Publications by authors named "Tamer Elbaz"

51 Publications

infection and the occurrence, characteristics, and survival of patients with hepatocellular carcinoma: an observational study over a decade.

Pathog Glob Health 2021 Sep 8:1-9. Epub 2021 Sep 8.

Endemic Medicine and Hepato-gastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

infection (SMI) is suspected to be directly and indirectly involved in hepato-carcinogenesis. This study evaluated the association of a previous SMI with hepatocellular carcinoma (HCC) development, patients, tumor characteristics, treatment outcomes, and survival. This observational study included patients with HCC with and without previous SMI who presented to the multidisciplinary HCC clinic, Kasr-Alainy hospital (November 2009 to December 2019). It also included 313 patients with liver cirrhosis without HCC. Clinical and laboratory features of the patients (complete blood count, liver/renal functions , alpha-fetoprotein, and hepatitis B/C status), tumor characteristics (Triphasic CT and/or dynamic MRI), liver stiffness (transient elastography), HCC treatment outcome, and overall survival were studied. This study included 1446 patients with HCC; 688(47.6%) composed group-1, defined by patients having a history of SMI, and 758(52.4%) were in group-2 and without history of SMI. Male sex, smoking, diabetes mellitus, splenomegaly, deteriorated performance status, synthetic liver functions, and platelet count were significantly higher in group-1. The groups did not differ with regard to liver stiffness, tumor characteristics, or the occurrence of post-HCC treatment hepatic decompensation or recurrence. HCC treatment response was better in group-2. Group-1 showed lower sustained virological response to hepatitis C direct-acting antivirals (DAAs) compared with group-2 (60% versus 84.3%, respectively, P = 0.027). Prior SMI was associated with HCC (adjusted odds ratio = 1.589, 95% confidence interval = 1.187-2.127), and it was concluded that it increases the risk of HCC. In addition, it significantly affects the performance status, laboratory characteristics, response to DAAs, and overall survival.
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http://dx.doi.org/10.1080/20477724.2021.1975081DOI Listing
September 2021

Role of circulating microRNA-21 and microRNA-215 in the diagnosis of hepatitis C related hepatocellular carcinoma.

J Infect Dev Ctries 2021 07 31;15(7):997-1003. Epub 2021 Jul 31.

Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

Introduction: Several micro ribonucleic acids (miRNAs) are deregulated in hepatocellular carcinoma (HCC). Others are linked to clinical pathological features of HCC. The goal of this study was to investigate whether miRNA-21 and miRNA-215 gene expression could be used as a non-invasive diagnostic tool to diagnose HCC.

Methodology: The gene expression of mature miRNA -21 and miRNA -215 in serum was analysed retrospectively using singleplex TaqMan two-step stem-loop quantitative real-time reverse-transcription PCR in 40 patients with HCC, 40 with chronic hepatitis C virus (HCV) with cirrhosis and 40 apparently healthy controls.

Results: Expression of miRNA -21 was significantly more down regulated in patients with HCC than in those with non-cirrhotic HCV (P = 0.007; odds ratio = 5; 95% confidence interval 1.6-15.4). The receiver operating curve analysis of the ability of miRNA-21 expression to discriminate between HCC and non-cirrhotic HCV revealed an area under the curve of 0.712 with 70% sensitivity and 68% specificity at a cut-off of ≤ 1.4468. Thus, the expression level of miRNA -21 could discriminate HCC from non-cirrhotic HCV. Significant positive correlation was observed between expression levels of microRNA-21 and miRNA -215 (r = 0.783, p < 0.001), but no association was observed between expression level of miR-215 and HCC or chronic HCV (p = 0.474).

Conclusions: MiRNA-21 may be a useful, non-invasive tool for diagnosing HCC. Non-cirrhotic HCV patients have five times the risk of developing HCC when the miRNA -21 level ≤ 1.4468.
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http://dx.doi.org/10.3855/jidc.12230DOI Listing
July 2021

Impact of successful HCV treatment using direct acting antivirals on recurrence of well ablated hepatocellular carcinoma.

Expert Rev Anti Infect Ther 2021 Jul 15:1-8. Epub 2021 Jul 15.

Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

Background: There are many contradictory studies that dealt with hepatocellular carcinoma (HCC) recurrence rate of well ablated hepatitis C virus (HCV) related HCC. We aim to assess the recurrence rate of previously ablated HCC in patients who received direct acting antiviral (DAA) for their HCV.

Research Design And Methods: This is a retrospective data analysis of 523 HCV patients who have a history of successfully ablated HCC and eligible for HCV treatment. Retrieval was done to demographic/clinical data, HCV pretreatment investigations, HCV treatment outcome. Follow up for survival and HCC recurrence was done every 3 months using abdominal ultrasound and alfa-fetoprotein.

Results: Mean age was 53.83 years. Sofosbuvir/daclatasvir/ribavirin was the most used regimen (35.4%) with 438 patients (83.7%) achieved sustained virologic response (SVR). The median duration for surveillance was 159 weeks. Hundred and five patients developed recurrent HCC, with a crude recurrence rate of 20.1%. There was no difference between HCV responders and non-responders in crude recurrence rate (p = 0.94) but HCC developed earlier in non-responders (p = <0.01).

Conclusion: Recurrence of HCC remains a threat in HCV patients even after achieving an SVR. Implementation of long-term surveillance programs is highly recommended.
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http://dx.doi.org/10.1080/14787210.2021.1951230DOI Listing
July 2021

Efficacy of combined Sofosbuvir and Daclatasvir in the treatment of COVID-19 patients with pneumonia: a multicenter Egyptian study.

Expert Rev Anti Infect Ther 2021 Jul 15:1-5. Epub 2021 Jul 15.

Endemic medicine department, Cairo University Hospitals, Cairo, Egypt.

Background: Limited experimental and clinical evidence suggests a potential role for sofosbuvir/daclatasvir in treating COVID19. We aim to evaluate the efficacy of generic sofosbuvir/daclatasvir in treating COVID-19 patients with pneumonia.

Research Design And Methods: This multicenter prospective study involved 174 patients with COVID-19. Patients were randomized into two groups. Group A (96 patients) received sofosbuvir (400 mg)/daclatasvir (60 mg) for 14 days in combination with conventional therapy. Group B (78 patients) received conventional therapy alone. Clinical, laboratory, and radiological data were collected at baseline, after 7, 14, and 28 days of therapy. Primary endpoint was rate of clinical/virological cure.

Results: A lower mortality rate was observed in group (A) (14% vs 21%, P = 0.07). After 1 month of therapy, no differences were found in rates of ICU admission, oxygen therapy, or ventilation. Additionally, a statistically significant shorter duration of hospital stay (9% vs 12%, P < 0.01) and a faster achievement of PCR negativity at day 14 (84% versus 47%, P < 0.01) were noticed in group (A).

Conclusion: Adding sofosbuvir/daclatasvir to conventional therapy of COVID-19 is promising. Their use is associated with shorter hospital stay, faster PCR negativity and may be reduced mortality.
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http://dx.doi.org/10.1080/14787210.2021.1950532DOI Listing
July 2021

Pregnancy outcome of anti-HCV direct-acting antivirals: Real-life data from an Egyptian cohort.

Liver Int 2021 07 11;41(7):1494-1497. Epub 2021 May 11.

Department of Pediatrics and Clinical Research Center, Faculty of Medicine, Ain Shams University, Cairo, Egypt.

We aimed to assess the pregnancy outcome in women with chronic HCV who had negative pregnancy test prior to the anti-HCV course and had unintended pregnancy while on HCV treatment. Hundred patients with a mean age of 30 ± 6.7 y were included and advised to withhold antivirals and continue follow-up in viral hepatitis and obstetrics centres till delivery. All patients received a 12-weeks regimen of anti-HCV [sofosbuvir plus daclatasvir (SOF/DCV): n = 95, SOF/DCV plus ribavirin: n = 3, and paritaprevir/ritonavir/ombitasvir plus ribavirin: n = 2]. Only nine patients completed the full antiviral course against medical advice, and 91 stopped between on-treatment weeks 4 and 8. Eighty-eight patients delivered full-term babies, eight had preterm babies and two had abortions. Of the nine patients who completed the full course of DAAs, seven (77.8%) delivered normal babies, attended their post-treatment week 12 visit, and all (100%) achieved sustained virological response. No major antiviral-related adverse events were reported.
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http://dx.doi.org/10.1111/liv.14913DOI Listing
July 2021

Survival and recurrence rates of hepatocellular carcinoma after treatment of chronic hepatitis C using direct acting antivirals.

Eur J Gastroenterol Hepatol 2022 Feb;34(2):227-234

Endemic Medicine Department, Faculty of Medicine, Cairo University.

Background: Conflicting studies were proposed either suggested or denied the relationship between early hepatocellular carcinoma (HCC) recurrence and the use of direct-acting antivirals (DAAs) for chronic hepatitis C management.

Aim Of The Study: To evaluate HCC recurrence rate post-DAAs and potential predictive factors.Study This prospective cohort study included all HCC patients achieved complete response attending our multidisciplinary HCC clinic, Cairo University, from November 2013 to February 2018. Group I (60 patients) who received DAAs after HCC ablation and group II (273 patients) who were DAAs-untreated. We studied factors that could play a role in HCC recurrence.

Results: The sustained virological response rate was 88.3% among DAA-treated patients. HCC recurrence rate was 45% in the post-DAA group vs. 19% in the non-DAAs group; P < 0.001. Mean survival was significantly higher in the post-DAA group (34.23 ± 16.16 vs. 23.92 ± 13.99 months respectively; P value <0.001). There was a significant correlation between HCC recurrence rate and age, male gender, mean size of tumors and time interval between complete HCC ablation and occurrence of HCC recurrence.

Conclusion: Our study reports high rate of HCC recurrence post-DAA therapy in patients treated with transarterial chemoembolization but not in those treated with curative measures. DAA therapy after curative treatment for HCC led to significantly earlier HCC recurrence, which correlated with specific clinic-pathologic features in our prospective single-institution study. However, future independent prospective randomized studies are warranted to evaluate this correlation which may lead to a change in the current standard-of-care approach to patients with hepatitis C virus-related HCC.
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http://dx.doi.org/10.1097/MEG.0000000000001972DOI Listing
February 2022

Machine Learning Prediction Models for Diagnosing Hepatocellular Carcinoma with HCV-related Chronic Liver Disease.

Comput Methods Programs Biomed 2020 Nov 23;196:105551. Epub 2020 May 23.

Endemic Hepatogastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt. Electronic address:

Background And Objective: Considered as one of the most recurrent types of liver malignancy, Hepatocellular Carcinoma (HCC) needs to be assessed in a non-invasive way. The objective of the current study is to develop prediction models for Chronic Hepatitis C (CHC)-related HCC using machine learning techniques.

Methods: A dataset, for 4423 CHC patients, was investigated to identify the significant parameters for predicting HCC presence. In this study, several machine learning techniques (Classification and regression tree, alternating decision tree, reduce pruning error tree and linear regression algorithm) were used to build HCC classification models for prediction of HCC presence.

Results: Age, alpha-fetoprotein (AFP), alkaline phosphate (ALP), albumin, and total bilirubin attributes were statistically found to be associated with HCC presence. Several HCC classification models were constructed using several machine learning algorithms. The proposed HCC classification models provide adequate area under the receiver operating characteristic curve (AUROC) and high accuracy of HCC diagnosis. AUROC ranges between 95.5% and 99%, plus overall accuracy between 93.2% and 95.6%.

Conclusion: Models with simplistic factors have the power to predict the existence of HCC with outstanding performance.
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http://dx.doi.org/10.1016/j.cmpb.2020.105551DOI Listing
November 2020

Hepatocellular Carcinoma Multidisciplinary Clinic-Cairo University (HMC-CU) score: A new simple score for diagnosis of HCC.

Arab J Gastroenterol 2020 Jun 18;21(2):102-105. Epub 2020 May 18.

Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

Background And Study Aims: The risk of hepatocarcinogenesis depends on background liver factors, of which fibrosis is a major determinant. Serum markers and scores are of increasing importance in non-invasive diagnosis of hepatic fibrosis. Our aim was to predict the occurrence of hepatocellular carcinoma (HCC) using a non-invasive fibrosis score calculated using routine patient data.

Patients And Mthods: Our retrospective study included 1,291 hepatitis C related-HCC Egyptian patients (Group 1) recruited from the multidisciplinary HCC clinic, Faculty of Medicine, Cairo University in the period between February 2009 and June 2016 and 1072 chronic hepatitis C-naïve patients (Group 2) with advanced fibrosis (≥F3) and cirrhosis (F4). King score, Fibro Q score, Aspartate aminotransferase-to-platelet ratio index (APRI), AST to ALT ratio (AAR), LOK score, Göteborg University Cirrhosis Index (GUCI), Fibro-α and Biotechnology Research Center (BRC) scores were calculated for all patients. Regression analysis and receiver operating characteristics (ROC) were used to calculate the sensitivity, specificity and predictive values for significant scores with the best cut-off for predicting HCC. A regression equation was used to calculate predicted probabilities of HCC using the following variables; age, gender, haemoglobin, international normalised ratio (INR), albumin and alpha fetoprotein. The appropriate score cut-off points yielding optimal sensitivity and specificity were determined by ROC curve analysis.

Results: There was a highly significant difference between the two groups for all calculated scores (P = 0.0001). Our new score, the Hepatocellular Carcinoma Multidisciplinary Clinic-Cairo University (HMC-CU) score (Logit probability of HCC =  - 2.524 + 0.152*age - 0.121*Hb - 0.696*INR - 1.059*Alb + 0.022*AFP + 0.976*Sex. Male = 1, Female = 0), with a cut-off of 0.559 was superior to other scores for predicting HCC, having a sensitivity of 90% and specificity of 80.6%.

Conclusion: The HMC-CU score is a promising, easily calculated, accurate, cost-effective score for HCC prediction in chronic HCV patients with advanced liver fibrosis.
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http://dx.doi.org/10.1016/j.ajg.2020.04.001DOI Listing
June 2020

Predictors of recurrence and survival of hepatocellular carcinoma: A prospective study including transient elastography and cancer stem cell markers.

Arab J Gastroenterol 2020 Jun 18;21(2):95-101. Epub 2020 May 18.

Endemic Medicine and Hepato-gastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

Background And Study Aims: To investigate whether the measurement of liver stiffness (LSM) using fibroscan and the serum Cancer Stem Cells (CSC): Ep-CAM and cytokeratin-19, could predict the recurrence of hepatocellular carcinoma (HCC) and their impact on clinical outcome and overall survival.

Patients And Methods: This is a prospective study, including 179 HCV-related HCC patients. All patients were treated following the BCLC guidelines. All HCC patients had transient elastography, measurements of Ep-CAM and cytokeratin-19 before and six months post-treatment. We looked for predictors of recurrence and performed a survival analysis using Kaplan-Meier estimates.

Results: TACE was the most common procedure (77.1%), followed by microwave ablation (15.6%). Complete ablation was achieved in 97 patients; 55 of them developed HCC recurrence. After treatment, LSM increased significantly with a significant reduction in CSCs levels in complete and partial response groups. The median time to observe any recurrence was 14 months. LSM increased significantly post-treatment in patients with recurrence versus no recurrence. Higher levels of CSCs were recorded at baseline and post-treatment in patients with recurrence but without statistical significance. We used univariate analysis to predict the time of recurrence by determining baseline CK-19 and platelet levels as the key factors, while the multivariate analysis determined platelet count as a single factor. The univariate analysis for prediction of overall survival included several factors, LSM and EpCAM (baseline and post-ablation) among them, while multivariate analysis included factors such as Child score B and incomplete ablation.

Conclusion: Dynamic changes were observed in LSM and CSCs levels in response to HCC treatment and tumour recurrence. Child score and complete ablation are factors that significantly affect survival.
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http://dx.doi.org/10.1016/j.ajg.2020.04.002DOI Listing
June 2020

Emerging from the screening of 57 million citizens and treating 4 million patients: future strategies to eliminate hepatitis C from Egypt.

Expert Rev Anti Infect Ther 2020 07 23;18(7):637-642. Epub 2020 Apr 23.

Endemic Medicine Department, Faculty of Medicine, Helwan University , Cairo, Egypt.

Introduction: Egypt succeeded in establishing a successful model of care for hepatitis C virus (HCV) management in the country with the highest worldwide disease prevalence. The Egyptian ministry of health announced an optimistic goal of near disease elimination. More steps are still required to achieve such a goal.

Areas Covered: This review covers the efforts made in treatment and prevention of HCV by the Egyptian National Committee for the Control of Viral Hepatitis (NCCVH) with emphasis on the extensive screening program that was able to screen more than 57 million citizens, and future strategies implemented to ensure eradicating the virus from the country.

Expert Opinion: Despite the great efforts and the proven success in controlling the HCV epidemic in Egypt, some facets of the Egyptian program still need to be upgraded to reach the HCV elimination goal. A significant workload with follow up programs for those who were successfully treated, and treatment failure cases are existing. More enhancement for the currently performed prevention and control measure is missing. Also, we strongly recommend conducting a recent nationwide survey to document the actual infection rates of HCV after all these efforts.
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http://dx.doi.org/10.1080/14787210.2020.1758065DOI Listing
July 2020

Impact of treating chronic hepatitis C infection with direct-acting antivirals on the risk of hepatocellular carcinoma: The debate continues - A mini-review.

J Adv Res 2019 May 7;17:43-48. Epub 2019 Mar 7.

Endemic Medicine and Hepatogastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

Hepatitis C virus clearance is expected in more than 95% of patients treated with direct-acting antivirals (DAAs). However, an extensive debate about the impact of DAAs on the development of hepatocellular carcinoma (HCC) is currently ongoing. This review aimed to explore currently available evidence about the relationship between DAAs and HCC development. The American studies and some European studies clearly showed no relation, while the Japanese and Egyptian studies and the other European studies showed an increased risk of developing HCC after DAA exposure. These conflicting results may be due to geographical and ethnic variations and differences in the design and inclusion criteria among the studies. After reviewing the data from these different studies, it seems that some patients are at increased risk of developing HCC after DAA exposure. Identifying those at increased risk is very important for the management of HCC in light of the potentially major consequences of HCC for the patients' quality of life and the subsequent major burden imposed on healthcare resources.
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http://dx.doi.org/10.1016/j.jare.2019.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526204PMC
May 2019

Genetic variations in death receptor domain 4 gene and the susceptibility to hepatitis C related hepatocellular carcinoma.

J Med Virol 2019 08 25;91(8):1537-1544. Epub 2019 Apr 25.

Dpartment of Clinical Pathology Hematology, Theodor Bilharz Research Institute, Cairo, Egypt.

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide, particularly in Egypt. The role of apoptosis in tumorigenesis has been well-documented and resistance to apoptosis is a hallmark of cancer. Several studies discussed the association between death receptor 4 (DR4) genetic variants and HCC risk.

Aim: To study the possible link between DR4 gene polymorphisms and the susceptibility to HCC.

Methods: Genotyping of DR4-C626G, -A683C, and DR4-A1322G single nucleotide polymorphisms (SNP) was determined by polymerase chain reaction assay for 100 de novo HCV-related HCC patients, 100 chronic hepatitis C-related liver cirrhosis patients, and 150 healthy controls.

Results: DR4-A1322G polymorphic genotypes (AG and GG) were significantly higher in HCC and cirrhotic patients than controls. The AG genotype conferred two-fold increased risk of HCC (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.56-3.51) and the risk increased to three-fold for the GG genotype (OR, 3.51; 95%CI, 2.33-5.28). The frequency of DR4-C626G and -A683C SNPs in HCC and cirrhotic patients were not significantly different from the controls. Combined genotype analysis showed that coinheritance of the polymorphic genotypes of DR4-C626G and -A1322G conferred nine-fold increased risk of HCC (OR, 9.34; 95%CI, 3.76-23.12). The risk increased to be 12-fold when DR4-A683C and -A1322G variants were coinherited (OR, 11.9; 95%CI, 4.82-29.39). Coexistence of the variant genotypes of the three SNPs conferred almost 10-fold increased risk of HCC (OR, 9.75; 95%CI, 1.86-51.19).

Conclusions: The G allele of DR4 -A1322G could be considered as a novel independent molecular predictor for HCV-related HCC in the Egyptian population.
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http://dx.doi.org/10.1002/jmv.25476DOI Listing
August 2019

Liver stiffness measurement changes following hepatocellular carcinoma treatment with percutaneous microwave ablation or transarterial chemoembolization: a cohort study.

Eur J Gastroenterol Hepatol 2019 Jun;31(6):685-691

Endemic Medicine Department.

Background: Liver stiffness increases after the development of hepatocellular carcinoma (HCC). Transient elastography for liver stiffness measurement (LSM) using fibroscan is a simple noninvasive method of proven efficacy. This study aims to assess the changes in LSM following HCC treatment.

Patients And Methods: This study included 150 patients with hepatitis C virus related HCC attending the multidisciplinary HCC clinic, Kasr Al-Ainy Hospital between March 2014 and October 2015 who underwent either transarterial chemoembolization (TACE) or microwave ablation (MWA). Baseline LSM was carried out 3 and 6 months after treatment. The response rate was calculated according to the modified Response Evaluation Criteria in Solid Tumors criteria; overall survival and LSM changes were then compared between the two procedures.

Results: MWA showed higher rates of complete ablation (77.4%) than did TACE (31.7%) (P=0.004). Increase in LSM 3 and 6 months after treatment was statistically significant in the TACE group (P<0.001) but not in the MWA group (P=0.4). Patients who showed complete ablation had statistically significant lower baseline LSM than those with incomplete ablation, and their 6 months increase in LSM was also significantly lower. Logistic regression revealed that with each unit increase in baseline stiffness, 3% reduction in the odds of complete ablation is expected, and this did not change after controlling for the type of treatment. Child-Pugh class, number, and size of HCCs were our independent prognostic factors by Cox proportional analysis.

Conclusion: The increase in LSM is significant after TACE than after MWA. Moreover, lower pre-ablation LSM is a predictor of complete ablation.
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http://dx.doi.org/10.1097/MEG.0000000000001343DOI Listing
June 2019

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

Eur J Gastroenterol Hepatol 2019 01;31(1):75-79

Endemic Medicine Department.

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.
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http://dx.doi.org/10.1097/MEG.0000000000001264DOI Listing
January 2019

Evaluation of liver steatosis, measured by controlled attenuation parameter, in patients with hepatitis C-induced advanced liver fibrosis and hepatocellular carcinoma.

Eur J Gastroenterol Hepatol 2018 11;30(11):1384-1388

Department of Hepatology, Gastroenterology and Infectious Diseases, Faculty of Medicine, Benha University, Benha, Egypt.

Introduction: Steatosis is a documented feature of chronic hepatitis C (CHC). There is an association between steatosis decrease and fibrosis progression. The association between steatosis and advanced fibrosis versus hepatocellular carcinoma (HCC) development has not been precisely evaluated. The controlled attenuation parameter (CAP) was applied as an immediate and efficient process to detect and quantify hepatic steatosis with adequate accuracy.

Aims: The aim of this study was to assess the difference in liver steatosis between patients with hepatitis C virus-related advanced hepatic fibrosis versus HCC.

Patients And Methods: This cross-sectional study included 130 patients with HCC, attending the multidisciplinary HCC clinic, Cairo University, and 54 patients with CHC between October 2015 and June 2016. Clinical and laboratory characteristics were recorded. Liver stiffness and CAP were obtained by using the FibroScan 502, touch.

Results: All included patients had genotype 4. The mean CAP value was significantly lower in HCC (209.5±57.1 dB/m) versus CHC (259.9±54.9 dB/m). Receiver operating characteristic curve revealed an area under the curve of 0.75 for the differentiation between groups. At a cutoff value of 237 dB/m, sensitivity was 72.3%, specificity was 70.7%, positive likelihood ratio was 2.5, and negative likelihood ratio was 0.4 in the differentiation between CHC versus HCC. Logistic regression analysis revealed an odds ratio of 6.4 for the diagnosis of HCC with CAP of less than 237 dB/m. Multivariate analysis, controlling for age, sex, BMI, triglycerides, and cholesterol levels, revealed a significantly increased odds for HCC diagnosis (odds ratio: 4.3, P=0.006).

Conclusion: The progression of CHC is associated with a decrease in steatosis, particularly toward advanced fibrosis and HCC. Steatosis reduction less than 237 dB/m is likely to be associated with HCC.
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http://dx.doi.org/10.1097/MEG.0000000000001196DOI Listing
November 2018

Efficacy and safety of sofosbuvir and daclatasvir with or without ribavirin in elderly patients with chronic hepatitis C virus infection.

J Med Virol 2019 02 8;91(2):272-277. Epub 2018 Nov 8.

Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Giza, Egypt.

Hepatitis C virus (HCV) infection is considered as a major public health problem that, worldwide, chronically affects 170 million people. Elderly patients are more likely than younger patients to have increased duration of infection, increased rate of disease progression, and subsequently increased incidence of advanced liver disease. Natural history models predicted that the prevalence of HCV infection and its chronic sequelae as well as extrahepatic manifestations will eventually increase through the next decade and will mostly affect those who are greater than 60 years of age. Moreover, polytherapy and polypharmacy are frequent in elderly patients due to associated comorbidities. As advanced age is associated with increasing risk of development of cirrhosis and hepatocellular carcinoma, elderly patients are in special need of safe and effective antiviral therapies. Achievement of sustained viral responses (SVR) is associated with reduced liver-related complications and overall mortality in such patients with the advanced liver disease. With the recent introduction of interferon-free direct-acting antivirals, successful treatment for chronic HCV infection had dramatically improved, with overall cure rates that exceed 90% SVR. In our study, we aimed to study the efficacy and safety of combined sofosbuvir and daclatasvir, with or without ribavirin, in management of chronically infected HCV elderly patients who are more than 60 years old.
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http://dx.doi.org/10.1002/jmv.25287DOI Listing
February 2019

Evaluation of accuracy of elastography point quantification versus other noninvasive modalities in staging of fibrosis in chronic hepatitis C virus patients.

Eur J Gastroenterol Hepatol 2018 08;30(8):882-887

Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University.

Background: Elastography point quantification (ElastPQ) is a newly noninvasive method incorporated into a conventional ultrasound system for staging of liver fibrosis in patients with chronic liver diseases.

Aim: The aim was to evaluate ElastPQ reproducibility and its accuracy in staging of liver fibrosis in hepatitis C virus (HCV) patients in comparison with transient elastography (TE) and fibrosis scores [FIB-4 and aspartate aminotransferase-to-platelet ratio index (APRI)] using liver biopsy as a reference standard and also to predict the sensitivity and specificity of ElastPQ as well as proposing a cut-off for advanced fibrosis.

Patients And Methods: A single-center, cross-sectional study enrolled 72 chronic HCV patients. Baseline demographic and laboratory data were recorded. ElastPQ and TE were performed. Fibrosis scores were calculated. The performance of ElastPQ was compared with that of TE and noninvasive methods (FIB-4, APRI) using liver biopsy as a reference standard using receiver operating characteristic curve analysis.

Results: ElastPQ is a valuable diagnostic tool for the diagnosis of F≥1, F≥2, and F≥3, with area under the receiver operating characteristic curve of 0.79, 0.74, and 0.83, respectively. The best cut-off values for ElastPQ were 4.9, 6.6, and 10.7 kPa for mild fibrosis, significant fibrosis, and advanced fibrosis, respectively. ElastPQ correlated positively with all other fibrosis indices (TE, APRI, and FIB-4) as well as liver biopsy. Area under the curve for the diagnosis of advanced fibrosis (F3/F4) using ElastPQ was 0.83 at a cut-off value of 10.7 kPa (P<0.01).

Conclusion: ElastPQ is a promising noninvasive US-based method for assessing liver fibrosis in HCV-related chronic liver disease patients with good diagnostic performance comparable to that of liver biopsy and TE.
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http://dx.doi.org/10.1097/MEG.0000000000001151DOI Listing
August 2018

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.

J Med Virol 2018 09 25;90(9):1508-1515. Epub 2018 May 25.

Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

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.
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http://dx.doi.org/10.1002/jmv.25210DOI Listing
September 2018

HCV in Egypt, prevention, treatment and key barriers to elimination.

Expert Rev Anti Infect Ther 2018 04 11;16(4):345-350. Epub 2018 Mar 11.

b Endemic Hepatogastroenterology, Faculty of Medicine , Cairo University , Cairo , Egypt.

Introduction: Currently, direct-acting antivirals (DAAs) are considered the ideal choice for the treatment of chronic HCV patients due to their proven efficacy (SVR> 90%), and minimal adverse effects. Egypt launched a large treatment program aimed at providing treatment coverage for Egyptian HCV- infected patients. Areas covered: This review covers the treatment and prevention efforts made by the Egyptian National Committee for the Control of Viral Hepatitis (NCCVH) with the available model of care for HCV patients in Egypt, in addition to the barriers that prevent elimination of HCV from Egypt. Expert commentary: Egypt could provide a model for establishing the largest HCV management system aimed at eliminating HCV from the country with the highest worldwide prevalence. Despite the huge efforts and achieved results in combating the HCV epidemic in Egypt, certain improvements are needed in order to attain HCV elimination, such as the development of an enhanced screening program working in parallel to the present treatment options.
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http://dx.doi.org/10.1080/14787210.2018.1448709DOI Listing
April 2018

A new prognostic score can predict survival after hepatocellular carcinoma treatment in a cohort of 1302 Egyptian hepatocellular carcinoma patients.

Eur J Gastroenterol Hepatol 2018 May;30(5):514-519

Departments of Endemic Medicine and Hepatogastroenterology.

Introduction: Survival of hepatocellular carcinoma (HCC) differs between regions and countries according to the different underlying factors and the degree of standard of care that enables early diagnosis and management. Our aim was to identify the most potent predictive factors of survival in Egyptian HCC patients receiving curative or palliative treatments.

Patients And Methods: This retrospective study included 1302 HCC patients attending the HCC multidisciplinary clinic, Cairo University, between February 2009 and December 2016. Clinical, laboratory, tumor characteristics, and treatment data were collected. Prognostic scores for each of the treatment categories, curative or palliative, were developed using routine laboratory tests.

Results: Patients were predominantly men, mean age 57.79±7.56 years. All cases developed HCC in addition to cirrhosis, mainly hepatitis C virus-related (88.2%). Most of the patients were Child-Pugh A (56.8%) or B (34.4%) and had single lesions. Transarterial chemoembolization was the most common line of treatment (42.08%). The overall median survival was 18.3 months from the date of diagnosis. Cigarette smoking, Child-Pugh score, performance status, number and size of the focal lesion, α-fetoprotein, and application of a specific treatment, particularly curative treatment, were the significant independent prognostic factors for survival. We found no impact of diabetes mellitus or hypertension on survival. Multidisciplinary HCC clinic predictive scores of survival after palliative and curative treatments were developed including independent prognostic factors, age, and portal vein status.

Conclusion: A new Egyptian prognostic score of tumor and patients factors can predict the survival of patients with HCC after palliative and curative treatments.
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http://dx.doi.org/10.1097/MEG.0000000000001085DOI Listing
May 2018

Novel scores combining AFP with non-invasive markers for prediction of liver fibrosis in chronic hepatitis C patients.

J Med Virol 2018 06 12;90(6):1080-1086. Epub 2018 Mar 12.

Department of Endemic Medicine and Hepatology, Cairo University, Cairo, Egypt.

Serum levels of alpha-fetoprotein (AFP) were reported to increase in patients with significant or advanced hepatic fibrosis. Combination of non-invasive tests decreases the use of liver biopsy in large proportion of chronic HCV patients. The aim of the study was to compare and combine AFP with commonly used non-invasive fibrosis tests in novel scores for prediction of different stages of hepatic fibrosis. Six hundred and fifty two treatment naïve chronic hepatitis C patients were enrolled. Demographic data, basic pre-treatment laboratory tests including complete blood count (CBC), liver biochemical profile and renal functions test, international normalized ratio (INR) in addition to AFP, liver stiffness measurement (LSM) by Fibroscan and liver biopsies were retrospectively analyzed. AST to Platelet Ratio Index (APRI) and FIB-4 scores were calculated. Different predictive models using multivariate logistic regression analysis were generated and presented in equations (scores) composed of a combination of AFP, LSM plus FIB-4/APRI scores. AFP was correlating significantly with LSM, FIB-4, and APRI scores. Areas under receiver operating characteristic curves (AUROCs) for predicting significant hepatic fibrosis, advanced hepatic fibrosis, and cirrhosis were 0.897, 0.931, and 0.955, respectively, for equations (scores) containing AFP, LSM, and FIB-4. AUROCs for predicting significant hepatic fibrosis, advanced hepatic fibrosis and cirrhosis were 0.897, 0.929, and 0.959, respectively, for equations (scores) containing AFP, LSM, and APRI. The study shows that combining AFP to serum biomarkers and LSM increases their diagnostic performance for prediction of different stages of liver fibrosis.
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http://dx.doi.org/10.1002/jmv.25026DOI Listing
June 2018

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

Eur J Gastroenterol Hepatol 2018 Jan;30(1):39-43

Departments of Endemic Medicine and Hepato-gastroenterology.

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.
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http://dx.doi.org/10.1097/MEG.0000000000001004DOI Listing
January 2018

Evaluation of trail receptor 1 (DR4) polymorphisms C626G and A683C as risk factors of hepatocellular carcinoma.

J Med Virol 2018 03 20;90(3):490-496. Epub 2017 Oct 20.

Department of Endemic Hepatogastroenterolog, Faculty of Medicine, Cairo University, Cairo, Egypt.

Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) plays an important role in many cancers including hepatocellular carcinoma (HCC). The aim of this study is to investigate the association of the DR4 polymorphisms C626G (Thr209Arg, rs20575) and A683C (Glu228Ala, rs20576) with the occurrence of HCC in Egyptian patients chronically infected with HCV. The study included 80 patients with HCV-related HCC (group 1) and 80 patients with HCV-related liver cirrhosis (group 2) who are naïve to treatment. Clinical and laboratory data were recorded. Genotyping of TRAIL receptor DR4 polymorphism C626G rs20575 and A683C rs20576 SNP was done by Real-Time PCR using taqman probes technology. The mean age of HCC patients was 57.6 ± 8.4 years with 62 patients (77.5%) were males. While group 2 mean age was 49.5 ± 10.29 years with 50% were males. The frequency distribution of rs20575 genotypes showed a statistically significant difference between the two studied groups (P = 0.02), the carriers of the C allele were 2.01 times more likely to develop HCC than the carriers of the G allele (P = 0.003), while no significant difference in rs20576 genotypes distribution was found between the studied groups (P = 0.680). On combining the carriers of C allele of rs20575 and the carriers of A allele of rs20576, a significant difference was detected (P > 0.001) with 2.85 higher risk of HCC development in patients who carried both genetic risk alleles simultaneously. The significant difference in DR4 polymorphisms among HCC and cirrhotic patients suggests their role as potential risk factors of HCC development.
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http://dx.doi.org/10.1002/jmv.24964DOI Listing
March 2018

Effectiveness of ravidasvir plus sofosbuvir in interferon-naïve and treated patients with chronic hepatitis C genotype-4.

J Hepatol 2017 Sep 19. Epub 2017 Sep 19.

National Liver Institute, Menoufiya University, Shebeen EL Kom, Egypt. Electronic address:

Background & Aims: Although treatment of hepatitis C virus (HCV) and HCV-genotype-4 (GT4) has become very effective, it remains very expensive, and affordable options are needed, especially in limited resource countries. The aim of this study was to assess the efficacy and safety of the combination of ravidasvir (an NS5A inhibitor) and sofosbuvir to treat patients with chronic HCV-GT4 infection.

Methods: A total of 300 patients with HCV-GT4 infection were recruited in three groups: treatment-naïve patients with or without compensated Child-A cirrhosis (Group 1); interferon-experienced patients without cirrhosis (Group 2); and interferon-experienced patients with cirrhosis (Group 3). Groups 1 and 2 received ravidasvir 200 mg QD plus sofosbuvir 400 mg QD for 12 weeks and were randomized 1:1 to treatment with or without weight-based ribavirin. Group 3 patients received ravidasvir plus sofosbuvir with ribavirin and were randomized 1:1 to a treatment duration of 12 weeks or 16 weeks. The primary endpoint was sustained virologic response at 12 weeks post-treatment (SVR12).

Results: A total of 298 patients were enrolled: 149 in Group 1, 79 in Group 2 and 70 in Group 3. SVR12 was achieved in 95.3% of all patients who started the study, including 98% of patients without cirrhosis and 91% of patients with cirrhosis, whether treatment-naïve or interferon-experienced. Ribavirin intake and history of previous interferon therapy did not affect SVR12 rates. No virologic breakthroughs were observed and the study treatment was well tolerated.

Conclusions: Treatment with ravidasvir plus sofosbuvir, with or without ribavirin, was well tolerated and associated with high sustained virologic response rate for HCV-GT4 infected patients with and without cirrhosis, regardless of previous interferon-based treatments.

Trial Registration Number: ClinicalTrials.gov Identifier: NCT02371408.

Lay Summary: This study evaluated efficacy and safety of the new oral hepatitis C drug ravidasvir in combination with the approved oral drug sofosbuvir in 298 patients infected with hepatitis C type 4. Our results showed that treatment with ravidasvir plus sofosbuvir, with or without ribavirin, was well tolerated and associated with high response rate in patients with and without cirrhosis.
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http://dx.doi.org/10.1016/j.jhep.2017.09.006DOI Listing
September 2017

Serious Adverse Events with Sofosbuvir Combined with Interferon and Ribavirin: Real-Life Egyptian Experience.

J Interferon Cytokine Res 2017 08;37(8):348-353

1 Faculty of Medicine, Endemic Medicine and Hepatology Department, Cairo University , Cairo, Egypt .

Viral hepatitis is a serious problem worldwide that was under-recognized till recently. The prevalence of chronic hepatitis C virus (HCV) is estimated to be 180 million people worldwide. Treatment of chronic HCV using combined pegylated interferon and ribavirin (PEG/RIBA) has long been the standard of care with modest response. In our study, we will report the real-life experience of serious adverse events (SAEs) that were reported by the National Committee for Control of Viral Hepatitis (NCCVH, Cairo, Egypt) program while treating chronic HCV using the triple therapy, sofosbuvir combined with pegylated interferon and ribavirin (PEG/RIBA/SOF), which led to premature discontinuation of treatment. This retrospective analysis included a total of 6,989 chronic HCV patients who were treated by the NCCVH. They received the triple antiviral therapy in 26 treatment centers in Egypt using PEG/RIBA/SOF for 12 weeks. Among 6,989 patients who were treated in 26 treatment centers related to NCCVH, 406 cases (5.9%) reported SAEs and prematurely stopped their treatment. Triple therapy PEG/RIBA/SOF was an important intermediate milestone between interferon-based therapy and the interferon-free all-oral direct acting antiviral agents (DAAs). Results of this study were the leading cause of discontinuation of interferon-based therapy and introduction of interferon-free all-oral treatment protocols, incorporating DAAs from different classes as soon as they gain approval.
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http://dx.doi.org/10.1089/jir.2016.0131DOI Listing
August 2017

A New Potent NS5A Inhibitor in the Management of Hepatitis C Virus: Ravidasvir.

Curr Drug Discov Technol 2018 ;15(1):24-31

Endemic Hepatogastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

Background: Chronic hepatitis C virus (HCV) is a worldwide health problem that can lead to liver cirrhosis, liver cell failure and numerous subsequent complications such as hepatocellular carcinoma. Till the near past, pegylated interferon was the standard of care therapy. However, it was associated with suboptimal success rates and many side effects. Thereafter, direct antiviral agents (DAA) appeared and played the key role in management of HCV. One of those recent DAAs is ravidasvir.

Summary: It is a potent NS5A inhibitor that was formerly known as PPI-668. It is produced by the cooperation of Presidio pharmaceuticals and Pharco International pharmaceutical company. Since its first production, it has been enrolled in different successive clinical trials. Phase 1 and 2 trials confirmed its safety and tolerability and its great efficacy in suppressing viral loads in short periods. It has a pangenotypic activity with favorable pharmacokinetic properties. Ravidasvir inhibits the replication of HCV variants that develop resistance mutations for different DAA classes. Even more, HCV variants that had reduced susceptibility to ravidasvir are completely susceptible to other DAA. Finally, a large multicenteric registrational phase 3 clinical trial that included large percentages of difficult to treat patients (such as cirrhotic and interferon experienced patients) has been fully accomplished and proved great SVR12 rates.

Conclusion: Ravidasvir is a potent new NS5A inhibitor with excellent safety and tolerability in management of genotype 4 HCV patients.
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http://dx.doi.org/10.2174/1570163814666170713104435DOI Listing
April 2019

Discovery and preclinical development of dasabuvir for the treatment of hepatitis C infection.

Expert Opin Drug Discov 2017 Jun 5;12(6):635-642. Epub 2017 May 5.

b Endemic Hepatogastroenterology, Faculty of Medicine , Cairo University , Cairo , Egypt.

Introduction: Hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality. Positively, the introduction of new directly-acting antivirals (DAAs) have led to dramatic improvements in response rates to antiviral therapy. Furthermore, newer generations of DAAs have demonstrated better safety profiles as well as efficacy than older generations. Current treatment recommendations are based on different combinations of DAAs. Current combination therapies rely on agents that target the different steps of viral replication by using different molecules from various DAAs families. Areas covered: In this review, the authors summarize data from of one of the recently developed NS5B polymerase inhibitors, dasabuvir, formerly known as ABT-333. Herein, the authors discuss the drug discovery data for dasabuvir including data from preclinical, toxicological resistance studies. The authors also review dasabuvir's clinical efficacy across various clinical challenges, in addition to its limitations in clinical practice. Expert opinion: Dasabuvir represents an important medical advance when used as a combination therapy for HCV. Unfortunately, it does present limitations like low genotypic coverage and further research is still required to address some of the lingering issues.
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http://dx.doi.org/10.1080/17460441.2017.1322955DOI Listing
June 2017

Characteristics, management, and outcomes of patients with hepatocellular carcinoma in Africa: a multicountry observational study from the Africa Liver Cancer Consortium.

Lancet Gastroenterol Hepatol 2017 02 3;2(2):103-111. Epub 2016 Dec 3.

Department of Internal Medicine, School of Medical Sciences, Cape Coast, Ghana.

Background: Hepatocellular carcinoma is a leading cause of cancer-related death in Africa, but there is still no comprehensive description of the current status of its epidemiology in Africa. We therefore initiated an African hepatocellular carcinoma consortium aiming to describe the clinical presentation, management, and outcomes of patients with hepatocellular carcinoma in Africa.

Methods: We did a multicentre, multicountry, retrospective observational cohort study, inviting investigators from the African Network for Gastrointestinal and Liver Diseases to participate in the consortium to develop hepatocellular carcinoma research databases and biospecimen repositories. Participating institutions were from Cameroon, Egypt, Ethiopia, Ghana, Ivory Coast, Nigeria, Sudan, Tanzania, and Uganda. Clinical information-demographic characteristics, cause of disease, liver-related blood tests, tumour characteristics, treatments, last follow-up date, and survival status-for patients diagnosed with hepatocellular carcinoma between Aug 1, 2006, and April 1, 2016, were extracted from medical records by participating investigators. Because patients from Egypt showed differences in characteristics compared with patients from the other countries, we divided patients into two groups for analysis; Egypt versus other African countries. We undertook a multifactorial analysis using the Cox proportional hazards model to identify factors affecting survival (assessed from the time of diagnosis to last known follow-up or death).

Findings: We obtained information for 2566 patients at 21 tertiary referral centres (two in Egypt, nine in Nigeria, four in Ghana, and one each in the Ivory Coast, Cameroon, Sudan, Ethiopia, Tanzania, and Uganda). 1251 patients were from Egypt and 1315 were from the other African countries (491 from Ghana, 363 from Nigeria, 277 from Ivory Coast, 59 from Cameroon, 51 from Sudan, 33 from Ethiopia, 21 from Tanzania, and 20 from Uganda). The median age at which hepatocellular carcinoma was diagnosed significantly later in Egypt than the other African countries (58 years [IQR 53-63] vs 46 years [36-58]; p<0·0001). Hepatitis C virus was the leading cause of hepatocellular carcinoma in Egypt (1054 [84%] of 1251 patients), and hepatitis B virus was the leading cause in the other African countries (597 [55%] of 1082 patients). Substantially fewer patients received treatment specifically for hepatocellular carcinoma in the other African countries than in Egypt (43 [3%] of 1315 vs 956 [76%] of 1251; p<0·0001). Among patients with survival information (605 [48%] of 1251 in Egypt and 583 [44%] of 1315 in other African countries), median survival was shorter in the other African countries than in Egypt (2·5 months [95% CI 2·0-3·1] vs 10·9 months [9·6-12·0]; p<0·0001). Factors independently associated with poor survival were: being from an African countries other than Egypt (hazard ratio [HR] 1·59 [95% CI 1·13-2·20]; p=0·01), hepatic encephalopathy (2·81 [1·72-4·42]; p=0·0004), diameter of the largest tumour (1·07 per cm increase [1·04-1·11]; p<0·0001), log α-fetoprotein (1·10 per unit increase [1·02-1·20]; p=0·0188), Eastern Cooperative Oncology Group performance status 3-4 (2·92 [2·13-3·93]; p<0·0001) and no treatment (1·79 [1·44-2·22]; p<0·0001).

Interpretation: Characteristics of hepatocellular carcinoma differ between Egypt and other African countries. The proportion of patients receiving specific treatment in other African countries was low and their outcomes were extremely poor. Urgent efforts are needed to develop health policy strategies to decrease the burden of hepatocellular carcinoma in Africa.

Funding: None.
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http://dx.doi.org/10.1016/S2468-1253(16)30161-3DOI Listing
February 2017

Transarterial Chemoembolization Combined with Either Radiofrequency or Microwave Ablation in Management of Hepatocellular Carcinoma

Asian Pac J Cancer Prev 2017 01 1;18(1):189-194. Epub 2017 Jan 1.

Endemic Medicine and Hepatogastroenterology Department, Cairo University, Cairo, Egypt. Email:

Introduction: Local ablative therapy and trans arterial chemoembolization (TACE) are applied to ablate non resectable hepatocellular carcinoma (HCC). Combination of both techniques has proven to be more effective. We aimed to study combined ablation techniques and assess survival benefit comparing TACE with radiofrequency (RFA) versus TACE with microwave (MWA) techniques. Methods: We retrospectively studied 22 patients who were ablated using TACE-RFA and 45 with TACE-MWA. All were classified as Child A-B and lesions did not exceed 5 cm in diameter. TACE was followed within two weeks by either RFA or MWA. We recorded total and partial ablation rates and complication rates. Survival analysis was then performed. Results: TACE-MWA showed a higher tendency to provide complete response rates than TACE-RFA (P 0.06). This was particularly evident with lesions sized 3-5 cm (P 0.01). Rates of complications showed no significant difference between the groups. Overall median survival was 27 months. The overall actuarial probability of survival was 80.1% at 1 year, 55% at 2 years, and 36.3% at 3 years. The recurrence free survival at 1 year, 2years and 3 years for the TACE-RFA group was 70%, 42% and 14% respectively and for TACE-MWA group 81.2%, 65.1% and 65.1% without any significant difference (P 0.1). In relation to the size of focal lesions, no statistically significant difference in the survival rates was detected between the groups. Conclusion: TACE-MWA led to better response rates than TACE-RFA with tumors 3-5 cm, with no difference in survival rates.
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http://dx.doi.org/10.22034/APJCP.2017.18.1.189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5563099PMC
January 2017

Portal Vein Thrombosis in Unresectable Hcc Cases: a Single Center Study of Prognostic Factors and Management in 140 Patients

Asian Pac J Cancer Prev 2017 01 1;18(1):183-188. Epub 2017 Jan 1.

Diagnostic and Interventional Radiology Department, Faculty of medicine, Cairo University, Egypt. Email: [email protected] yahoo.com

Objective: Hepatocellular carcinoma with portal vein thrombosis is considered a relative contraindication for transarterial chemoembolization (TACE). The aim of our study was to evaluate the prognostic factors and management in patients with hepatocellular carcinoma with portal vein thrombosis (PVT). Methods: Between February 2011 and February 2015, 140 patients presented to our specialized multidisciplinary HCC clinic. All were assessed by imaging at regular intervals for tumor response and the data compared with baseline laboratory and imaging characteristics obtained before treatment. Results: At the end of the follow up in February 2015, 78 (55.7%) of the 140 patients had died, 33.1% in the 1st year and 20.7% in the 2nd year. The overall median survival was 10 months from the date of diagnosis. Clinical progression was noted in 45 (32.1%). Univariate analysis revealed that, the Child-Pugh score, the performance states (Eastern Cooperative Oncology Group “ECOG” 0-1) and the presence of ascites exerted non-significant affects on survival. Similarly, the serum albumen level and AFP >400 ng/ml were without influence. However, patients with =>2 tumors, abdominal lymphadenopathy and serum bilirubin >2mg/dl had a significantly worse prognosis. Specific treatment significantly increased survival compared to patients left untreated (P value = 0.027). Conclusion: Application of specific treatments (curative or palliative) significantly increased survival in HCC patients with PVT. TACE can be considered as a promising procedure for unresectable PVT-associated HCCs. The main predictors of survival in our study were the serum bilirubin level and specific treatment application.
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http://dx.doi.org/10.22034/APJCP.2017.18.1.183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5563098PMC
January 2017
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