Biocompatibility of mineral trioxide aggregate and biodentine as root-end filling materials: an in vivo study.

This study evaluated the biocompatibility of mineral trioxide aggregate (MTA) and Biodentine (BD) as root-end filling materials. Six mongrel dogs were divided into two equal groups according to the evaluation period; group A: one month and group B: three months. Three premolars of the same quadrant in each arch were used, summing up 36 teeth (6 teeth/dog). These teeth were randomly subdivided into three subgroups according to the root-end filling material used: MTA, BD and no root-end filling material (control). Endodontic access cavities were performed for induction of periapical pathosis. After the infection period, root canal instrumentation and obturation were accomplished. One day after root canal procedures, root-end surgery was performed. Surgical access was achieved and the root-end was resected approximately 3 mm above the apex. Root-end cavity was prepared ultrasonically and filled with the tested materials. All samples were evaluated by radiography and histopathology (Inflammation and new hard tissue formation). Data were collected and subjected to statistical analysis. In group A, MTA subgroup exhibited significant higher mean inflammatory score than BD subgroup (P < 0.05) while no significant difference was recorded between MTA and BD subgroups in group B (P > 0.05). Regarding mean mineralization score, there was no significant difference between all subgroups in both groups A and B (P > 0.05). Biodentine exhibited favorable biocompatibility in the initial stage of healing than MTA and comparable biomineralization. Clinical relevance: Biodentine could be considered as an acceptable alternative to MTA in peri-radicular surgeries.

Vaccination trials on hold: malicious and low credibility content on Twitter during the AstraZeneca COVID-19 vaccine development.

The development of COVID-19 vaccines during the global pandemic that started in 2020 was marked by uncertainty and misinformation reflected also on social media. This paper provides a quantitative evaluation of the Uniform Resource Locators (URLs) shared on Twitter around the clinical trials of the AstraZeneca vaccine and their temporary interruption in September 2020. We analyzed URLs cited in Twitter messages before and after the temporary interruption of the vaccine development on September 9, 2020 to investigate the presence of low credibility and malicious information. We show that the halt of the AstraZeneca clinical trials prompted tweets that cast doubt, fear and vaccine opposition. We discovered a strong presence of URLs from low credibility or malicious websites, as classified by independent fact-checking organizations or identified by web hosting infrastructure features. Moreover, we identified what appears to be coordinated operations to artificially promote some of these URLs hosted on malicious websites.

Assessment of circulating levels of microRNA-326, microRNA-424, and microRNA-511 as biomarkers for hepatocellular carcinoma in Egyptians.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common cancer. Differential expression of microRNAs (miRNAs)-326, miRNA-424, and miRNA-511 has been associated with the diagnosis and prognosis of HCC in different populations. However, limited information is available regarding their expression in Egyptian HCC patients. AIM: To assess the role of circulating miRNAs-326, miRNA-424, and miRNA-511 in Egyptian HCC patients. METHODS: This prospective observational study included 70 HCC patients and 25 healthy controls. The circulating levels of these three miRNAs were evaluated by real-time PCR. Receiver operating characteristic curve analysis was used to test the diagnostic accuracy of microRNA expression levels. RESULTS: All miRNAs were differentially expressed in HCC patients; miRNAs326 and miRNA-424 were upregulated, while miRNA-511 was downregulated. Both miRNA-326 and miRNA-424 showed sensitivity and specificity of 97%, 71.4%, and 52%, 60%, respectively, to differentiate HCC from controls. Moreover, miRNA-326 was associated with survival and could differentiate between Child grades (A vs B); miRNA-424 significantly differentiated early vs intermediate stages of HCC; while miRNA-511 was significantly correlated with response to modified Response Evaluation Criteria in Solid Tumors (mRECIST). CONCLUSION: We conclude that miRNA-326, miRNA-424, and miRNA-511 have diagnostic and prognostic roles in Egyptian patients with hepatitis C virus-related HCC and should be considered for better disease management.

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.

Changes in Serum Interferon Gamma and Interleukin-10 in Relation to Direct-Acting Antiviral Therapy of Chronic Hepatitis C Genotype 4: A Pilot Study.

Introduction: This study analyzes the changing levels of circulating inflammatory cytokines Interferon gamma (IFN-γ) and interleukin (IL)-10 (as the main cytokines of T-helper-1 and T-helper-2 immune responses) in patients with chronic hepatitis C virus (HCV) infection undergoing therapy with direct-acting antivirals (DAAs) and to correlate them with laboratory markers. Methods: This Pilot study included 50 HCV monoinfected patients who received DAAs for 12 or 24 weeks. They were followed up monthly during therapy and 3 months after the end of the treatment. Liver disease was determined by transient elastography, in addition to FIB-4 indices. Analysis of IFN-gamma and IL-10 was carried out using an enzyme-linked immunosorbent assay. Results: All patients carried HCV genotype 4. The Sustained virological response was 100% and 92% in cirrhotics and noncirrhotics, respectively. There was no significant difference between groups in baseline IL-10 or IFN-gamma. In noncirrhotics, IL-10 showed a significant reduction at Week 4 after treatment start. In cirrhotics, IL-10 showed a significant reduction at Week 4 after treatment starts and a significant reduction at Week 12 after the end of the treatment. At Week 12 after the end of the treatment, serum IL-10 levels were significantly lower in cirrhotics. IFN-γ showed nonsignificant changes in noncirrhotics. A significant increase of IFN-γ occurred in cirrhotics from Week 4 after treatment starts to 12 weeks after the end of the treatment. IFN-γ was significantly higher in cirrhotics at Week 12 after the end of the treatment. IFN-γ and IL-10 showed different correlations with laboratory markers. Conclusion: Viral eradication induced by DAAs caused a significant change in IL-10 and IFN-gamma.

Plasma cell-free DNA integrity index and hepatocellular carcinoma treated or not with direct-acting antivirals: A case-control study.

BACKGROUND AND STUDY AIMS: The clinical value of the cell-free DNA (cf-DNA) integrity index as a diagnostic biomarker of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) was investigated and correlated with alpha-fetoprotein (AFP). PATIENTS AND METHODS: This case-control study was conducted on 160 patients with HCV genotype 4-related liver cirrhosis. Group 1 consisted of 80 patients with HCC, including 40 patients naïve to direct-acting antivirals (DAAs) and 40 patients who received DAAs and achieved sustained virological response. Group 2 comprised 80 patients with cirrhosis without HCC. Plasma cf-DNA integrity index using ALU 115 and ALU 247 sequences was assessed using SYBR Green-based real-time polymerase chain reaction (RT-PCR). The cf-DNA integrity index was calculated as the ratio of Q247/Q115 where Q115 and Q247 are the ALU-qPCR results obtained using ALU 115 and ALU 247, respectively. RESULTS: Patients with HCC had significantly lower plasma cf-DNA integrity index than those with liver cirrhosis. No significant difference in the cf-DNA integrity index was observed between patients with HCC who received DAAs and those who did not. Receiver operating characteristic (ROC) analysis revealed an area under the ROC curve of 0.965 and 0.886 for detecting HCC using the cf-DNA integrity index and AFP, respectively. The combination of the cf-DNA integrity index and AFP improved the sensitivity from 81.6% to 94.7%, positive predictive value from 93.4% to 94.7%, negative predictive value from 84.4% to 94.9%, and accuracy from 88.4% to 94.8%. CONCLUSION: The cf-DNA integrity index can predict the occurrence of HCV genotype 4-related HCC. No significant difference in the cf-DNA integrity index was observed between patients with HCC who received DAAs and those without previous DAAs. The combination of the cf-DNA integrity index and AFP provides better HCC prediction accuracy.

P53 is a risk factor of de-novo hepatitis C-related hepatocellular carcinoma treated with direct-acting antivirals: a case-control study.

BACKGROUND: The mechanisms underlying de-novo hepatocellular carcinoma (HCC) after direct-acting antivirals (DAAs) is still under investigation. This work aims to study P53 and hepatocyte growth factor (HGF) as possible diagnostics of de-novo hepatocellular carcinoma (HCC) following DAAs in comparison to alpha-fetoprotein (AFP). METHOD: This case-control study included 166 patients with liver cirrhosis divided into group-1: patients without HCC (n = 50), group-2: patients with de-novo HCC following DAAs, and achieved sustained virological response (n = 50), and group-3: patients with HCC without DAAs (n = 66). P53 antibody and HGF were determined using a quantitative sandwich enzyme immunoassay technique (Cusabio Co, Houston, USA). RESULTS: Patients with HCC showed significantly higher HGF. Patients with de-novo HCC following DAAs had significantly higher P53 than HCC without DAAs (P < 0.0001). The multiple logistic regression analysis showed that the P53 levels were significantly associated with susceptibility to de-novo HCC (P value = 0.004). The best overall formula was constructed for HCC diagnosis by entering significant markers into the regression model. A three markers model was developed = (1.22 + AFP X 0.002 + HGF X 0.001 + P53 X 0.001). The medians (percentiles) of combined three markers were 1.8 (1.0-2.1) in liver cirrhosis and 2.2 (2.0-2.9) in all HCC (P < 0.00001). The AUC of combined markers was greater than a single marker. The AUC was 0.87 to differentiate HCC from liver cirrhosis; AUC 0.91 to differentiate de-novo HCC after DAAs from liver cirrhosis. CONCLUSION: P53 may serve as a diagnostic marker for de-novo HCC after DAAs therapy. HGF may serve as a diagnostic marker for HCC but not specific for de-novo HCC after DAAs therapy.

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

Schistosoma mansoni 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.

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

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.

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.

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

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.

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

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.

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

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.

Sealing ability of Biodentine versus ProRoot mineral trioxide aggregate as root-end filling materials.

AIM: This study evaluated the sealing ability of ProRoot MTA and Biodentine as root-end filling materials. METHOD: In total, twenty (N = 20) extracted human maxillary central incisor teeth were decontaminated, cleaned and decoronated. Instrumentation was performed according to the step back technique using #50 Flex-o-file. Then the canals were flared to #70 Flex-o-file. Obturation was performed with conventional gutta percha and a resinous sealer (AH26) using the lateral condensation technique. Resection of 3 mm of apical end of each root was achieved perpendicular to the long axis of the root. Root-end cavity was prepared in each sample ultrasonically then filled with tested materials (N = 10). Fluid filtration method was used to assess the sealing ability of each tested material at three different experimental periods; one day, one week and one month after setting. All data were tabulated and statistically analyzed with a level of significance set at P ≤ .05. RESULTS: At each specific time interval, the leakage mean values were not consistent among the tested materials. At one day interval, ProRoot MTA samples had a higher leakage mean value than Biodentine samples. However, this difference in leakage was not statistically significant (P > .05). At one week interval, both materials showed an increased degree of leakage mean value with no significant difference (P > .05). At one month interval, ProRoot MTA samples showed a decrease in leakage mean value, while the Biodentine samples showed a further increase in leakage mean value. This difference was statistically significant (P < .05). CONCLUSION: Although the sealing ability of ProRoot MTA is superior to Biodentine, Biodentine could be considered as an acceptable alternative to ProRoot MTA in peri-radicular surgeries.

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

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.

Spur-of-the-Moment Modification in National Treatment Policies Leads to a Surprising HCV Viral Suppression in All Treated Patients: Real-Life Egyptian Experience.

The aim of this study was to retrospectively analyze the outcome of an unscheduled change in national Egyptian policies for the treatment of hepatitis C virus (HCV), which was transpired as a result of a reduction in interferon supplies, and to manage patients who already started interferon-based therapy. After completing a priming 4-weeks course of sofosbuvir/pegylated interferon/ribavirin (SOF/PEG IFN/RBV), a 12-weeks course of sofosbuvir/daclatasvir (SOF/DCV) combination was initiated. We evaluated the sustained virologic response at 12 weeks posttreatment (SVR12) for 2 groups of patients; Group 1, which included patients who had the previous regimen with IFN priming, and group 2, which included the first consecutive group of patients who received SOF/DCV for 12 weeks from the start without IFN priming. All group 1 patients (1,214 patients) achieved SVR12 (100%) and this was statistically significant when compared with the overall SVR12 in group 2 [8,869 patients with sustained virologic response [SVR] of 98.9%] (P value <0.001). No serious adverse events were reported in both groups. In this real-life treatment experience, interferon-based directly acting antiviral treatment with SOF/PEG IFN/RBV as a priming for 4 weeks, followed by SOF/DCV combination for 12 weeks, led to HCV viral suppression in all treated patients.

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

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.

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

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.

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

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.

Aggressive Treatment of Performance Status 1 and 2 HCC Patients Significantly Improves Survival - an Egyptian Retrospective Cohort Study of 524 Cases.

BACKGROUND: In the Barcelona Clinic Liver Cancer (BCLC) system, only sorafenib is suggested for HCC patients having performance status (PS) 1 or 2 even if they have treatable lesions. In the current study, we aimed to explore the outcome of using aggressive treatment for HCC patients with PS 1 and 2. MATERIALS AND METHODS: Five hundred and twenty four patients with HCC were enrolled in this study and divided into 2 groups: 404 PS 1 and 120 PS 2. Of the included 524 patients, 136 recceived non-aggressive supportive treatment and sorafenib, while 388 patients were offered aggressive treatment in the form of surgical resection, transplantation, percutaneous ablation, trans-arterial chemoembolization and/or chemoperfusion. All the patients were followed up for a period of 2 years to determine their survival. RESULTS: Most HCC patients were CHILD A and B grades (89.4% versus 85.0%, for PS1 and PS2, respectively). Patients with PS1 were significantly younger. Out of the enrolled 524 patients, 388 were offered aggressive treatment, 253 (65.2%) having their lesions fully ablated, 94 (24.2%) undergoing partial ablation and 41 patients with no ablation (10.6%). The median survival of the patients with PS 1 who were offered aggressive treatment was 20 months versus 9 months only for those who were offered supportive treatment and sorafenib (<0.001). Regarding HCC patients with PS 2, the median survivals were similarly 19.7 months versus 8.7 months only (<0.001). CONCLUSIONS: Aggressive treatment of HCC patients with PS 1 and 2 significantly improves their survival. Revising the BCLC guidelines regarding such patients is recommended.