Clinical and Experimental Hepatology最新文献

Aim of the study: Chronic hepatitis C (CHC) infection remains one of the most prevalent chronic liver disease worldwide. A sustained virological response (SVR) can be achieved at high rates for CHC patients receiving direct-acting antivirals (DAAs). However, even small subsets of patients achieving SVR still have a risk of developing hepatocellular carcinoma (HCC). Metabolic-associated fatty liver disease (MAFLD) is associated with increased risk of HCC. We aimed to summarize the effect of MAFLD on HCC development on CHC patients, even after achieving SVR.

Material and methods: We conducted a search of PubMed and Google Scholar from inception to July 7^th 2024, for studies assessing the association between the presence of MAFLD or metabolic dysfunction-associated steatotic liver disease (MASLD) or non-alcoholic fatty liver disease (NAFLD) and HCC risk in CHC patients who achieved SVR. The quality of included studies was evaluated using the Newcastle-Ottawa Scale (NOS). We analyzed the pooled hazard ratios (HRs) with 95% confidence intervals (CIs) using a fixed and random-effects model. Heterogeneity was assessed using I ².

Results: Five studies with a total of 7,034 patients were included. The quality of studies ranged from 6 to 8 stars. Metabolic dysfunction is associated with increased risk of HCC after SVR in CHC patients (HR = 2.02, 95% CI: 1.61-2.54, p < 0.00). No heterogeneity was present.

Conclusions: Metabolic dysfunction is associated with increased risk of HCC progression in CHC patients even after achieving SVR.

Aim of the study: The primary objective of this study was to assess the impact of thromboelastography (TEG) on the decision-making process of gastroenterologists and hepatologists regarding blood component (BC) transfusions in patients with decompensated cirrhosis before invasive manipulations.

Material and methods: This study was a prospective, single-center, randomized controlled trial. Throughout the trial, the decision-making process was not actively influenced. However, TEG results were made available to the physicians, offering recommendations regarding the need for specific BC transfusions. To assess whether the availability of TEG data influences clinical decision-making, a subsequent statistical analysis was conducted.

Results: After application of exclusion criteria, 20 patients were enrolled in the study. The results showed that in the TEG group, the need for BC transfusions was 20% lower than in the control group, although this difference was not statistically significant (p = 0.384). When hypothesizing that all patients in the TEG group would have received BC transfusions prior to the procedure, TEG was estimated to reduce transfusion requirements by 69.2%. However, this reduction was also not statistically significant (p > 0.05).

Conclusions: In settings where nearly all physicians were familiar with the concept of hemostatic changes in liver cirrhosis, TEG was estimated to reduce transfusion requirements by 20%.

Aim of the study: Data concerning the clinical manifestation and outcomes of lean metabolic dysfunction-associated steatotic liver disease (MASLD) are scarce and inconsistent. The aim of the study was to evaluate the clinical characteristics of MASLD and predictors of its occurrence.

Material and methods: The study included patients from the Polish Gallstone Surgery Registry diagnosed with MASLD according to the current criteria.

Results: Among 3,419 patients, MASLD was diagnosed in 24.2%. Lean MASLD was diagnosed in 11.3% of patients with MASLD. Independent predictors of lean MASLD were atherogenic dyslipidaemia (OR = 94.16, CI: 45.54-197.71, p < 0.0001), diabetes mellitus or prediabetes conditions (OR = 9.26, CI: 4.42-19.38, p < 0.0001) and hypertension (OR = 2.97, CI: 1.38-6.41, p = 0.0054).

Conclusions: Lean MASLD is not a rare form of the disease, and in the lean MASLD group there are patients with a high rate of metabolic abnormalities which may significantly increase cardiovascular risk and the risk of MASLD progression.

Aim of the study: Primary biliary cholangitis (PBC) is a complex, chronic, cholestatic liver disease with an autoimmune etiology. While plasma metabolites are crucial indicators of physiological and pathological states, their involvement in PBC pathogenesis remains unclear. To address this knowledge gap, we performed a rigorous two-sample Mendelian randomization (MR) analysis to assess the causal associations of 1,400 plasma metabolites with PBC.

Material and methods: Genome-wide association data for 1,400 plasma metabolites and PBC were obtained from established public databases. The inverse-variance weighted (IVW) method was the primary method used for MR analysis. Sensitivity analyses and heterogeneity tests were conducted to assess the stability of the MR results. A reverse MR analysis was performed to investigate the possibility of reverse causality.

Results: Four plasma metabolites were identified as potential predictors for the occurrence of PBC. Specifically, sphingosine 1-phosphate (OR = 0.65, 95% CI: 0.42-0.98, p = 0.04) and docosadienoate (22:2n6) (OR = 0.57, 95% CI: 0.36-0.90, p = 0.01) were implicated in conferring a protective effect against PBC. Conversely, homoarginine (OR = 1.34, 95% CI: 1.04-1.72, p = 0.02) and campesterol (OR = 1.19, 95% CI: 1.01-1.40, p = 0.03) were associated with an increased risk of PBC. There was no evidence of reverse causality between PBC and the identified plasma metabolites.

Conclusions: This study utilized a two-sample Mendelian randomization approach to explore the causal relationship between 1,400 plasma metabolites and PBC. We identified four plasma metabolites that may have a causal relationship with the development of PBC. The metabolites identified hold promise as prognostic indicators and could illuminate novel pathways for therapeutic intervention in PBC.

Introduction: It appears that type 1 diabetes mellitus (T1DM) and autoimmune liver diseases (AILDs) are associated, but there is no evidence linking them causally or in a specific direction. This study aims to evaluate the causal relationship between T1DM and AILDs.

Material and methods: We performed a two-sample Mendelian randomization (MR) analysis. Following thorough evaluation, the dataset from the genome-wide association study was utilized to identify potential candidate single nucleotide polymorphisms. Inverse variance weighting (IVW) served as the primary analytical method, complemented by four sensitivity analysis approaches to evaluate result robustness.

Results: Mendelian randomization analysis demonstrated a significant positive causal association between genetically elevated risk of T1DM and autoimmune hepatitis (AIH) (OR = 1.168, 95% CI: 1.060-1.287, p = 0.001), primary biliary cholangitis (PBC) (OR = 1.186, 95% CI: 1.050-1.341, p = 0.006), as well as primary sclerosing cholangitis (PSC) (OR = 1.291, 95% CI: 1.016-1.642, p = 0.037). MR-Egger regression analysis suggested a potential influence of horizontal pleiotropy on the causal association for these conditions (AIH: intercept = -0.026, p = 0.451; PBC: intercept = 0.014, p = 0.745; PSC: intercept = -0.013, p = 0.862). Sensitivity analysis utilizing the leave-one-out method supported the robustness of the Mendelian randomization findings. Conversely, reverse Mendelian randomization analysis revealed that genetically predisposed PBC also raises the likelihood of developing T1DM (OR = 1.236, 95% CI: 1.085-1.407, p = 0.001). Conversely, no causal association was found between AIH and T1DM (OR = 1.032, 95% CI: 0.983-1.084, p = 0.207) or between PSC and T1DM (OR = 0.989, 95% CI: 0.849-1.152, p = 0.888).

Conclusions: Employing two-sample MR analysis, we explored the association between T1DM and AILDs, finding that T1DM elevates the risk of AIH, PBC, and PSC. Further elucidation of the genomic landscape of T1DM and AILDs necessitates large-scale cross-disease genome-wide association studies (GWAS).

Aim of the study: The aim of this study was to analyze changes in liver stiffness and steatosis using noninvasive methods in children aged 6 to 18 years up to one year after successful treatment with sofosbuvir/velpatasvir (SOF/VEL).

Material and methods: Evaluation of liver stiffness and steatosis was performed in 49 patients at 12 weeks and one year after treatment using noninvasive methods. Liver stiffness measurement (LSM) and the controlled attenuation parameter (CAP) were obtained by transient elastography (FibroScan 530, Echosens).

Results: At baseline, LSM corresponded to a METAVIR F score of 0/1 in 48/49 (98%) participants. There was a decrease in mean LSM values from baseline to posttreatment visits (from 4.63 kPa to 4.26 kPa at 12 weeks, and 4.15 kPa at one year after treatment). In one girl who presented with significant fibrosis (LSM 11.3 kPa, F3) before the treatment, regression of stiffness was observed to 7.6 kPa (F2) at 12 weeks after treatment and 5.4 kPa (F0/1) at one year after treatment. There was an increase in the mean CAP value of +12.44 dB/m at 12 weeks after treatment compared to baseline, but the difference at one year after treatment was insignificant. A correlation between higher CAP values and older participants' age was observed at all the visits. Children with body mass index (BMI) z-score values > 1.0 presented with higher CAP values both before and after treatment.

Conclusions: Most children with chronic hepatitis C present with normal liver stiffness. However, its regression may occur to some extent after successful treatment with SOF/VEL. A transient increase in hepatic steatosis was observed after eradication of HCV, which requires further investigation.

Drug-induced liver injury (DILI) is a growing clinical problem. Antibiotics remain the most common cause of DILI in Europe. Their clinical spectrum is very broad, from asymptomatic to acute liver failure. Currently, DILI is categorized as hepatocellular (R ≥ 5), cholestatic (R ≤ 2) or mixed (R = 2-5) injury based on the serum alanine aminotransferase (ALT)/alkaline phosphatase (ALP) ratio. DILI is a diagnosis of exclusion and requires a wide differential diagnosis. The most important step in management is discontinuation of the drug suspected of causing liver damage. The list of specific antidotes that eliminate the effects of hepatotoxins is unfortunately very short. In symptomatic treatment, glucocorticosteroids and ursodeoxycholic acid have been used in selected cases. Liver transplantation is an optional treatment in patients with acute liver failure.

Aim of the study: Hepatocellular carcinoma (HCC) in Malaysia is a growing health concern, despite regular liver ultrasound and α-fetoprotein (AFP) surveillance. The GALAD model incorporates AFP, lens culinaris agglutinin- reactive α-fetoprotein (AFP-L3), protein induced by vitamin K antagonist-II (PIVKA-II), gender and age to predict the probability of HCC. Our objective was to evaluate the diagnostic ability of GALAD compared to AFP in HCC screening.

Material and methods: A single-centre, case control study recruited newly diagnosed HCC and cirrhotic patients. Serum biomarkers were quantified using a microfluidic-based automated immunoanalyzer. The diagnostic ability of AFP, AFP-L3, PIVKA-II and GALAD was assessed using receiver operating characteristic curve (ROC) and corresponding area under the curve (AUC) analysis.

Results: Among the 44 HCC cases, GALAD score achieved the highest AUC value of 0.94 (95% confidence interval [CI]: 0.90-0.98, p < 0.0001) significantly surpassing AFP (0.89), AFP-L3 (0.84) and PIVKA-II (0.88). The GALAD score demonstrated 84.1% sensitivity and 93.8% specificity at the standard cut-off (-0.63) and 88.6%/92.2% at its best cut-off (-1.035) for detecting any stage of HCC, outperforming AFP (79.5%/92.2%), AFP-L3 (59.1%/94.9%) and PIVKA-II (79.5%/84.9%). The sensitivity of the GALAD score was 100% in earlystage HCC (BCLC0/A).

Conclusions: GALAD outperformed conventional biomarkers, facilitating early detection, improved treatment options and ultimately a higher survival rate for HCC patients.

The diagnosis of autoimmune hepatitis (AIH) is based on clinical criteria and histopathological findings. Interpretation of lesions observed in liver biopsy specimens, in cases of suspected AIH, requires correlation with clinical data and communication between hepatologists and pathologists. The diagnostic criteria have been modified over the years, and the latest guidelines were proposed in 2022. Implementation of the current recommendations improves diagnostic accuracy for autoimmune hepatitis and related pathologies. This article presents the clinicopathological characteristics of AIH and an overview of the histopathological diagnostic approach in the light of the modern guidelines.

Patients with chronic liver diseases, particularly those with liver cirrhosis, are more vulnerable to severe superinfections compared to the general population. They face an increased risk of liver function decompensation and mortality when contracting viral or bacterial infections. Vaccination is crucial in mitigating these risks, yet its efficacy in this patient group may be limited. Despite the safety of vaccines, their effectiveness in individuals with chronic liver diseases remains constrained. A significant challenge is the inadequate implementation of vaccination protocols, often due to insufficient communication and recommendations from physicians, including hepatologists, and the high cost of vaccines.