Liver International最新文献

Background: Secondary sclerosing cholangitis (SSC), is one of the phenotypes of DILI first described in the 1980s. Check point inhibitors (CPIs) are currently the most frequent cause of SCC.

Aims: To describe the epidemiology, clinical and biochemical features at presentation, differential diagnoses, pathophysiology, imaging, histological characteristics and management associated with SSC.

Materials and methods: A language and date-unrestricted Medline literature search was conducted to identify case reports and clinical series on SSC with special emphasis on CPIs (2007-2023).

Results: We identified 19 different drugs that have been shown to induce SSC. A total of 64 cases with SSC due to CPIs are presented. This was mostly seen in patients treated with anti-Programmed cell death (PD)-1/PD-L1 inhibitors. The most frequent presenting signs and symptoms were abdominal pain and jaundice. Large-duct cholangitis induced by CPIs is a very rare condition while small-duct cholangitis is more common. Nivolumab and pembrolizumab were the most commonly implicated agents. Biopsies have revealed predominant CD8+ T cell infiltration in biliary strictures. Corticosteroids is linked to a low frequency of success and is the only agent recommended to begin the treatment.

Conclusions: CPIs-induced SSC seems to affect the entire biliary system. Clinicians should consider and suspect SSC when a probable CPIs-induced hepatitis does not respond to corticosteroids. Additionally, further randomized, controlled trials should prospectively investigate alternative therapies for treatment.

Introduction: The safety of continuing anticoagulation therapy during endoscopic variceal ligation (EVL) remains controversial. We performed a systematic review and meta-analysis to evaluate the safety of anticoagulation therapy in EVL.

Methods: We systematically searched four electronic databases from their inception until 1 June 2024, for studies that evaluated anticoagulation use and risk of rebleeding among patients undergoing EVL. The primary endpoint was rebleeding after EVL. The secondary endpoints were post-banding ulcer bleeding (PBUB) and variceal eradication rate. The PROSPERO registration number is CRD42024556094.

Results: A total of 5617 participants from nine studies (eight cohort studies and one randomised trial) were included. The most common type of anticoagulation is low-molecular-weight heparin, followed by warfarin and direct oral anticoagulants (DOAC). The pooled risk of rebleeding was 10.9% (95%CI: 6.3-16.5; I² = 65.5%). Concurrent anticoagulation during EVL did not increase the risk of overall rebleeding (OR, 1.10; 95%CI: 0.85-1.42, I² = 0%), PBUB (OR, 1.04; 95%CI, 0.48-2.24; I² = 24%) or severe bleeding (OR, 0.94; 95%CI, 0.31-2.85; I² = 0%). Variceal eradication rates were similar, regardless of the use of anticoagulation therapy during EVL.

Conclusion: Anticoagulation did not increase the risk of rebleeding in patients who underwent EVL. Since the certainty of evidence is low, these findings should be confirmed in future randomised trials.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is caused by metabolic triggers and genetic predisposition. Among the genetic MASLD risk variants identified today, the common PNPLA3 148M variant exerts the largest effect size of MASLD heritability. The PNPLA3 148M protein is causatively linked to the development of liver steatosis, inflammation and fibrosis in experimental studies and is therefore an appealing target for therapeutic approaches to treat this disease. Several PNPLA3 targeted approaches are currently being evaluated in clinical trials for the treatment of metabolic dysfunction-associated steatohepatitis (MASH), the most severe form of MASLD and promising proof of principle data with reduced liver fat content in homozygous PNPLA3 148M risk allele carriers has been reported from phase 1 trials following hepatic silencing of PNPLA3. Thus, targeting PNPLA3, the strongest genetic determinant of MASH may hold promise as the first precision medicine for the treatment of this disease. A histological endpoint-based phase 2b study has been initiated and several more are expected to be initiated to evaluate treatment effects on histological MASH and liver fibrosis in participants being homozygous for the PNPLA3 148M risk allele variant. The scope of this mini-review is to briefly describe the PNPLA3 148M genetics, function and preclinical experimental evidence with therapeutic approaches targeting PNPLA3 as well as to summarise the PNPLA3 based therapies currently in clinical development.

Background and aims: Individuals with primary sclerosing cholangitis (PSC) have expressed a need for more dietary information. The aim of this study was to evaluate the dietary intake of individuals with PSC and compare it with Nordic nutrition recommendations 2023 (NNR2023).

Methods: A cross-sectional assessment of dietary intake was performed using a food-frequency questionnaire among 120 individuals with PSC from five regions across Sweden. Macro- and micronutrient intake was compared to NNR2023. Dietary quality was evaluated using an index developed by the National Food Agency in Sweden.

Results: The median age was 47 years (IQR 18), and median body mass index (BMI) was 25.2 kg/m² (IQR 5.9). Eight percent had a BMI < 20, and 13% had a BMI > 30. The average fibre intake was 18 g (IQR 18). Median energy distribution included 36% from fat (15% saturated, 4.6% polyunsaturated), 17% from protein and 43% from carbohydrates, highlighting an imbalanced diet with low carbohydrate, fibre and polyunsaturated fat intake and high saturated fat consumption. More than half reported suboptimal intake of zinc, selenium and vitamins C, D and K and > 30% suboptimal intake of vitamins A, B6, E, niacin, folate, potassium, magnesium and iron. Forty percent had poor dietary quality. Longer PSC duration and previous colectomy were associated with a lower dietary quality.

Conclusions: Many individuals with PSC do not reach the recommended levels of various micronutrients, especially fat-soluble vitamins and report a poor dietary quality. The results highlight the need for a comprehensive approach to nutritional management in this population.

Trial registration: ClinicalTrials.gov identifier: NCT04133792.

Background: Portal hypertension (PH) is a critical complication in patients with hepatic diseases. Its accurate evaluation is essential for early diagnosis, risk stratification, and management. Endoscopic ultrasound (EUS) has emerged as a promising diagnostic tool, offering high-resolution imaging of the portal venous system, hepatic vasculature, and surrounding structures.

Aims: This review aims at providing an overview of the evolving role of EUS in PH evaluation in patients with liver disease.

Materials and methods: A systematic search was conducted in PubMed and Google Scholar until 31 May 2024. Relevant studies were identified using keywords related to EUS and PH. Additional references were included based on expert knowledge and citation analysis. Only full-length papers and abstracts in English were considered.

Results: EUS demonstrates significant utility in PH assessment, offering high-resolution imaging and advanced tools like contrast enhancement (CE) and shear-wave elastography (SWE) for evaluating liver stiffness and correlating it with PH severity. EUS-guided portal pressure gradient (PPG) measurement provides a less invasive method for evaluating PH, potentially offering a safer alternative to conventional techniques.

Discussion: EUS offers unique advantages in PH assessment, enabling comprehensive evaluation in a single session. Despite its potential, limitations such as invasiveness, sedation-related variability, and restricted availability persist. Emerging techniques require further validation in larger cohorts and standardised training.

Conclusion: EUS is a valuable diagnostic tool for PH evaluation, with the potential to improve outcomes through earlier diagnosis and better stratification. Addressing its limitations through further research and standardised protocols is critical to optimize its clinical utility.

Trial registration: NCT04115046, NCT05728697, NCT05097963 and NCT03155282.

Background and aims: Tissue factor-expressing microvesicles (MV-TF) have been found to correlate with thrombotic complications in various diseases. Simultaneously, there is expanding research regarding the effect of the coagulation cascade on liver fibrosis progression. The aim of our manuscript was to evaluate MV-TF activity in patients with cirrhosis and its correlation with disease severity.

Methods: We prospectively enrolled 82 patients [11 with cirrhosis and hepatocellular cancer (Group 1), 50 with cirrhosis (Group 2) and 21 controls (Group 3)]. Extensive workup for disease staging and exclusion criteria was undertaken. Exclusion criteria included thrombophilia, history of thrombosis, recent hospitalisation, ongoing infection, alcohol dependence, cancer, haematological diseases and use of anticoagulant, antiplatelet or contraceptive drugs. Plasma tissue factor antigen concentration and MV-TF activity were assessed.

Results: MV-TF showed median values of 4.03 [1.57], 3.17 [1.59] and 2.26 [1.23] pg/mL in Groups 1, 2 and 3, respectively. There was a statistically significant difference between Groups 1 and 3 (p < 0.001) and Groups 2 and 3 (p = 0.003), while Group 1 had higher values than Group 2 without statistical significance (p = 0.088). In Group 2, the patients' Child-Pugh (CP) stage was A in 56%, B in 26% and C in 18% of cases. MV-TF activity significantly correlated with decompensated cirrhosis (p = 0.005) and higher CP stage (p = 0.011). Finally, MV-TF activity significantly correlated with 12-month mortality (p = 0.021).

Conclusions: MV-TF activity is elevated in patients with cirrhosis, showing a significant correlation with disease severity. MV-TF may play a role in the procoagulant imbalance of liver cirrhosis and their contribution in disease progression should be studied further.