HCV-related Cirrhotic Patients Research Articles

Association of Serum M2BPGi Levels with Nutritional Status (Using CONUT score) in Hepatitis C Virus Related Compensated Liver Cirrhosis Patients

Abstract Background Protein-energy malnutrition (PEM), which is one of the most common complications seen in LC patients and associated with high morbidity and mortality. So, predicting the presence of PEM and providing appropriate nutritional support help improve the prognosis of those patients. Mac-2-binding protein glycosylation isomer (M2BPGi) was recently identified as a serum glycobiomarker for liver fibrosis. However, the relationship between M2BPGi and malnutrition in patients with chronic liver disease (CLD) is unclear. Aim of the Work The aim of this study is to evaluate the role of serum M2BPGi levels as a surrogate marker for malnutrition in HCV related cirrhotic patients, correlated with CONUT score as the nutritional status marker. Patients and Methods This is a Cross-sectional - Analytic study that included patients with chronic HCV infection and normal control group selected from patients attending to Hepatology Outpatient Clinics at Ain Shams University Hospital. This study was carried out from 30 patients (child A) attending to Hepatology Outpatient Clinics at Ain Shams University Hospital and 30 healthy individuals as a control. Results The M2BPGi levels increased with CONUT score. The correlation coefficient between M2BPGi and CONUT score was r = 0.315 (p = 0.05), indicating a positive weak correlation between M2BPGi and CONUT score. The cut-off for M2BPGi to predict CONUT low vs. moderate was 1.43 with a sensitivity 93.33% and specificity 100% when AUC =0.9 and CONUT moderate vs. severe was 1.7 with a sensitivity 91.67% and specificity 100% when AUC =0.9. Conclusion We found that there is correlation between M2BPGi and CONUT score and both can be useful as a marker for malnutrition in HCV related cirrhotic patients cut of point

Interaction of peripheral CD4+CD25+CD127− Tregs with prolactin in HCV hepatocellular carcinoma: oncogenic or immunogenic mechanisms

Background and objectiveThere is little and conflicting data about the peripheral CD4+CD25+CD127− Tregs in patients with hepatocellular carcinoma (HCC) of various etiologies. The expressed membrane-bound transforming growth factor (mTGF-β1) on these Tregs is a marker of their suppressive function. Prolactin suppresses Tregs function in healthy subjects but enhances local Tregs in breast cancer. Our study is the first to assess the frequency and function of CD4+CD25+CD127−Tregs and their association with clinicopathological features and staging in HCV-related HCC and to determine whether prolactin acts as an oncogenic growth factor or participates in the regulation of the immune response mediated by peripheral Tregs. In patients with HCV- elated HCC, HCV-cirrhotic patients, and healthy subjects, we measured the frequency of peripheral traditional CD4+ CD25+ Tregs and well-characterized CD4+CD25+CD127−Tregs and their mTGF-β1 using flow cytometric analysis and measured serum prolactin level.ResultsThe frequency of CD4+ CD25+ and CD4+CD25+CD127− Tregs was comparable between HCC and cirrhotic patients and healthy subjects. Serum prolactin and mTGF-β1 on traditional and CD4+CD25+CD127− Tregs were significantly higher in HCC and cirrhotic patients than healthy subjects with an insignificant difference between HCC and cirrhotic patients. Roc curve analysis revealed that cutoff value for mTGF-β1 on Tregs ≥ 13.5% is a good specific (87%) but low sensitive (54%) test in discriminating HCC patients from healthy subjects. The frequency of Tregs and mTGF-β1 were not correlated to clinicopathological characteristics or staging of HCC. Prolactin was higher in the multifocal lesions and negatively correlated to expressed mTGFβ1. The expressed mTGF-β1 was positively correlated with hemoglobin and alanine transaminase. The traditional Tregs was positively correlated with hemoglobin and albumin.ConclusionmTGFβ1, as a marker for suppressive function of peripheral CD4 + CD25 + CD127-Tregs, has a diagnostic role in discriminating HCV-related HCC patient from healthy subjects, unfortunately not from HCV-related cirrhotic patients. Serum prolactin has an oncogenic role as it is correlated to multiple focal lesions. It also impedes the suppressive function of peripheral Tregs as an immunogenic role. mTGF-β1 is related to hemoglobin and hepatic inflammation.

Fibroscan in Grading and Prediction of the Risk of Bleeding of Gastro-Esophageal Varices in HCV related Cirrhotic Patients

Fibroscan in Grading and Prediction of the Risk of Bleeding of Gastro-Esophageal Varices in HCV related Cirrhotic Patients

Serum serotonin as a non-invasive marker of portal hypertensive gastropathy in Egyptian patients with HCV-related liver cirrhosis.

Portal hypertensive gastropathy (PHG) is an important complication of portal hypertension (PHT) in cirrhotic patients. We aimed in the current study to investigate the validity of serum serotonin as a probable non-invasive marker for PHG in cirrhotic patients with PHT. We conducted this study on 100 HCV-related cirrhotic patients divided into three groups according to their endoscopic findings; group I: patients with no endoscopic signs of PHG; group II: patients with mild PHG; and group III: patients with severe PHG. All subjects had routine laboratory investigations, serum serotonin level using ELISA kits, calculation of Child's score, abdominal ultrasound, and upper GIT endoscopy. Serum serotonin was significantly higher in those with PHG than those without (t= 5.128, p <0.001). Moreover, it was significantly higher in patients with severe degree of PHG than those with mild PHG (t=7.357, p<0.001). Furthermore, a significant positive correlation was observed between serum serotonin and Child Pugh score (t=7.357, p<0.001). Roc curve analysis revealed that serum serotonin at a level ? 26.5 ng/ml had a 78.82% sensitivity, 73.33% specificity, and accuracy of 78% to discriminate between those with signs of PHG and those without. Serum serotonin is a valuable non-invasive marker of PHG in HCV-cirrhotic patients. Furthermore, its serial measurements could be used to monitor disease progression.

O-3 TRENDS IN DECEASED DONOR AND LIVING DONOR LIVER TRANSPLANTATION IN LATIN AMERICAN COUNTRIES DURING A DECADE (2010-2019) . THE ALEH SPECIAL INTEREST GROUP, INTERNATIONAL SURVEY 2020

Brazilian public health system currently provides universal free all oral direct-acting antiviral (DAA) therapy for patients with hepatitis C virus (HCV) infection. Despite high rates of sustained virological response (SVR), patients with cirrhosis remain at risk for hepatocellular carcinoma (HCC). The aim of this study was to investigate incidence, risk factors and tumor pattern at presentation in a cohort of Brazilian HCV-related cirrhotic patients treated with DAAs. This prospective cohort study included patients with HCV-related cirrhosis treated with DAAs and followed for at least 24 weeks after therapy at the Viral Hepatitis Outpatient Clinic of Hospital de Clinicas de Porto Alegre, Brazil, between August 2016 and November 2017. Ultrasound screening was performed within 24 weeks before DAA therapy and patients with presumed past or current HCC were excluded. Primary outcome was HCC incidence. Secondary outcomes were risk factors for HCC ocurrence and tumor pattern at presentation. Multivariate analysis was used to identify independent variables associated with HCC development. A total of 234 patients with HCV cirrhosis were included. Fifty-six percent were males with a mean age of 61.2±10.9 years. Overall SVR was 97.4%. Child-Turcotte-Pugh (CTP) A, B and C at baseline was found, respectively, in 89.3%, 9.4% and 1,3%. Mean Model for End Stage Liver Disease (MELD) score was 9.17 ± 2.82. Esophageal varices were found in 43.6% of the patients. Type 2 diabetes was present in 18.8%. De novo HCC was diagnosed in 9% (21/234) of the patients during follow-up. Tumor pattern at presentation according to BCLC staging was 0, A, B, C and D in 19,1%, 47.6%, 4.8%, 28.6% and 0%, respectively. Multivariate analysis showed significant relative risk (RR) for HCC occurrence associated with the following variables: baseline MELD score ≥10 (RR: 1.8; p =0.05); absence of SVR (RR: 6.9; p =0.04); baseline platelet count <120 × 10 9 /L (RR: 5.0; p =0.04) and baseline albumin level <3.5 mg/dL (RR: 4.6. A high incidence of HCC was found after DAA therapy compared to the literature, particularly among patients with more advanced cirrhosis, particularly those with baseline albumin levels < 3.5 g/dL plus platelets < 120 × 10 9 /L. Absence of SVR was also significantly associated with HCC development. The majority of patients presented with very early (BCLC 0) or early (BCLC A) HCC, although a significant proportion showed advanced stage (BCLC C) at presentation.

O-19 INCIDENCE, PATTERN OF PRESENTATION AND RISK FACTORS FOR HEPATOCELLULAR CARCINOMA AFTER DIRECT ACTING ANTIVIRAL TREATMENT IN PATIENTS WITH HEPATITIS C VIRUS CIRRHOSIS

Brazilian public health system currently provides universal free all oral direct-acting antiviral (DAA) therapy for patients with hepatitis C virus (HCV) infection. Despite high rates of sustained virological response (SVR), patients with cirrhosis remain at risk for hepatocellular carcinoma (HCC). The aim of this study was to investigate incidence, risk factors and tumor pattern at presentation in a cohort of Brazilian HCV-related cirrhotic patients treated with DAAs. This prospective cohort study included patients with HCV-related cirrhosis treated with DAAs and followed for at least 24 weeks after therapy at the Viral Hepatitis Outpatient Clinic of Hospital de Clinicas de Porto Alegre, Brazil, between August 2016 and November 2017. Ultrasound screening was performed within 24 weeks before DAA therapy and patients with presumed past or current HCC were excluded. Primary outcome was HCC incidence. Secondary outcomes were risk factors for HCC ocurrence and tumor pattern at presentation. Multivariate analysis was used to identify independent variables associated with HCC development. A total of 234 patients with HCV cirrhosis were included. Fifty-six percent were males with a mean age of 61.2±10.9 years. Overall SVR was 97.4%. Child-Turcotte-Pugh (CTP) A, B and C at baseline was found, respectively, in 89.3%, 9.4% and 1,3%. Mean Model for End Stage Liver Disease (MELD) score was 9.17 ± 2.82. Esophageal varices were found in 43.6% of the patients. Type 2 diabetes was present in 18.8%. De novo HCC was diagnosed in 9% (21/234) of the patients during follow-up. Tumor pattern at presentation according to BCLC staging was 0, A, B, C and D in 19,1%, 47.6%, 4.8%, 28.6% and 0%, respectively. Multivariate analysis showed significant relative risk (RR) for HCC occurrence associated with the following variables: baseline MELD score ≥10 (RR: 1.8; p =0.05); absence of SVR (RR: 6.9; p =0.04); baseline platelet count <120 × 10 9 /L (RR: 5.0; p =0.04) and baseline albumin level <3.5 mg/dL (RR: 4.6. A high incidence of HCC was found after DAA therapy compared to the literature, particularly among patients with more advanced cirrhosis, particularly those with baseline albumin levels < 3.5 g/dL plus platelets < 120 × 10 9 /L. Absence of SVR was also significantly associated with HCC development. The majority of patients presented with very early (BCLC 0) or early (BCLC A) HCC, although a significant proportion showed advanced stage (BCLC C) at presentation.

Serum level of cytokeratin 19 as a diagnostic and prognostic marker in patients with HCV-related hepatocellular carcinoma

BackgroundThe heterogeneous nature of human hepatocellular carcinoma (HCC) impedes both treatment strategies and prognostic predictions. Several markers have been proposed for the diagnosis of HCC. Cytoskeleton-associated proteins have been known as cellular integrators in neoplasm formation. Hepatic progenitor cells are thought to express alpha-fetoprotein (AFP) and hematopoietic as well as biliary markers such as cytokeratin 19 (CK 19) and cytokeratin 7. The aim of this study was to verify the role of serum CK 19 alone or in combination with AFP as a diagnostic marker of HCC and to assess the changes in its levels after ablation of HCV-related HCC to evaluate its role as a predictor marker for recurrence of HCC after ablation. The study was conducted on 102 HCV-related cirrhotic patients categorized into three different groups according to the clinical, laboratory, and radiological evaluation: group I—62 patients with early or intermediate HCC who underwent locoregional intervention, group II—20 patients with advanced HCC not fit for any intervention apart from best supportive treatment, and group III—20 cirrhotic patients with no evidence of HCC as proved by two imaging techniques.ResultsThe mean serum levels of CK 19 were 6.5 ± 5.7, 10.5 ± 12.5, and 6.8 ± 2.8 ng/ml in groups I, II, and III, respectively, with no significant difference between groups. Sensitivity, specificity, positive, and negative predictive values of combined AFP and human CK 19 at cutoff levels of 25.5 ng/ml and 6.25 ng/ml were 93.9%, 45%, 87.5%, and 64.3%, respectively. In group I patients, CK 19 levels were comparable in patients with ablated focal lesion and those who did not at baseline; then, it was significantly higher in ablated patients than in patients with residual tumor 1 and 6 months after the intervention.ConclusionsCombination of both AFP and CK 19 levels could increase the diagnostic accuracy of suspected HCCs. CK 19 levels are good predictors of ablation/recurrence in patients who underwent interventional procedures minimizing the need for follow-up imaging modalities.

Low Serum 25-Hydroxy Vitamin D (25-OHD) and Hepatic Encephalopathy in HCV-Related Liver Cirrhosis.

Background Patients with liver cirrhosis experience a large variety of metabolic disorders associated with more hepatic decompensation. Hepatic encephalopathy (HE) is a significant complication in liver cirrhosis patients, presenting a wide spectrum of neuropsychological symptoms. A deficiency of 25-hydroxy vitamin D (25-OHD) in the general population is associated with a loss of cognitive function, dementia, and Alzheimer's disease. Aim of the Study. Our study aims to check the relationship between low serum 25-OHD and HE in patients with HCV-related liver cirrhosis and assess its link with patient mortality. Patients and Methods. This study was observationally carried out on 100 patients with HCV-related liver cirrhosis. The patients were divided into 2 groups: Group A—included 50 HCV-related cirrhotic patients with HE, and Group B—included 50 HCV-related cirrhotic patients without HE. Assessment of disease severity using the end-stage liver disease (MELD) model and Child Turcotte Pugh (CTP) scores were done, and 25-OHD levels were measured. Comparison of vitamin D levels in different etiologies and different CTP categories was made using one-way ANOVA. Pearson's correlation between the level of vitamin D and other biomarkers was applied. Results There was a statistically significant Vitamin D level difference between the two groups. A lower level of vitamin D was observed in the HE group where the severe deficiency was 16%, while it was 6% in the other group and the moderate deficiency was 24% in HE group as compared to 10% in the other group. The insufficient vitamin D level represented 46% of the non-HE group while none of the HE group falls in this category. Vitamin D level was statistically higher in Grade 1 HE than in Grade 2 which is higher than in Grades 3 to 4. Vitamin D level was also significantly higher in those who improved from HE as compared to those who died. Conclusion The lower levels of 25-OHD were associated with the higher incidence of HE in cirrhotic HCV patients. The worsening vitamin D deficiency was associated with increased severity of the liver disease, so vitamin D may be considered a prognostic factor for the severity of liver cirrhosis and high mortality rate in HE patients.

Sudomotor Changes in Hepatitis C Virus Infection with or without Diabetes Mellitus: A Pilot Study in Egyptian Patients.

Hepatitis C virus (HCV) infection can affect the neurological system, and neuropathy is one of these manifestations. Hepatitis C virus infection is associated with diabetes mellitus (DM) type II, and diabetic patients are at higher risk of acquiring HCV infection. Sweat function has been proposed to assess early autonomic neuropathy. This study aimed to evaluate small fiber neuropathy in asymptomatic HCV-related cirrhotic patients with or without DM through sweat function assessment by Sudoscan test. Three groups were involved: 47 healthy controls, 48 HCV-related cirrhotic patients without DM (group 1), and 49 HCV-related cirrhotic patients with DM type II (group 2). All participants were subjected to liver panel tests, renal function tests, cell blood counts, HbA1c, and abdominal ultrasound. Sweat function was assessed in all patients and controls by measuring hand and feet electrochemical skin conductance (ESC, microSiemens [µS]) using Sudoscan. Peripheral neuropathy was detected in none of the controls, 39% of group 1 patients, and 62% of group 2 patients (P < 0.0001). The mean feet ESC (FESC) was 88.3 ± 6.8 µS in controls, 67.2 ± 19.2 µS in group 1, and 57.9 ± 19.4 µS in group 2 (P < 0.0001). A significant correlation was observed between FESC and bilirubin, albumin, creatinine, international normalized ratio, transaminases, and splenic size. Electrochemical skin conductance measurement is a valuable, noninvasive method for early detection of small fiber neuropathy in asymptomatic HCV-related cirrhosis, with or without DM.

Novel markers of endothelial dysfunction in hepatitis C virus-related cirrhosis: More than a mere prediction of esophageal varices.

BACKGROUNDHepatitis C virus (HCV) infection may affect lipid metabolism by enhancing the circulating levels of inflammatory cytokines, together with its impact on endothelial function. AIMTo evaluate the potential correlation of changes in lipid profile, carotid intima-media thickness (CIMT), and ankle-brachial index with the severity of fibrosis, grades of esophageal varices (EVs), and fibrosis indices.METHODSThe study included 240 subjects who were divided into 3 groups; group 1 (n = 90, HCV-related cirrhotic patients with EVs), group 2 (n = 90, HCV-related cirrhotic patients without EVs), and group 3 (n = 60, served as the healthy control group). All patients underwent routine laboratory tests, including a lipid profile assay. Low-density lipoproteins (LDL)/platelet count and platelet/splenic diameter ratios were calculated. Abdominal ultrasonography, CIMT by carotid Doppler, bedside ankle-brachial index (ABI), liver stiffness measurement, and upper gastrointestinal endoscopy were performed.RESULTSMultivariate logistic regression revealed that very-low-density lipoprotein (VLDL) (β = 0.988, odds ratio 2.5, P = 0.001), LDL/platelet count ratio (β = 1.178, odds ratio 3.24, P = 0.001), CIMT (β = 1.37, odds ratio 3.9, P = 0.001), and ABI (β = 2.3, odds ratio 5.9, P = 0.001) were the key variables associated with significant fibrosis, EVs and endothelial dysfunction. CIMT and LDL/platelet count ratio were predictive of advanced fibrosis and EVs at cutoff values of 1.1 mm and 1 mm, respectively, with an area under the curve (AUC) of 0.966 and 0.960 (P = 0.001), while VLDL and ABI at a cutoff of 16.5 mg/dL and 0.94 were predictive of advanced fibrosis and EVs with an AUC of 0.891 and 0.823, respectively (P = 0.001).CONCLUSIONCIMT, ABI, VLDL, LDL/platelet count ratio are good non-invasive predictors of advanced fibrosis, presence of EVs, and endothelial dysfunction in liver cirrhosis.

Role of abbreviated MRI protocol for screening of HCC in HCV related cirrhotic patients prior to direct-acting antiviral treatment

BackgroundChronic HCV infection is a global health problem causing progressive hepatic fibrosis, cirrhosis, and ultimately hepatocellular carcinoma (HCC). Recent advantage of direct-acting antiviral drugs (DAA) with a high sustained virologic response (SVR) reduces overall HCV-related morbidity and mortality, yet recent studies report a high recurrence rate of HCC after DAA; this calls availability of a reliable screening method to properly exclude HCC before DAA treatment.The primary objective of our cohort study was to assess the feasibility of an abbreviated MRI protocol as a screening tool for the detection of hepatic focal lesions/early HCC in patients with HCV-related liver cirrhosis.The study included 41 patients with HCV-related cirrhosis candidates to DAA therapy. All patients underwent routine screening for HCC by combined abdominal ultrasound and serum alfa-fetoprotein. An abbreviated MRI protocol (Abr-MR) including combined T2-weighted image and diffusion-weighted imaging (DWI) followed by dynamic contrast-enhanced MRI (CE-MRI) was performed for all subjects, assessing for presence and characterization of focal lesions.ResultsFor all included 41patients, no elevation of the alpha-fetoprotein was shown. Ultrasound detected a single focal lesion in one patient. Abbreviated MR demonstrated 15 focal lesions; for detected lesions, 1 lesion shows “shine though” and the rest showing moderate and high degrees of restriction. CE-MRI characterized lesions as 1 lesion = LIRADS-1, 3 lesions = LR-M, and 11 lesions = LR-5.The standard screening using combined ultrasound and alpha-fetoprotein had sensitivity, specificity, PPV, and NPV of 6.6 % (95% CI = 0.0034–0.29), 100% (95% CI = 0.89–1.000), 100% (95% CI = 0.051–1.000), and 68.8% (95% CI = 0.54–0.80). Abr-MR protocol showed sensitivity, specificity, PPV, and NPV of 100% for all parameters (95% CI = 0.79–1.000, 0.89–1.000, 0.79–1.000, and 0.89–1.000 respectively).ConclusionIn our study, we demonstrate the superiority of a proposed cost-effective Abr-MR protocol in the detection of hepatic focal lesions and small-sized HCC compared to routine screening using alpha-fetoprotein and ultrasound in HCV-related liver cirrhosis.

“Helicobacter pylori infection in HCV related liver cirrhotic patients; prevalence and association with upper gastrointestinal bleeding.”

“Helicobacter pylori infection in HCV related liver cirrhotic patients; prevalence and association with upper gastrointestinal bleeding.”

Prognostic value of serum autotaxin in liver cirrhosis and prediction of hepatocellular carcinoma

BackgroundAutotaxin is a lysophospholipase D related to liver fibrosis; its clinical role in liver cirrhosis is still unknown or limited. In this study we investigate the relation of autotaxin serum levels and prognosis of liver disease and/or prediction of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV) patients.Patients and methodsThis observational, prospective case–control study included 180 participants, 60 patients with HCV-related liver cirrhosis, 60 HCV noncirrhotic patients, and 60 healthy controls. They were enrolled from inpatients and clinics of a tertiary-care hospital. Baseline characteristics, serum autotaxin, Child–Turcotte–Pugh and model of end-stage liver disease scores were determined. Abdominal ultrasound and upper gastrointestinal endoscopy were done at the beginning of the study. Cirrhotic patients were prospectively followed up for 6 months.ResultsPatients with liver cirrhosis had the highest level of autotaxin (106±24 μg/ml) compared with noncirrhotic HCV patients (81.9±21 μg/ml) and healthy controls (42.5±11 μg/ml) using one-way analysis of variance test (P=0.000). Spearman’s correlation analysis showed no significant correlation between autotaxin and Child–Turcotte–Pugh score (r=0.02; P<0.70), and model of end-stage liver disease score (r=0.15; P<0.41). At 6 months of follow-up, patients who developed HCC or encephalopathy had significantly higher baseline autotaxin level (141±55 μg/ml; P=0.02, 117±56.6 μg/ml; P=0.000), respectively, than patients who did not (102±34, 90.7±40 μg/ml). Cutoff values of autotaxin for the prediction of HCC and encephalopathy were 95 and 92μg/ml, respectively, with 91 and 92% sensitivity.ConclusionAutotaxin is a sensitive predictor for the development of HCC and encephalopathy in HCV-related cirrhotic patients. However, it was not related to disease severity.

Are there differences in risk factors, microbial aspects, and prognosis of cellulitis between compensated and decompensated hepatitis C virus-related cirrhosis?

Background/AimsCellulitis is a common infection in patients with liver cirrhosis. We aimed to compare risk factors, microbial aspects, and outcomes of cellulitis in compensated and decompensated hepatitis C virus (HCV)-related cirrhosis.MethodsSix hundred twenty consecutive HCV-related cirrhotic patients were evaluated for cellulitis. Demographic and clinical data were evaluated, along with blood and skin cultures. Severity of cirrhosis was assessed using Child-Pugh score. In-hospital mortality was assessed.ResultsSeventy-seven (12.4%) cirrhotic patients had cellulitis (25 with compensated and 52 with decompensated disease). Smoking and venous insufficiency were risk factors of cellulitis in compensated cirrhosis. Leg edema, ascites, hyperbilrubinemia and hypoalbuminemia were risk factors in decompensated cirrhosis. Gram-positive bacteria (Staphylococcus spp. and Streptococcus pyogenes) were the infective organisms in compensated patients, while gram negative bacteria (Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) were the predominant organisms in decompensated cirrhosis. Fungi (Candida albicans and Aspergillus niger) were detected in 3 decompensated cases. In-hospital mortality in patients with cellulitis was 27.3%, approaching 100% in decompensated patients with gram-negative cellulitis. Prolonged hospitalization, higher model for end-stage liver disease (MELD)-Na score, septic shock, local complication, and recurrent cellulitis were predictors of mortality.ConclusionsCellulitis in compensated cirrhosis is different from that of decompensated patients regarding microorganisms, pathogenesis, and prognosis. Cellulitis has a poor prognosis, with mortality rates approaching 100% in decompensated patients with gram-negative cellulitis. Stratifying patients according to severity of cirrhosis is important to identify the proper empirical antibiotic and to decide the proper means of care.

Impact of direct-acting antivirals on leukocytic DNA telomere length in hepatitis C virus-related hepatic cirrhosis.

Direct-acting antiviral (DAAs) represent advancement in the management of hepatitis C virus (HCV)-related hepatic cirrhosis. A high proportion of patients achieve a sustained virologic response; eradication of HCV is coupled with a decreased risk of hepatocellular carcinoma. Recent evidence suggests that shortening of the DNA telomere may be linked to cellular senescence as well as predisposition to malignant transformation. This study aimed to assess pretreatment leukocytic DNA telomere length in HCV-related cirrhosis and post viral eradication using DAAs. This study included 24 patients with HCV-related cirrhosis, Child-Pugh A. Whole-blood samples were obtained from patients before treatment and 12 weeks after the end of treatment, as well as from 24 healthy controls. Terminal restriction fragment, corresponding to telomere length, was measured using a nonradioactive Southern blot technique, detected by chemiluminescence. DNA telomere length was significantly shorter before treatment compared with 12 weeks after end of treatment in HCV-related cirrhotic patients. Also, it was significantly shorter in patients before treatment compared with healthy individuals. Telomere elongation in blood leukocytes can be considered a marker of recovery of inflammation after DAAs-induced HCV eradication. Still, the possibility of activation by cancer initiation cannot be excluded.

Portal hypertensive colopathy in Egyptian cirrhotic patients: an endoscopic study

BackgroundHepatitis C virus (HCV) infection is a major health problem in Egypt. It is often complicated by liver cirrhosis and portal hypertension, resulting in gastroesophageal varices, gastropathy, and colopathy. However, there is still lack of data with respect to the prevalence and clinical relevance of colopathy in this kind of liver disease. The aim of this study was to determine the prevalence of colopathic lesions in HCV-related cirrhotic patients, and to study their associations with the severity of liver disease and manifestations of portal hypertensionPatients and methodsThis cross-sectional study included 60 patients with liver cirrhosis who were submitted to thorough clinical, laboratory, and ultrasonographic examinations. In addition, both upper and lower gastrointestinal endoscopy were performed to detect portal hypertensive complications including colopathic lesions. According to their severity, colopathic lesions were graded into three grades. Patients with higher colopathic grading (grade 2 and 3) were compared with the remaining participants with respect to the severity of the liver disease and other manifestations of portal hypertension.ResultsThe prevalence of colopathy in cirrhotic patients with underlying HCV etiology was 91%. Patients with higher grades of colopathy were characterized by more severe liver disease. Moreover, they had increased frequency of both esophageal and gastric varices, and prior sclerotherapy or band ligation, as well as more collaterals and gastropathy, and higher grades of esophageal varices.ConclusionColopathic lesions are frequent in patients with HCV-induced cirrhosis. Getting endoscopic treatment for varices is a risk factor for developing higher grades of colopathy. The latter could be considered as a marker of a worse prognosis in patients with HCV cirrhosis.

Evaluation of Glycated Albumin to Glycated Hemoglobin Ratio as a Predictor for Esophageal varices and its Risk of Bleeding

Background: Variceal hemorrhaging due to portal hypertension is a severe complication of liver cirrhosis. Although several biomarkers have been reported as predictors of the presence of varices, it is still difficult to assess the risk of variceal bleeding without esophagogastroduodenoscopy (EGD). The ratio of glycated albumin (GA) to glycated hemoglobin (HbA1c) was reported to increase with the progression of liver fibrosis. The aim of the study was to investigate whether the GA/HbA1c ratio is related to the severity and bleeding risk of the varices. Aim of the work: goal of our study was to assess the value of Glycated albumin to Glycated hemoglobin ratio in the prediction of esophageal varices and assessing its risk of bleeding. Methods: We measured the GA/HbA1c ratio of HCV-related cirrhotic patients and analyzed its relationship with the presence and bleeding risk of varices. Results: The GA/HbA1c ratio was higher in the patients who had the varices with a high risk of hemorrhage than in the patients with a low risk of bleeding. In addition, the GA/HbA1c ratio was higher in patients with varices than that in patients without varices. Furthermore, the GA/HbA1c ratio was the most significantly different parameter of all the factors examined, including the platelet count, prothrombin activity and albumin level. Conclusion: The GA/HbA1c ratio is increased in patients with varices and with the bleeding risk of the varices.

Evaluation of Glycated Albumin to Glycated Hemoglobin Ratio as a Predictor for Esophageal varices and its Risk of Bleeding

Background: Variceal hemorrhaging due to portal hypertension is a severe complication of liver cirrhosis. Although several biomarkers have been reported as predictors of the presence of varices, it is still difficult to assess the risk of variceal bleeding without esophagogastroduodenoscopy (EGD). The ratio of glycated albumin (GA) to glycated hemoglobin (HbA1c) was reported to increase with the progression of liver fibrosis. The aim of the study was to investigate whether the GA/HbA1c ratio is related to the severity and bleeding risk of the varices. Aim of the work: goal of our study was to assess the value of Glycated albumin to Glycated hemoglobin ratio in the prediction of esophageal varices and assessing its risk of bleeding. Methods: We measured the GA/HbA1c ratio of HCV-related cirrhotic patients and analyzed its relationship with the presence and bleeding risk of varices. Results: The GA/HbA1c ratio was higher in the patients who had the varices with a high risk of hemorrhage than in the patients with a low risk of bleeding. In addition, the GA/HbA1c ratio was higher in patients with varices than that in patients without varices. Furthermore, the GA/HbA1c ratio was the most significantly different parameter of all the factors examined, including the platelet count, prothrombin activity and albumin level. Conclusion: The GA/HbA1c ratio is increased in patients with varices and with the bleeding risk of the varices.

Reversal of hypercoagulability in patients with HCV-related cirrhosis after treatment with direct-acting antivirals.

The long-term impact of sustained virological response (SVR) after direct-acting antivirals (DAAs) on the hypercoagulability associated with HCV cirrhosis is unknown. We longitudinally evaluated the effect of DAAs treatment on cirrhotic coagulopathy. Pro- and anticoagulant factor levels and thrombin generation were assessed in patients with HCV-related cirrhosis at baseline, end of therapy (EOT), at 12, 24 and 48weeks (W) after EOT. Fifty-eight patients were enrolled (86% Child's A). SVR was 100%. Median factor VIII activity significantly decreased at EOT, 12weeks and 24weeks compared with baseline, whereas protein C significantly increased at 24weeks and 48weeks. Cirrhotic patients showed a slight but sustained increase in endogenous thrombin potential (ETP) with a statistically significant difference at EOT, 12weeks, 24weeks and 48weeks compared with baseline. Conversely, thrombomodulin-modified ETP was elevated before treatment and decreased over time to normal levels at 24weeks and 48weeks. The ETP ratio decreased slowly at EOT and 12weeks, and was significantly decreased at 24weeks and 48weeks compared with baseline (P<.001 for both comparisons), being not statistically different from ETP ratio measured in healthy controls. Child's B patients showed a significantly higher ETP ratio compared to Child's A at baseline and did not show any significant improvement in ETP ratio through 12weeks. Two Child's B patients developed PVT with an incidence rate of 1.1% p-yrs (95%CI, 0.18 to 3.58). DAAs therapy in HCV-related cirrhotic patients is associated with significant changes in thrombin generation suggesting a reversal of hypercoagulability particularly in Child's A patients.

Hepatocellular carcinoma risk assessment by the measurement of liver stiffness variations in HCV cirrhotics treated with direct acting antivirals

BackgroundDirect-acting antivirals (DAA) are an effective treatment for hepatitis C virus infection. However, sustained virologic response (SVR) after DAA treatment does not seem to reduce the risk of hepatocellular carcinoma (HCC) development in these patients. Liver stiffness measurement (LSM) may predict the risk of developing HCC in liver cirrhosis patients. AimsThe aim of our study was to evaluate the role of LSM variation as predictor of HCC development in patients treated with DAA. MethodsIn 139 HCV-related cirrhotic patients, LSM and laboratory tests were carried out at baseline (BL) and at the end of DAA treatment (EOT). Patients were followed for at least 6 months after the EOT. LSM reduction was expressed as Delta LS (∆LS). Cox regression analysis was used to identify prognostic factors for HCC development after DAA. ResultsMedian LSM values were significantly reduced from BL to EOT (from 18.6 to 13.8 kPa; p < 0.001). The median ∆LS was −26.7% (IQR: −38.4% −13.6%). During a median follow-up of 15 months after DAA treatment, 20 (14.4%) patients developed HCC. Significant LSM reduction was observed both in patients who developed HCC and in those who did not, but this was significantly lower in the patients who developed HCC (−18.0% vs −28.9% p = 0.005). At multivariate analysis, ∆LS lower than −30%, Child-Turcotte-Pugh-B and history of HCC were independently associated with HCC development. ConclusionOur results indicate that ∆LS is a useful non-invasive marker for predicting HCC development after DAA treatment.