Risk Of Liver Fibrosis Progression Research Articles

The Link between Abdominal Obesity Indices and the Progression of Liver Fibrosis: Insights from a Population-Based Study.

There is currently no available information on the correlation between abdominal obesity indices and the risk of liver fibrosis progression. We aimed to investigate the relationship between the body mass index (BMI), waist circumference (WC), and the visceral adiposity index (VAI) with the progression of liver fibrosis. The study also evaluated the association between these indices and the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and liver fibrosis. A total of 1403 subjects participated in the cross-sectional and longitudinal population-based study. Liver stiffness was assessed via transient elastography, at baseline and follow-up (median: 4.2 years). The subgroup with dysglycemia was also analyzed. In the cross-sectional study, the highest quartile of VAI, BMI ≥ 30 kg/m2, and abdominal obesity showed significant associations with the prevalence of MASLD and liver fibrosis, as well as with fibrosis progression. However, VAI showed no association with MASLD incidence. Among the dysglycemic subjects, there was no observed association between VAI and the incidence of MASLD or the progression of fibrosis. In conclusion, the BMI, WC, and the VAI are associated with an increased risk of progression to moderate-to-advanced liver fibrosis in the general population. However, the VAI does not perform better than the BMI and WC measurement.

The Janus of a disease: Diabetes and metabolic dysfunction-associated fatty liver disease

Metabolic Dysfunction-Associated Fatty Liver Disease and Diabetes Mellitus are two prevalent metabolic disorders that often coexist and synergistically contribute to the progression of each other. Several pathophysiological pathways are involved in the association, including insulin resistance, inflammation, and lipotoxicity, providing a foundation for understanding the complex interrelationships between these conditions. The presence of MASLD has a significant impact on diabetes risk and the development of microvascular and macrovascular complications, and diabetes significantly contributes to an increased risk of liver fibrosis progression in MASLD and the development of hepatocellular carcinoma. Moreover, both pathologies have a synergistic effect on cardiovascular events and mortality.Therapeutic interventions targeting MASLD and diabetes are discussed, considering lifestyle modifications, pharmacological agents, and emerging treatment modalities. The review also addresses the challenges in managing these comorbidities, such as the need for personalized approaches and the potential impact on cardiovascular health. The insights gleaned from this analysis can inform clinicians, researchers, and policymakers in developing integrated strategies for preventing, diagnosing, and managing these metabolic disorders.

RESULTS OF ANTIFIBROTIC THERAPY IN PATIENTS WITH CHRONIC HEPATITIS B+C

Modern antiviral therapy regimens for patients with chronic viral hepatitis aim to achieve either long-term suppression of pathogen replication (e.g., nucleoside analogs in chronic hepatitis B) or complete elimination of the virus (such as direct-acting antiviral drugs in chronic hepatitis C). However, antiviral agents do not have a significant impact on the complete restoration of biochemical processes or the prevention of further progression of morphological changes in the liver. These limitations emphasize the ongoing need for new therapeutic strategies that target the processes of fibrogenesis.
 The aim of the work is to assess the possibility of the effect of the drug "Bicyclol" on fibrotic changes in patients with chronic hepatitis B+C using a non-invasive scale of the rate of fibrosis.
 Materials and methods
 An analysis of the dynamics of 62 patients with chronic hepatitis B and C (HCV+C) was conducted. All patients received long-term antiviral therapy consisting of pegylated interferon for 48 weeks. In the main group (Group I), patients with chronic hepatitis B and C were prescribed the drug "Bicyclol" after completing antiviral treatment with interferon. The control group (Group II) followed the principles of proper nutrition and took traditional hepatoprotectors. Based on the identified correlations, a non-invasive scale was proposed to assess the individual risk of liver fibrosis progression.
 Research results
 Against the background of the use of an antiviral treatment regimen, the normalization of cytolysis indicators was observed in most patients with CHB+C, but in some patients it was short-lived. Treatment with the drug "Bicyclol" contributed to a further decrease in cytolysis indicators, in the vast majority of patients with CHB+C, the activity of ALT and AST reached the upper limit of the norm. In patients with CHB+C who received only basic treatment without an antifibrotic component, a tendency to maintain an elevated level of transaminases was observed.
 Conclusions.
 Thus, the use of the hepatoprotector "Bicyclol" for 12 months ensures a decrease in cytolysis in the liver, is accompanied by a decrease in the severity of fibrosis, and in some patients - its reverse development. The use of the proposed prognostic scale makes it possible to assess the need for early appointment of antifibrotic therapy.

Identifying a distinct fibrosis subset of NAFLD via molecular profiling and the involvement of profibrotic macrophages

BackgroundThere are emerging studies suggesting that non-alcoholic fatty liver disease (NAFLD) is a heterogeneous disease with multiple etiologies and molecular phenotypes. Fibrosis is the key process in NAFLD progression. In this study, we aimed to explore molecular phenotypes of NAFLD with a particular focus on the fibrosis phenotype and also aimed to explore the changes of macrophage subsets in the fibrosis subset of NAFLD.MethodsTo assess the transcriptomic alterations of key factors in NAFLD and fibrosis progression, we included 14 different transcriptomic datasets of liver tissues. In addition, two single-cell RNA sequencing (scRNA-seq) datasets were included to construct transcriptomic signatures that could represent specific cells. To explore the molecular subsets of fibrosis in NAFLD based on the transcriptomic features, we used a high-quality RNA-sequencing (RNA-seq) dataset of liver tissues from patients with NAFLD. Non-negative matrix factorization (NMF) was used to analyze the molecular subsets of NAFLD based on the gene set variation analysis (GSVA) enrichment scores of key molecule features in liver tissues.ResultsThe key transcriptomic signatures on NAFLD including non-alcoholic steatohepatitis (NASH) signature, fibrosis signature, non-alcoholic fatty liver (NAFL) signature, liver aging signature and TGF-β signature were constructed by liver transcriptome datasets. We analyzed two liver scRNA-seq datasets and constructed cell type-specific transcriptomic signatures based on the genes that were highly expressed in each cell subset. We analyzed the molecular subsets of NAFLD by NMF and categorized four main subsets of NAFLD. Cluster 4 subset is mainly characterized by liver fibrosis. Patients with Cluster 4 subset have more advanced liver fibrosis than patients with other subsets, or may have a high risk of liver fibrosis progression. Furthermore, we identified two key monocyte-macrophage subsets which were both significantly correlated with the progression of liver fibrosis in NAFLD patients.ConclusionOur study revealed the molecular subtypes of NAFLD by integrating key information from transcriptomic expression profiling and liver microenvironment, and identified a novel and distinct fibrosis subset of NAFLD. The fibrosis subset is significantly correlated with the profibrotic macrophages and M2 macrophage subset. These two liver macrophage subsets may be important players in the progression of liver fibrosis of NAFLD patients.

FibroScan Predicts Liver Fibrosis Progression in Chronic HBV Infection Patients with No Clear Indication for Antiviral Therapy: A Retrospective Cohort Study.

Chronic hepatitis B virus (HBV) infection patients who do not fulfill the typical treatment indications should be followed up. This study aimed to evaluate the risk of liver fibrosis progression (LFP) and assess the role of noninvasive tests (NITs) of liver fibrosis in monitoring LFP in these patients. A total of 116 patients with active HBV replication, persistently normal or minimally elevated alanine aminotransferase (ALT) levels, and no or mild hepatic necroinflammation or fibrosis based on liver biopsy tests at baseline and followed by a repeated liver biopsy assessment during follow-up. LFP was defined as increase in METAVIR fibrosis score by 1 score or more. Among 116 patients, 40 (34.5%) progressed by at least one fibrosis stage, 16 (13.8%) progressed by at least two fibrosis stages at a median follow-up interval of 27 months (IQR: 12-36). Multivariate analysis confirmed the significant association of an increase in liver stiffness measurement (LSM) value with LFP on histology (p =0.005). The AUROC of LSM value increase rate is significantly higher than that of serum-based NITs of liver fibrosis for the prediction of LFP (p < 0.05). An increase in LSM by 20% is the optimal cutoff for the prediction of LFP. LFP is non-negligible in patients with active HBV replication, persistently normal or minimally elevated ALT, and initially no or minimal hepatic necroinflammation or fibrosis. Serial LSM tests would be more reliable in identifying LFP than serum-based NITs, and easier to obtain than serial liver biopsy tests.

Оценка некоторых предикторов прогрессирования фиброза печени у больных гепатитом С после успешной элиминации вируса

Objective. To determine environmental and genetic factors associated with fibrosis progression after virus elimination as a result of direct-acting antiviral therapy by follow-up dispensary observation of patients with chronic hepatitis C with moderate and severe liver fibrosis (F2–F3 according to the METAVIR scoring system). Patients and methods. This study included 301 patients (166 men and 135 women) aged 20-64 years with chronic hepatitis C virus (HCV). A sustained virologic response was achieved in all patients after therapy with direct-acting antiviral agents. Patients were followed up for an average of 38 weeks (16–64). Patients were divided into two groups in order to perform comparative evaluation: group I included 257 patients with regression of liver fibrosis and group II – 44 patients with progression of liver fibrosis. Questionnaire and clinical and laboratory data were assessed. In addition, genetic studies of 24 singlenucleotide polymorphisms of genes involved in intracellular immune signaling pathway activation, interferon synthesis, metabolic regulation and cell proliferation were performed in both groups. Results. It was revealed that validated predictors of liver fibrosis progression in patients with chronic HCV after successful virus elimination as a result of therapy with direct-acting antiviral agents are the presence of concomitant type 2 diabetes mellitus, low ALT activity and serum osteopontin levels over 80 ng/mL at the beginning of therapy. Genetic predisposition to liver fibrosis progression is mediated by carriage of the AA genotype of HNF4α rs4812829 (OR = 3.55; 95% CI 1.21–10.41; p = 0.015). Additionally, the G-allele of NAT2 rs1495741, which marks fast xenobiotic acetylation, was found to have protective properties in the dominant genetic model. Carriers of GG- and GA-genotypes had an almost 2-fold lower risk of liver fibrosis progression after antiviral therapy than AA-genotype carriers (OR = 0.49; 95% CI 0.25–0.94; p = 0.029). Conclusion. The risk after successful hepatitis C virus elimination is significantly higher in patients with concomitant type 2 diabetes mellitus. ALT activity and serum osteopontin levels at the beginning of therapy can be estimated as predictors of liver fibrosis progression among laboratory parameters. Moreover, some genetic markers in the form of single-nucleotide polymorphisms of the HNF4α and NAT2 genes were established, which can be used to predict the development of liver fibrosis in patients with hepatitis C after therapy with direct-acting antiviral agents. Key words: hepatitis C, liver fibrosis, predictors, risk factors, diabetes mellitus, osteopontin, single-nucleotide polymorphisms, HNF4α gene, NAT2 gene

Non-invasive diagnosis of nonalcoholic fatty liver disease in patients with type 2 diabetes.

Liver disease has emerged as a significant cause of death in people with type 2 diabetes (T2D). Due to a common underlying pathogenic mechanism, namely insulin resistance, T2D represents the main risk factor for nonalcoholic fatty liver disease (NAFLD), characterized by a buildup of fat in the liver. Globally, NAFLD is the most common liver disease, affecting a quarter of the general adult population. The development of nonalcoholic steatohepatitis (NASH) signifies an increased risk of liver fibrosis progression that can result in cirrhosis, hepatocellular carcinoma (HCC), and death. Liver fibrosis progression and development of cirrhosis is mostly asymptomatic until complications from decompensated end-stage liver disease arise. Traditionally, liver biopsy is used to diagnose NASH and stage fibrosis, however, it is invasive and costly. Non-invasive diagnostic alternatives include serum biomarkers and imaging techniques. Early identification of advanced liver fibrosis is pivotal to prompt initiation of targeted surveillance, including screening for HCC, as well as providing options for current and investigational therapeutic interventions to reduce fibrosis progression. This review gives an update on non-invasive diagnostic tools for NAFLD and liver fibrosis in the specific context of T2D, providing clinicians a pragmatic diagnostic approach to this frequent comorbidity in diabetes medicine.

Chitinase 3-like 1 is a profibrogenic factor overexpressed in the aging liver and in patients with liver cirrhosis

Older age at the time of infection with hepatitis viruses is associated with an increased risk of liver fibrosis progression. We hypothesized that the pace of fibrosis progression may reflect changes in gene expression within the aging liver. We compared gene expression in liver specimens from 54 adult donors without evidence of fibrosis, including 36 over 40 y old and 18 between 18 and 40 y old. Chitinase 3-like 1 (CHI3L1), which encodes chitinase-like protein YKL-40/CHI3L1, was identified as the gene with the greatest age-dependent increase in expression in liver tissue. We investigated the cellular source of CHI3L1 in the liver and its function using liver tissue specimens and in vitro models. CHI3L1 expression was significantly higher in livers of patients with cirrhosis of diverse etiologies compared with controls represented by patients who underwent liver resection for hemangioma. The highest intrahepatic CHI3L1 expression was observed in cirrhosis due to hepatitis D virus, followed by hepatitis C virus, hepatitis B virus, and alcohol-induced cirrhosis. In situ hybridization of CHI3L1 messenger RNA (mRNA) identified hepatocytes as the major producers of CHI3L1 in normal liver and in cirrhotic tissue, wherein hepatocytes adjacent to fibrous septa showed higher CHI3L1 expression than did those in more distal areas. In vitro studies showed that recombinant CHI3L1 promotes proliferation and activation of primary human hepatic stellate cells (HSCs), the major drivers of liver fibrosis. These findings collectively demonstrate that CHI3L1 promotes liver fibrogenesis through a direct effect on HSCs and support a role for CHI3L1 in the increased susceptibility of aging livers to fibrosis progression.

MTHFR rs1801133 Polymorphism Is Associated With Liver Fibrosis Progression in Chronic Hepatitis C: A Retrospective Study.

Background: The MTHFR (methylenetetrahydrofolate reductase) rs1801133 polymorphism leads to higher circulating levels of homocysteine, which is related to several liver diseases. We aimed to evaluate the relationship between MTHFR rs1801133 polymorphism and liver fibrosis progression in HCV-infected patients.Methods: We conducted a preliminary retrospective cohort study in 208 non-cirrhotic HCV-infected patients. These subjects had at least two liver stiffness measurements (LSM), which were assessed using transient elastography, and no patient had cirrhosis at baseline. We analyzed the association between MTHFR rs1801133 and outcome variables using Generalized Linear Models.Results: HCV-infected patients were 47 years old, around 54% were males, a low frequency of high alcohol intake (13.5%) or prior use of intravenous drugs (10.1%). A total of 26 patients developed cirrhosis (LSM1 ≥ 12.5) during a median follow-up of 46.6 months. The presence of the rs1801133 C allele showed an inverse association with the LSM2/LSM1 ratio (adjusted AMR = 0.90; 95%CI = 0.83–0.98; p = 0.020) and the cirrhosis progression (adjusted OR = 0.43; 95%CI = 0.19–0.95; p = 0.038). Besides, rs1801133 CT/CC genotype had an inverse association with the LSM2/LSM1 ratio (adjusted AMR = 0.80; 95%CI = 0.68–0.95; p = 0.009) and the cirrhosis progression (adjusted OR= 0.21; 95%CI = 0.06–0.74; p = 0.015).Conclusions: MTHFR rs1801133 C allele carriers presented a diminished risk of liver fibrosis progression and development of cirrhosis than rs1801133 T allele carriers. This statement supports the hypothesis that MTHFR rs1801133 polymorphism appears to play a crucial role in chronic hepatitis C immunopathogenesis.

Evolution of liver fibrosis and steatosis markers in patients with type 2 diabetes after metformin treatment for 2 years.

Type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) share pathophysiological mechanism. Metformin is a widely used first-line anti-diabetic drug. We investigated the evolution of liver fibrosis and steatosis during 2-year use of metformin in patients with T2DM. Between 2006 and August 2010, patients newly diagnosed with T2DM who received metformin as the first-line treatment were recruited. Fibrosis-4 index (FIB-4) > 2.67 and hepatic steatosis index (HSI) > 36.0 was used to define advanced liver fibrosis and fatty liver, respectively. A total of 1292 (mean age 60.8 years, 57% men and 43% women) patients were recruited. The mean FIB-4 and HSI scores were 1.38 and 27.3, respectively. At enrollment, 83 (6.4%) patients had advanced liver fibrosis and 429 (33.2%) had fatty liver. After 2 years of metformin treatment, the mean FIB-4 score increased from 1.38 to 1.51 (p < 0.001), whereas the mean HSI score decreased from 27.3 to 26.5 (p < 0.001). During follow-up, advanced liver fibrosis additionally developed in 52/1209 (4.3%) patients, whereas 48/83 (57.8%) experienced fibrosis regression. Older age (odds ratio [OR] = 1.007), lower platelet count (OR = 0.993), and lower serum albumin (OR = 0.325) were independently associated with the increased risk of advanced liver fibrosis development after 2-years of metformin treatment. In our cohort of patients with metformin treatment, a small proportion of patients developed liver fibrosis and steatosis after 2 years. Optimized follow-up strategy is required according to different risk of liver fibrosis progression in patients with T2DM.

Patients with suboptimal hepatitis B virus diagnostic characterization are at risk of liver fibrosis progression.

Many patients with chronic hepatitis B virus infection remain infradiagnosed and untreated. In a national health system with unrestricted access to treatment, our aims were to assess the level of compliance with clinical guidelines and the characteristics and risk of fibrosis progression in patients with suboptimal diagnosis. In a cohort of patients with positive hepatitis B surface antigen from January 2011 to December 2013, data were registered to assess characteristics and compliance with guidelines. For assessing the risk of liver fibrosis, positive hepatitis B surface antigen patients from January 2008 to December 2013 were grouped depending on DNA request. Liver fibrosis was estimated by serological scores. Of 41 158 subjects with hepatitis B surface antigen request, 351 (0.9%) tested positive, and DNA was not available from 110 patients (66.4% male, mean 42.4 ± 14.5 years) after a median of 25.6 months (range 12.0-43.5). Most of these patients (76%) were assessed by primary care. Half of the patients (47.2%) showed hypertransaminasemia, at least significant fibrosis, or both conditions. After long follow-up (mean 90.1 ± 45.2 months), these patients had a higher risk of achieving at least significant fibrosis during follow-up (log-rank 8.73; P = 0.003). In more than one-third of patients with positive hepatitis B surface antigen, DNA was not requested despite showing hypertransaminasemia and significant fibrosis. Patients without DNA request are at high risk of liver fibrosis progression. Thus, educational measures and other strategies are necessary, especially targeting primary care, to improve access to treatment.

Dyslipidemia as a risk factor for liver fibrosis progression in a multicentric population with non-alcoholic steatohepatitis

Background: Nonalcoholic fatty liver disease (NAFLD) is a serious worldwide health problem, with an estimated global prevalence of 24%; it has a notable relationship with other metabolic disorders, like obesity and type 2 diabetes mellitus (T2DM). Nonalcoholic steatohepatitis (NASH) is one of the most important clinical entities of NAFLD, which is associated with an increased risk of progression to liver cirrhosis and hepatocellular carcinoma (HCC). Mexico is one of the countries with the highest prevalence of metabolic diseases; therefore, we sought to investigate the impact that these clinical entities have in the progression to advanced fibrosis in Mexican patients with NASH. Methods: We performed a multicenter retrospective cross-sectional study, from January 2012 to December 2017. A total of 215 patients with biopsy-proven NASH and fibrosis were enrolled. NASH was diagnosed according NAS score and liver fibrosis was staged by the Kleiner scoring system. For comparing the risk of liver fibrosis progression, we divided our sample into two groups. Those patients with stage F0-F2 liver fibrosis were included in the group with non-significant liver fibrosis (n=178) and those individuals with F3-F4 fibrosis were included in the significant fibrosis group (n=37). We carried out a multivariate analysis to find risk factors associated with liver fibrosis progression. Results: From the 215 patients included, 37 had significant liver fibrosis (F3-4). After logistic regression analysis T2DM (p=0.044), systemic arterial hypertension (p=0.014), cholesterol (p=0.041) and triglycerides (p=0.015) were the main predictor of advanced liver fibrosis. Conclusions: In a Mexican population, dyslipidemia was the most important risk factor associated with advanced liver fibrosis and cirrhosis.

PNPLA3 rs738409 C >G variant is associated with a higher risk of liver fibrosis progression assessed by FIB-4 and stiffness by fibroscan in patients with non-alcoholic fatty liver disease

Background&Aims: A single nucleotide polymorphism in patatin-like phospholipase domain-containing-3(PNPLA3) gene has been associated with a higher prevalence of NASH and severity of fibrosis, hepatocellular carcinoma and liver decompensation, but there are no data from prospective studies about fibrosis progression with this polymorphism.We investigated whether in NAFLD,PNPLA3rs738409 variant associates with fibrosis progession evaluated by noninvasive tools like FIB-4 and liver stiffness measurement(LSM) by FibroScan.

Dyslipidemia as a risk factor for liver fibrosis progression in a multicentric population with non-alcoholic steatohepatitis.

Background: Nonalcoholic fatty liver disease (NAFLD) is a serious worldwide health problem, with an estimated global prevalence of 24%; it has a notable relationship with other metabolic disorders, like obesity and type 2 diabetes mellitus (T2DM). Nonalcoholic steatohepatitis (NASH) is one of the most important clinical entities of NAFLD, which is associated with an increased risk of progression to liver cirrhosis and hepatocellular carcinoma (HCC). Mexico is one of the countries with the highest prevalence of metabolic diseases; therefore, we sought to investigate the impact that these clinical entities have in the progression to advanced fibrosis in Mexican patients with NASH. Methods: We performed a multicenter retrospective cross-sectional study, from January 2012 to December 2017. A total of 215 patients with biopsy-proven NASH and fibrosis were enrolled. NASH was diagnosed according NAS score and liver fibrosis was staged by the Kleiner scoring system. For comparing the risk of liver fibrosis progression, we divided our sample into two groups. Those patients with stage F0-F2 liver fibrosis were included in the group with non-significant liver fibrosis (n=178) and those individuals with F3-F4 fibrosis were included in the significant fibrosis group (n=37). We carried out a multivariate analysis to find risk factors associated with liver fibrosis progression. Results: From the 215 patients included, 37 had significant liver fibrosis (F3-4). After logistic regression analysis T2DM (p=0.044), systemic arterial hypertension (p=0.014), cholesterol (p=0.041) and triglycerides (p=0.015) were the main predictor of advanced liver fibrosis. Conclusions: In a Mexican population, dyslipidemia was the most important risk factor associated with advanced liver fibrosis and cirrhosis.

Polymorphisms of Antioxidant System Genes in HCV Infection and Their Role in the Development of Chronic Hepatitis C

To study the contribution of polymorphic variants of antioxidant system enzyme genes to the susceptibility to chronic hepatitis C (CHC) and to elicit their associative relationships with a clinical course of the disease. Single nucleotide polymorphisms (SNPs) of antioxidant enzymes genes, superoxide dismutase SOD2 (rs4880, C47T), and catalase CAT (rs1001179, G262A) were studied in 100 patients with CHC, 86 “anti-HCV carriers,” and 64 healthy individuals. The study involved a genomic DNA analysis with the use the diagnostic kit “SNP Screen.” DNA was extracted from samples collected from the cheek epithelium. There was a statistically significant relationship between CAT SNPs (rs1001179, G262A) and a high risk of chronic hepatitis C. It has been found that the presence of the CAT gene (G262A) G allele increases the susceptibility to chronic hepatitis C. Patients with the CAT SNP (G262A) G allele (GG and GA genotypes) had significantly higher ALT levels than those with the A allele (AA genotype). The study has demonstrated that CHC patients with the CAT SNP (G262A) G allele (G/G G/A genotype) had a significantly higher risk of liver fibrosis progression as compared with those with the A/A genotype. Thus, with hepatitis C virus infection, polymorphic variants of CAT genes (G262A) are risk factors for the development of chronic hepatitis C and affect a clinical course of the disease, including the development of hepatic cytolysis, and as a result, the formation of liver fibrosis. The roles of genes polymorphisms coding for the anti-oxidant enzyme which play a role in the development of CHC were evaluated. The G/A genotype of CAT SNP (rs1001179, G262A) is a genetic risk factor for the development of chronic hepatitis C, with the G/G genotype of CAT SNP (rs1001179, G262A) being a risk factor for liver fibrosis.

Impact of DARC rs12075 Variants on Liver Fibrosis Progression in Patients with Chronic Hepatitis C: A Retrospective Study.

The Duffy antigen receptor for chemokines (DARC) rs12075 polymorphism regulates leukocyte trafficking and proinflammatory chemokine homeostasis. Hepatitis C virus (HCV)-mediated liver fibrosis is associated with an uncontrolled inflammatory response. In this study, we evaluate the association between the DARC rs12075 polymorphism and liver stiffness progression in HCV-infected patients. We carried out a retrospective cohort study (repeated measures design) in 208 noncirrhotic patients with chronic hepatitis C (CHC) who had at least two liver stiffness measurements (LSM) with a separation of at least 12 months. We used generalized linear models to analyze the association between DARC rs12075 polymorphism and outcome variables. During a follow-up of 46.6 months, the percentage of patients with stages of fibrosis F0/F1 decreased (p < 0.001), while LSM values and the percentage of patients with cirrhosis increased (p < 0.001). This pattern of changes was maintained in each of the groups of patients analyzed according to their rs12075 genotypes (AA or AG/GG). However, the variations in liver stiffness characteristics were lower in patients with the rs12075 AG/GG genotype (AG/GG versus AA). Thereby, in the adjusted analysis, patients with the rs12075 AG/GG genotype had a lower risk of an increased value of LSM2/LSM1 arithmetic mean ratio (AMR = 0.83; p = 0.001) and of an increase in LSM ≥ 5 kPa (odds ratio (OR) = 0.28; p = 0.009). Besides, patients with rs12075 AG/GG had a lower risk of cirrhosis progression (OR = 0.24; p = 0.009). No significant associations were found for an increase in LSM ≥ 10 kPa. We found an association between the DARC rs12075 single nucleotide polymorphism (SNP) and CHC progression. Specifically, patients with the DARC rs12075 AG/GG genotype had a lower risk of liver fibrosis progression and development of cirrhosis.

The Myeloid-Epithelial-Reproductive Tyrosine Kinase (MERTK) rs4374383 Polymorphism Predicts Progression of Liver Fibrosis in Hepatitis C Virus-Infected Patients: A Longitudinal Study.

Background: The myeloid-epithelial-reproductive tyrosine kinase (MERTK) is involved in hepatic steatosis, inflammation, and liver fibrosis. Here we evaluated the association between the MERTK rs4374383 single nucleotide polymorphism (SNP) and liver fibrosis progression in hepatitis C virus (HCV)-infected patients. Methods: We performed a retrospective study (repeated measures design) in 208 patients who had liver stiffness measurement (LSM), which was assessed using transient elastography. No patient had cirrhosis at baseline (LSM ≥ 12.5 kPa). Results: At baseline, 53.8% were male, the median age was 47.1 years, 13.5% reported a high intake of alcohol, 10.1% were prior injection drug users, 85.3% were infected with HCV genotype 1, and 22.6% had previously failed antiviral therapy (pegylated-interferon-alpha/ribavirin). During a median follow-up of 46.6 months, 26 patients developed cirrhosis. The rs4374383 G carriers had a higher risk of increasing LSM (adjusted arithmetic mean ratio (aAMR) = 1.14; p = 0.006) and a higher likelihood of having an increase in LSM greater than 5 kPa (ΔLSM ≥ 5 kPa) (adjusted odds ratio (aOR) = 2.37; p = 0.029), and greater than 7 kPa (ΔLSM ≥ 7 kPa) (aOR = 3.24; p = 0.032), after controlling for confounding. The SNP’s association with cirrhosis progression was close to statistical significance (aOR = 2.18; p = 0.070). Conclusions: MERTK rs4374383 A carriers had a lower risk of liver fibrosis progression than G carriers, supporting the hypothesis that this SNP seems to have a critical role in the pathogenesis of liver disease in HCV-infected patients.

Association of coffee consumption and liver fibrosis progression in patients with HBeAg-negative chronic hepatitis B: A 5-year population-based cohort study

Although coffee consumption has been associated with decreased risk of liver fibrosis progression, cirrhosis or hepatocellular carcinoma in patients with HCV infection or fatty liver diseases, its effect on hepatitis B patients remains unclear. We aimed to examine the effect of coffee consumption on liver fibrosis progression and cirrhosis-related complications in patients with chronic HBV infection. Coffee consumption was assessed in 2604 participants who were previously recruited from a population-based GERD survey. The primary endpoints of this study were the impact of coffee consumption on the development of cirrhosis-related complications, including liver cirrhosis, esophageal varices, or hepatocellular carcinoma at the end of 5-year follow-up. The secondary endpoints were the declines of serum predicting indices of liver fibrosis (AST/ALT, APRI, FIB-4, Hui score) or liver function tests (AST, ALT). 328 patients with chronic HBV infection were enrolled into this study. At baseline, coffee consumption was associated with higher education level, more frequent tobacco use and normal blood pressure (p<0.05 for all). Patients with higher coffee consumption had a significant lower serum AST, APRI and FIB-4 index value than non-coffee drinkers [adjusted HR 0.30, 95% CI(0.11-0.82) for AST; 0.30, 95% CI (0.11-0.84) for APRI; 0.30, 95% CI (0.13-0.69) for FIB-4]. However, higher coffee consumption didn't change serum AST levels, APRI, FIB-4 index values or incidences of cirrhosis-related complications at the end of 5-year follow-up. Coffee consumption was not associated with fibrosis progression or HCC risk in chronic hepatitis B patients over the 5-year observation period.

The IL7RA rs6897932 polymorphism is associated with progression of liver fibrosis in patients with chronic hepatitis C: Repeated measurements design.

The polymorphisms at the α-chain of the IL-7 receptor (IL7RA) have been related to T-cell homeostasis and development and may contribute to immune system deregulation. In the present study, we analyzed the association between IL7RA polymorphisms and the progression of liver fibrosis in patients infected with HCV. We carried out a retrospective study with a design consisting of repeated measurements in 187 HCV-infected patients, to study the risk prediction of liver fibrosis progression using genetic factors. We genotyped the rs6897932, rs987106 and rs3194051 IL7RA polymorphisms using the Agena Bioscience’s MassARRAY. Transient elastography was used to measure liver stiffness. The used cut-offs were: <7.1 kPa (F0-F1), 7.1–9.4 kPa (F2; significant fibrosis), 9.5-12.4 kPa (F3; advanced fibrosis), and ≥12.5 kPa (F4; cirrhosis). All HCV genotypes were analyzed. The median of follow-up time was 47.9 months. Baseline liver stiffness measurement (LSM) values did not show significant statistical differences for IL7RA genotypes (p>0.05). In univariate analysis, the rs6897932 T allele had a positive relationship with an increase in LSM (arithmetic mean ratio (AMR) = 1.21 (95%CI = 1.08; 1.36); p = 0.001), progression to advanced fibrosis (F≥3) (odds ratio (OR) = 2.51 (95%CI = 1.29; 4.88); p = 0.006) and progression to cirrhosis (F4) (OR = 2.71 (95%CI = 0.94; 5.03); p = 0.069). In multivariable analysis, the rs6897932 T allele was related to a higher increase of LSM values during follow-up (adjusted AMR = 1.27 (95%CI = 1.13; 1.42); p<0.001) and higher odds of progression to advanced fibrosis [adjusted OR = 4.46 (95%CI = 1.87; 10.62); p = 0.001], and progression to cirrhosis [adjusted OR = 3.92 (95%CI = 1.30; 11.77); p = 0.015]. Regarding IL7RA rs987106 and rs3194051 polymorphisms, we did not find significant results except for the relationship between IL7RA rs987106 and the increase in LSM values [adjusted OR = 1.12 (95%CI = 1.02; 1.23); p = 0.015]. The IL7RA rs6897932 polymorphism seems to be related to increased risk of liver fibrosis progression in HCV-infected patients. Thus, the rs6897932 polymorphism could be related to the physiopathology of CHC and might be used to successfully stratify the risk of CHC progression.

PS-094 - Risk of liver fibrosis progression in patients with undiagnosed hepatitis C virus infection

PS-094 - Risk of liver fibrosis progression in patients with undiagnosed hepatitis C virus infection