Liver International最新文献

Background and aims: To investigate the association between air pollution and hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients treated with nucleotide/nucleoside analogues.

Methods: We enrolled 1298 CHB patients treated with nucleotide/nucleoside analogues and analysed the incidence and risk factors for HCC. Daily estimates of air pollutants were estimated since the previous year from the enrolment date.

Results: The annual incidence of HCC was 2.1/100 person-years after a follow-up period of over 4840.5 person-years. Factors with the strongest association with HCC development were liver cirrhosis (hazard ratio [HR]/95% confidence interval [CI]: 3.00/1.55-5.81; p = 0.001), male sex (2.98/1.51-5.90; p = 0.02), body mass index (1.11/1.04-1.18; p = 0.002) and age (1.06/1.04-1.09; p < 0.001). Among patients with cirrhosis, the factors associated with HCC development were male sex (HR/95% CI: 2.10/1.00-4.25; p = 0.04) and NO₂ (per one-unit increment, parts per billion; 1.07/1.01-1.13; p = 0.01). Moreover, patients with the highest quartile of annual NO₂ exposure had more than a three-fold risk of HCC than those with the lowest quartile of annual exposure (HR/95% CI: 3.26/1.34-7.93; p = 0.01). Among patients without cirrhosis, the strongest factors associated with HCC development were male sex (HR/95% CI: 5.86/1.79-19.23; p = 0.004), age (1.12/1.07-1.17; p < 0.001) and platelet count (0.99/0.98-1.00; p = 0.04).

Conclusions: Air pollution influences HCC development in CHB patients who receive nucleotide/nucleoside analogue therapy. Long-term NO₂ exposure might accelerate HCC development in CHB patients with cirrhosis receiving nucleotide/nucleoside analogue treatment.

Marti-Aguado D, Arnouk J, Liang JX, Lara-Romero C, Behari J, Furlan A, Jimenez-Pastor A, Ten-Esteve A, Alfaro-Cervello C, Bauza M, Gallen-Peris A, Gimeno-Torres M, Merino-Murgui V, Perez-Girbes A, Benlloch S, Pérez-Rojas J, Puglia V, Ferrández-Izquierdo A, Aguilera V, Giesteira B, França M, Monton C, Escudero-García D, Alberich-Bayarri Á, Serra MA, Bataller R, Romero-Gomez M, Marti-Bonmati L. Development and validation of an image biomarker to identify metabolic dysfunction associated steatohepatitis: MR-MASH score. Liver Int. 2024 Jan; 44(1):202-213. doi: 10.1111/liv.15766. Epub 2023 Oct 30. PMID: 37904633. It has come to our attention that there was a mistake in the published version of our manuscript. The mistake in page 5 has resulted in an error in the units of the variable height from the MR-MASH score. The height should be expressed in meters and not in centimetres. The correct MR-MASH formula is as follows: [Formula: see text] This has been corrected in the online version. We apologise for this error.

Cover Image: The cover image is based on the Article The Freiburg Index of Post-TIPS Survival accurately predicts mortality in patients with acute decompensation of cirrhosis by Eric Kalo et al., https://doi.org/10.1111/liv.16098

Cover Image: The cover image is based on the Article Fibrosis, biomarkers and liver biopsy in AAT deficiency and relation to liver Z protein polymer accumulation by Anandini Suri et al., https://doi.org/10.1111/liv.16094

Background: Obesity can result in persistent metabolic changes despite weight loss, which may affect liver health. We aimed to investigate associations between young adulthood obesity and metabolic dysfunction-associated steatotic liver disease (MASLD), at-risk steatohepatitis and increased liver stiffness measurement (LSM) in a general population setting.

Methods: We studied NHANES 2017-2020 community-dwelling participants aged > 40 years with BMI ≥ 18.5 and no heart failure. Weight at age 25 was obtained through questionnaires and compared to current weight. Assessment included controlled attenuation parameter (CAP) and LSM. Associations between obesity status change with MASLD or at-risk metabolic dysfunction-associated steatohepatitis (MASH) and increased LSM were investigated and adjusted for demographics and metabolic health.

Results: The cohort comprised 4,580 participants (57% stable non-obesity, 33% gained obesity, 2% lost obesity and 8% stable obesity). Compared to stable no-obesity, stable obesity was strongly associated with MASLD (odds ratio [OR]: 5.47, 95% confidence interval [95%CI]: 3.97-7.66) as was gained obesity (OR: 4.68, 95% CI: 3.93-5.59), whereas no increased risk was demonstrated for lost obesity (OR: 1.26, 95% CI: 0.76-2.10). Similar associations for stable obesity and gained obesity with at-risk MASH and LSM ≥ 8 kPa were demonstrated. No residual risk was found for lost obesity (MASH-OR: 1.05 95% CI: 0.36-2.49; LSM ≥ 8 kPa-OR: 0.85, 95% CI: 0.29-1.97). Results were consistent in sensitivity analysis where obesity change was calculated over the past 10 years and weight change was stratified in normal weight/overweight/obesity.

Conclusion: Young adulthood obesity is an important risk factor for MASLD, at-risk MASH and increased LSM among the general population aged 40-80 years. Losing obesity resulted in normalisation of odds for MASLD, at-risk MASH and increased LSM. These findings underline the importance of preventing and treating young adulthood obesity to maintain liver health.

Background and aims: Holmium-166 (¹⁶⁶Ho) radioembolization could offer a more individualized approach in terms of imaging and dosimetry. We aim to evaluate the feasibility and safety of ¹⁶⁶Ho selective internal radiation therapy (SIRT) using a higher tumour dose than previously administered determined by ¹⁶⁶Ho-scout as a surrogate marker in HCC patients.

Methods: This is an open-label, prospective, non-randomized, single-centre pilot study that included patients with HCC that received ¹⁶⁶Ho-SIRT if the work-up using ¹⁶⁶Ho-scout showed a tumour-absorbed dose ≥150 Gy, a non-tumoural liver absorbed dose less than 60 Gy and a lung absorbed dose less than 30 Gy. Primary endpoints were feasibility and safety-toxicity profiles at 24-48 h and 1 month. Overall response rates (ORR) at 3 months (mRECIST, RECIST 1.1 and metabolic response by FDG and choline PET CT) and time to progression (TTP) represented the secondary endpoints.

Results: Fifteen patients with large tumours (mean diameter 55.67 ± 28.42 mm) received 17 ¹⁶⁶Ho-SIRT treatments between July 2020 and June 2022. All the attempted treatments were accomplished. Mean administered tumour dose was 183.18 ± 71.71 Gy, while non-tumour liver dose was 30.29 ± 14.56 Gy. Median time of follow-up was 12 months (IQR 9-16). Only grade 1-2 clinical and biological AEs were observed. There were no liver decompensations. At 3 months, objective response was achieved for all target lesions (CR 78.57%, PR 21.43% according to mRECIST). Median TTP was 18.8 (range 2.9; n.e.) months.

Conclusion: Personalized ¹⁶⁶Ho-SIRT with a tumour delivered dose ≥150 Gy was feasible and safe for HCC patients with promising response rates.

Background & aims: Glecaprevir/Pibrentasvir (GLE/PIB) has been approved by the European Medicine Agency (EMA) and by the US Food and Drug Administration (US-FDA) for the treatment of children and adolescents from 3 years of age with chronic hepatitis C virus (CHC) infection. The aim of this study was to confirm the real-world effectiveness and safety of GLE/PIB in children and adolescents (3 to < 18 years old) with CHC.

Methods: This prospective, multicentre study involved 11 Italian centres. Children and adolescents (from 3 to < 18 years of age) received a weight-based dose (up to 300/120 mg) of GLE/PIB once daily for 8 weeks. The effectiveness endpoint was sustained virological response 12 weeks after the end of treatment (SVR12). Safety was assessed by adverse events (AE) and clinical/laboratory data.

Results: Sixty-one patients (median age 12 years, interquartile range 5) were enrolled and treated between June 2020 and October 2023. Genotype distribution was as follows: 24/61 genotype 1 (39.4%), 13/61 genotype 2 (21.3%), 18/61 genotype 3 (29.5%) and 6/61 genotype 4 (9.8%). Sixty (98.4%) patients completed treatment and follow-up. SVR12 was obtained by 60/61 patients (98.4%). One patient died because of an oncological illness while on treatment. AE occurred in 13.1% of the patients, were mild and no patients prematurely stopped treatment.

Conclusions: This study confirmed the real-life effectiveness and safety of the 8-week therapy with GLE/PIB for treatment of CHC in children and adolescents.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects up to 30% of Western populations. While obesity is a recognized risk factor, MASLD does not develop in all obese individuals, highlighting the need to understand genetic and environmental interactions. The PNPLA3 I148M variant has been identified as a key genetic risk factor, significantly increasing the likelihood of MASLD development and progression.

Methods: We reviewed current literature on the role of PNPLA3 I148M in MASLD, focusing on gene-environment interactions involving diet, physical activity, obesity, and insulin resistance. We included studies analysing ethnic differences in PNPLA3 I148M prevalence and its association with MASLD. Additionally, we reviewed data on how PNPLA3 I148M influences the response to therapies, including lipid-lowering medications and GLP-1 agonists.

Results: The PNPLA3 I148M variant markedly heightens MASLD risk, particularly in Hispanic populations, where a higher prevalence of MASLD is observed. Lifestyle factors such as high sugar intake, alcohol consumption, and physical inactivity exacerbate MASLD risk among I148M carriers. Evidence shows that insulin resistance amplifies MASLD risk associated with the I148M variant, especially in non-diabetic individuals. Moreover, the PNPLA3 I148M variant interacts with other genetic loci, further modifying MASLD risk and disease course. The variant also influences treatment response, with variability observed in effectiveness of lipid-lowering therapies and GLP-1 agonists among carriers.

Conclusion: The interplay between PNPLA3 I148M and environmental factors underscores the need for personalized MASLD prevention and treatment strategies. Targeting both genetic and lifestyle contributors may enhance MASLD management, offering a tailored approach to reducing disease burden.