Screening for maternal cytomegalovirus infection during pregnancy and pregnancy outcome in patients with liver disease: an observational study.

BACKGROUND: Cytomegalovirus (CMV) infection among pregnant females could induce CMV hepatitis with possible changes in liver stiffness measurement (LSM) which could be reversibly increased during normal pregnancies, particularly in the third trimester. This study aimed to detect the prevalence of CMV infection among pregnant females with and without chronic liver disease and to evaluate the effects of CMV infection on LSM and pregnancy outcomes in comparison to non-CMV-infected pregnant females. METHODS: This is an observational prospective study that included 201 pregnant ladies presented to the liver disease with pregnancy clinic, Cairo University from March 2018 to April 2019. We assessed the laboratory results, abdominal ultrasonography, LSM using ARFI elastography, and pregnancy outcomes. RESULTS: Two hundred and one pregnant ladies were divided into ; group 1: pregnant ladies with normal pregnancy (n = 128), group 2: pregnant ladies with chronic liver diseases not related to pregnancy (n = 35), and group 3: pregnant ladies with pregnancy-related liver diseases (n = 38). Positive CMV serology (either/or, +ve CMV-IgM, IgG) was detected in 106/201 patients (52.74%), and fifteen of them had an active infection (IgG +, IgM+, PCR+). Pregnant females with chronic liver diseases not related to pregnancy had significantly higher serum levels of CMV IgM, IgG, and PCR. Moreover, LSM had a significant correlation with CMV IgG and CM_PCR in normal pregnant ladies. Maternal mortality occurred only in pregnant females with chronic liver diseases in 5.7% (2/35). CONCLUSION: Maternal CMV infection carries a significant risk to pregnant females with chronic liver disease. Routine CMV screening for women planning to be pregnant, especially those with chronic liver disease could help to avoid bad maternal and fetal outcomes.

Development of a gene signature for predicting cirrhosis risk score of chronic liver disease associated with HCV infection in Egyptians.

BACKGROUND: Complex diseases such as fibrosis are likely polygenic. Lately, cirrhosis risk score (CRS) clearly discriminated Chronic HCV patients with high-risk versus those with low-risk for cirrhosis better than clinical factors. METHODS: Herein, the CRS was assessed via genotyping by allelic discrimination assays in 243 HCV Egyptian patients categorized into 164 patients didn't develop HCC (93 mild, 71 advanced fibrosis); and 79 patients developed HCC. APRI and FIB-4 scores were calculated, compared with CRS and correlated with degree of fibrosis progression. RESULTS: Median of the three CRS, APRI and FIB-4 scores were significantly elevated in late fibrotic and HCC patients (p < 0.001); however CRS displayed proper discrimination (mild fibrosis (0.59; 0.4-0.75), advanced fibrosis (0.75; 0.7-0.86) and HCC (0.73; 0.57-0.77); (p < 0.001)). The ROC analysis of CRS score displayed modest accuracy to discriminate between mild and advanced fibrotic patient; AUC was 0.73; p < 0.0001), while AUC was only 0.57 (p = 0.05) for the discrimination between HCC and no HCC. Moreover, the combination of CRS, APRI and FIB4 lessened the power of correlation (AUC, 0.63 (p < 0.0001)) in fibrosis prognosis. In HCC prognosis, the combination of CRS, APRI and FIB4 in HCC patients showed modest accuracy with AUC, 0.59 (p = 0.0001). CONCLUSION: The diagnostic accuracy of FIB-4 for predicting liver fibrosis was nearly identical to that of CRS, however the strength of CRS score stemmed from that it is built on 7 SNPs host genetic factor. Our study validates non invasive algorithms for fibrosis prognosis purposes which may aid in decision making for therapeutic intervention.

Efficacy and safety of sofosbuvir-based therapy in hepatitis C virus recurrence post living donor liver transplant: A real life egyptian experience.

BACKGROUND AND AIM: Direct acting antiviral has offered treatment of hepatitis C virus (HCV) recurrence post liver transplantation (LT) with an all-oral regimen for short duration, excellent safety profile, and high sustained virological response (SVR). The aim of this study was to evaluate the efficacy and safety of sofosbuvir (SOF)-based regimens in the real world among a cohort of Egyptian patients with recurrent HCV post living donor LT (LDLT). METHODS: Patients with HCV-G4 recurrence post-LDLT were recruited from National Committee of Control of Viral Hepatitis, Egypt, from November 2014 to May 2017. They received different SOF-based regimens according to the treatment protocols available during this period. Patients' outcome and Adverse effects (AE) were evaluated. RESULTS: One hundred ninety patients (170 males, mean age 56.8 ± 7.9 years) were included. Calcineurin inhibitors were the main immunosuppression used (173 patients). Out of 190, 119 (62.6%) received SOF/ribavirin (RBV), 38 (20%) SOF/simeprevir (SMV), 22 (11.6%) SOF/daclatasvir (DSV)/ ± RBV, and 11 (5.8%) received SOF/LDV/ ± RBV. Overall SVR12 was 89.5%, 84.9% in SOF/RBV group, 94.7% in SOF/SMV, 100% in SOF/DCV, and 100% in SOF/LDV with no statistically significant difference ( P = 0.104). The AE reported were as follows: anemia (n = 65, 34.4%) mainly in SOF/RBV group, transient hyperbilirubinemia during SOF/SMV in 13 patients (34%), mild Acute cellular rejection in eight patients (4.2%), and hepatocellular carcinoma in two patients (1%) mainly driven by underlying liver condition. Two deaths were unlikely related to HCV therapy. CONCLUSION: Different SOF-based regimens were effective with high SVR12 rates in a difficult-to-treat population, recurrent HCV post LDLT.

Planning and prioritizing direct-acting antivirals treatment for HCV patients in countries with limited resources: Lessons from the Egyptian experience.

BACKGROUND AND AIMS: The introduction of direct-acting antivirals for hepatitis C virus (HCV) in Egypt led to massive treatment uptake, with Egypt's national HCV treatment program becoming the largest in the world. The aim of this paper is to present the Egyptian experience in planning and prioritizing mass treatment for patients with HCV, highlighting the difficulties and limitations of the program, as a guide for other countries of similarly limited resources. METHODS: Baseline data of 337,042 patients, treated between October 2014 to March 2016 in specialized viral hepatitis treatment centers, were grouped into three equal time intervals of six months each. Patients were treated with different combinations of direct-acting antivirals, with or without ribavirin and pegylated interferon. Baseline data, percentage of patients with known outcome, and sustained virological response at week 12 (SVR12) were analyzed for the three cohorts. The outcomes of 94,258 patients treated in the subsequent two months are also included. RESULTS: For cohort-1, treatment was prioritized for patients with advanced fibrosis (F3-F4 fibrosis, liver stiffness ≥9.5 kPa, or Fibrosis-4 ≥3.25). Starting cohort-2, all stages of fibrosis were included (F0-F4). The prioritization strategy in the initial phase caused delays in enrollment and massive backlogs. Cohort-1 patients were significantly older, and more had advanced fibrosis compared to subsequent cohorts. The percentage of patients with known SVR12 results were low initially, and increased with each cohort, as several methods to capture patient results were adopted. Sofosbuvir-ribavirin therapy for 24 weeks had the lowest SVR12 rate (82.7%); while other therapies were associated with SVR12 rates between 94% and 98%. CONCLUSION: Prioritization based on fibrosis stage was not effective and enrollment increased greatly only after including all stages of fibrosis. The availability of generic drugs reduced costs, and helped massively increase uptake of the program. Post-treatment follow-up was initially very low, and although this has increased, further improvement is still needed. LAY SUMMARY: We are presenting the largest national program for HCV treatment in the world. We clearly demonstrate that hepatitis C can be cured efficiently in large scale real-life programs. This is a clear statement that global HCV eradication is foreseeable, providing a model for other countries with limited resources and prevalent HCV. Moreover, the availability of generic products has influenced the success of this program.

Improvement of liver stiffness measurement, acoustic radiation force impulse measurements, and noninvasive fibrosis markers after direct-acting antivirals for hepatitis C virus G4 recurrence post living donor liver transplantation: Egyptian cohort.

Progression of recurrent hepatitis C is accelerated in liver transplant (LT) recipients. Direct-acting antivirals (DAAs) have recently emerged as a promising therapeutic regimen for the treatment of hepatitis C virus infection. Rates of sustained virological response (SVR) have drastically improved since the introduction of DAAs. The aim is to elucidate the changes in liver stiffness measurement (LSM) by transient elastography (TE) as well as acoustic radiation force impulse (ARFI) elastography and fibrosis scores after DAA treatment in LT recipients with hepatitis C virus recurrence. A single-center, prospective study including 58 LT recipients with hepatitis C recurrence who received different sofosbuvir-based treatment regimens. Transient elastography and ARFI elastography values were recorded as well as fibrosis 4 score (FIB-4) and aspartate aminotransferase-to-platelet ratio index were calculated at baseline and SVR at week 24 (SVR24). The outcome was improvement in LSM and at least a 20% decrease in LSM at SVR24 compared with baseline. The sustained virological response was 98.1%. There was improvement of platelet counts, alanine aminotransferase, and aspartate aminotransferase, which in turn caused improvement in fibrosis scores at SVR24. LSM by TE and ARFI elastography decreased from the baseline median value of 6.3 kPa (interquartile range [IQR]; 4.6 to 8.8 kPa) and 1.28 m/s (IQR; 1.07 to 1.53 m/s) to an SVR24 median value of 6.2 kPa (IQR; 4.85 to 8.9 kPa) and 1.12 (IQR; 0.97 to 1.30 m/s), respectively. Logistic regression analysis showed that baseline viral load was the only significant predictor of improvement in LS after DAA therapy at SVR24. Sofosbuvir-based treatment resulted in an early improvement in parameters of liver fibrosis in post-LT patients with hepatitis C recurrence.

Longitudinal assessment of hepatic fibrosis in responders to direct-acting antivirals for recurrent hepatitis C after liver transplantation using noninvasive methods.

Successful eradication of recurrent hepatitis C virus (HCV) infection following liver transplantation (HCV) improves graft survival. This study aimed at evaluation of hepatic fibrosis changes among long-term responders to DAA therapy for recurrent HCV after liver transplantation using noninvasive methods. Patients with significant hepatic fibrosis (≥F2) who achieved SVR12 after treatment with DAAs for recurrent HCV were included (n = 52). Hepatic fibrosis status was assessed, noninvasively, by calculation of fibrosis-4 score (FIB-4) and Aspartate Aminotransferase Platelet Ratio Index (APRI) and by measurement of graft stiffness using FibroScan at baseline and 12 and 18 months post-treatment. Acoustic radiation force imaging (ARFI) was done for all patients 12 and 18 months post-treatment. Patients were classified into two groups based on baseline liver stiffness measurement (LSM) by FibroScan; significant fibrosis (F2; n = 28) and advanced fibrosis groups (≥F3). Over 18-month follow-up period, there was serial improvement of FIB-4, APRI, and LSM by FibroScan in both groups. Higher baseline LSM and delayed initiation of antiviral therapy were significant predictors of lack of fibrosis regression (P-value 0.01 and 0.04, respectively). Fibroindices and LSM improved over time in liver transplant recipients who responded to DAAs. Baseline LSM can predict post-treatment fibrosis regression.

Extracellular Matrix Proteins Substantiate IL-28B T allele Effect on Histological Outcome of Chronic Hepatitis C.

INTRODUCTION AND AIM: The correlation between interleukin-28B (IL-28B) polymorphisms and chronic hepatitis C (CHC) progression is debatable. Here, we aimed to evaluate the relation between IL-28B C/T genotypes and the development of cirrhotic liver. Extracellular matrix (ECM) proteins, FibroScan and model for end-stage liver disease (MELD) were used to substantiate the severity of liver disease. MATERIAL AND METHODS: IL-28B rs12979860, liver stiffness and ECM proteins were assessed in 272 CHC patients. RESULTS: Cirrhosis percentage increased to 10%, 52% and 96% with the increasing number of T alleles (CC, CT and TT, respectively). Also, elevated ECM proteins levels were correlated with the increasing number of T alleles. Interestingly, among cirrhotic patients, liver stiffness, MELD and ECM proteins were significantly (P < 0.0001) higher in patients with TT more than CT genotype. FibroScan, hyaluronic acid, Laminin, Collagen IV and the N-terminal pro-peptide of collagen type III have high accuracy to differentiate liver status in CC from TT genotype. Area under receiver-operating characteristic curve (95% CI) were 1.0 (1.0-1.0), 0.97 (0.96- 1.0), 0.93 (0.85-1.0), 0.98 (0.97-1.0) and 0.93 (0.91-0.97), respectively. CONCLUSION: This study suggests that IL-28B T allele affects the natural course of CHC type 4 and also suggests that carriage of the IL-28B C allele protects from unfavorable clinical outcomes in CHC as coexistence of C allele with T allele reduced cirrhosis severity.

Improvement of glycemic state among responders to Sofosbuvir-based treatment regimens: Single center experience.

Chronic HCV infection has emerged as a complex multifaceted disease with manifestations extending beyond the liver. HCV plays a direct role in glucose metabolism leading to both insulin resistance and type 2 diabetes. To evaluate the changes in the glycemic state following Sofosbuvir-based treatment regimens in diabetic HCV patients. Four hundred chronic hepatitis C patients who underwent Sofosbuvir-based treatment regimens were retrospectively screened. Sixty-five diabetic HCV patients only enrolled in our analysis. Baseline demographic and laboratory data were recorded. Pretreatment Transient elastography was performed. At 24-week post EOT (SVR24), Fasting Plasma glucose, and Hemoglobin A1c were re-evaluated and compared with baseline. All enrolled diabetic patients were responders. They showed statistically significant decline in Fasting Plasma glucose and Hemoglobin A1c values at SVR24. Whatever the degree of hepatic fibrosis, the level of Fasting Plasma glucose and Hemoglobin A1c decreased at SVR24 in comparison to baseline level. Fifty-one patients showed improvement in their Hemoglobin A1c values at SVR24 and this improvement was more likely to occur among patients with low Body mass index. The reduction in Fasting Plasma glucose >20 mg/dL (>1.1 mmol/L) and Hemoglobin A1c ≥0.5% was not associated with age, gender or hepatic fibrosis stage. Sofosbuvir-based regimens are a highly efficient antiviral therapy for diabetic chronic HCV patients resulted in improvement in Fasting Plasma glucose and Hemoglobin A1c.

Real life Egyptian experience of efficacy and safety of Simeprevir/Sofosbuvir therapy in 6211 chronic HCV genotype IV infected patients.

BACKGROUND & AIMS: Major changes have emerged during the last few years in the therapy of chronic HCV. Several direct acting antiviral agents have been developed showing potent activity with higher rates of sustained virological response, even in difficult-to-treat patients. This study explores real life experience concerning efficacy, safety and possible predictors of response for the first cohort of Egyptian patients with chronic HCV genotype IV treated with Sofosbuvir/Simprevir combination therapy. METHODS: This real life study recruited the first (6211) chronic HCV genotype IV Egyptian patients, who received antiviral therapy in viral hepatitis specialized treatment centres affiliated to the National committee for control of viral hepatitis. All enrolled patients received 12 weeks course of daily combination of sofosbuvir (400 mg) and simeprevir (150 mg). Patients were closely monitored for treatment safety and efficacy. RESULTS: Overall sustained virological response 12 rate was 94.0% while the end of treatment response rate was 97.6%. sustained virological response 12 rates in easy and difficult-to-treat groups were 96% and 93% respectively. Univariate and multivariate logistic regression analysis revealed significant association of low albumin (<3.5), cirrhosis and Fib-4 score (>3.25) with treatment failure. Fatal adverse events occurred in 23/6211 cases (0.37%) due to liver cell failure adverse events or SAEs leading to treatment discontinuation occurred in 97 patients (1.6%). CONCLUSION: Sofosbuvir/Simeprevir combination is an effective and well tolerated regimen for patients with chronic HCV genotype IV.

Transluminal retroperitoneal endoscopic necrosectomy with the use of hydrogen peroxide and without external irrigation: a novel approach for the treatment of walled-off pancreatic necrosis.

BACKGROUND: Transluminal retroperitoneal endoscopic necrosectomy (TREN) is an attractive NOTES technique alternative to surgery for treatment of walled-off pancreatic necrosis (WOPN). The main limitations to this technique are the need for repeated sessions, prolonged external irrigation, and EUS availability. In our study, we introduced new modifications, including the use of hydrogen peroxide, and abandoning the use of EUS and external irrigation. METHODS: This is a retrospective study of outcome of consecutive patients who underwent TREN for WOPN between April 2011 and August 2012. The technique included (1) non-EUS-guided transluminal drainage, and (2) direct endoscopic debridement using hydrogen peroxide and different accessories. No external irrigation was used. RESULTS: Ten patients were included. Initial clinical and technical success was achieved in all patients. Complete radiological success and long-term clinical efficacy was achieved in nine patients (1 patient had an inaccessible left paracolic gutter collection and died 62 days after endotherapy). Mean number of sessions was 1.4 (range 1-2). Complications included bleeding, which was self-limited in three patients and endoscopically controlled in one. All patients avoided surgery, and no recurrence was reported during median follow-up of 289 (range 133-429) days. CONCLUSIONS: TREN is a safe and effective treatment for WOPN and could be performed safely without EUS guidance in selected cases. Hydrogen peroxide played a major role in reduction of number of sessions and timing. External irrigation of WOPN is not necessary, if adequate debridement could be achieved.

The Interrelation Between Hypothyroidism and Non-alcoholic Fatty Liver Disease, a Cross-sectional Study.

Background: Thyroid hormones play an important role in the regulation of diverse metabolic processes and might play a crucial role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, their association remains controversial. Therefore, our aim is to clarify whether overt or subclinical hypothyroidism was associated with NAFLD. Methods: This cross-sectional study included 60 participants with a new diagnosis of hypothyroidism and 30 age- and gender-matched healthy participants with thyroid-stimulating hormone (TSH) level <4.5 mIU/L. Anthropometric measurements, laboratory parameters, plasma fibroblast growth factor 21 (FGF21), and hepatic steatosis diagnosed via controlled attenuation parameter (CAP) using transient elastography between the hypothyroid groups and control group were analyzed. Results: Participants with hypothyroidism displayed significantly higher serum aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, total cholestrol, triglycerides, low-density lipoprotein cholesterol, TSH, hemoglobin A1c, fasting insulin, and homeostatic model assessment of insulin resistance (HOMA-IR) but significantly lower serum albumin, high-density lipoprotein cholesterol, and free thyroxine levels than the control group (P = <0.001). The CAP values were significantly higher in participants with overt and subclinical hypothyroidism than the control group (P = <0.001). The only significant independent predictors of steatosis in our study were free T4, body mass index, and HOMA-IR after using multivariate logistic regression. The mean serum FGF21 levels were increased in hypothyroid participants with hepatic steatosis than those without hepatic steatosis (126.9 ± 272.6) pg/ml vs. (106.8 ± 138.7) pg/ml, P = 0.8). Receiver operating characteristic (ROC) curve showed that FGF21 was not a significant marker for hepatic steatosis in hypothyroid participants (area under curve (AUC) = 0.44, P = 0.54). Conclusion: Individuals with subclinical or overt hypothyroidism were more likely to have NAFLD than those with normal thyroid function. Serum FGF21 levels were increased in hypothyroid individuals and its role as a marker of hepatic steatosis in hypothyroid individuals needs further assessment.

The Impact of interferon lambda 3 Polymorphism on Hepato-Cellular Carcinoma Progression in Hepatitis C Virus Patients: Treatment-Naïve and Experienced.

OBJECTIVES: In this study, we investigated the association between the IFN-λ3 rs12979860 single nucleotide polymorphism (SNP) and the transition from late fibrosis to HCC in Egyptian HCV-chronically infected patients. METHODS: The rs12979860 SNP was genotyped using real-time PCR in DNA from the whole blood of healthy subjects (n=60) and HCV patient   s (n=342). We stratified the patients into (1) treatment-naïve patients (n=218) with advanced fibrosis (F2-F4, n=123) and HCC (n=95 Treatment-experienced patients (n=124)  who received SOF-based therapy for 12 weeks and achieved SVR (SVR12). DAA-treated patients were divided into 2 groups: group I (n=63) included patients with advanced hepatic fibrosis (F2-F4) who did not develop HCC within a year after treatment, and group II (n=61) included patients who were free of focal hepatic lesions before starting DAA therapy but developed HCC within a year. RESULTS: Our results demonstrated that treatment-naïve patients with the CT/TT genotypes and the T allele were more likely to have HCC (odds ratio 3.1, 95% CI 1.44-6.71, P = 0.003 and odds ratio 1.89, 95% CI 1.28-2.76, P = 0.001, respectively). Binary regression analysis defined 3 independent predictors associated with HCC development: age (odds ratio 1.039, 95% CI 1.004-1.076, P = 0.028), alanine aminotransferase (odds ratio 1.008, 95% CI 1.002-1.015, P = 0.010), and rs12979860 (odds ratio 3.65, 95% CI 1.484-8.969, P = 0.005). CONCLUSIONS: However, the rs12979860 SNP did not show any correlation with the progression of HCC post-treatment. Despite the debate on the contribution of IFN-λ3 rs12979860 to susceptibility to HCV-related HCC, our data confirm the role of this SNP in this context.

Clinical Significance of Evaluation of Monocytic Receptors in Patients with Hepatitis C Virus Infection.

Monocytes in hepatitis C virus (HCV) infection play a critical role in chronic liver inflammation and fibrosis. We studied circulating monocytes and monocyte receptors in patients with HCV infection who were naive to treatment and those who received direct acting antiviral therapy and achieved sustained virological response. CD64+ CCR2+ (M1-like) and CD206+ CD163+ CX3CR1+ (M2-like) monocyte numbers and receptor expression were evaluated by flow cytometry. Higher expression of the monocyte chemokine receptor CCR2 predicted the severity of liver fibrosis, independent of successful treatment and viral clearance (R2 = 0.235, p = 0.002), whereas monocyte CX3CR1 expression was lower in both treated and untreated patients compared with controls (p = 0.011). The expression of the scavenger receptor CD163 was lower in patients with successful treatment (p = 0.005), supporting its role as a marker of treatment response. CD64+ CCR2+ (M1-like) and CD206+ CD163+ CX3CR1+ (M2-like) monocyte numbers were not altered with fibrosis progression or treatment response. Our findings reflect the diverse functions of monocytes in liver inflammation, fibrosis, and therapy. However, HCV clearance did not lead to complete monocyte reconstitution. Targeting monocytes and their chemokine receptors bears therapeutic potential to reduce liver fibrosis and improve disease outcome.

Health-related quality of life in Egyptian patients after liver transplantation.

UNLABELLED: INTRODUCTION-AIM: Health-Related Quality of Life (HRQOL) has become an important focus of patient care and clinical outcomes research with the improvement in patient and graft survival after liver transplantation (LT). The current study was designed to evaluate the post-transplant HRQOL profiles using the Liver Disease Quality of Life 1.0 (LDQOL 1.0) Questionnaire and demonstrate the possible effect of peri-transplant clinical covariates on these profiles. MATERIAL AND METHODS: Participants included pre-transplant group (waiting-list patients n = 50) and post-transplant group (mean 5 ± 4 years after deceased or living donor LT n = 103) who were recruited from 3 specialized centers in Egypt. We applied the LDQOL 1.0 questionnaire; a 111-item containing the Short Form-36 version 2.0 (SF-36v2) as a generic component supplemented by 75 disease-specific items. The etiology of cirrhosis, co-morbidities, model for end-stage liver disease (MELD), Child-Pugh class and post-operative complications were analyzed. RESULTS: All recipients had significant higher HRQOL scores than patients in waiting-list using both questionnaire components. Recipients with pre-LT MELD ≥ 15, Child-Pugh class C, history of hepatocellular carcinoma (HCC) demonstrated low HRQOL scores. Recipients without post-operative surgical complications had a statistically better HRQOL using the disease-specific, but not the SF-36v2 component. On the other hand, both components demonstrated non-significant lower scores in recipients with rejection episodes, cytomegalovirus (CMV) infection and hepatitis C recurrence had compared to those without medical complications. CONCLUSION: Generally HRQOL improves dramatically after LT as assessed by LDQOL questionnaire. Moreover, combined questionnaires can provide accurate information about the possible impaired HRQOL post-LT due to pre-transplant disease severity and post-operative complications.

Seven gene signature explores the impact of DAAs on the appearance of hepatocellular carcinoma in HCV infected patients.

HCV damages the hepatocytes ending with hepatocellular carcinoma (HCC). The direct-acting antivirals (DAAs) treatment has raised hopes for reducing the incidence of HCC. However, several scientific debate regarding the impact of DAAs on the occurrence of HCC in patients with cirrhosis. We aimed to study the Cirrhosis Risk Score (CRS), several clinical factors and tumor characteristics between patients who developed HCC either with or without DAAs treatment "DAA-exposed HCC patients" and "DAA-unexposed HCC patients". Methods: CRS was assessed via genotyping by allelic discrimination assays in HCV patients who developed de novo HCC (with DAAs (DAA-exposed HCC patients, n = 50), and without DAAs treatment (DAA-unexposed HCC patients, n = 40)). APRI, FIB-4 scores, and tumor characteristics were assessed. Results: Around 60% and 48% of DAA-exposed HCC patients and DAA-unexposed HCC patients; respectively had high CRS scores without significant difference. DAA-exposed HCC patients showed elevated Albumin, Hemoglobin and decreased ALT, AST compared with DAA-unexposed HCC patients (P = 0.002, 0.04, <0.001 and 0.006; respectively). FIB4 and APRI didn't reach the statistical difference between the studied groups. DAA-exposed HCC patients have higher overall survival (OS) than DAA-unexposed HCC patients (median: 30 & 15 months; respectively (p = 0.019)). Moreover, no significant differences were observed between the two groups in their focal lesion characteristics. Conclusion: All studied patients are genetically predisposed to develop HCC. Moreover, DAAs significantly improved the OS and the biochemical parameters. No differences between the two groups were detected regarding their tumor characteristics. Accordingly, the appearance of HCC after treatment is attributed to the natural course of cirrhosis.

The diagnostic utility of microRNA 222-3p, microRNA 21-5p, and microRNA 122-5p for HCV-related hepatocellular carcinoma and its relation to direct-acting antiviral therapy.

BACKGROUND AND STUDY AIMS: Recent reports have emphasized the increased risk of hepatocellular carcinoma (HCC) post direct-acting antiviral (DAAs) therapy in chronic hepatitis C virus (HCV) patients. Unfortunately, reliable diagnostic markers for HCC are still lacking. In this context, serum microRNAs have become promising diagnostic targets. Thus, the current study aims to elaborate the diagnostic utility of microRNA 122-5p, microRNA 21-5p, and microRNA 222-3p in the serum of Egyptian patients presenting with HCV infection and HCC post DAA therapy. PATIENTS AND METHODS: Qiagen specific microRNA assays were utilized to assess the expression levels of the chosen microRNAs in the serum samples collected from 3 groups: (1) 50 patients with HCV-related HCC, (2) 50 patients with HCC post DAA therapy, and 20 healthy control. RESULTS: The mean serum values of microRNA 21-5p and microRNA 122-5p were significantly lower in the HCC post DAA therapy group than in both the group with HCC without prior exposure to DAAs (P < 0.001) and control group (P 0.05 and 0.02, respectively). A significant upregulation was observed for both microRNA 21-5p and microRNA 122-5p in the HCV-related HCC group compared with the control group (P < 0.001 and = 0.011, respectively). On the other hand, the mean serum value of microRNA 222-3p was significantly raised in the HCC post DAA therapy group than in the control group (P = 0.007), whereas no statistically significant difference was observed between both groups with HCC and between the group with HCV-related HCC without prior exposure to DAAs and control group. CONCLUSION: This is the first study to introduce microRNA 21-5p, microRNA 122-5p and microRNA 222-3p as noninvasive biomarker candidates for HCC post DAA therapy. Their altered expression among treatment-naive HCC and HCC post DAA therapy might assume a different microRNA profiling in both HCC groups.

The Role of Interleukin 1 Beta in Differentiating Malignant from Benign Pancreatic Cysts.

Background and Aim: The frequency of detection of pancreatic cystic lesions (PCLs) in magnetic resonance imaging performed for reasons unrelated to the pancreas reaches up to 13.5%. The aim of this study was to evaluate the role of cyst fluid interleukin 1 beta (IL1ß) and different endoscopic ultrasound (EUS) features in differentiating premalignant/malignant from benign pancreatic cysts. In addition, to evaluate the role of pancreatic cyst fluid carcinoembryonic antigen (CEA) in differentiating mucinous from nonmucinous pancreatic cysts. Methods: This study was conducted on 73 patients with PCLs. EUS-guided fine-needle aspiration (EUS-FNA) was performed on all patients. Estimation of IL1ß and CEA levels in aspirated specimens were carried out. Results: Pancreatic cyst fluid IL1ß level could not differentiate between premalignant/malignant and benign pancreatic cysts. At a cutoff value of 19.81 ng/mL pancreatic cyst fluid CEA has 64.3% sensitivity and 84.4% specificity in differentiating mucinous from nonmucinous pancreatic cyst. EUS can differentiate between premalignant/malignant pancreatic cysts and benign cysts with a sensitivity of 66.7%, specificity of 69.2% Conclusions: Pancreatic cyst fluid IL1ß level cannot differentiate between premalignant/malignant and benign pancreatic cysts. CEA level can help in differentiation between mucinous and nonmucinous cysts. EUS can be useful in differentiation between premalignant/malignant pancreatic cysts and benign cysts.

Diagnosis and staging of HCV associated fibrosis, cirrhosis and hepatocellular carcinoma with target identification for miR-650, 552-3p, 676-3p, 512-5p and 147b.

BACKGROUND: Chronic HCV infection progresses to fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The latter represents the third most common cause for cancer mortality. Currently, there is no reliable non-invasive biomarker for diagnosis of HCV mediated disorders. OBJECTIVE: Profiling expression signature for circulatory miRNAs in the plasma of 167 Egyptian patients (40 healthy, 48 HCV fibrotic, 39 HCV cirrhotic and 40 HCV-HCC cases). METHODS: QRTPCR was used to quantify expression signature for circulatory miRNAs. RESULTS: MiR-676 and miR-650 were powerful in discriminating cirrhotic and late fibrosis from HCC. MiR-650 could distinguish mild (f0-f1) and advanced (f2-f3) fibrosis from HCC cases. MiR-650 and miR-147b could distinguish early fibrosis from healthy controls meanwhile miR-676 and miR-147b could effectively distinguish between mild chronic and (f1-f3) cases from healthy individuals. All studied miRNAs, except miR-512, can differentiate between (f0-f3) cases and healthy controls. Multivariate logistic regression revealed three potential miRNA panels for effective differentiation of HCC, cirrhotic and chronic liver cases. MiR-676-3p and miR-512-5p were significantly correlated in (f1-f3) fibrosis meanwhile miR-676 and miR-512 could differentiate between cirrhosis and (f0-f3) cases. Both miR-650 and miR-512-5p were positively correlated in the cirrhotic group and in (f0-f4) group. Putative targets for investigated miRNAs were also determined. CONCLUSIONS: Investigated miRNAs could assist in staging and diagnosis of HCV associated disorders.

Acoustic radiation force impulse to measure liver stiffness and predict hepatic decompensation in pregnancy with cirrhosis: A cohort study.

BACKGROUND AND STUDY AIMS: Pregnancy in association with cirrhosis is a rather uncommon and highly risky situation for both mother and child. We aim to study all factors and the utility of liver stiffness (LS) measurement by Acoustic Radiation Force Impulse elastography (ARFI) to predict hepatic decompensation in pregnant cirrhotic patients. PATIENTS AND METHODS: We prospectively recruited 224 pregnant women at the multidisciplinary clinic of liver disease with pregnancy, Cairo University. LS was measured using ARFI (Siemens ACUSON S3000 ultrasound system) during the second trimester and 8-12 weeks post-delivery. The outcome of pregnancy and the incidence of hepatic decompensation were assessed. RESULTS: Our cohort comprised 128 normal pregnancies, 37 patients with pregnancy-related liver disease (Intrahepatic cholestasis (n = 6), preeclampsia (n = 23), and hyperemesis gravidarum (n = 8)) and 59 patients with an established chronic liver disease not related to pregnancy. In all patients, LS significantly decreased after delivery from 1.19 m/s to 0.94 m/s (P < 0.001). In multivariate analysis, LS was an independent predictor for the outcome of pregnancy in all patients (odds ratio (OR) = 5.442 (3.01-6.82), cut-off = 1.21 m/s). Patients with cirrhosis, mean LS was 1.57 ± 0.66 m/s and 26 (44%) patients had hepatic decompensation (hepatocellular jaundice (n = 8), ascites (n = 9) and variceal bleeding (n = 6)). In multivariate analysis; LS, platelets, albumin, and bilirubin were independent predictors of decompensation post-delivery and the OR for LS was 6.141(4.32-7.98). The optimal cut off value of LS to predict decompensation was 1.46 m/s (8.4 kPa) with AUROC of 0.827. CONCLUSION: LS can be used to predict hepatic decompensation after delivery in pregnant women with manifest cirrhosis.

Hepatitis B Reactivation Following Eradication of HCV with Direct-Acting Antiviral Drugs (DAAs) in a Cohort of Patients from Different Institutions in Egypt.

Background: Concerns about HBV reactivation (HBVr) have been raised with the introduction of DAA for HCV treatment. The aim of the study was to assess the risk of HBVr in chronic HCV patients during or after DAA. Methods: A cohort of 166 chronic HCV patients who were treated with SOF-based DAA regimens and initially positive for HBcAb total were evaluated; 10 HBsAg-positive, 156 had past HBV exposure (HBsAg-negative/HBcAb-positive). Laboratory investigations, including liver functions tests, HBV-DNA, LSM by Transient elastography, and ARFI together with serum markers of fibrosis; APRI and FIB-4 were done at baseline and after 12 weeks of DAAs therapy. HBV-DNA levels and liver functions were monitored for assessment of HBVr. Results: Virological HBVr was diagnosed by ≥ 1 log10 IU/ml HBV-DNA levels in 2/166 patients (1.2%) among the whole HCV cohort, who were initially positive for HBsAg; 20%. Clinical HBVr (>3 folds liver enzyme elevation) was detected in one patient with virological HBVr. Conversely, none of past HBV-infected patients experienced HBVr. All patients achieved SVR12 and had a significant decline in serum transaminases, bilirubin, APRI, and LSM measurements after HCV eradication. Conclusion: HBVr might be considered after successful eradication of HCV following DAAs therapy, especially among patients who are positive for HBsAg, while past HBV infection does not seem to be a predisposing condition to HBVr.