Annals of hepatology最新文献

Introduction and Objectives

Hepatic fibrosis (HF) is characterized by the progressive accumulation of extracellular matrix (ECM), which destroys the physiological architecture of the liver. Pathologically, chronic liver diseases lead to damaged hepatocytes and infiltration of immune cells that activate collagen-producing hepatic stellate cells (HSCs), leading to excessive ECM production, and causing uncontrolled scarring. Maresin1 is a derivative of -3 docosahexaenoic acid (DHA), which has been shown to have pro-resolving and anti-inflammatory effects in various organs like those observed for DHA. This study aimed Mar1+DHA supplementation would prevent the development of fibrosis and promote regeneration in an animal model of chronic liver damage.

Materials and Methods

FH was induced in Sprague-Dawley rats by injections of diethylnitrosamine (DEN, 50 mg/kg) and treated with MaR1 (4ng/g) and/or DHA (375 mg/kg) for five weeks. Transaminases, liver histology, and proteins were analyzed by western blot.

Results

the DHA+ MaR1 group showed a greater positive response (significant) than MaR1 in terms of normalization of AST and ALT levels, and architecture of the liver. Reducing inflammation and necrosis. Furthermore, both MaR1 and DHA reduced the levels of TGF-, its receptor TGFRII, and TIMP1, increasing MMP1. Results that coincide with the quantification of type I collagen fibers in tissue. On the other hand, they would promote liver regeneration by increasing Cyclin D1.

Conclusions

Both MaR1 and MaR1/DHA improve regeneration and DEN-induced liver fibrosis parameters, promoting regeneration and acting as an antifibrotic agent. Results that open the possibility that MaR1/DHA are potential therapeutic agents in fibrosis and other liver pathologies.

Introduction and Objectives

Latin Americans experience some of the highest global rates of non-alcoholic fatty liver disease (NAFLD) and the prevalence of cirrhosis is increasing in this population. The rs641738 C>T single nucleotide polymorphism (SNP) of MBOAT7 has been associated with NAFLD development and cirrhosis in Europeans with NAFLD. However, the impact of this SNP in Latin Americans is unclear. We aimed to evaluate a cohort of Latin Americans with NAFLD to determine if MBOAT7 effects the risk of cirrhosis in this understudied population.

Materials and Methods

Individuals with NAFLD from 6 South American countries (Argentina, Ecuador, Brazil, Chile, Peru and Colombia) were prospectively recruited via the ESCALON network. Genotyping was performed with the TaqMan-genotyping assay. Genotype frequencies for MBOAT7 were compared using chi-square. Those with hepatocellular carcinoma were excluded.

Results

A total of 278 patients were included, 189 with cirrhosis and 89 without cirrhosis. 55% of the cirrhosis cohort were females compared to 61% of the cohort without cirrhosis (p=0.337). The median ages of those with and without cirrhosis were 64 (IQR 59-70) and 60 years (IQR 52-65), respectively. The MBOAT7 TT genotype was present in 36/189 (19%) of subjects with cirrhosis and 7/89 (8%) of subjects without cirrhosis (OR=2.76, 95% CI: 1.17-6.47, p=0.016). We evaluated the minor allele frequency (MAF) of MBOAT7 in our cirrhosis cohort compared to the Latin American population in the gnomAD database, a genome database with 17,720 sequences belonging to Latin Americans. MAF was elevated in cirrhotics compared to the general Latin American population (43% vs. 33% respectively, OR=1.54, 95% CI: 1.25-1.89, p<0.001).

Conclusions

The rs641738 C>T SNP of MBOAT7 was associated with cirrhosis in a cohort of Latin Americans with NAFLD. Identification of genetic risk factors for liver disease may lead to improved risk stratification and interventional strategies in this population with an increasing burden of liver disease.

Introduction and Objectives

In the diagnostic process of liver diseases the clinical history and hepatic biochemical profile are fundamental. Liver biopsy is the gold standard for diagnosis, evaluation of activity, fibrosis status or therapeutic response. It is an invasive procedure with risk of complications. With respect to fibrosis staging, a key point in decision making in follow-up and treatment, non-invasive tests have been developed that are easily accessible and without resorting to biopsy. The calculation of the FIB-4 and APRI indices is useful in general practice, but not sufficient to determine the degree of fibrosis in early and intermediate stages. Liver fibrosis increases stiffness and decreases tissue elasticity and can be assessed by Elastography, this technique is sensitive to differentiate patients without fibrosis from those with advanced fibrosis, in a fast and well tolerated way. This study aims to describe the diagnostic performance for detecting liver fibrosis of FibroScan compared with APRI and FIB4 indices versus liver biopsy in patients with liver disease in Bogota.

Materials and Methods

Retrospective cohort study, cross-sectional, consecutive sampling, performed in the period 2019-2022, the APRI, FIB4 and Fibroscan indices were compared with the biopsy result, the diagnostic accuracy measures for APRI, FIB4 and FibroScan were described and an area under the curve analysis (ACOR) was performed.

Results

Biopsy was positive for fibrosis in 40%, FibroScan showed excellent performance for detecting fibrosis, with an ACOR of 0.90 (CI: 0.83 - 0.97), APRI indices of 0.52 (CI: 0.35- 0.68) and FIB4 of 0.52 (CI:0.37 - 0.68).

Conclusions

FibroScan is a useful tool for the diagnosis and follow-up of chronic liver disease, it should be used in combination with other diagnostic tests and clinical evaluation. FibroScan showed excellent performance in discriminating patients with liver fibrosis compared to APRI and FIB4 indices and is better at detecting advanced stages.

Introduction and Objectives

Chronic liver diseases (CLD) are a major global health burden and are the 11th leading cause of death and the 15th cause of morbidity worldwide. CLD could be associated with steatosis and fibrosis and progress to cirrhosis, with the concomitant liver failure. Currently, there is no approved treatment and it is only recommended to eliminate the causative agent or give palliative treatments. The immune response, particularly hepatic macrophages (Kupffer cells), play a fundamental role in the development of liver disease. It is known that well-differentiated populations coexist in the liver, including: F4/80+CD11b- (sessile) and F4/80+CD11b+ (migrated from bone marrow). These populations could be modified their phenotype from M1 (inflammatory) to M2 (anti-inflammatory), which is of pharmacological interest. We aimed to study the administration of Maresin-1, a derivative of omega-3 fatty acids, promote a restorative state by an increase in the CD206+CD86-CD11c- i.e. M2 Kupffer cell population.

Materials and Methods

male C57bl/c mice were subjected to liver fibrosis by i.p diethylnitrosamine (DEN) 50 mg/kg twice a week and treated with MaR1 (4ng/g) for 9 weeks. The liver macrophages were isolated: real-time qPCR flow and cytometry were made. In addition, MaR1 was administered to healthy mice to observe the role MaR1 on hepatic macrophage populations.

Results

The administration of MaR1 modifies the Kupffer cells populations, generating an increase in the subpopulations of M2 F4/80+CD11b-CD206+ and F4/80intCD11b+CD206+, with a decrease in the CD86+CD11c+, both in the fibrosis as in healthy mice. This was accompanied by an increase in IL-10 cytokines and a fall in TNF-a values.

Conclusions

Taken together, these results indicate that Mar1 switches the Kupffer cells towards an anti-inflammatory, restorative and resolving state, acting as a hepatoprotective agent.

Introduction and Objectives

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide. We aimed to explore HCC-related population-wide public health policies (PHP) worldwide.

Materials and Methods

We conducted a 43-item survey about HCC: policies and civil society (18 questions), clinical guidelines (5 questions), epidemiology (7 questions), and care management (13 questions). The survey was completed electronically (2022–2023). Data were collected in a spreadsheet, revised by two independent reviewers, and verified with governmental institutions, regulatory agencies, scientific societies, and scientific publications. We classified policies into eight dimensions, including criteria for low, moderate, and strong PHP establishment. We estimated an index using multiple correspondence analysis.

Results

We obtained 134 responses from 66 countries/territories (Africa N=16, the Americas N=18, Asia N=10, Europe N=21, and Oceania N=1). The median index was 43.7 [IQR: 30.9–59.3]. The lower scores were observed in Sierra Leone (0), Lebanon (5.5), and Pakistan (5.5), while Italy (79.7), Brazil (94.1), and Sweden (100) obtained the highest scores (Figure). In particular, 46 (69.7%) countries had a written national cancer strategy or action plan, but only 5 (7.6%) had a specific written national strategy or action plan on HCC. Thirty-two (48.5%) countries had national clinical practice guidelines on HCC and 54 (81.8%) countries had a national disease registry that included HCC. The most common strategies for staging HCC were Barcelona Clinic Liver Cancer (BCLC)(85%) and TNM classification (10%). The survey reflects important differences in the availability of treatments, including surgery (98.4%), tyrosine kinase inhibitors (95.1%), chemoembolization (85.2%), radiofrequency or alcohol ablation (82%), immunotherapy plus anti-VEGF (82%), liver transplant (74.2%), stereotactic body radiation therapy (42.6%), and radioembolization (36.4%).

Conclusions

The existence of PHP on HCC is insufficient worldwide. The most common strategy for staging is BCLC, but there are important differences in treatment availability across countries, especially regarding curative therapies.

Introduction and Objectives

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Reliable knowledge of the prevalence of occult CAD, particularly anatomically confirmed CAD is limited and cardiovascular risk (CVR) models only predict the risk of an acute coronary event within a set period. It has been described that a FIB-4 score is associated with a higher CVR. Determine what is the utility of noninvasive markers of liver fibrosis in CAD.

Materials and Patients

A cross-sectional study was conducted in two tertiary centers in central and western Mexico from March 2019 to April 2023. Patients who required percutaneous coronary angiography were studied and demographic data and coronary angiographic were recorded. Noninvasive fibrosis indexes were calculated. Continuous variables were subjected to a distribution analysis and equality of variances to subsequently perform a mean comparison analysis with U-Mann-Whitney test between patients with monovascular, bivascular and trivascular involvement. A correlation analysis was also performed between the invasive markers and the Syntax index.

Results

A total of 168 patients were included with a mean age of 66 ± 12 years with a predominance of male sex with 75.6% (n= 127). Angiographic findings included 37.5%, monovascular, 32.7%, bivascular and 29.8% trivascular involvement. Comparison of means of noninvasive markers of fibrosis demonstrated a significant difference in HFS between patients with monovascular (0.17 ± 0.18), bivascular (0.27 ± 0.18) and trivascular (0.30 ± 0.25) coronary artery disease, p=< 0.001. A correlation was also demonstrated between non-invasive markers and Syntax score: FIB-4 (r=: 820, p=<0.001), APRI (r=: 766, p=<0.001), HFS (r= 869, p=<0.001), (r= 820, p=<0.001), NFS (r= 807 p=<0.001)

Conclusions

The score of noninvasive tools to assess liver fibrosis correlates positively with the complexity of CAD and could be considered as noninvasive tools to be used in the assessment CVR.

Introduction and Objectives

Metabolic Dysfunction-associated Fatty Liver Disease (MAFLD) has been recognized as the hepatic component of metabolic syndrome and has become a growing public health concern. Early and accurate detection of MAFLD is crucial for implementing appropriate intervention strategies and preventing progression to serious complications such as liver cirrhosis. We aimed to describe the diagnostic performance of the Hepatic Steatosis Index (HSI) in subjects with MAFLD and compare it with the Homeostatic Model Assessment of Insulin Resistance (HOMA), Waist-to-Hip Ratio (WHR), and Visceral Fat (SECA).

Materials and Methods

Retrospective design study. Bioanthropometric, clinical, and biochemical variables were collected. The HSI was calculated using the formula HSI = 8 * ALT/AST + BMI + 2 (if diabetic) + 2 (if female). ROC curves and their areas were generated. Statistical significance was determined at p < 0.05.

Results

A total of 585 subjects were evaluated, of whom 279 were classified with MAFLD (65.5% females) and 306 without MAFLD (76.8% females). Subjects with MAFLD exhibited higher values of age, BMI, WHR, HOMA, CAP, and HSI (Table 1). The HSI showed a diagnostic performance with an area under the curve (AUC) of 0.80. A cutoff point of 39.9 was established for the HSI, with a sensitivity of 63%, specificity of 74%, positive predictive value (PPV) of 73%, and negative predictive value (NPV) of 64%. The HSI demonstrated superior diagnostic performance compared to visceral fat (0.70), HOMA (0.70), and WHR (0.66) (Fig 1).

Conclusions

The results of this study demonstrate that HOMA, visceral fat, and ICC can be useful as screening strategies in MAFLD. However, the Hepatic Steatosis Index (HSI) showed superior diagnostic performance compared to the other evaluated biomarkers. Therefore, it is suggested that HSI be considered a useful diagnostic tool in MAFLD.

Introduction and Objectives

Hepatocellular carcinoma represents the most frequent malignant tumor of the liver, being the 5th most frequent cancer in men and the 7th in women worldwide; it is the 3rd cause of death from cancer in the world. To present a case of hepatocellular carcinoma presenting with gastrointestinal bleeding.

Materials and Patients

A 39-year-old female began her condition two days ago with the presence of hematemesis, accompanied by nausea, asthenia, and adynamia. On examination, icteric conjunctivae, globose abdomen, with the presence of abdominal distension, grade I ascites. Edema in the lower limbs +. Liver ultrasound with liver nodular lesions, chronic lithiasic cholecystitis, and free fluid in the abdominopelvic cavity. A simple and contrasted CT scan of the abdomen is requested with the presence of tumor activity at the level of the liver, portal thrombosis, free fluid in the abdominal cavity, and marginal T12-L1 osteocytes.

Results

We proceeded to perform sclerotherapy of esophageal varices and ligatures. Later, alpha-fetoprotein was requested, which reports 3680 ng/ml. The diagnosis of hepatocarcinoma was established and he was referred to the oncology service.

Conclusions

The best results are obtained with multidisciplinary teams for the diagnosis and treatment of this disease.

Introduction and Objectives

Worldwide, cirrhosis secondary to the hepatitis C virus is the first indication for liver transplantation. In Mexico, alcohol abuse, viral hepatitis, and obesity are the highlighted causes. Hepatitis C virus (HCV) eradication leads to reduced morbidity, mortality and transmission. Hemodialysis users are a high-risk group with high prevalence of HCV. The aim of this study was to identify patients with liver damage in hemodialysis users and their relationship with viral hepatitis, diagnosis, and management.

Materials and Patients

We reviewed the electronic medical records of hemodialysis users from January 1, 2017, to December 31, 2019. All patients who underwent at least one hemodialysis procedure were included. We used descriptive statistics with the SPSS v21 program.

Results

We analyzed 362 patients, 57% of whom were men, with a mean age of 52. The most frequent etiology attributable to kidney damage was hypertension 96% and diabetes mellitus 59%. The mean time on hemodialysis was 19 months. The biochemical and serological characteristics of the group are show in Table 1. We found forty-seven patients with transaminasemia, of which thirteen had liver cirrhosis, evaluated by FIB4/APRI. A viral load was requested for hepatitis C in only one patient, with a positive result, who received treatment with glecaprevir/pibrentasvir for 12 weeks without complications. Retrospective review limits us in identifying the cause for which the patients did not undergo molecular tests for hepatitis B and C. These patients have significant depression of immunity with negative serology on the presence of viral replication “hidden infection.”

Conclusions

Hemodialysis users should be exhaustively studied, and molecular tests should be performed on suspicion of viral hepatitis.

Introduction and Objectives

: Metabolic alterations and alcohol consumption are the most common etiological agents related to hepatic steatosis (HS) development. There is little evidence that shows the effects generated by synergy of both etiologic agents. N-acetyl cysteine (NAC) is a drug whose efficacy in the early stages of SH, generated by a hypercaloric diet plus alcohol consumption, is unknown.

The aim of this work was to evaluate NAC effects on oxidative stress, and metabolic alterations induced in HS experimentally induced by chronic ethanol consumption plus a hypercaloric diet.

Materials and Patients

C57BL/6J mice (n=4) grouped into 1) Control; 2) HF/OH, administrated with hypercaloric diet and ethanol; 3) HF/OH+NAC, same treatments of group 2 plus NAC. Serum markers of liver damage and anorexigenic and orexigenic adipokines were evaluated; oxidative stress markers in liver samples were analyzed; finally, a H&E stain was performed. This project was conducted in accordance with the guidelines of the University of Guadalajara under the approval number of the bioethics, research, and ethics research committees CI-02920.

Results

NAC prevents weight gain and metabolic alterations generated by concomitant consumption of a hypercaloric diet and alcohol; this drug improves changes in anorexigenic and orexigenic adipokines such as leptin, ghrelin, resistin, GLP-1, and modulates total, HDL, and LDL cholesterol levels. On the other hand, NAC reduces CYP2E1 and alcohol dehydrogenase expression, as well as the oxidative environment induced by both etiological agents, by avoiding an increase in malondialdehyde levels, promoting Nrf2 transcription factor expression and superoxide dismutase; also preventing an increase in the expression of Catalase. Finally, H&E staining showed that NAC prevents the development of tissue alterations in the liver parenchyma generated by the consumption of a hypocaloric diet plus alcohol.

Conclusions

In this work, we demonstrate that NAC prevents metabolic alterations and oxidative damage related to early phases of HS induced by concomitant consumption of alcohol plus a hypercaloric diet. These effects would slow down the development of more severe stages of this disease.