Changes in liver stiffness measurements and fibrosis scores following sofosbuvir based treatment regimens without interferon.

BACKGROUND AND AIM: Accurate evaluation of the degree of liver fibrosis in patients with chronic liver diseases is crucial, as liver fibrosis is important in order to make therapeutic decisions, determine prognosis of liver disease and to follow-up disease progression. Multiple non-invasive methods have been used successfully in the prediction of fibrosis; however, early changes in non-invasive biomarkers of hepatic fibrosis under effective antiviral therapy are widely unknown. The aim of this study is to evaluate changes of transient elastography values as well as FIB-4 and AST to platelet ratio index (APRI) in patients treated with Sofosbuvir-based treatment regimen. METHODS: This is a retrospective study including 337 chronic HCV Egyptian patients with genotype 4 mainly. They were treated with Sofosbuvir-based treatment regimen. Transient elastography values were recorded as well as FIB-4 and APRI were calculated at baseline and SVR12. RESULTS: There was a significant improvement of platelets counts, ALT and AST levels, which in turn cause significant improvement in FIB-4 and APRI scores at SVR12. Liver stiffness measurements were significantly lower in SVR12 (14.8 ± 10.7 vs 11.8 ± 8.8 kPa, P = 0.000). About 77% of responders and 81.1% of cirrhotic patients showed improvement in liver stiffness measurements at SVR12.Univariate and multivariate regression analysis showed that failure to achieve improvement in liver stiffness measurements were significantly associated with relapsers and low baseline liver stiffness measurement. CONCLUSION: Sofosbuvir-based treatment resulted in a clinically significant improvement in parameters of liver fibrosis.

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

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

Curcumin Loaded Chitosan-Protamine Nanoparticles Revealed Antitumor Activity Via Suppression of NF-κB, Proinflammatory Cytokines and Bcl-2 Gene Expression in the Breast Cancer Cells.

Nano drug delivery has been recently used to enhance the stability and bioavailability of chemotherapeutic agents. In this study, Chitosan/protamine nanocarrier was synthesized and used to encapsulate curcumin (CUR). The physicochemical properties of the empty carrier (CHPNPs) and curcumin-containing carrier (CU-CHPNPs) were characterized by TEM imaging, Zetasizer, and FT-IR spectroscopy. The antitumor activity of the prepared nanoparticles was assessed by determination of cell count, cell viability, the level of NF-κB, IL-6, and TNF-α and Bcl-2 gene expression in breast cancer cells (MCF-7). The results revealed that the obtained CU-CHPNPs had an average hydrodynamic size of 200 nm, zeta potential of +26.66 mv, and showed a drug encapsulation efficiency of 67%, and drug loading capacity of 40.20%. The cell-based assay showed a significant reduction in the cell viability, and NF-κB, TNF-α, and IL-6 levels upon treatment with CU-CHPNPs as compared to free CUR. Finally, the (CU-CHPNPs) downregulated the expression of the Bcl-2 anti-apoptotic gene more effectively than CUR and the CHPNPs comparing with the ß Actin housekeeping gene. This study concluded that the nano-encapsulation of CUR significantly enhances its antitumor efficacy via inhibition of NF-κB, IL-6, and TNF-α and downregulation of Bcl-2.

Long-term clinical outcomes in sustained responders with chronic hepatitis C after treatment with direct-acting antivirals.

OBJECTIVE: Little is known about how the achievement of sustained virological response (SVR) after treatment with direct-antiviral agents (DAAs) affects fibrosis and clinical outcomes in the long term. Our study aimed to evaluate the impact of achieving SVR on long-term changes in fibrosis and clinical outcomes in CHC patients treated with different DAAs-based regimens. METHODS: a prospective, 3-year follow-up study of 113 CHC patients who had achieved SVR after treatment with different DAAs-based regimens between January and June 2015 was conducted. The clinical outcomes of SVR on the biochemical profile, changes in fibrosis, ALBI score and grade and occurrence of liver-related events were analyzed. RESULTS: Overall, liver function parameters and serum alpha-fetoprotein level showed improvement from baseline to SVR12 and remained steady thereafter. Moreover, the ALBI score showed nonsignificant change at baseline to SVR12 (P = 0.2) but it was significantly better at 3-years follow-up than at SVR12 (P = 0.001). Regarding liver stiffness (LS) by transient elastography, a significant decrease in TE values was observed between baseline to SVR12 (P ≤ 0.0001) as well as between SVR12 to 3-years follow-up (P = 0.0005). Stratified by fibrosis stage, patients with advanced fibrosis and cirrhosis showed a more pronounced and significant improvement of LS during follow-up after SVR compared to patients with less advanced fibrosis stage. During the follow-up period, 3 (5.2%) cirrhotic patients developed liver-related events, including 2 (3.4%) patients with de novo HCC and one (1.7%) patient experienced ascites for the first time. CONCLUSION: This 3-year follow-up study provides evidence for the durability of SVR, improvement of liver function parameters and ALBI score and grade in patients with an advanced stage of fibrosis, in particular, and reduction of the clinical events after successful treatment with DAAs.

Covid-19: Urgent Call to Action.

Novel Corona Virus 2019 (COVID-19) is a new virus spread rapidly all over the world. It has specific respiratory or gastrointestinal tract symptoms. Its reported complications include respiratory distress, systemic inflammatory response syndrome, and septic shock. Due to heavy cytokines released by the virus; corticosteroids (40-120 mg / day) were given to severe cases to reduce pneumonia. It's a difficult task to control the spread of SARS-CoV-2, and to invent proper vaccines and treatments. In this review, the existing understanding of fatal, pandemic human coronavirus SARS-Cov2 (COVID-19), with special reference to its diagnosis, origin, transmission, and different approaches to develop its therapeutics, will be discussed.

SARS-CoV-2 infection among asymptomatic healthcare workers of the emergency department in a tertiary care facility.

BACKGROUND: Healthcare workers (HCWs) represent a high-risk category during the coronavirus disease 2019 (COVID-19) pandemic crisis, with frontline HCWs at emergency departments (EDs) may be at an even higher risk. Determining the spread of infection among HCWs may have implications for infection control policies in hospitals. This study aimed to detect severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection among asymptomatic HCWs of the ED of a large tertiary center in Cairo, Egypt. METHODS: The study was conducted from June 1st to June 14th, 2020. All the recommended national and international indications on infection control measures were followed. Two hundred and three HCWs were included in the study and tested by nasopharyngeal swab (NPS) and rapid serological test (RST). Descriptive statistical analyses were used to summarize the data. RESULTS: Of the 203 HCWs, 29 (14.3 %) tested positive by real-time reverse transcription polymerase chain reaction (RT-PCR). Thirty-seven (18.2 %) HCWs tested positive with RST: 20 with both IgM and IgG; 14 with IgM only, and 3 with IgG only. Age, gender, and/or occupation were not risk factors for SARS-CoV-2 infection. CONCLUSIONS: Point prevalence of COVID-19 in asymptomatic HCWs in ED of tertiary care facility is 14.3 % by RT-PCR. This illustrates the importance of screening all HCWs regardless of symptoms, and the need for strict measures in securing HCWs to reduce transmission from healthcare facilities to the community during the current pandemic.

Prevalence of SARS-CoV-2 infection and dynamics of antibodies response among previously undiagnosed healthcare workers in a university hospital: A prospective cohort study.

BACKGROUND: Healthcare workers (HCWs) are a presumed high-risk population for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Identifying factors associated with seroprevalence can help establish better practices in healthcare settings. In this study, we evaluate prevalence of SARS-CoV-2 infection among previously undiagnosed HCWs and describe profiling of antibody responses against SARS-CoV-2, including neutralizing antibodies (NAbs). METHODS: We analyzed a cohort of 386 HCWs in a university hospital in Egypt and 725 volunteers not affiliated to any healthcare facility (non-healthcare workers - NHCWs). Participants provided a nasopharyngeal swab and serum samples for SARS-CoV-2 nucleic acid and SARS-CoV-2-specific antibodies, respectively. HCWs who tested positive by either test were sequentially monitored. RESULTS: At baseline, point prevalence of viral carriage was 11.4% in HCWs (n = 44/386) and 11.9% in NHCWs (86/725). The cumulative prevalence of SARS-CoV-2 infection among HCWs considering all studies was 25.6%, which was statistically lower than in NHCWs (41.0%). Prevalence was greatest among janitorial staff (45.9%) and the most affected departments were gastroenterology (31.1%), and emergency medicine (30.0%). Prior anosmia, fever or headache were associated with higher odds of positivity for SARS-CoV-2 infection. Regarding serial antibody measurements, RT-PCR-positive HCWs displayed IgG detection rates of 29.5%, 70% and 60% at visit 1, visit 2 and visit 3, respectively with slow decline of median IgG antibody titers, whereas, corresponding detection rates for total Ig antibodies were 50%, 90.3%, and 88.9%, respectively with increasing median titers. NAbs measured at each time point were positively correlated with total Ig levels, whereas IgG levels were positively correlated with NAbs at visit 1 and visit 3. CONCLUSION: Our results demonstrate lower cumulative prevalence of SARS-CoV-2 infection in HCWs than general population and suggest that asymptomatic HCWs exhibit considerable IgG and total Ig antibodies response as well as NAbs for up to 120 days, with positive correlation in between.

SARS-CoV-2 infection among healthcare workers of a gastroenterological service in a tertiary care facility.

BACKGROUND AND STUDY AIMS: Frontlines healthcare workers (HCWs) during the coronavirus disease 2019 (COVID-19) pandemic are at increased risk of infection by SARS-CoV-2, but there are limited data on the prevalence of COVID-19 among HCWs in Egypt. This study aimed to assess SARS-CoV-2 infection among HCWs providing gastroenterological services. SUBJECTS AND METHODS: Seventy-four HCWs at the gastroenterological service of Al-Manial University Hospital, the main hospital of the largest tertiary university hospitals complex in Egypt (Kasr Al-Ainy Faculty of Medicine, Cairo University) were tested using real-time reverse transcription-polymerase chain reaction (RT-PCR) on nasopharyngeal samples, and rapid serological IgM/IgG tests (RST). A questionnaire was used to collect demographic, occupational and clinical data. RESULTS: Of the 74 HCWs, 10 tested positive by RT-PCR (13.5%). In 9/74 (12.2%) HCWs, antibodies could be detected by RST: three with both IgM and IgG lines; six with IgM line only and none with IgG line only. Frequency of positive tests was more among subjects with minor symptoms compared to completely asymptomatic HCWs (50% vs 16.1%, respectively). Neither age, gender or occupation was a risk factor for SARS-CoV-2 infection. CONCLUSIONS: Point prevalence of COVID-19 in gastroenterology HCWs is 13.5% by RT-PCR. Continued measures are warranted to assure HCWs safety and reduce transmission from healthcare settings to the community during COVID-19 pandemic. Presence of positive test results among asymptomatic HCWs illustrates the importance of screening all HCWs irrespective of symptoms.

MiR-155 and MiR-665 Role as Potential Non-invasive Biomarkers for Hepatocellular Carcinoma in Egyptian Patients with Chronic Hepatitis C Virus Infection.

BACKGROUND AND OBJECTIVES: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer associated death globally. Serum micro RNAs are full of potential as noninvasive biomarkers. Here, we aim to assess the performance of serum MicroRNA-155 and MicroRNA-665 as diagnostic biomarker for HCC comparing to AFP. METHODS: Serum samples were collected from 200 subjects (40 healthy control, 80 chronic hepatitis C patients with cirrhosis and without HCC (LC) and 80 HCC patients currently infected by hepatitis C infection and didn't start the treatment). The HCC patients didn't include alcoholic liver disease, nonalcoholic fatty liver disease nor autoimmune liver disease. MicroRNA-155 and MicroRNA-665 expression were measured by real-time quantitative PCR (RT-qPCR), while AFP level was assessed by ELISA method. RESULTS: Both miR-155 and miR-665 were significantly elevated in HCC group as compared to both control and LC groups. The comparison between LC and HCC patients revealed that the serum level of miR-155 was a significant increase in HCC patients compared to LC patients; however, the serum level of miR-665 didn't show any significant difference between the same two groups. MiR-665 expression level showed a direct correlation with tumor size in HCC patients. CONCLUSIONS: Using measurement against AFP level in serum, miR-665 is considered a promising serum biomarker for the diagnosis of HCC patients among the LC patients without HCC. MiR-155 didn't provide a better performance than serum AFP as a diagnostic biomarker among the same group. MiR-665 may serve as a good indicator for HCC prognosis.