Liver International最新文献

Introduction: The cumulative impact of metabolic syndrome (MetS) components on micro- and macrovascular disease in metabolic dysfunction-associated steatotic liver disease (MASLD) is unclear. We aimed to determine whether the number of the MetS components increases the risk of micro- and macrovascular disease in patients with MASLD.

Methods: We performed a retrospective cohort study of electronic medical records using the TriNetX network, a global federated database. The exposure arm was patients with hepatic steatosis (defined via International Classification of Diseases, 10th Revision coding, or modified hepatic steatosis index), and ≥1 MetS components (obesity/central adiposity, insulin resistance, hypertension, or dyslipidaemia), compared with a reference arm of adults without any MetS components or hepatic steatosis. Our propensity score matched (1:1) for confounders with 5 years of follow-up. Primary outcomes included microvascular (peripheral neuropathy, retinopathy, and nephropathy) and macrovascular (cardiovascular events, cerebrovascular accidents, and peripheral vascular disease) disease. Secondary analyses assessed the impact of additional MetS components on these outcomes, as well as the impact of sex.

Results: MASLD, defined by hepatic steatosis and insulin resistance (n = 15 937), carried the highest risk of microvascular disease (HR 13.93 (95% CI 8.55-22.68)), whilst MASLD, defined by hepatic steatosis and hypertension (n = 53 028), carried the highest risk of macrovascular disease (7.23 (6.45-8.13)). MASLD with all MetS components carried greatest risk of both micro- (31.20 (28.88-33.70) (n = 462 789)) and macrovascular (8.04 (7.33-8.82) (n = 336 010)) disease.

Conclusion: We demonstrate a differential effect of MetS components on micro- and macrovascular disease risk in patients with MASLD, with a cumulative impact of multiple MetS on overall risk. The impact of MetS components was most pronounced in women. Aggressive metabolic risk factor management is critical for prevention of micro- and macrovascular complications.

Background and aims: The impact of hepatitis C virus (HCV) eradication via direct-acting antiviral (DAA) therapy on overall mortality, particularly non-liver-related mortality, is understudied.

Methods: We recruited 4180 patients with chronic HCV infection who achieved sustained virological response (SVR) (HCV eradication) through DAA therapy (n = 2501, SVR group) or who did not receive antiviral therapy (n = 1679, non-SVR group); 1236 from each group were chosen using propensity score matching. Causes of death and all-cause mortality, including non-liver-related diseases, were investigated.

Results: Of the 4180 patients, 592 died during the follow-up period. In the SVR group, the mortality rates from liver-related and non-liver-related diseases were 16.5% and 83.5%, respectively. Compared to the non-SVR group, mortality rates from liver-related and non-liver-related diseases were 50.1% and 49.9%, respectively (p < .001). In non-cirrhotic patients, multivariable analysis revealed that SVR was an independent factor associated with both liver-related (hazard ratio [HR], .251; 95% confidence interval [CI], .092-.686) and non-liver-related (HR, .641; 95% CI, .415-.990) mortalities. In cirrhotic patients, multivariable analysis revealed that SVR remained an independent factor significantly associated with liver-related mortality (HR, .151; 95% CI, .081-.279). In propensity score-matched patients, the eradication of HCV (SVR group) decreased both liver-related (p < .001) and non-liver-related mortality (p = .008) rates compared to persistent HCV infection (non-SVR group).

Conclusions: The elimination of HCV via DAA therapy reduced not only liver-related mortality but also non-liver-related mortality in patients with chronic HCV.

Background and aims: Patients with overt or occult hepatitis B virus (HBV) infection receiving immunosuppressive treatments have a wide risk of HBV reactivation (HBVr). We performed meta-analysis with decision curve analyses (DCA) to estimate the risk of HBVr in HBsAg-negative anti-HBc-positive patients naïve to nucleos(t)ide analogues (NAs) receiving immunosuppressive treatments.

Approach and results: Studies were identified through literature search until October 2022. Pooled estimates were obtained using random-effects model. Subgroup analyses were performed according to underlying disease and immunosuppressive treatments. DCA was used to identify the threshold probability associated with the net benefit of antiviral prophylaxis in HBsAg-negative anti-HBc-positive patients. We selected 68 studies (40 retrospective and 28 prospective), including 8034 patients with HBsAg negative anti-HBc positive. HBVr was 4% (95% CI 3%-6%) in HBsAg-negative anti-HBc-positive patients, with a significantly high heterogeneity (I² 69%; p < .01). The number-needed-to-treat (NNT) by DCA ranged from 8 to 24 for chemotherapy plus rituximab, from 12 to 24 for targeted therapies in cancer patients and from 13 to 39 for immune-mediated diseases. Net benefit was small for monoclonal antibodies.

Conclusions: Our DCA in HBsAg-negative anti-HBc-positive patients provided evidence that NA prophylaxis is strongly recommended in patients treated with chemotherapy combined with rituximab and could be appropriate in patients with cancer treated with targeted therapies and in patients with immune-mediated diseases. Finally, in patients with cancer treated with monoclonal antibodies or with chemotherapy without rituximab, the net benefit is even lower.

Background and aims: Wilson disease (WD) is a rare disorder of copper metabolism, leading to liver and neurological disease. Existing literature on WD in pregnancy is scarce, limiting preconception and obstetrical counselling. In this systematic review with meta-analysis, we determine the prevalence of various adverse pregnancy and neonatal outcomes in WD, as well as evaluate the impact of WD treatment on these outcomes.

Methods: Scopus, MEDLINE and EMBASE were searched until 12 May 2023, for studies of pregnant individuals with WD and at least one pregnancy or neonatal outcome of interest. Meta-analysis of single proportions was conducted to pool prevalence data for each outcome. Outcome rates were compared between treated and untreated groups in a meta-analysis of dichotomous events.

Results: Sixteen studies, published from 1975 to 2022, were included in the systematic review. Thirty-seven percent of pregnancies reported at least one adverse pregnancy outcome. Spontaneous abortions (20%), liver diseases of pregnancy (4.5%) and preterm births (2%) were the most frequent adverse pregnancy outcomes in patients with WD. The prevalence of spontaneous abortions was significantly lower in pregnant individuals with WD who received treatment during pregnancy (OR: .47, 95% CI: 35%-63%). The prevalence of any adverse pregnancy outcome was also significantly lower with treatment (OR: .53, 95% CI: .37-.76), which appears to be mostly driven by the reduction of spontaneous abortions.

Conclusions: There is low to moderate quality evidence to suggest that preconception and obstetrical counselling for patients with WD should include a discussion on the potentially high frequency of adverse pregnancy outcomes in this population, as well as the importance of continuing WD treatment during pregnancy to ensure satisfactory pregnancy course and potentially minimize the risk of spontaneous abortions.

Background & aims: There is an unmet need for a reliable and reproducible non-invasive measure of fatty liver content (FLC) for monitoring steatotic liver disease in clinical practice. Sonographic FLC assessment is qualitative and operator-dependent, and the dynamic quantification range of algorithms based on a single ultrasound (US) parameter is unsatisfactory. This study aims to develop and validate a new multiparametric algorithm based on B-mode images to quantify FLC using Magnetic Resonance (MR) values as standard reference.

Methods: Patients with elevated liver enzymes and/or bright liver at US (N = 195) underwent FLC evaluation by MR and by US. Five US-derived quantitative features [attenuation rate(AR), hepatic renal-ratio(HR), diaphragm visualization(DV), hepatic-portal-vein-ratio(HPV), portal-vein-wall(PVW)] were combined by mixed linear/exponential regression in a multiparametric model (Steatoscore2.0). One hundred and thirty-four subjects were used for training and 61 for independent validations; score-computation underwent an inter-operator reproducibility analysis.

Results: The model is based on a mixed linear/exponential combination of 3 US parameters (AR, HR, DV), modelled by 2 equations according to AR values. The computation of FLC by Steatoscore2.0 (mean ± std, 7.91% ± 8.69) and MR (mean ± std, 8.10% ± 10.31) is highly correlated with a low root mean square error in both training/validation cohorts, respectively (R = 0.92/0.86 and RMSE = 5.15/4.62, p < .001). Steatoscore2.0 identified patients with MR-FLC≥5%/≥10% with sensitivity = 93.2%/89.4%, specificity = 86.1%/95.8%, AUROC = 0.958/0.975, respectively and correlated with MR (R = 0.92) significantly (p < .001) better than CAP (R = 0.73).

Conclusions: Multiparametric Steatoscore2.0 measures FLC providing values highly comparable with MR. It is reliable, inexpensive, easy to use with any US equipment and qualifies to be tested in larger, prospective studies as new tool for the non-invasive screening and monitoring of FLC.