Ras Association Domain Family 1A Gene Promoter Methylation as a Biomarker for Chronic Viral Hepatitis C-related Hepatocellular Carcinoma.

Background One of the most prevalent aberrant epigenetic modifications found in hepatocellular carcinoma (HCC) is abnormal DNA methylation. Our study aimed to evaluate serum Ras association domain family 1A (RASSF1A) gene promoter methylation in patients with chronic viral hepatitis C (HCV)-associated liver cirrhosis with and without HCC as a potential new marker for the early detection of HCC. Methodology The 60 participants who participated in the trial were divided into the following three groups: 20 patients with newly diagnosed primary HCC on top of HCV-related liver cirrhosis, 20 patients with HCV-related liver cirrhosis, and 20 age- and sex-matched healthy individuals as a control group. All participants underwent methylation-specific polymerase chain reaction testing to detect the blood level of the RASSF1A gene's methylated promoter. Results Methylated RASSF1A was found in 30% of patients with liver cirrhosis caused by HCV and in 65% of patients with HCC, but not in any of the controls. It was discovered that the serum methylation RASSF1A had an accuracy of 82.50% and an area under the curve (AUC) of 0.825 for separating HCC patients from healthy controls. With an AUC of 0.675 and an accuracy of 67.50%, it was able to differentiate patients with HCC from those with HCV-related liver cirrhosis. Additionally, there was no statistically significant association between RASSF1A methylation status and HCC mass size (p = 0.449). Conclusions Serum RASSF1A promoter methylation status detection could be useful for detecting HCC early, especially in high-risk individuals such as those with HCV.

The advantages of drinking mineral water in the rehabilitation of patients with viral hepatitis C with accompanying non-alcoholic fatty liver disease after suffering from COVID-19.

INTRODUCTION AND OBJECTIVE: Past COVID-19 significantly worsens Chronic viral hepatitis C patients with concomitant NAFLD. The aim of the study was to assess effectiveness of including mineral water in the rehabilitation complex in patients with chronic hepatitis C with concomitant non-alcoholic fatty liver disease who contracted COVID-19. MATERIAL AND METHODS: 71 patients with chronic hepatitis C with concomitant NAFLD wo contracted COVID-19 were examined. Group I (control) - 39 patients prescribed dietary nutrition and exercise therapy. Group II (main) - 32 patients, in addition to the above, received packaged 'Shayanskaya' mineral water. Methodology comprised anamnestic, anthropometric and clinical, general clinical, biochemical, serological, and molecular genetic (markers of hepatitis C virus, HCV RNA PCR (qualitative and quantitative determination, genotyping), enzyme-linked immunosorbent assay, ultrasonographic examination of digestive organs, and statistical methods. RESULTS: Due to the treatment, there were significant improvements in carbohydrate and lipid metabolism, as well as the cytokine profile. CONCLUSIONS: The effectiveness was established of the use of silicon low-mineralized bicarbonate sodium mineral water in the complex rehabilitation of patients with chronic hepatitis C and suputor NAFLD after contracted COVID-19. There was a significant improvement in the clinical course of the disease and improvement in the functional state of the liver.

THE STRUCTURAL AND FUNCTIONAL STATE OF THE PANCREAS AND LIVER IN CHRONIC PANCREATITIS IN COMBINATION WITH CHRONIC VIRAL HEPATITIS C DEPENDING ON THE INDEX OF THE SURVEY ACCORDING TO THE INTERNATIONAL CAGE QUESTIONNAIRE.

OBJECTIVE: The aim: To conduct a comparative analysis of parameters of the structural and functional state of the liver and pancreas in patients with chronic pancreatitis in comorbidity with treated etiologically chronic viral hepatitis C, depending on the results of testing according to the international CAGE questionnaire. PATIENTS AND METHODS: Materials and methods: 100 ambulatory patients with CP with concomitant HCV, treated etiotropically, were examined. All patients were examined ac-cording to generally accepted algorithms. To establish the role of alcohol on the formation of CP and the condition of patients with treated HCV, latent craving for alcohol was verified using the international CAGE questionnaire. The study of the density of the liver parenchyma and the liver of the patients was carried out not only according to the ultrasound data in the B-mode, but also with the simultaneous measurement of the shear wave elastography (SWE) method on the Ultima PA scanning ultrasound device with the further determination of the median of the parameters, which characterizes the stiffness in kilopascals (kPa). Determination of the presence and depth of pancreatic exocrine insufficiency (PEI) was carried out by the content of fecal elastase-1 (FE-1), which was determined by the enzyme immunoassay method. RESULTS: Results: Screening-testing of patients with CP on the background of etiotropically treated HCV using the CAGE scale made it possible to state that 65.0% of such patients had a hidden craving for alcohol, and 21.0% of this cohort were women, which needs to be taken into account in the management of such patients. It has been proven that in the group of patients with CAGE≥2.0, the level of functional and structural changes in the liver and liver was significantly more severe (according to the deepening of the PEI, a decrease in fecal α-elastase by 13.01%, according to an increase in the total index of the coprogram by 15.11% and the total US-indicator of the pancreas structure by 28.06%, and the total US-indicator of the liver structure - by 40.68% (p<0.05) and corresponded to the average degree of severity of the process in panceas according to the criteria of the Marseille-Cambridge classification, and in the group with CAGE<2.0 - only a mild degree. CONCLUSION: Conclusions: The negative effect of the factor of increased alcohol use according to CAGE was proven by increasing the density of the echostructure of the liver by 5.73% (p<0.05), and the liver by 5.16% (p<0.05). According to the results of the correlation analysis of the dependence of the structural state of the liver and PW of the studied patients on the value of the CAGE scale, which was R=0.713, p<0.05, and R=0.686, p<0.05, respectively, it was established that there is a strong direct dependence of the structural state of the liver and PW from the value of the CAGE questionnaire, which proved an independent, reliably significant role of alcohol consumption for patients with a comorbid course of CP and HCV.

Features of clinical, biochemical, and sonographic parameters in patients with chronic viral hepatitis C with concomitant non-alcoholic fatty liver disease.

INTRODUCTION AND OBJECTIVE: Introduction. Difficulties encountered in treating patients with chronic viral hepatitis C (CHC) are associated with the presence of concomitant liver pathology, namely fatty degeneration, which contributes to the progression of HCV infection. The above circumstances prompted the authorsled to thoroughly examine of this category of patients for further development of a new pathogenetically directed course of treatment. Objective. To study clinical, biochemical, and instrumental features of the course of liver disease in CHC patients with concomitant non-alcoholic fatty liver disease (NAFLD). MATERIAL AND METHODS: Tested 339 patients with chronic hepatitis C with concomitant NAFLD; and 175 patients with СНС. Methodology: anamnestic, anthropometric and clinical, general clinical, biochemical, serological, and molecular genetic (markers of hepatitis C virus, HCV RNA PCR (qualitative and quantitative determination, genotyping), enzyme-linked immunosorbent assay, ultrasonographic examination of digestive organs, statistical methods. RESULTS: Conducted clinical, instrumental, and laboratory studies have shown that CHC patients with concomitant NAFLD are characterized by various disorders - a violation of the functional state of the liver, a violation of carbohydrate and lipid metabolism, an imbalance of the cytokine system, the presence of histological and non-inflammatory activity in the liver. CONCLUSIONS: The presence of concomitant NAFLD in patients with CHC aggravates the clinical picture, manifesting itself in a significant lipid metabolism disorder that provokes the rapid formation of liver fibrosis. An additional complicating factor is the development of insulin resistance, leading to persistent morphological changes in the liver parenchyma.

Dynamic personalized prediction of the individual liver-related risk after sustained viral response in HCV patients.

Sustained viral response (SVR) significantly improves the prognosis in patients with hepatitis C virus (HCV) chronic infection but does not totally alleviate the risk of liver-related complications (LRC). We aimed to evaluate whether the dynamics of multiple measurements of simple parameters after SVR enable the development of a personalized prediction of prognosis in HCV patients. HCV mono-infected patients who experienced SVR in two prospective cohorts (ANRS CO12 CirVir cohort: derivation set; ANRS CO22 HEPATHER cohort: validation set) were included. The study outcome was LRC, a composite criterion including decompensation of cirrhosis and/or hepatocellular carcinoma. Joint latent class modelling accounting for both biomarker trajectory and event occurrence during follow-up was developed in the derivation set to compute individual dynamic predictions, with further evaluation in the validation set. In the derivation set (n = 695; 50 LRC during the median 3.8 [1.6-7.5] years follow-up), FIB4 was identified as a biomarker associated with LRC occurrence after SVR. Joint modelling used sex and the dynamics of FIB4 and diabetes status to develop a personalized prediction of LRC. In the validation set (n = 7064; 273 LRC during the median 3.6 [2.5-4.9] years follow-up), individual dynamic predictions from the model accurately stratified the risk of LRC. Time-dependent Brier Score showed good calibration that improved with the accumulation of visits, justifying our modelling approach considering both baseline and follow-up measurements. Dynamic modelling using repeated measurements of simple parameters predicts the individual residual risk of LRC and improves personalized medicine after SVR in HCV patients.

Utility of On-Treatment Viral Loads During Treatment With Direct-Acting Antivirals in Patients Infected With Chronic Viral Hepatitis C.

Background: Direct-acting antiviral (DAA) agents have revolutionized the treatment of chronic hepatitis C virus (HCV) infection. Current data regarding the utility of on-treatment HCV viral load (VL) monitoring are conflicting and limited data are available in HIV-coinfected patients. Objective: The objective of the study was to determine whether on-treatment VLs are predictive of HCV cure in a real-world population. Method: A single-center, retrospective cohort study was conducted using patients who received a prescription for DAA therapy for HCV treatment at a large, tertiary ambulatory care clinic. Results: A total of 219 patients were included in the final analysis. The average age was 56 years. Most patients were male (64.4%), African American (73.1%), and insured by Medicaid (61.6%). Most patients were treatment-naive, noncirrhotic, and infected with HCV genotype 1a (73.1%). About 22.4% of patients were coinfected with HIV. The most common regimen was 12 weeks of ledipasvir/sofosbuvir (53.9%). On-treatment VLs were most commonly obtained at treatment week 4 (42.5%), of which 45.2% of patients were detectable. Sustained virologic response (SVR) was achieved in 96.8% of the total population and 95.9% of HIV-coinfected patients. Of the 7 patients who did not achieve SVR, 3 patients had undetectable on-treatment VLs in the first 8 weeks of therapy. Conclusion: Sustained virologic response rates were similar between HCV-monoinfected patients and HCV-HIV-coinfected patients. This research further supports that on-treatment VLs may not be a valuable indicator of treatment failure but may be helpful to engage patients in care and ensure treatment adherence and ultimately cure.

acNASH index to diagnose nonalcoholic steatohepatitis: a prospective derivation and global validation study.

BACKGROUND: There is an unmet need for non-invasive biomarkers for the diagnosis of nonalcoholic steatohepatitis (NASH) in non-specialized settings. We aimed to develop and validate a non-invasive test for diagnosing NASH in individuals with biopsy-proven nonalcoholic fatty liver disease (NAFLD). METHODS: We developed a non-invasive test named the acNASH index that combines serum creatinine and aspartate aminotransferase levels in a derivation cohort of 390 Chinese NAFLD patients admitted to the hepatology center of the First Affiliated Hospital of Wenzhou Medical University (China) between December 2016 and September 2019 and subsequently validated in five external cohorts of different ethnicities of patients with biopsy-confirmed NAFLD (pooled n=1,089). FINDINGS: The performance of the acNASH index for identifying NASH (defined as NAFLD activity score ≥5 with score of ≥1 for each steatosis, lobular inflammation and ballooning) was good in the derivation cohort with an area under receiver operating characteristics (AUROC) of 0·818 (95%CI 0·777-0·860). A cutoff of acNASH index <4·15 gave a sensitivity (Se) of 91%, a specificity (Sp) of 48% and a negative predictive value (NPV) of 83% for ruling-out NASH, conversely, a cutoff of acNASH >7·73 gave a Sp of 91%, Se of 53% and a positive predictive value (PPV) of 85% for ruling-in NASH. In the pooled validation cohort (n=1,089), the diagnostic performance of the index was also good with AUROC=0·805 (95%CI 0·780-0·830), NPV of 93% for ruling-out NASH and PPV of 73% for ruling-in NASH. Subgroup analyses showed similar performance in patients with diabetes or subjects with normal serum transaminase levels. INTERPRETATION: The acNASH index shows promising utility as a simple non-invasive biomarker for diagnosing NASH among adults with biopsy-proven NAFLD of different ethnicities from different countries. FUNDING: The National Natural Science Foundation of China (82070588), High Level Creative Talents from Department of Public Health in Zhejiang Province (S2032102600032) and Project of New Century 551 Talent Nurturing in Wenzhou.

THE ROLE OF GALECTIN-9 IN PATIENTS WITH CHRONIC VIRAL HEPATITIS C AND ITS CONNECTION WITH THE TYPE OF THERAPY, THE DEGREE OF FIBROSIS, CLINICAL, LABORATORY, AUTOIMMUNE AND INTEGRATIVE INDICATORS.

OBJECTIVE: The aim: To establish the dependence of the concentration of galectin-9(CGal-9) in the serum of patients with chronic viral hepatitis C (CVHC) on the type of antiviral therapy (AVT), clinical-laboratory, autoimmune and integrative parameters, non-invasive methods of assessing the degree of fibrosis. PATIENTS AND METHODS: Materials and methods: CGal-9 in serum were determined in 68 patients with CVHC and 20 healthy individuals, and clinical-laboratory and integrative parameters, noninvasive methods for assessing the degree of fibrosis were studied. RESULTS: Results:There were three groups: baseline (I), pegylated interferon (PEG-IFN) with ribavirin (II), velpatasvir with sofosbuvir (III). In pations from group I, compared with healthy people, CGal-9 was 1.7 times higher (p <0.05); in patients from group II it was 4.2 times higher (p<0.05); in patients from group III it did not differ from healthy individuals. All patients had a directly proportional correlation between CGal-9 and the frequency of splenomegaly detection; in patients who did not receive AVT, directly proportional - with De Ritis ratio, non-invasive methods of liver fibrosis, inversely proportional - with platelet count (p<0,05). There was a higher probability of positive indicators of antinuclear antibodies (ANA) at 12 weeks of treatment with PEG-IFN and ribavirin, with higher CGal-9 at 4 weeks of AVT (p<0,05). CONCLUSION: Conclusions: Correlations between CGal-9 and the frequency of splenomegaly detection, platelet count, De Ritis ratio, degree of lever fibrosis in correlation with METAVIR, APRI, FIB-4, ANA, NI were determined. The possibility of predicting the occurrence of splenomegaly, liver cirrhosis and positive ANA in patients with CVHC has been proven.

Liver transplantation as potential curative method in severe hemophilia A: case report and literature review.

The authors present clinical case of orthotopic liver transplantation for cirhosis due to chronic viral hepatitis C in a subject with severe hemophilia A. Preoperatively performed pharmacokinetic study with recombinant F VIII confirmed satisfactory in vivo recovery of 2.1 %. A bolus application of 52 units F VIII/kg body weight with target F VIII activity over 100.0 % was administred shortly before the transplantation started. Totally, 30 000 units of recombinant F VIII, 3 thrombocyte concentrates, 2 erythrocyte concentrates, 5 units of virally inactivated plasma, 1 unit of fresh frozen plasma and 3 500 antithrombin units were used. There were no perioperative or postoperative bleeding complications, F VIII substitution was stopped on postoperative day 3. The patient was discharged on twentieth postoperative day.

Factors That Influence the Virological Response in Patients with Chronic Hepatitis C Treated with Pegylated Interferon and Ribavirin.

INTRODUCTION: The success of the antiviral treatment in patients with chronic hepatitis C depends on the factors related to the virus and the host. The aim of the study is the analysis of the antiviral therapy which is a combination of pegylated interferon and ribavirin, considering various factors that will identify the predictors of the sustained virological response. MATERIAL AND METHODS: This retrospective study included 226 patients, divided in two groups. Patients with sustained virological response and patients without sustained virological response were compared in terms of the following factors: genotype, viral load, gender, age, inflammatory and fibrotic changes in the liver, metabolic abnormalities, obesity and fatty liver. RESULTS: The rate of the sustained virological response is 83.6%, more frequently in patients with genotype 3, with evidenced statistical significance (90.54%). The factors that significantly contribute to sustained virological response are related to the age (p = 0.0001), genotype (p = 0.002), mode of transmission (p = 0.005), inflammatory changes in the liver (p = 0.028), body mass index (p = 0.022) and insulin resistance (p = 0.039). The high rate of sustained virological response is related to the younger age of the patients which indirectly means short Hepatitis C Virus infection duration, absence of advanced liver disease and lack of significant co-morbid conditions. Single confirmed independent predictors of sustained virological response are the age (OR 0.928, p = 0.0001) and genotype (OR 3.134, p = 0.005). CONCLUSIONS: Factors that are related to the virological response are the age, genotype, mode of transmission, inflammatory changes in the liver, body mass index and insulin resistance, but still, independent predictors of sustained virologic response are the age and the genotype.

HEPATOPROTECTIVE ROLE OF PLACENTA HYDROLISAT - LAENNEC IN THE TREATMENT OF PATIENTS WITH VIRAL AND PARASITIC LIVER DISEASES.

The article presents data on non-alcoholic fatty liver disease and chronic viral hepatitis C in combination with opisthorchosis invasion. With the system approach considers the specific features of the clinical, laboratory and functional data in patients with combined pathology. Observed frequency of the pain, asthenic and allergic cholestatic syndromes, the latter as part of the triad Paltsev. The high efficiency of the placenta hydrolisat - laennec, as means of pathogenetic therapy.

Non-invasive assessment of liver fibrosis in chronic viral hepatitis.

BACKGROUND: Hyaluronic acid (HA), ASAT to Platelet Ratio Index (APRI), ASAT/ALAT ratio, Fibrosis 4 score (FIB4) and FibroScan were studied as non-invasive markers of liver fibrosis (F) in chronic viral hepatitis B (CHB) and C (CHC), in an attempt to avoid the complications of liver puncture biopsy, considered the gold standard in the evaluation of F. The aim of our research was to study whether HA, APRI, ASAT/ALAT ratio, FIB4 and FibroScan are useful non-invasive markers in predicting severe F in Romanian patients. PATIENTS AND METHODS: This was a prospective multicenter transversal and observational study, which included 76 patients with CHB/CHC. The independent effect of studied markers was tested using multiple binary logistic regression. RESULTS: In patients with CHB and CHC, the APRI cut-off value for F4 was 0·70 ng/mL (Se = 77%, Sp = 78%), the FIB4 cut-off value was 2·01 (Se = 77%, Sp = 69%), and the FibroScan cut-off value was 13·15 (Se = 92%, Sp = 88%). For patients with CHB/CHC, there was a significant linear positive correlation between F and HA (r = 0·42, P = 0·001), FibroScan (r = 0·67, P < 0·001), APRI (r = 0·46, P < 0·001) and FIB4 (r = 0·51, P < 0·001). Considering age, sex and body mass index as possible confounding factors or covariates in multivariable logistic modelling, FibroScan was the unique test that able to significantly highlight the presence of F4 score in CHB/CHC patients (P = 0·009) while FIB4 test seems to have a tendency to statistical significance. CONCLUSION: FibroScan, APRI and FIB4 are useful non-invasive tests for the evaluation of F4 in patients with CHB and CHC.

[Bilateral non-arteritic ischemic optic neuropathy during treatment of viral hepatitis C with pegylated interferon and Ribavirin]. / Neuropathie optique ischémique non artéritique bilatérale au cours du traitement de l'hépatite virale C par l'association interféron pégylé et Ribavirine®

INTRODUCTION: Hepatitis C is a serious viral infection, for which the current treatment is based on the combination of pegylated interferon (IFN) and Ribavirin(®). Ophthalmic complications observed with PEG-IFN are infrequent and of variable prognosis. They often include an ischemic retinopathy with typical cotton-wool spots, hemorrhage and retinal edema, and rarely acute non-arteritic anterior ischemic optic neuropathy as illustrated by our report. OBSERVATION: We report the case of a 51-year-old man followed for chronic active hepatitis C, who presented in the fourth month of treatment with pegylated interferon and vidarabine with a sharp decline in visual acuity secondary to acute bilateral non-arteritic anterior ischemic optic neuropathy. The hepatitis C treatment was discontinued. His course was notable by the third week for a significant regression of papilledema with improvement in visual acuity in the right eye and no change in the left eye, remaining at counting fingers. After regressing for four years, the disease progressed to bilateral temporal optic atrophy without change in visual acuity. CONCLUSION: Pegylated interferon and Ribavirin(®) are commonly used in the treatment of chronic hepatitis C. They are the source of various ophthalmologic complications of varied severity. The pathophysiology of this ocular toxicity currently remains hypothetical. Non-arteritic ischemic optic neuropathy is still a relatively rare complication with a poor functional prognosis, often requiring discontinuation of treatment. Thus, careful ophthalmologic monitoring before and during antiviral treatment of patients with hepatitis C appears necessary.