well as its incidence in different types of common cancers, including hepatocellular carcinoma. Treatment recommendations according to the most current guidelines are also provided.

Longitudinal outcomes of obeticholic acid therapy in ursodiol-nonresponsive primary biliary cholangitis: Stratifying the impact of add-on fibrates in real-world practice.

BACKGROUND: Suboptimal response to ursodeoxycholic acid occurs in 40% of primary biliary cholangitis (PBC) patients, affecting survival. Achieving a deep response (normalisation of alkaline phosphatase [ALP] and bilirubin ≤0.6 upper limit of normal) improves survival. Yet, the long-term effectiveness of second-line treatments remains uncertain. AIMS: To evaluate the long-term effectiveness of obeticholic acid (OCA) ± fibrates. Focusing on biochemical response (ALP ≤1.67 times the upper limit of normal, with a decrease of at least 15% from baseline and normal bilirubin levels), normalisation of ALP, deep response and biochemical remission (deep response plus aminotransferase normalisation). METHODS: We conducted a longitudinal, observational, multicentre study involving ursodeoxyccholic acid non-responsive PBC patients (Paris-II criteria) from Spain and Portugal who received OCA ± fibrates. RESULTS: Of 255 patients, median follow-up was 35.1 months (IQR: 20.2-53). The biochemical response in the whole cohort was 47.2%, 61.4% and 68.6% at 12, 24 and 36 months. GLOBE-PBC and 5-year UK-PBC scores improved (p < 0.001). Triple therapy (ursodeoxycholic acid plus OCA plus fibrates) had significantly higher response rates than dual therapy (p = 0.001), including ALP normalisation, deep response and biochemical remission (p < 0.001). In multivariate analysis, triple therapy remained independently associated with biochemical response (p = 0.024), alkaline phosphatase normalisation, deep response and biochemical remission (p < 0.001). Adverse effects occurred in 41.2% of cases, leading to 18.8% discontinuing OCA. Out of 55 patients with cirrhosis, 12 developed decompensation. All with baseline portal hypertension. CONCLUSION: Triple therapy was superior in achieving therapeutic goals in UDCA-nonresponsive PBC. Decompensation was linked to pre-existing portal hypertension.

Impact of immune-mediated diseases in inflammatory bowel disease and implications in therapeutic approach.

Inflammatory bowel diseases (IBD) belong to the group of immune-mediated diseases (IMIDs). The effect of associated IMIDs in the prognosis in IBD is nowadays unknown. To describe IMIDs associated to IBD patients and evaluate differences linked to the presence or absence of IMIDs. A unicentric retrospective descriptive study was designed. A cohort of 1,448 patients were categorized according to the presence of IMIDs. Clinical characteristics were obtained from IBD database. Univariate and multivariate analysis were performed. 385 patients were diagnosed with associated IMIDs while 1,063 had no associated IMIDs. A prevalence of 26.6% IMIDs associated to IBD was observed. Asthma, skin psoriasis and rheumatoid diseases were most commonly found. Factors associated to the presence of IMIDs were women (OR 1.48; 95 CI 1.17-1.87) and Crohn's disease (OR 1.35; 95 CI 1.07-1.70). Patients with associated IMIDs required more immunomodulator (OR 1.61; 95 CI 1.27-2.43) and biological treatment (OR 1.81; 95 CI 1.47-2.43). More surgical risk was observed in multivariate analysis in those patients diagnosed with IMIDs prior to the onset of IBD (OR 3.71; 95% CI 2.1-6.56). We considered the presence of IMIDs a poor prognostic factor and suggest a closer monitoring of these patients.