Functional and morphological myocardial changes in hepatitis C virus patients with end-stage liver disease.

BACKGROUND AND OBJECTIVES: Cardiovascular complications are common in liver transplant recipient. This study aims to evaluate functional and morphological myocardial changes in hepatitis C virus (HCV) patients with end-stage liver disease (ESLD) by cardiac magnetic resonance (CMR). METHODS: This cross-sectional study included 84 patients with HCV-related ESLD. They were subjected to 2D-echocardiography and CMR. The presence, distribution, and percentage of delayed myocardial enhancement (DME) were estimated. RESULTS: The mean Model for End-Stage Liver Disease score was 21.5 ± 6.3. In CMR, all patients showed good global left ventricular (LV) systolic function (mean ejection fraction = 66.5 ± 8.6%; range: 55-80) with normal wall thickness and motion. Left ventricle was mildly dilated in 25 patients (30%). Grade I and grade II diastolic dysfunction was detected in 81 patients (96.4%) with dilated left atrium in 25 patients (30%). Variable degrees of DME were detected in 70 patients (83.3%) with mean percentage of DME (%DME) being 19.5 ± 16% (range: 4-52). A significant negative correlation was found between %DME and LV ejection fraction (r = -0.7; p < 0.001), cardiac output (r = -0.5; p = 0.013), cardiac index (r = -0.5; p = 0.02), and serum albumin level (r = -0.5; p = 0.01). The %DME ≥19% was associated with 85.7% sensitivity and 85.7% specificity for detection of LV ejection fraction <60% as assessed by echocardiography (area under curve = 0.89; p = 0.001). CONCLUSION: DME with CMR is a common finding among patients with HCV-related ESLD. The extent of DME is significantly associated with global LV systolic function.

Can transient elastography, Fib-4, Forns Index, and Lok Score predict esophageal varices in HCV-related cirrhotic patients?

BACKGROUND: Gastroesophageal varices are present in approximately 50% of patients with liver cirrhosis. The aim of this study was to evaluate liver stiffness measurement (LSM), Fib-4, Forns Index and Lok Score as noninvasive predictors of esophageal varices (EV). METHODS: This prospective study included 65 patients with HCV-related liver cirrhosis. All patients underwent routine laboratory tests, transient elastograhy (TE) and esophagogastroduodenoscopy. FIB-4, Forns Index and Lok Score were calculated. The diagnostic performances of these methods were assessed using sensitivity, specificity, positive predictive value, negative predictive value, accuracy and receiver operating characteristic curves. RESULTS: All predictors (LSM, FIB-4, Forns Index and Lok Score) demonstrated statistically significant correlation with the presence and the grade of EV. TE could diagnose EV at a cutoff value of 18.2kPa. Fib-4, Forns Index, and Lok Score could diagnose EV at cutoff values of 2.8, 6.61 and 0.63, respectively. For prediction of large varices (grade 2, 3), LSM showed the highest accuracy (80%) with a cutoff of 22.4kPa and AUROC of 0.801. Its sensitivity was 84%, specificity 72%, PPV 84% and NPV 72%. The diagnostic accuracies of FIB-4, Forns Index and Lok Score were 70%, 70% and76%, respectively, at cutoffs of 3.3, 6.9 and 0.7, respectively. For diagnosis of large esophageal varices, adding TE to each of the other diagnostic indices (serum fibrosis scores) increased their sensitivities with little decrease in their specificities. Moreover, this combination decreased the LR- in all tests. CONCLUSION: Noninvasive predictors can restrict endoscopic screening. This is very important as non invasiveness is now a major goal in hepatology.

Survival and outcomes for co-infection of chronic hepatitis C with and without cirrhosis and COVID-19: A multicenter retrospective study.

BACKGROUND: Chronic liver disease, particularly cirrhosis, is associated with worse outcomes in patients infected with coronavirus disease 2019 (COVID-19). AIM: To assess outcomes of COVID-19 infection among patients with pre-existing hepatitis C with or without liver cirrhosis. METHODS: This multicenter, retrospective cohort study included all cases of confirmed co-infection of severe acute respiratory syndrome coronavirus 2 and chronic hepatitis C with or without liver cirrhosis who were admitted to six hospitals (Al-Sahel Hospital, Al-Matareya Hospital, Al-Ahrar Hospital, Ahmed Maher Teaching Hospital, Al-Gomhoreya Hospital, and the National Hepatology and Tropical Medicine Research Institute) affiliated with the General Organization for Teaching Hospitals and Institutes in Egypt. Patients were recruited from May 1, 2020, to July 31, 2020. Demographic, laboratory, imaging features, and outcomes were collected. Multivariate regression analysis was performed to detect factors affecting mortality. RESULTS: This retrospective cohort study included 125 patients with chronic hepatitis C and COVID-19 co-infection, of which 64 (51.20%) had liver cirrhosis and 40 (32.00%) died. Fever, cough, dyspnea, and fatigue were the most frequent symptoms in patients with liver cirrhosis. Cough, sore throat, fatigue, myalgia, and diarrhea were significantly more common in patients with liver cirrhosis than in non-cirrhotic patients. There was no difference between patients with and without cirrhosis regarding comorbidities. Fifteen patients (23.40%) with liver cirrhosis presented with hepatic encephalopathy. Patients with liver cirrhosis were more likely than non-cirrhotic patients to have combined ground-glass opacities and consolidations in CT chest scans: 28 (43.75%) vs 4 (6.55%), respectively (P value < 0.001). These patients also were more likely to have severe COVID-19 infection, compared to patients without liver cirrhosis: 29 (45.31%) vs 11 (18.04%), respectively (P value < 0.003). Mortality was higher in patients with liver cirrhosis, compared to those with no cirrhosis: 33 (51.56%) vs 9 (14.75%), respectively (P value < 0.001). All patients in Child-Pugh class A recovered and were discharged. Cirrhotic mortality occurred among decompensated patients only. A multivariate regression analysis revealed the following independent factors affecting mortality: Male gender (OR 7.17, 95%CI: 2.19-23.51; P value = 0.001), diabetes mellitus (OR 4.03, 95%CI: 1.49-10.91; P value = 0.006), and liver cirrhosis (OR 1.103, 95%CI: 1.037-1.282; P value < 0.0001). We found no differences in liver function, COVID-19 disease severity, or outcomes between patients who previously received direct-acting antiviral therapy (and achieved sustained virological response) and patients who did not receive this therapy. CONCLUSION: Patients with liver cirrhosis are susceptible to higher severity and mortality if infected with COVID-19. Male gender, diabetes mellitus, and liver cirrhosis are independent factors associated with increased mortality risk.

Evaluation of Serum and Gene Expression of Galectin-4, Interleukin-27, and Complement-7 in Hepatitis C Virus-Infected Egyptian Patients.

BACKGROUND: Hepatitis C virus (HCV) is considered a major global public health problem. Recently, there are great advances in HCV therapy, but there are some limitations that are creating an urgent need for assessment of some cytokines that have a potent antiviral effect in the immune system and anti-inflammatory effects to provide a potential novel immunotherapeutic target in HCV infection. OBJECTIVE: This study was directed to assess the serum levels and gene expression levels of Galectin-4 (LEG4), Interleukin-27 (IL-27), and Complement-7 (C-7) and their correlation with the viral load in HCV infection. Subjects and Methods. This work was conducted on 80 subjects, Group 1 (n = 40) early detected HCV patients and Group 2 (n = 40) healthy controls. LEG4, IL-27, and C-7 were assessed at the protein levels by ELISA, and their gene expression was assessed by RT-qPCR. The viral load was measured by PCR. RESULTS: There were significant elevations in the mean levels of gene expression and serum levels of all studied parameters LEG4, IL-27, and C-7 in the HCV group compared to the control group. Significant negative correlations between the viral load and each of the serum proteins and gene expressions of both LEG4 and IL-27 in HCV patients were found. The gene expression levels of LEG4, IL-27, and C-7 were positively correlated with their corresponding serum proteins in HCV patients. CONCLUSION: LEG4 and IL-27 showed significant negative correlations with the viral load, which could be an immune response to the control of the extent of hepatic inflammation, thus creating a potential novel immunotherapeutic approach in HCV infection for further studies or therapeutic clinical trials.

Tumor behavior of hepatocellular carcinoma after hepatitis C treatment by direct-acting antivirals: comparative analysis with non-direct-acting antivirals-treated patients.

INTRODUCTION: Scarce reports have commented on hepatocellular carcinoma (HCC) behavior after direct-acting antivirals (DAAs). AIM: To analyze differences in tumor behavior between patients with hepatitis C virus (HCV)-induced HCC and were either treated or not using DAAs. PATIENTS AND METHODS: This case-control study includes patients with HCV-related HCC who received generic DAAs (group I) and all non-DAA treated patients with HCC who presented to our clinic during the same period (group II). Patient and tumor characteristics, treatment types and outcome were compared between the two groups. RESULTS: Group I included 89 patients and group II included 207 patients. No significant difference was detected between groups regarding HCC number or size. Group I showed a more infiltrative HCC pattern, whereas group II had more circumscribed and delineated lesions. The incidence of portal vein thrombosis and significant lymphadenopathy was significantly higher in group I (P=0.03 and 0.03, respectively). Serum levels of α-fetoprotein were significantly higher in group I (P=0.02). These factors significantly affected the response to HCC management (P=0.03). Incidence of complete responses were 47.2 and 49.8% for groups I and II, respectively, whereas incomplete responses were 12.4 and 25.1%, respectively. Supportive treatment was applied to 40.4% in group I and 25.1% in group II. CONCLUSION: HCC behavior was more aggressive in DAA-treated patients regarding portal vein thrombosis, malignant lymphadenopathy, and HCC imaging characteristics, which affected the chance of ablation and the treatment response.

De-novo versus recurrent hepatocellular carcinoma following direct-acting antiviral therapy for hepatitis C virus.

INTRODUCTION: A recent appearance of direct-acting antivirals (DAAs) led to a surge in hepatitis C virus (HCV) management. Nowadays, a large proportion of treated patients have cirrhosis with a retained possibility to develop hepatocellular carcinoma (HCC) even after complete cure. We aimed to study tumoral differences between patients who developed HCC after DAAs as either a recurrence or de-novo HCC. METHODS: We retrospectively analyzed 89 patients who presented to our HCC multidisciplinary clinic with HCC lesions following DAA therapy. A total of 45 patients had complete response to HCC according to the modified Response Evaluation Criteria in Solid Tumors before DAAs intake. Another 44 patients developed de-novo lesions after DAA treatment. Both groups were compared regarding their baseline characteristics, tumor criteria, response to DAAs as well response to HCC treatment. RESULTS: Both groups showed no significant difference regarding their baseline characteristics (age, sex, Child-Pugh score, and performance status) or response to DAAs (P=0.5). No significant difference was present between groups according to number, site, and size of lesions. However, time elapsed between the end of DAAs therapy and first diagnosis of HCC was significantly longer in de-novo group (15.22±16.39 months) versus recurrence group (6.76±5.1 months) (P=0.008). In addition, response to ablation was significantly better in de-novo lesions compared with recurrent HCC (P=0.03). CONCLUSIONS: Although de-novo HCC lesions significantly developed later than recurrent lesions in DAAs-treated patients, their response rates were significantly better. No differences were detected between both groups in their response to DAAs and their tumoral characteristics.

Serum Zinc Deficiency and its Relation to Liver Fibrosis in Chronic HCV: a Real-Life Egyptian Study.

Zinc is essential for the activation of approximately 300 metallo-enzymes. Serum and hepatic zinc is decreased in chronic liver disease patients, and zinc depletion has been suggested to accelerate liver fibrosis. The study was designed to assess Zinc status in chronic HCV Egyptian patients and its relationship to fibrosis stage diagnosed by FibroScan. This was a cross-sectional study on 297 Egyptian patients with naïve chronic HCV. All patients underwent laboratory tests (including assessment of serum Zinc) and liver stiffness measurement (LSM) by Transient Elastography (FibroScan®). The study included 170 (57.2%) females and 127 (42.8%) males with a mean age 52.4 ± 10.2 years. Most of the patients had zinc deficiency as the mean zinc level was 55.5 ± 30.7 µg/dl. The FibroScan scores showed that 97 patients had mild to moderate fibrosis (≤F2), while 200 patients had advanced to severe fibrosis (˃F2). Zinc level was significantly lower in patients with ˃F2 than those with ≤F2 (52 ± 30.7 vs 62.5 ± 29.7, p value: 0.005), as the zinc values decreased with the progression of liver fibrosis. Serum zinc level had a negative significant correlation with INR and negative significant correlation with FibroScan score but no correlation to bilirubin, ALT, AST, or albumin. Most of Egyptian chronic liver disease patients had zinc deficiency. Zinc level gets significantly lower with progression of fibrosis. Zinc supplementation is essential before and during antiviral therapy for HCV.

Aberrant p16INK4A methylation: Relation to viral related chronic liver disease and hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is currently the fifth most common solid tumor worldwide and the third leading cause of cancer related deaths. Several studies have shown that the tumor suppressor gene p16INK4A is frequently downregulated by aberrant methylation of the 5'-cytosine-phosphoguanine island within the promoter region. AIM: To find out the frequency of methylated p16INK4A in the peripheral blood of HCC and cirrhotic patients and to evaluate its role in hepatocarcinogenesis. PATIENTS AND METHODS: This study was performed on 58 subjects: 30 HCC patients, 20 cirrhotic patients, and eight healthy volunteers. Methylation of p16INK4A was examined using methylation specific polymerase chain reaction (PCR) (MSP). Comparison of quantitative variables between the study groups was done using Mann-Whitney U test for independent samples when not normally distributed. For comparing categorical data, Chi-square (χ(2)) test was performed. Exact test was used instead when the expected frequency was less than 5. RESULTS: Methylation of p16INK4A was found in 6.7% of HCC patients, 5% of liver cirrhosis (LC) patients, and none of the healthy volunteers; 66.67% of the p16INK4A-methylated cases (2/3) were positive for anti-hepatitis C virus (HCV) antibodies (one of them had HCC). All HCC cases with aberrant p16INK4A methylation show very high serum alpha fetoprotein (AFP) level (9,080; 30,000 µg/mL). There were no significant associations between the status of p16INK4A methylation and tumor size. CONCLUSION: Hypermethylation of p16INK4A was found to be infrequent among Egyptian patients with HCC.

Evaluation of serum LINE-1 hypomethylation as a prognostic marker for hepatocellular carcinoma.

BACKGROUND AND STUDY AIMS: Global hypomethylation is one of the most consistent epigenetic changes in cancer. Development of hepatocellular carcinoma (HCC) must be understood as a multistep process with accumulation of genetic and epigenetic alterations. In the last decades, in addition to genetic alterations, epigenetic changes have been recognized as an important and alternative mechanism in tumourigenesis. We investigated the clinical implications of global hypomethylation in the sera of patients with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: PCR was used to assess the methylation status of long interspersed nuclear element type 1 (LINE-1) repetitive sequences in genomic DNA derived from sera of 50 patients with HCC, 20 patients with cirrhosis, 20 patients with chronic hepatitis C and 10 healthy subjects. RESULTS: Serum genome hypomethylation was significantly increased in patients with HCC (p<0.001). The levels of serum LINE-1 hypomethylation at initial presentation correlated significantly with tumour size, tumour number and alpha-foetoprotein level. Moreover high serum LINE-1 hypomethylation correlates significantly with poor survival. CONCLUSION: Serum LINE-1 hypomethylation may serve as a prognostic marker for patients with HCC.

Can transient elastography, Fib-4, Forns Index, and Lok Score predict esophageal varices in HCV-related cirrhotic patients?

BACKGROUND: Gastroesophageal varices are present in approximately 50% of patients with liver cirrhosis. The aim of this study was to evaluate liver stiffness measurement (LSM), Fib-4, Forns Index and Lok Score as noninvasive predictors of esophageal varices (EV).Methods This prospective study included 65 patients with HCV-related liver cirrhosis. All patients underwent routine laboratory tests, transient elastograhy (TE) and esophagogastroduodenoscopy. FIB-4, Forns Index and Lok Score were calculated. The diagnostic performances of these methods were assessed using sensitivity, specificity, positive predictive value, negative predictive value, accuracy and receiver operating characteristic curves. Results All predictors (LSM, FIB-4, Forns Index and Lok Score) demonstrated statistically significant correlation with the presence and the grade of EV. TE could diagnose EV at a cutoff value of 18.2 kPa. Fib-4, Forns Index, and Lok Score could diagnose EV at cutoff values of 2.8, 6.61 and 0.63, respectively. For prediction of large varices (grade 2, 3), LSM showed the highest accuracy (80%) with a cutoff of 22.4 kPa and AUROC of 0.801. Its sensitivity was 84%, specificity 72%, PPV 84% and NPV 72%. The diagnostic accuracies of FIB-4, Forns Index and Lok Score were 70%, 70% and76%, respectively, at cutoffs of 3.3, 6.9 and 0.7, respectively. For diagnosis of large esophageal varices, adding TE to each of the other diagnostic indices (serum fibrosis scores) increased their sensitivities with little decrease in their specificities. Moreover, this combination decreased the LR− in all tests. Conclusion Noninvasive predictors can restrict endoscopic screening. This is very important as non invasiveness is now a major goal in hepatology

ANTECEDENTES: Aproximadamente, el 50% de los pacientes con cirrosis hepática presentan varices gastroesofágicas. El objetivo de este estudio es evaluar la medida de rigidez hepática (LSM, por su nombre en inglés), FIB-4, el índice de Forns y el índice de Lok como predictoresno invasivos de varices esofágicas (VE).MÉTODOS: Este estudio prospectivo incluyó a 65 pacientes con cirrosis hepática asociada a VHC. Todos los pacientes fueron sometidos a pruebas de laboratorio rutinarias, elastografía de transición (ET) y endoscopia de las vías digestivas altas. Se calculó el FIB-4, el índice de Fornsy el índice de Lok. Se evaluó el rendimiento de estos métodos respecto al diagnóstico mediante la medición de sensibilidad, especificidad, valor predictivo positivo (VPP), valor predictivo negativo (VPN), precisión y curvas ROC. RESULTADOS: todos los predictores (LSM, FIB-4, índice de Fornse índice de Lok) mostraron una correlación estadísticamente significativa entre la presencia y el grado de EV. La elastografía de transición diagnosticó EV con un valor de corte de 18,2 KPa. El valor de corte para Fib-4, índice de Forns, índice de Lok fue de 2,8; 6,61 y 0,63 respectivamente. En la predicción de varices grandes (grado 2, 3) LSM mostró la precisión más elevada (80%) con un punto de corte de 22,4 KPa y una AUROC de 0,801. Su sensibilidad fue del 84%, la especificidad del 72%, el VPP de 84% y el VPN de 72%. La precisión diagnóstica de FIB-4, índice de Forns e índice de Lok fueron del 70, 70 y 76% respectivamente, con puntos de corte de 3,3; 6,9 y 0,7 respectivamente. Para el diagnóstico de varices esofágicas grandes, la adición de la ET a cada uno de los demás índices de diagnóstico (puntuaciones séricas de fibrosis) aumentó la sensibilidad con poca disminución de la especificidad. Además, dicha combinación disminuyó el índice de probabilidad negativo (LR-) en todas las pruebas. CONCLUSIÓN: los predictores no invasivos pueden reducir el uso de pruebas endoscópicas. Esto es muy importante puesto que el empleo de pruebas no invasivas es en la actualidad una meta importante en hepatología