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Circulating cell-free DNA (cfDNA) is a noninvasive substitute to liver biopsy for hepatocellular carcinoma (HCC) molecular profiling. This study aimed to use cfDNA to investigate copy number variation (CNV) in the BCL9 and RPS6KB1 genes and its impact on prognosis in HCC. Real-Time Polymerase Chain Reaction was used to determine the CNV and cfDNA integrity index in 100 HCC patients. CNV gain in BCL9 and RPS6KB1 genes was detected in 14% and 24% of patients, respectively. Gain in CNV of BCL9 associated with risk of HCC in alcohol drinkers and hepatitis C seropositivity. In patients with RPS6KB1 gain, HCC risk increased with a high body mass index, smoking, schistosomiasis, and Barcelona clinical liver cancer stage (BCLC) A. Gain in both genes showed a high risk of HCC with elevated liver enzymes, Schistosomiasis, BCLC C, and PS > 1. The integrity of cfDNA was higher in patients with CNV gain in RPS6KB1 than those harboring CNV gain in BCL9. Lastly, BCL9 gain and BCL9 + RPS6KB1 gain led to higher mortality rates and reduced survival times. cfDNA was used to detect BCL9 and RPS6KB1 CNVs, which influence prognosis and can be used as independent predictors of HCC patient survival. [ABSTRACT FROM AUTHOR]

Efforts toward eradicating the Hepatitis C virus (HCV) have advanced rapidly, due to the development of direct-acting antivirals (DAAs), especially with the appearance of pan-genotypic combinations. Real-world studies, in particular, have verified the efficacy and safety of DAA combinations documented in registration trials. This review documents the results of using DAA combinations in real-life settings in everyday clinical practice in Egypt, the country with the highest prevalence of HCV. The significant number of treated patients in Egypt, which exceeded four million allowed tremendous data about the results of HCV management in real-life settings for different treatment regimens and disease conditions. DAA combinations have resulted in high sustained virologic response rates (SVR12) and few adverse reactions in real-life settings. SVR12 rates ranged from 90% to 100%, depending on the combination of drugs used, the HCV genotype, and the stage of liver disease. Most adverse reactions reported in real-world settings were mild and resulted in treatment discontinuation in only a minority of cases. Data from real-life studies covered most aspects of HCV management that were lacking after initial approval studies. More research is needed to tailor treatment and produce generic HCV combinations to overcome the residual limitations of the currently available DAAs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

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. 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. 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). Recurrence of HCC remains a threat in HCV patients even after achieving an SVR. Implementation of long-term surveillance programs is highly recommended. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: During the last few years, treatment of hepatitis C virus (HCV) revolutionized with the appearance of direct antiviral agents especially for patients with HCV genotypes 1 and 4 infections. Elbasvir (NS5A inhibitor) and grazoprevir (NS3/4A protease inhibitor) are newly developed drugs that are presented in fixed dose combination tablets. Areas covered: This review covers the mechanism of action, pharmacokinetic and pharmacodynamics properties, clinical uses, safety and efficacy of elbasvir/grazoprevir in managing a wide variety of easy and difficult to treat populations (such as presence of cirrhosis, treatment experienced, co-infection with HIV and patients with inherited blood disorders). Expert commentary: Elbasvir/grazoprevir combination showed great efficacy with high rates of sustained virological response rates in genotypes 1 and 4 HCV infection. In addition, it retained a good safety profile and is generally well tolerated. [ABSTRACT FROM AUTHOR]

Objective. Limited therapies are offered for large hepatocellular carcinoma (HCC). It carries dismal prognosis and efforts tried changing its management from a palliative to a curative mode. Transarterial chemoembolization (TACE) is a palliative procedure that may have survival benefit if compared to non-management of large lesions. Microwave ablation (MWA) has emerged as a relatively new technique with promise of larger and faster ablation. We aim to evaluate the efficacy and safety of percutaneous MWA versus TACE for large tumors (5-7 cm) and to assess their effects on local tumor progression and survival. Patients and methods. Sixty-four patients with large lesions are managed in our multidisciplinary HCC clinic and were divided into two groups treated either by MWA or TACE. Complete response rate, local recurrence, de novo lesions, and overall survival analysis are compared between both procedures. Results. Both groups were comparable as regards the demographic and ultrasonographic features. MWA showed higher rates of complete ablation (75%) with fewer sessions, lower incidence of tumor recurrence ( p = 0.02), development of de novo lesions ( p = 0.03), occurrence of post-treatment ascites ( p = 0.003), and higher survival rates ( p = 0.04). The mean survival of the microwave group was 21.7 months with actuarial probability of survival at 12 and 18 months 78.2% and 68.4%, respectively. The mean survival of the TACE group was 13.7 months with actuarial probability of survival at 12 and 18 months being 52.4% and 28.6%, respectively. Conclusion. MWA showed better results than TACE in the management of large HCC lesions. [ABSTRACT FROM AUTHOR]