Journal of Clinical and Experimental Hepatology最新文献

Objective: To assess the effects of inferior vena cava and/or hepatic vein (IVC±HV) venoplasty on liver volumetry and function in individuals with Budd Chiari syndrome (BCS) who present with ascites and at least one patent hepatic vein.

Methods: A retrospective analysis was conducted on the clinical data of 17 patients with BCS (6 males and 11 females, average age of 42.3 ± 11.9 years) who underwent IVC venoplasty for ascites caused by IVC blockage and at least one patent HV, either pre- or post-venoplasty. Liver function tests and abdominal CT scans were performed before the procedure and at three and six months post-venoplasty. The changes in liver function and volume before and after venoplasty were analyzed.

Results: Each of the 17 patients successfully underwent IVC±HV venoplasty. During the median follow-up period of six months, all patients survived. Comparisons with preoperative conditions showed significant improvements in ascites and liver function three and six months after the procedure (P < 0.05). The liver volumes measured before and at three- and six-months post-procedure were 2077.06 ± 185.53 cm³, 1742.00 ± 124.62 cm³, and 1632.71 ± 108.29 cm³, respectively. There was a significant decrease in liver volume between the pre-operative measurements and the three-month follow-up, as well as between the three-month and six-month follow-ups (P < 0.05).

Conclusions: IVC±HV venoplasty produced satisfactory clinical results in BCS patients. Following the intervention, there was a progressive decrease in hepatic congestion and an improvement in liver function which correlated with decrease in liver volume.

Suspicion of vascular injury during endoscopic retrograde cholangiopancreatography (ERCP) should be raised in the event of intraprocedural bleeding, persistent hyperbilirubinemia, and sepsis despite biliary stenting. Most inadvertent portal vein (PV) cannulations during ERCP are innocuous, and mere withdrawal of guidewire and catheter suffices. However, unintentional PV stenting, particularly with larger metallic stents, increases the likelihood of significant bleeding. Thus, endoscopic removal of a malpositioned stent from the PV should be carried out in the interventional radiology suite so that PV stent grafting can be performed in case of unexpected bleeding. Here, we describe a case of bleeding from a malpositioned 10-French plastic stent within the PV during ERCP in a 79-year-old male. The bleeding was effectively controlled by inserting a 16-mm covered stent into the PV via a transjugular route.

Post-Kasai portoenterostomy (KPE) cholangitis is one of the most common complications that has a negative impact on liver function and native liver survival. Early diagnosis and judicious empiric antimicrobial management are, therefore, important to prevent further liver damage and decompensation. However, there is no consensus regarding the standard definition of post-KPE cholangitis, and established guidelines on evaluation and management are also lacking. Metagenomic next-generation sequencing, a new molecular diagnostic technique, has the potential for detecting broader spectrum of pathogens, especially in blood culture-negative patients. Antibiotic prophylaxis to prevent cholangitis has been widely used, but questions over the choice of antibiotics, route of administration, and optimal duration remain unsettled. The available evidence on the efficacy of antibiotic prophylaxis in preventing cholangitis has shown conflicting results. This review offers a summary of the current research on advances in diagnostic approaches, including molecular techniques, and therapeutic challenges in managing intractable cholangitis.

Background: There are limited studies assessing whether prophylactic platelet transfusions prior to high-risk procedures reduce the risk of bleeding in patients with liver cirrhosis.

Methods: We performed a post hoc analysis of two prior randomized clinical trials (CTRI/2017/12/010822 and CTRI/2021/05/033464), which compared thromboelastography-guided prophylactic platelet transfusion to standard-of-care (empirical prophylactic transfusion for all patients prior to the procedure) or on-demand transfusion (no prophylactic transfusions). We aimed to assess the risk of major procedure-related bleeding or mortality among patients who had received prophylactic platelet transfusions versus those who did not (on-demand transfusions).

Results: A total of 118 patients were included in the analysis, with baseline demographics well matched between groups. The leading etiologies of cirrhosis were cryptogenic (42, 35.6%) and autoimmune liver disease (30, 25.4%). The most common procedures performed were percutaneous liver biopsy (73, 61.8%), followed by transjugular intrahepatic portosystemic shunt (14, 11.9%) and transarterial chemoembolization (14, 11.9%). No episode of major bleeding or procedure-related mortality occurred in either group, though minor bleeding occurred in 5 patients. A significantly lower number of patients in the on-demand group required platelet transfusions than those receiving empirical transfusions as part of standard care.

Conclusion: Procedure-related bleeding rates were not significantly higher among patients with liver cirrhosis undergoing high-risk procedures without prophylactic platelet transfusions than in those who received them. Larger randomized trials are required to validate these findings from our post hoc analysis.

Introduction: Glycerol-3-phosphate dehydrogenase 1 (GPD1) deficiency is an autosomal recessive disorder causing hypertriglyceridemia, hepatomegaly, fatty liver, and hepatic fibrosis in infancy. It is an under-recognized cause of pediatric steatotic liver disease (SLD) with only 36 cases reported worldwide.

Method: We analyzed the clinical profile of our five cases diagnosed by exome sequencing (ES) and reviewed the published cases till December 2023 using PubMed search.

Results: Five unrelated boys (6-24months) presented with hepatomegaly, hypertriglyceridemia, transaminase elevation, and fatty liver. ES revealed compound heterozygous mutations in two and homozygous mutation in three including two novel mutations (c.917T >C, c.905C > G). All received supportive therapy, and fenofibrate was successfully used in one case for progressive hypertriglyceridemia. Globally, 36 cases (age at diagnosis: 6 [1-164 months]) have been reported. Majority had hepatomegaly (94.4%), 22.2% each had splenomegaly and growth failure. Hypertriglyceridemia (97.2%) was nearly universal, 100% had fatty liver, and hypoglycaemia (11.2%) was uncommon. Liver biopsy (n = 18) demonstrated steatosis in all, fibrosis in 94.4%, and cirrhosis in 22.2%. During follow-up (11-376 months), hepatomegaly resolved in 35.2%, triglycerides, and transaminases normalized in 29.1% and 31.5%, respectively. No pancreatitis, cardiac events, or liver decompensation was reported.

Conclusion: GPD1 is an uncommon cause of SLD, raised transaminases and hypertriglyceridemia in young children. Diagnosis is confirmed by genetic testing. Supportive therapy, parental counseling about the disease nature and close follow-up is recommended.

Background: Liver fibrosis is a serious global health issue, but current treatment options are limited due to a lack of approved therapies capable of preventing or reversing established fibrosis.

Aim: This study investigated the antifibrotic effects of a synthetic peptide derived from α-lactalbumin in a mouse model of thioacetamide (TAA)-induced liver fibrosis.

Methods: In silico analyses were conducted to assess the physicochemical properties, pharmacophore features, and docking interactions of the peptide. Mice with induced fibrosis were treated with three different doses of the synthetic peptide (2.5, 5, or 10 μg/kg, twice weekly for 8 weeks). Immunohistochemistry, antioxidant enzyme levels, IGF-1 levels, and expression of fibrosis-related genes were assessed.

Results: Peptide interacted with human prothrombin's many sites with varying binding affinities. Besides, ligand similarity analysis identified 26 thrombin inhibitors with high Tanimoto scores. The peptide exhibited antifibrotic effects with dose-dependent improvements. The upregulated expression of IGF-1 in all treated groups compared with the pathological untreated group. In contrast, fibrotic markers such as TIMP, PDGF-α, and TGF-β were upregulated in the untreated pathological group but downregulated in the peptide-treated groups. The assessment of IGF-1 concentration in sera demonstrated that the peptide-treated groups exhibited an increase in IGF-1 levels. Histopathological examination of peptide-treated groups showed normal hepatic architecture with hepatocytes arranged in thin plates. Immunohistochemical results of high dose peptide-treated group showed a few numbers of positive αSMA with mild proliferating cell nuclear antigen expression.

Conclusion: The synthetic α-lactalbumin peptide shows promise as an antifibrotic therapy. Its safety and effectiveness are supported by in silico and in vivo analyses. The peptide's pharmacophore characteristics and potential as a thrombin inhibitor combine with its ability to downregulate fibrotic markers and maintain liver tissue integrity. These findings concluded the potential of this peptide as a promising therapeutic candidate for liver fibrosis, warranting further investigation.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) with onset in youth may be more consequential for adverse outcomes than that detected later in adulthood. Transaminitis in the general population is a marker of the prevalence of MASLD. There are no previous community-based studies in Indian youth assessing the prevalence of transaminitis. The purpose of this study was to find out the prevalence of transaminitis, MASLD and elevated Fibrosis-4 (FIB-4) index among young South Indian adults.

Methods: This was a cross-sectional study done over a period of 1 year from January 2022 among adults aged 18-30 years. Multistage sampling was used to recruit participants with body mass index (BMI) < 30 kg/m² and without moderate to heavy alcohol consumption from four different sociogeographic regions. Detailed history, physical examination and investigations including liver enzymes (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]), platelet count, and metabolic workup were carried out. FIB-4 index and Nonalcoholic fatty liver disease-liver fat score (NAFLD-LFS) were calculated. LFS ≥ -0.64 was used to rule in MASLD.

Results: A total of 2373 (1170 males) participants with a mean age of 24 ± 3.5 years were included. Transaminitis (AST or ALT≥35 IU/L) was seen in 25.9% of the cohort. MASLD by NAFLD-LFS was present in 27.4% of the population. FIB-4 index ≥1.3 was found in 54 (2.27%) participants. Neck circumference and Trivandrum Medical College adiposity index were associated with transaminitis, MASLD, and elevated FIB-4. Blood pressure, triglycerides, and low-density lipoprotein cholesterol were higher, and high-density lipoprotein cholesterol was lower among participants with transaminitis, but they were not different among those with elevated FIB-4 index. BMI and waist-hip ratio were not different among participants with and those without transaminitis or MASLD.

Conclusion: There is a high prevalence of transaminitis and MASLD in community-dwelling young adult Indians. We recommend screening all young adult Indians for MASLD and transaminitis.

Background/aim: Non-alcoholic fatty liver disease (NAFLD) is a global health concern with limited treatment options. The paucity of predictive i n v itro models in preclinical settings seems to be one of the limitations of identifying effective medicines. We therefore aimed to develop an i n v itro model that can display the key hallmarks of NAFLD, such as steatosis, inflammation, and fibrosis.

Methods: An in vitro model of steatohepatitis was developed using organoids prepared from hepatocytes of healthy individuals from a commercial source (HLOs) and the liver tissues collected from needle biopsies of NAFLD patients (HLO_NAFLD) using defined culture conditions. HLOs were treated with palmitic acid for 72 h to develop an i n v itro model of steatohepatitis, while HLO_NAFLD served as a natural model of steatohepatitis. Metformin and saroglitazar were used to validate the liver organoid model of steatohepatitis. Saroglitazar was also evaluated in the high-fat, high-fructose (HF-HF) diet-induced model of NAFLD using C57BL/6 mice to validate the findings from the i n v itro model.

Results: HLOs and HLO_NAFLD exhibited bipotent properties, showing the expression of markers of hepatocytes, ductal cells, and also stem cells. Furthermore, they demonstrated the expression of nonparenchymal cell markers such as stellate cells (CD166) and Kupffer-like cells (CD68 and EMR1). The steatohepatitis models developed using these organoids displayed markers associated with steatosis, inflammation and fibrosis, which were decreased by metformin and saroglitazar.

Conclusion: The in vitro models developed in our lab employing HLOs and HLO_NAFLD display all three key hallmarks of NAFLD: steatosis, inflammation, and fibrosis without the necessity for coculture with other nonparenchymal cells. The implementation of the HLO_NAFLD-based model is also expected to provide a more realistic assessment of test substances to develop therapeutics for NAFLD.

Background & aims: PNPLA3 rs738409 variant is a risk factor for onset and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to assess its global prevalence, clinical and histological characteristics, and long-term outcomes in patients with MASLD.

Methods: PubMed and Embase databases were searched until December 30, 2023, for observational studies on PNPLA3 genotyped adults with MASLD. Proportions were pooled using a generalized linear mixed model with Clopper-Pearson intervals. Continuous and dichotomous variables were analyzed using the DerSimonian-Laird method. International Prospective Register of Systematic Reviews registration number: CRD42023449838.

Results: A total of 109 studies involving 118,302 individuals with MASLD were identified. The overall minor allele frequency of the G allele [MAF(G)] at PNPLA3 was 0.45 (95% confidence interval [CI]: 0.43; 0.48) with high heterogeneity (I² = 98%). The highest MAF(G) was found in Latin America (0.63) and the lowest in Europe (0.38). No African countries were identified. Carriers of the PNPLA3 variant had reduced adiposity, altered fat metabolism, and worse liver damage/histology than noncarriers. There was significant heterogeneity in the clinical/histological analyses (I² > 50%). Only the PNPLA3 GG genotype was associated with higher mortality and liver-related events with no heterogeneity (I² = 0%). Metaregressions showed the influence of adiposity, age, diabetes mellitus, and glucose on some PNPLA3 expression parameters. Overall, there was a moderate risk of bias in the included studies.

Conclusions: This study reveals the global pattern of PNPLA3 and its clinical, histological, and outcome implications in MASLD. Patients with MASLD and PNPLA3 variant have different clinical features and worse liver severity, and only PNPLA3 GG has a higher risk of mortality and liver outcomes. Our findings highlight the importance of PNPLA3 genotyping in clinical trials and advocate for personalized medicine approaches.