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.

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.

Changes in serum interferon-γ-inducible protein-10 levels and liver stiffness among chronic hepatitis C Egyptian patients in response to directly acting antiviral agents.

BACKGROUND: Interferon-γ inducible protein-10 (IP-10) is chemokine biomarker of liver inflammation, elevated in patients with chronic hepatitis C infection. AIMS: Investigating if changes in serum IP-10 levels in response to directly acting antiviral agents (DAAs) treatment for chronic HCV patients are paralleled by changes in liver stiffness measurements (LSM), and assessing role of using serum IP-10 as a noninvasive accurate method to predict changes in hepatic necro-inflammation and fibrosis. MATERIAL AND METHODS: A prospective observational study included 92 Egyptian chronic HCV patients, who received treatment with sofosbuvir with daclatasvir regimen. Patients were classified into two groups; group I (53 patients) with non to mild significant liver fibrosis (F0-F1), and group II (39 patients) with significant to advanced liver fibrosis (F2-F4). Fibroscan and serum IP-10 were assessed pretreatment and 3 months after end of treatment. RESULTS: All patients achieved SVR. Both IP-10 and LSM showed significant decline after treatment in both groups. No significant correlation was found between changes in LSM and IP-10. IP-10 detected liver cirrhosis at cut off level of 17.8 pg/ml, with 75% sensitivity and 73.86% specificity, with area under the curve = 0.66, however, IP-10 had no statistical significance in detecting advanced fibrosis. CONCLUSION: IP-10 might be of significance as a noninvasive predictor of liver cirrhosis. IP-10 significant decline post-DAAs treatment in chronic HCV genotype IV infected patients reflects significant improvement in fibrosis stage and hepatic necro-inflammation in response to treatment. No significant correlation was detected in the changes of both IP-10 and LSM.

Depression in patients with chronic hepatitis-C treated with direct-acting antivirals: A real-world prospective observational study.

BACKGROUND: Direct-acting antiviral (DAAs) therapy showed high safety and efficacy profile in patients with chronic hepatitis C (CHC) particularly those with previous or current psychiatric illness. The aim of this study was to evaluate the incidence and potential risk factors of depression and psychological distress following DAAs therapy in CHC euthymic Egyptian patients with no previous or current diagnosis of any psychiatric disorders. METHODS: This is a prospective study that included 126 patients diagnosed with chronic hepatitis C virus genotype-4. Patients were candidate for DAAs therapy and were recruited consecutively (convenient sample) from the viral hepatitis center, Department of Endemic medicine, Kasr Al-Ainy Hospitals, Cairo University. Symptom Checklist 90-R, Beck Depression Inventory (BDI) and Structured Clinical Interview for DSM-IV (SCID IV) were performed at baseline and at 12 weeks post-treatment with DAAs. RESULTS: Forty-seven patients were included in the final analysis. Depression severity increased after treatment as BDI scores increased significantly than baseline scores (p= < 0.001). About one third of patients (32%) had moderate to severe depression. All Symptom Checklist-90 scores showed significant increase after treatment. LIMITATIONS: Dropout rate of patients for the 12 weeks post-treatment assessment was 33.8%. CONCLUSION: Depression and psychological distress can occur with DAAs treatments. Close psychosocial assessment and patient monitoring are still needed.

Circulatory miRNA-484, 524, 615 and 628 expression profiling in HCV mediated HCC among Egyptian patients; implications for diagnosis and staging of hepatic cirrhosis and fibrosis.

Circulatory microRNAs have recently emerged as non-invasive and effective biomarkers for diagnosis of various diseases. Currently there is no reliable biomarker for diagnosis, prognosis or even staging of fibrotic and cirrhotic complications arising from HCV infection. This study aimed at investigating plasma miR-484, miR-524, miR-615-5p and miR-628-3p expression signatures in Egyptian patients with HCV mediated cirrhosis, fibrosis and HCC. Plasma miRNAs expressions in 168 samples [(40 healthy controls, 47 with HCV liver fibrosis, 40 with HCV-cirrhosis and 41 with HCV-hepatocellular carcinoma (HCC)] were quantified using RT-PCR. The studied miRNAs were differentially expressed among all participating groups. Plasma miR-484 levels exhibited significant downregulation in advanced fibrosis as compared to mild fibrosis and HCC. Moreover, miR-484 showed significant upregulation in HCC versus cirrhosis. Both miR-524-5p and miR-615-5p were upregulated in cirrhotic group as compared to controls. Differential expression between HCC and controls was noticeable in miR-524-5p. Receiver operator characteristic curve analysis revealed promising diagnostic performance for miR-484 in discriminating late fibrosis from both mild fibrosis and HCC and also for miR-524 in distinguishing between cirrhosis and fibrosis. In conclusion, investigated miRNAs could serve as potential and sensitive biomarkers for staging, prognosis and early diagnosis of various HCV mediated hepatic disease progression.

Risk index for early infections following living donor liver transplantation.

INTRODUCTION: Post-operative infections in patients undergoing living donor liver transplantation (LDLT) are a major cause of morbidity and mortality. This study aims to develop a practical and efficient prognostic index for early identification and possible prediction of post-transplant infections using risk factors identified by multivariate analysis. MATERIAL AND METHODS: One hundred patients with post-hepatitic cirrhosis, HCV positive, genotype 4, Child B/C or MELD score 13-25 undergoing LDLT were included. All potential predictors of infection were analyzed by backward logistic regression. Cut-off values were obtained from ROC curve analysis. Significant predictors were combined into a risk index, which was further tested and compared by ROC curve analysis. RESULTS: Post-operative infection was associated with a significantly higher mortality (50.7% vs. 33.3%). Total leucocyte count, total bilirubin, early biliary complications, fever and C-reactive protein were found to be independent predictors of early infectious complications after LDLT. The risk index predicted infection with the highest sensitivity and specificity as compared with each predictor on its own (AUC = 0.91, 95% CI: 0.830-0.955, p < 0.0001). CONCLUSIONS: The use of a combined risk index for early diagnosis of post-operative infections can efficiently identify high risk patients.

High sustained virologic response rate using generic directly acting antivirals in the treatment of chronic hepatitis C virus Egyptian patients: single-center experience.

BACKGROUND: Hepatitis C virus (HCV) is a major health problem in Egypt, with a high prevalence of genotype 4. AIM: This study aimed to evaluate the safety and efficacy of generic sofosbuvir (SOF) plus generic daclatasvir (DAC) with or without ribavirin in the treatment of Egyptian chronic HCV patients compared with the use of brand drugs. MATERIALS AND METHODS: An observational study that included 234 Egyptian chronic HCV patients was carried out. Patients were classified into two groups: group A (101 patients) received brand SOF 400 mg plus brand DAC 60 mg and group B (134 patients) received generic SOF 400 mg plus generic DAC 60 mg with or without ribavirin for 12 weeks. The end point was a sustained virological response at 12 weeks after treatment. RESULTS: Thirty-eight (37.2%) patients in group A were treatment experienced compared with 12 (9.02%) patients in group B; there were 39 (38%) cirrhotic patients in group A and 22 (16.5%) cirrhotic patients in group B. In group A, 50% of patients received ribavirin, while in group B, 42.1% of patients received ribavirin. All patients were followed up; all of them attended their week 12 post-treatment visit with negative HCV RNA, with achievement of sustained virological response at 12 in 100% of patients receiving generic drugs (group B) and 99% of patients receiving brand drugs (group A). Generic SOF and DAC were well tolerated, with mild adverse events including fatigue and headache. CONCLUSION: Use of generic SOF and DAC with or without ribavirin is an extremely effective and a well-tolerated treatment for Egyptian chronic HCV patients.

Comparing the efficiency of Fib-4, Egy-score, APRI, and GUCI in liver fibrosis staging in Egyptians with chronic hepatitis C.

Assessment of hepatic fibrosis in chronic hepatitis C virus patients by liver biopsy is not widely accepted despite its accuracy, being invasive, carrying complications, and adding cost. This paved the way to development and use of non-invasive markers of fibrosis in diagnosis of hepatic fibrosis. We aimed at evaluating the efficiency of Fib-4, Egy-score, Aspartate-to-platelet ratio index (APRI), and Göteborg University Cirrhosis Index (GUCI) in comparison to liver biopsy, in the assessment of hepatic fibrosis in chronic hepatitis C patients. This was a cross sectional study including 200 chronic HCV patients were divided into two groups according to stage of fibrosis (Metavir score) into non-significant fibrosis (1.27, APRI >0.48, Egy-score >0.73, and GUCI >0.57 significantly predict significant fibrosis (P < 0.01). Fib-4 carries the best performance and significant reliability with AUROC 0.783, sensitivity 74%, specificity 69%, PPV 0.55, and NPV 0.86. The addition of BMI to Fib-4 improved the significant fibrosis AUROC curve performance but did not reach statistical significant improvement. We concluded that age and BMI are good predictors of hepatic fibrosis. Fib-4 (>1.27) is the best method of prediction of significant fibrosis compared to Egy-score, APRI, and GUCI. Addition of BMI to Fib-4 did not improve diagnostic value of Fib-4.

Serum Soluble CD14 in Egyptian Patients with Chronic Hepatitis C: Its Relationship to Disease Progression and Response to Treatment.

Hepatitis C virus (HCV) is a major public health problem. Soluble CD14 (sCD14) level was shown to be associated with HCV infection. In this study, we aimed to investigate the relationship between sCD14 concentration and disease progression, as well as the response to pegylated interferon/ribavirin (peg-IFN/RBV) therapy in Egyptian patients with chronic hepatitis C (CHC). The ELISA technique was used to test 80 patients with CHC and 20 healthy control persons for serum levels of sCD14 (pretreatment and after 12 weeks of treatment). CHC patients were 65 males and 15 females. Normal healthy controls included 20 age- and sex-matched volunteers. The mean age of the CHC patients was 39.94 years, while that of the controls was 39.2 years The serum sCD14 level was significantly higher in chronic HCV-infected patients (3.6±0.18 µg/mL) compared to healthy control subjects (3.1±0.18 µg/mL). The serum sCD14 level was significantly directly correlated with the hepatic fibrosis score (r=0.24, P=0.03), histological activity index (r=0.26, P=0.02), and serum aminotransferases [r=0.28, P=0.005 for alanine aminotransferase (ALT) and r=0.30, P=0.003 for aspartate aminotransferase (AST)]. The pretreatment sCD14 level was not significantly correlated to the treatment response, but it increased after 12 weeks of peg-IFN/RBV therapy and values were significantly higher in nonresponders (P=0.02). The pretreatment sCD14 level cannot predict the treatment response in chronic HCV patients receiving peg-IFN/RBV therapy. However, the serum sCD14 level after 12 weeks of treatment can serve as a negative predictor of treatment response.

Plasma proteosome level as a potential marker for hepatocellular carcinoma.

BACKGROUND AND STUDY AIMS: Hepatocellular carcinoma (HCC) is a fatal malignancy. Effective curative surgery is achieved when HCC is detected earlier. Proteosomes, the main non-lysosomal proteolytic structures organising the cellular mechanisms of cleaving proteins, can be considered a tumour marker in many kinds of malignancies. The aim of this study was to assess the plasma proteosome level in HCC and cirrhosis and, accordingly, evaluate its potential diagnostic ability in the detection of HCC in cirrhosis. PATIENTS AND METHODS: This study included 60 patients, divided into two groups: the HCC group and the liver cirrhosis group. Twenty normal subjects served as a control group. Serum levels of proteosome and alpha-foetoprotein (AFP) were measured using the enzyme-linked immunosorbent assay (ELISA) technique. RESULTS: Plasma proteosome levels were significantly higher in patients with HCC and in patients with cirrhosis without HCC when compared to controls individually (p>0.002 and p>0.001, respectively) but did not reach a significant differentiating level between them (area under curve (AUC)=0.641, p=0.061). Moreover, the plasma proteosome level was not correlated with the severity of HCC by the Milan criteria or with AFP level. In addition, it was not significantly related to laboratory or Child-Pugh scoring. Moreover, the combined use of plasma proteosome level and AFP measurements for the diagnosis of HCC was not effective. CONCLUSIONS: In this study, the plasma proteosome level was comparably recorded in both patients with cirrhosis and patients with HCC (mean value±standard deviation were 5.796±1.46 and 7.176±2.48µgml(-1), respectively), not reaching a significant differentiating level between them, although predictability of HCC using the plasma proteosome level was significant (p=0.017).