Liver Fibrosis Progression In Patients Research Articles

Association between changes in body composition and progression of liver fibrosis in patients with type 2 diabetes mellitus.

The correlation between type 2 diabetes mellitus (T2DM) and the occurrence of liver fibrosis is well-established. However, the longitudinal association between body composition and liver fibrosis progression in patients with T2DM remains incompletely explored. Total of 390 patients with T2DM underwent body composition assessments, followed by a median duration of 2.13 years. The calculated parameters included body mass index (BMI), fat mass index (FMI), trunk fat mass index (TFMI), appendicular skeletal muscle mass index (ASMI), muscle/fat mass ratio (M/F) and appendicular skeletal muscle mass/trunk fat mass ratio (A/T). Liver fibrosis was evaluated through liver stiffness measurement (LSM). Patients were classified according to BMI and body composition, followed by a comprehensive investigation into the impact of body composition changes on liver fibrosis outcomes. Among 72 patients with incident advanced liver fibrosis at readmission, ΔBMI, ΔFMI and ΔTFMI increased, while ΔM/F and ΔA/T decreased. Individuals who kept obese had a dramatically elevated hazard of incident advanced liver fibrosis compared to those who kept non-obese, with an adjusted odds ratio of 3.464. When TFMI heightened, the hazard of incident advanced liver fibrosis was 3.601 times higher compared to the decreased group. Additionally, individuals in increased ASMI and A/T groups showed a slight advantage in preventing incident advanced liver fibrosis compared to the stable groups. Stable obesity was associated with a greater hazard of liver fibrosis advancement, and an increase in TFMI may promote the progression of liver fibrosis. Maintaining a balanced muscle/fat ratio appeared to help prevent the progression.

IMPACT OF CORONARY ARTERY DISEASE ON STEATOTIC LIVER DISEASE PROGRESSION

Introduction. Metabolic dysfunction-associated steatotic liver disease and coronary artery disease often exacerbate each other, leading to a more severe course of both conditions. The aim of this study is to evaluate the role of coronary artery disease in dislipidemia and liver fibrosis progression in patients with metabolic dysfunction-associated steatotic liver disease. Materials and methods. Forty-six patients with metabolic dysfunction-associated steatotic liver disease were examined. Patients were divided into two groups based on the presence of concomitant coronary artery disease: group I (n=24) included patients with both metabolic dysfunction-associated steatotic liver disease and coronary artery disease, while group II (n=22) included patients with metabolic dysfunction-associated steatotic liver disease only. A third group (Group III) comprised healthy individuals. Specific lipid metabolism parameters, obesity stage, alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (GGT) activity, and platelet count were examined. Fibrosis stage was evaluated using the FIB-4 score. The findings obtained were statistically processed. Results. Arterial hypertension was more prevalent in patients with metabolic dysfunction-associated steatotic liver disease and concomitant coronary artery disease. In group I, arterial hypertension was observed in 95.8% of cases, whereas in group II, it was observed in 40.9% of cases (χ2=16.35, p=0.00005). Patients with metabolic dysfunction-associated steatotic liver disease exhibited elevated levels of total cholesterol, low-density lipoproteins, and triglycerides, leading to an increased atherogenic index. Conversely, high-density lipoprotein levels were decreased (p>0.05). The degree of fibrosis according to the FIB-4 score was 1.45 times higher in patients with metabolic dysfunction-associated steatotic liver disease and concomitant coronary artery disease compared to those without coronary artery disease.

The Use of Noninvasive Velacur® for Discriminating between Volunteers and Patients with Chronic Liver Disease: A Feasibility Study.

Nonalcoholic fatty liver disease is the leading cause of chronic liver disease globally and can progress to cirrhosis, liver failure, and liver cancer. Current AASLD, AGA, and ADA guidelines recommend assessment for liver fibrosis in all patients with NAFLD. Serum biomarkers for fibrosis, while widely available, have notable limitations. Imaging-based noninvasive testing for liver fibrosis/cirrhosis is more accurate and is becoming more widespread. We evaluated the feasibility of a novel shear wave absolute vibroelastography (S-WAVE) modality called Velacur® for assessing liver stiffness measurement (LSM) for fibrosis and attenuation coefficient estimation (ACE) in differentiating patients with chronic liver disease from normal healthy controls. Fifty-four healthy controls and 89 patients with NAFLD or cured HCV with a prior known LSM of >8 kPa were enrolled, and all subjects were evaluated with FibroScan® and Velacur®. Velacur® was able to discriminate patients with increased liver stiffness as determined by a FibroScan® score of >8 kPa from healthy controls with an AUC of 0.938 (0.88-0.96). For assessment of steatosis in NAFLD patients only, Velacur® could identify patients with steatosis from healthy controls with an AUC of 0.831 (0.777-0.880). The Velacur® scan quality assessment was superior in healthy controls, as compared to patients, and the scan quality, as assessed by the quality factor (QF) and interquartile range (IQR)/median, was affected by BMI. Velacur® was safe and well tolerated by patients, and there were no adverse events. Velacur® assessment of liver stiffness measurement and liver attenuation is comparable to results obtained by FibroScan® and is an alternative technology for monitoring liver fibrosis progression in patients with chronic liver disease. This trial is registered with NCT03957070.

Chronic viral hepatitis B and C in pediatric patients: possibilities of ultrasound techniques for patients’ management

Chronic viral hepatitis B and C have already become one of the medical and social problems of modern hepatology and paediatrics due to their high prevalence and ability to transform liver parenchyma and form additional complications. Nowadays, it is important to assess and examine patients by ultrasound techniques to estimate changes in morphometric, hemodynamic, and echoacoustic characteristics of the liver in patients with viral hepatitis B and C.
 The aim: to estimate ultrasound morphometric parameters and hemodynamic indexes, morphological deviations of the liver and spleen in pediatric patients with chronic viral hepatitis B and C by implementing of the system as Y. Davoudi diagnostic scale (2015) and analysis of echo-acoustic patterns.
 Materials and methods. 34 children were examined. 19 children with chronic viral hepatitis B and C formed group I, while 15 almost healthy children formed group II. All examined patients underwent collecting of anamnesis, general clinical examination, determination of the degree of liver fibrosis by non-invasive method (Fibrotest or fibroelastometry) and ultrasound examination of the abdominal cavity organs with the possibility of Doppler scanning. Differences at p<0.05 were considered statistically significant.
 Results. Obtained data showed that in patients of group, I index of Y. Davoudi grayscale was higher (2,6±0,26 U) compared with patients of group II (1,4±0,32 U) (p<0,01). Systolic blood flow velocities in the portal vein and the splenic vein were decreased in patients of group I (15,59±0,4 cm/s; 15,7±0,8 cm/s) compared with group II (17,68±0,8 cm/s; 17,54±0,42 cm/s) (p<0,05), resistance index in the hepatic artery was increased in patients of group I (0,78±0,02 IU) compared with patients of II group (0,68±0,04 IU) (p<0,05). Histogram indexes of the liver and liver-kidney region were higher in patients of group I (p<0,001).
 Сonclusions. Y.Davoudi diagnostic scale, hemodynamics parameters of the portal, splenic and hepatic vessels, echoacoustic patterns and other indexes could be prognostic factors which will indicate liver fibrosis progression in patients with chronic viral hepatitis B and C. The analysis of the obtained data showed that deviations in morphometric, echoacoustic and Doppler indexes of liver and spleen in paediatric patients with chronic viral hepatitis B and C were more clinically significant compared with almost healthy children and could be taken into account as liver fibrosis predictors

Development and validation of a potential biomarker to improve the assessment of liver fibrosis progression in patients with chronic hepatitis B.

We aimed to develop and validate a novel combined score to improve the assessment of liver fibrosis progression in patients with chronic hepatitis B (CHB). In this study, a total of 331 CHB patients from three cohorts who underwent liver biopsy were enrolled, and the Scheuer system was used for liver fibrosis classification. The combined score was derived by principal component analysis of key differentially expressed genes. For significant liver fibrosis (≥S2), the areas under the receiver operating characteristics curves (AUROCs) of the combined score were 0.838, 0.842, and 0.881 in the three cohorts, respectively. And for advanced liver fibrosis (≥S3), the AUROCs were 0.794, 0.801, and 0.901, respectively. Compared with the results of AUROCs for aspartate aminotransferase≥to≥platelet ratio (APRI) and fibrosis index based on four factors (FIB-4) in the validation cohorts, better clinical diagnostic value for assessing the progression of liver fibrosis was found in the combined score. Additionally, univariate ordered logistic regression analysis indicated that the combined score could serve as a more superior and stable risk factor than APRI and FIB-4 in the assessment of liver fibrosis. For CHB patients with normal alanine aminotransferase (ALT), our results further emphasized the diagnostic value of the combined score for significant fibrosis (≥S2) and advanced fibrosis (≥S3). Moreover, it was found that patients with the high combined score, who were associated with the advanced fibrosis stage, had higher levels of drug sensitivity and immune checkpoint expression. In conclusion, the novel combined score could serve as a potential biomarker and contribute to improving the assessment of fibrosis stage in CHB patients.

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

Congenital hepatic fibrosis (a case report)

Congenital hepatic fibrosis (CHF) is an autosomal recessive disorder of intrauterine morphogenesis of the portobiliary system, characterized by periportal fibrosis and defective remodeling of the bile ducts. The article describes the features of the clinical course, diagnosis and treatment of type I CHF in the different terms of a patient’s life: from birth to her pregnancy, during pregnancy and after childbirth. The aim of this work is to familiarize specialists with the problem of diagnosis and treatment of type I CHF in a patient with a provisional misdiagnosis of cryptogenic liver cirrhosis. Results. The features of type I CHF that determine a wider diagnostic testing in long-term unspecified liver pathology cases were identified. First-time decompensation of portal hypertension (PH) occurred at 35 weeks of gestation with the development of ascitic-edematous syndrome, hypersplenism, preeclampsia without signs of hepatic encephalopathy (HE). Cesarean section was performed at 37 weeks’ gestation and healthy baby was born. One year and 9 months after delivery, hypersplenism compensation was achieved by performing splenic artery embolization (SAE). There were no clinical manifestations of HE throughout the follow-up period. Conclusions. The diagnostic algorithm for a long-term compensated unspecified liver pathology with PH should confirm or rule out CHF. Type I CHF patients can give birth to a healthy child. SAE successfully compensates for hypersplenism and PH in type I CHF. Transient elastography is an effective method for the assessment of liver fibrosis progression in patients with type I CHF.

Presence of CAT genetic markers as an indicator of accelerated rate of liver fibrosis progression in patients with chronic hepatitis

Goal. To evaluate the genetic profi le of patients with chronic hepatitis C (CHC) by the CAT gene polymorphism in the region-262G/A (rs1001179), GPX4 in the region-718C/T (rs713041), IL28B in the region C/T (rs12979860) and VEGFA in the region- 634G/C (rs2010963) to analyze the association of the rate of progression of liver fi brosis with polymorphic genetic markers.Materials and methods. We examined 36 patients with CHC with a rapidly progressive rate of fi brosis (up to 10 years) and 56 patients with a slowly progressive course of the disease (more than 10 years). The study of single- nucleotide polymorphisms of genes was carried out by the method of polymerase chain reaction.Results. In the group with rapid progression of liver fi brosis, individuals with multiple risk alleles for the studied polymorphisms were more common, which confi rms the association of the risk of liver fi brosis progression with the genetic markers CAT in the region-262G/A (rs1001179) and GPX4 in the region-718C/T (rs713041) with their combined carrier. Among patients with rapid progression of fi brosis, a greater number of individuals had simultaneously 4–6 risk alleles in 27.5%, while patients with slow progression of the process only in 11% of cases.Conclusion. This set of genetic markers can be used as genetic testing of patients with liver fibrosis to determine the prognosis of the disease.

Serum Mac-2 Binding Protein Glycosylation Isomer (M2BPGi) Can Predict Mild or Significant Liver Fibrosis in Non-alcoholic Fatty Liver Disease

Background: The serum levels of M2BPGi increase with liver fibrosis progression in patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. However, the diagnostic performance of M2BPGi in non-alcoholic fatty liver disease (NAFLD) patients remains unclear. Objectives: To assess the severity of liver fibrosis in NAFLD patients and healthy controls by M2BPGi using acoustic radiation force impulse (ARFI) as the standard reference. Methods: Those suffering from NAFLD and healthy controls were recruited. NAFLD diagnosis was confirmed using fatty liver in imaging after excluding HCV, HBV, alcohol, drug, or other known causes of chronic liver disease. ARFI was used as the standard reference to determine the stage of liver fibrosis. Results: A total of 226 subjects were recruited, including 130 (57.5%) NAFLD patients who were divided into three groups according to the stage of liver fibrosis: F0, F1, and F ≥ 2. The serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), AST to platelet ratio index (APRI), M2BPGi, and the fatty liver grade were significantly different between the three groups. The levels of M2BPGi were correlated with median ARFI value (P < 0.001), APRI (P = 0.011), and fibrosis 4 index (FIB-4) (P < 0.001). The area under the curve (AUC) of M2BPGi test was 0.58 for F ≥ 1 and 0.68 for F ≥ 2, respectively (P = 0.039 and P = 0.024). Conclusions: The M2BPGi levels were correlated with ARFI, APRI, and FIB-4 scores in this study population. The level of M2BPGi could predict mild (F ≥ 1) and significant liver fibrosis (F ≥ 2) in NAFLD patients, suggesting a surrogate marker to differentiate between normal, mild, and significant fibrosis.

Diagnostic and risk stratification aspects of liver fibrosis progression in chronic hepatitis B and C viral infection

The treatment strategy and prognosis for chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection largely depend on the presence and stage of liver fibrosis. This study aimed to reveal the diagnostic and risk stratification aspects of liver fibrosis progression in patients with chronic HBV and HCV infection. The PubMed database, the Google Scholar search engine, the Cochrane systematic reviews, and the scientific electronic library eLibrary.Ru, as well as the reference lists, were used to search for scientific articles. Relevant aims of the publication review were selected over the period from 2005 to 2021 using the keywords chronic HBV infection, chronic HCV infection, liver fibrosis, diagnostics, and prognosis. Inclusion criteria were limited to liver fibrosis diagnostics in chronic HBV and HCV infection. Considering biopsy as a gold standard for studying morphological abnormalities in the liver, its indications for serum biomarkers of liver fibrosis and imaging methods assessments are currently significantly limited. Additionally, noninvasive methods are required to monitor the progression of liver fibrosis. The combined use of two unrelated noninvasive methods, for example, transient elastography and one of the serum biomarkers, can improve the accuracy of clinically diagnosing significant liver fibrosis. Considering that the development of liver fibrosis is an unfavorable event in the natural course of chronic HBV and HCV infection, the distribution of patients by risk groups will increase the efficiency of antiviral therapy and improve the disease prognosis.

Intensity of liver parenchym fibrosis in patients with alcoholic and non-alcoholic steatohepatitis depending on the presence of dysmetabolic iron overload syndrome

Objective — to establish the features of iron homeostasis in patients with steatohepatitis of alcoholic and nonalcoholic etiology depending on the presence of dysmetobolic iron overload syndrome, to identify the probable link between ferrokinetics and markers of biochemical syndromes of steatohepatitis, the intensity of endotoxicosis and fibrosing reactions.
 Materials and methods. The study was based on the clinical follow‑up of 125 individuals, including 60 patients with nonalcoholic steatohepatitis and 65 patients with alcoholic steatohepatitis, 25 practically healthy individuals of appropriate age and gender. Depending on the indicators of iron homeostasis, the examined patients were divided into 4 groups: alcoholic steatohepatitis with dysmetabolic iron overload syndrome — 40 patients, 25 patients without dysmetabolic iron overload syndrome; 18 patients with non‑alcoholic steatohepatitis and dysmetabolic iron overload syndrome and 42 patients — without dysmetabolic iron overload syndrome.
 Results. In alcoholic steatohepatitis, activation of collagen anabolism processes was observed through the growth of protein‑bound oxyproline in blood — in the presence of iron overload syndrome 2.5 times (p < 0.05), in the absence — 2.0 times (p < 0.05), as well as a significant increase in the intensity of collagen catabolism — by increasing the content of free oxyproline in blood, respectively — by 1.5 and 1.3 times (p < 0.05), which occurred due to a significant increase in collagenolytic activity of blood plasma (respectively in 1.6 and 1.4 times; p < 0.05) with the presence of a probable intergroup difference (p < 0.05) in all the cases. There was a significant increase in the content of hexosamines in blood: with iron overload syndrome 1.6 times (p < 0.05), in its absence — 1.5 times (p < 0.05), the content of sialic acids, respectively — 1.6 and 1.5 times (p < 0.05), and the accelerated degradation of fucoglycoprotein components of the extracellular matrix. In non‑alcoholic steatohepatitis, activation of collagen synthesis processes with an increase in blood protein‑bound oxyproline was established — in the presence of iron overload syndrome 1.6 times (p < 0.05), in the absence — 1.3 times (p < 0.05), as well as a slight increase in the intensity of collagen breakdown — with an increase in the content of free oxyproline in blood in non‑alcoholic steatohepatitis with iron overload syndrome — 1.2 times (p < 0.05). There was also a significant increase in the content of hexosamines in blood: in the presence of iron overload syndrome by 1.3 times (p < 0.05), in its absence — by 1.2 times (p < 0.05), the content of sialic acids, respectively — in 1.4 and 1.2 times (p < 0.05), and the accelerated degradation of fucoglycoproteins.
 Conclusions. The regularities of liver fibrosis progression in patients with alcoholic steatohepatitis with iron overload syndrome are inextricably linked with the activation of collagen anabolism, the increase in the intensity of collagen catabolism, which occurred due to a significant increase in collagenolytic activity of blood plasma. An important consequence of the activation of cytolysis and inflammation is a significant increase in the content of hexosamines in blood. In patients with nonalcoholic steatohepatitis, there was an activation of collagen synthesis, a slight increase in the intensity of collagen breakdown in the presence of iron overload syndrome, as well as a characteristic increase in blood hexosamines, and the accelerated degradation of fucoglycoproteins.

Circulating microRNA signatures that predict liver fibrosis progression in patients with HIV-1/hepatitis C virus coinfections.

The lack of available biomarkers for diagnosing and predicting different stages of liver disease with a noninvasive strategy is currently one of the main challenges that clinicians are facing. Recent evidence indicates that the plasma levels of specific microRNAs (miRNAs) may be significantly altered in patients with liver injury, including those with HIV type 1 (HIV-1) infections. Large-scale deep sequencing analysis of small RNA expression was performed on plasma samples from 46 patients with HIV-1/hepatitis C virus (HCV) coinfections that did not exhibit liver fibrosis at the time of sampling. A total of 1065 different miRNAs were identified. After a mean of 10.3 years, 26 out of the 46 patients developed liver fibrosis (stage F2-4) and 20 remained without signs of liver fibrosis (stage F0-1). We identified a signature of seven miRNAs: 100-5p, 192-5p, 99a-5p, 122-5p, 125b-2-3p, 1246 and 194-5p, which were highly correlated with progression to liver fibrosis. These seven miRNAs detected liver fibrosis progression with an area under the curve (AUC) of 0.910-0.806. Two miRNAs, 100-5p and 192-5p, which displayed the best AUC values, yielded a sensitivity of 88% and a specificity of 85% for detecting liver fibrosis progression. Our results demonstrated that circulating miRNA levels had potential in predicting liver fibrosis progression before the clinical detection of liver fibrosis or significant clinical signs, such as elevated liver transaminases or platelets. Thus, our results might facilitate predictions of liver injury progression in patients with HIV-1-infections.

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.

Non-alcoholic fatty liver disease and type 2 diabetes mellitus: issues of the liver fibrosis diagnostics

To evaluate the frequency of liver fibrosis progression to stage 34 among patients with non-alcoholic fatty liver disease (NAFLD), type 2 diabetes and obesity, to identify predictors of severe liver fibrosis, to propose an algorithm for diagnosing fibrosis in this category of patients. 160 patients with NAFLD, type 2 diabetes mellitus (DM) and obesity and 50 patients with NAFLD without diabetes were comprehensively examined. Patients underwent laboratory examination (clinical blood test, biochemical analysis, immunoglobulins G, M, autoantibody assay, coagulogram), liver ultrasound. All patients underwent determination of the liver fibrosis stage by two methods: the serological test FibroMax and indirect ultrasound elastometry of the liver; 40 patients underwent a liver biopsy. Statistical data processing was performed using the programming language and statistical calculations R: we used correlation analysis, multiple logistic regression method, one-way analysis of variance, multi-factor analysis, the Kruskal-Wallis method, and comparison of the number of patients using the Fisher test. DM is a risk factor for the liver fibrosis progression in patients with NAFLD. Significant markers of severe fibrosis in this category of patients are increased levels of GGTP, haptoglobin and alpha-2-macroglobulin, lower platelet and prothrombin levels. Obesity and isolated steatosis without steatohepatitis are not markers of severe liver fibrosis at present, but obesity can be considered a risk factor for the progression of fibrosis in the future. All patients with NAFLD in combination with diabetes need screening to detect advanced liver fibrosis: it is advisable to determine the levels of GGTP, haptoglobin and alpha-2-macroglobulin.

Genetic contribution of endoplasmic reticulum aminopeptidase 1 polymorphisms to liver fibrosis progression in patients with HCV infection.

The endoplasmic reticulum aminopeptidase ERAP1 regulates innate and adaptive immune responses, trimming peptides and loading onto HLA class I molecules. Coding single nucleotide polymorphisms within ERAP1 are associated with autoimmune diseases, viral infections, and cancer development. Our purpose was to analyze the influence of ERAP1 variants on fibrogenesis in hepatitis C virus (HCV)-infected patients. A range of ERAP1 polymorphisms were genotyped in 722 unrelated Caucasian patients diagnosed with chronic HCV from two Spanish cohorts. Patients were classified according to their fibrosis stage. Paraffin-embedded tissue microarrays were constructed to assess ERAP1 expression (HCV = 38; alcoholic = 20) by immunohistochemistry. A statistical algorithm was applied to derive a fibrogenesis prediction model. The ERAP1 variants rs30187/T (K528, pc < 0.001) and rs27044/G (Q730, pc < 0.001) were related with severe fibrosis. These results were validated in the two independent cohorts. Furthermore, patients with the rs30187/T allele had stronger ERAP1 protein expression than those with the rs30187/C (p < 0.05). The statistical model showed that patients with rs30187 C/T and T/T genotypes took 15.58years (median) to develop advanced fibrosis, but this value was 32.08years in patients carrying C/C genotype (p < 0.005). ERAP1 variants may influence the clinical course of fibrogenesis in HCV-infected patients. These polymorphisms could be exploited as constitutive new markers of fibrosis evolution. The results highlight the possibility of using modulators of ERAP1 to generate a protective immune response against chronic HCV infection. KEY MESSAGES: What is known Several ERAP1 polymorphisms are associated with autoimmune diseases and cancer. ERAP1 trims peptides to HLA class I presentation. What is new here ERAP1 polymorphisms are associated with fibrogenesis. The ERAP1 polymorphisms genotype could help us in clinical management of patients. Potential translational impact The use of modulators of ERAP1 could generate a protective response depending on SNPs.

Safely restarting GI endoscopy in the era of COVID-19

<h3>Background:</h3> The factors that influence liver fibrosis progression in patients co-infected with human immunodeficiency virus/hepatitis C virus (HIV/HCV) are not completely understood. It is not known if insulin resistance (IR),...

Diverse effects of hepatic steatosis on fibrosis progression and functional cure in virologically quiescent chronic hepatitis B

Concomitant non-alcoholic fatty liver disease is common in patients with chronic hepatitis B (CHB) infection, although its impact on liver-related outcomes remains controversial. We aimed to study the effect of hepatic steatosis on the risk of fibrosis progression and the likelihood of HBsAg seroclearance. Treatment-naïve patients with CHB, normal alanine aminotransferase and low viraemia (serum HBV DNA <2,000 IU/ml) were prospectively recruited for baseline and 3-year transient elastography assessment. Fibrosis staging was defined according to the EASL-ALEH guidelines, with fibrosis progression defined as ≥1 stage increment of fibrosis. Hepatic steatosis and severe hepatic steatosis were defined as controlled attenuation parameter (CAP) ≥248 dB/m and ≥280 dB/m, respectively. A total of 330 patients (median age 50.5 years, 41.2% male, median HBV DNA 189 IU/ml) were recruited. Twenty-two patients (6.7%) achieved HBsAg seroclearance during follow-up, and the presence of hepatic steatosis was associated with a significantly higher chance of HBsAg seroclearance (hazard ratio 3.246; 95% CI 1.278-8.243; p= 0.013). At baseline, 48.8% and 28.8% of patients had steatosis and severe steatosis, respectively, while 4.2% had F3/F4 fibrosis at baseline, increasing to 8.7% at 3 years. The rate of liver fibrosis progression in patients with persistent severe steatosis was higher than in those without steatosis (41.3% vs. 23%; p= 0.05). Persistent severe hepatic steatosis was independently associated with fibrosis progression (odds ratio 2.379; 95% CI 1.231-4.597; p= 0.01). CAP measurements have predictive value in patients with virologically quiescent CHB. The presence of hepatic steatosis was associated with a higher risk of fibrosis progression but, paradoxically, a 3-fold increase in HBsAg seroclearance rate. Co-existing fatty liver disease in patients with chronic viral hepatitis B infection leads to worsening liver fibrosis, but also increases the chance of cure from hepatitis B virus. Routine bedside assessment of liver fat content is important for risk assessment in treatment-naïve patients with chronic hepatitis B.

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.

Computer-aided assessment of liver fibrosis progression in patients with chronic hepatitis B: an exploratory research

Objective: To establish automatic liver fibrosis classification models by using traditional machine learning and deep learning methods and preliminaryly evaluate the efficiency. Methods: Gray scale ultrasound images and corresponding elastic images of 354 patients, 247 males and 107 females, mean age (54±12) years undergoing partial hepatectomy in Zhongshan Hospital of Fudan University from November 2014 to January 2016 were enrolled in this study. By using traditional machine learning and deep learning methods, an automatic classification model of liver fibrosis stages (S0 to S4) were established through feature extraction and classification of ultrasound image data sets and the accuracy in different classification categories of each model were calculated, by using liver biopsy as the reference standard. Results: Pathological examination showed 73 cases in pathological stage S0, 40 cases in S1, 49 cases in S2, 41 cases in S3, and 151 cases in S4. The traditional machine classification model based on support vector machine (SVM) classifier and sparse representation classifier and the deep learning classification model based on LeNet-5 neural network, their accuracy rates in the two categories (S0/S1/S2 and S3/S4) were 89.8%, 91.8% and 90.7% respectively; the accuracy rates in the three categories (S0/S1 and S2/S3 and S4) were 75.3%, 79.4% and 82.8% respectively; the accuracy in the three categories (S0 and S1/S2/S3 and S4) were 79.3%, 82.7% and 87.2% respectively. Conclusions: Computer-aided assessment of liver fibrosis progression in patients with chronic hepatitis B has a high accuracy, and can achieve a more detailed classification. This method is expected to be applied in the non-invasive evaluation of liver fibrosis in patients with hepatitis B in clinical work in the future.

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.