Resolved hepatitis B infection in patients receiving immunosuppressive therapy: Monitor versus prophylaxis against viral reactivation.

Risk of hepatitis B virus reactivation (HBVr) in patients with resolved HBV infection receiving immunosuppressive therapy has been a growing concern, particularly in the era of biological and targeted therapies. HBV monitoring versus antiviral prophylaxis against HBVr in those patients remains controversial. The aim of the study was to determine the incidence of HBVr and HBV-related hepatitis in resolved HBV patients who received immunosuppressive therapy with or without antiviral prophylaxis. This retrospective study included 64 patients with resolved HBV infection who received different regimens of immunosuppressive medications, with moderate risk of HBVr, for variable underlying diseases. Patients who had chronic HBV infection or other viral infections were excluded. Patients who received B-cell depleting therapies were ruled out. They were divided into 2 groups: group 1 included 31 patients who received immunosuppressive therapy without antiviral prophylaxis, and group 2 included 33 patients who received antiviral prophylaxis (entecavir) within 2 weeks of commencing the immunosuppressive therapy. HBVr, HBV-related hepatitis, and HBV-unrelated hepatitis were assessed along a 1-year duration. The overall HBVr incidence was 1.56% (1/64). This patient who had HBVr was seen in group 1. There were no significant differences between the 2 groups regarding the incidence of HBVr, HBV-related hepatitis, HBV-unrelated hepatitis, and immunosuppressive therapy interruption along a 1-year duration. Based on this retrospective study, close monitoring was equal to antiviral prophylaxis regarding the outcome of resolved HBV patients who received moderate risk immunosuppressive therapy. HBV treatment should commence once HBVr is confirmed.

Sofosbuvir/Ledipasvir for Treatment of Chronic Hepatitis C Infection in Adult Patients with ß- Thalassemia Major: A Real-Life Study.

BACKGROUND & AIMS: Patients with thalassemia have a lifelong need for blood transfusion, which makes them more risky to hepatitis C virus (HCV). Iron overload and chronic HCV are considered risk factors for patients with thalassemia to develop liver insults. The aim of the present study is to investigate the safety and efficacy of sofosbuvir/ledipasvir in the treatment of chronic HCV infection in Egyptian adult patients with ß- thalassemia major. METHODS: A retrospective study included 53 patients with ß-thalassemia major with chronic HCV treated with sofosbuvir (400 mg) and ledipasvir (90 mg) as a single pill fixed-dose combination once daily for 12 weeks. The effectiveness of the treatment was assessed by the sustained virologic response (SVR) at 12 weeks after the end of the treatment. RESULTS: SVR was achieved in 96.23% of patients. 47.17% of patients had minor side effects. There was a significant reduction in ALT, AST, and serum ferritin 12 weeks post-therapy. There was an insignificant change in hemoglobin level or blood transfusion requirement 12 weeks posttherapy. There was no change in iron chelators doses throughout the study period. CONCLUSION: Sofosbuvir/ledipasvir regimen seems to be safe and highly effective in the treatment of chronic HCV in patients with ß-thalassemia major.

Retrospective study of Dana Farber Consortium Protocol in newly diagnosed Egyptian adolescents and young adults with acute lymphoblastic leukemia: Tanta experience.

BACKGROUND: Intensive acute lymphoblastic leukemia (ALL) regimens in children improve the 5-year event-free survival (EFS) to reach ~ 90%. Adolescents and young adults (AYA) have EFS (30% to 45%). Young AYA ALL patients treated with pediatric chemotherapy protocols such as Dana Farber Consortium Protocol (DFCP) experience a better prognosis. This study aimed to assess the efficacy [EFS and overall survival (OS)] and the toxicity of DFCP in the treatment of Egyptian AYA with newly diagnosed ALL. A retrospective study was performed on 41 patients with newly diagnosed ALL (15 and 39 years) who were treated with DFCP. EFS and OS were estimated using the Kaplan-Meier method. RESULTS: Thirty-eight patients (92.68%) achieved complete remission (CR). Eleven patients (26.83%) relapsed. Ten (24.39%) patients died. One, two, and three years of EFS were 75.61%, 72.91%, and 67.51% respectively. One, two, and three years OS were 85.3%, 77.26%, and 74.39% respectively. Neutropenia was the most common adverse event observed in 100% of patients. CONCLUSION: DFCP can be considered as an effective ALL protocol for the AYA group of patients with good CR, EFS, and OS rates. DFCP seemed to be feasible in AYA despite the toxicities experienced.

Hepatitis C Virus Infection and Treatment as Independent Prognostic Factors in Diffuse Large B-Cell Lymphoma Egyptian Patients.

BACKGROUND: Egypt is one of the highest hepatitis C virus (HCV) endemic areas. Chronic HCV infection has extra-hepatic manifestations, including non-Hodgkin lymphoma (NHL). Diffuse large B-cell lymphoma (DLBCL) is commonly associated with HCV infection. The prognostic value of HCV infection and HCV treatment in patients with DLBCL remains unclear until now. OBJECTIVE: The aim of our study is to evaluate the impact of HCV infection and HCV treatment as independent prognostic factors on the event-free survival (EFS) and overall survival (OS) in Egyptian patients with HCV associated DLBCL. METHODS: This study included 353 patients with DLBCL, collected retrospectively. While 34 patients with HCV who received HCV antiviral therapy were collected prospectively. Patient's characteristics were collected from the patient records at the time of diagnosis. The status of the patients about HCV infection and HCV treatment were also recorded. Disease progression, relapse, retreatment or deaths were also verified through medical records. EFS and OS were calculated. RESULTS: EFS and OS significantly decrease in HCV infected and HCV non-treated patients when compared with HCV non-infected and HCV treated patients, respectively. HCV infection but not HCV treatment was independently associated with EFS and OS using univariate and multivariate analysis. CONCLUSION: Hepatitis C virus infection is an independent prognostic factor for EFS and OS in diffuse large B-cell lymphoma. HCV treatment is associated with higher EFS and OS but can not be considered as an independent prognostic factor.

Impact of CD40 gene polymorphisms on the risk of immune thrombocytopenic purpura.

OBJECTIVES: To evaluate the relationship between two common single nucleotide polymorphisms (SNPs) of CD40 gene (rs1883832 C/T and rs4810485 G/T) and the risk of immune thrombocytopenia (ITP) in the Egyptian population. METHODS: A case-control study was conducted retrospectively on 101 cases with ITP and 97 healthy subjects. Two SNPs of CD40 gene (rs1883832 C/T and rs4810485 G/T) were genotyped via Taqman allele discrimination real-time PCR. The frequencies of different genetic models of both SNPs were calculated and compared between ITP cases and controls. Linkage analysis was performed between the studied SNPs. Odds ratio (OR) and 95% confidence interval (CI) were assessed using multinomial logistic regression analysis to determine the association of CD40 gene SNPs genotypes, alleles, and haplotypes with the risk of ITP. The odds ratio was further adjusted to the confounders for risk stratification. RESULTS: CD40 (rs1883832) TT genotype carriers have a significantly higher risk of ITP when compared to CC genotype carriers (adjusted OR: 3.792, 95%CI: 1.252-11.49, P = 0.018). T allele also represents 1.711-fold increased risk of ITP which is more evident in males (P = 0.016). No significant difference was observed in the frequency of CD40 (rs4810485 G/T) genetic models between cases and controls. Linkage disequilibrium was found between the two SNPs and revealed four main haplotypes (C-G; C-T; T-G; T-T) with a significantly higher frequency of T-G haplotype in ITP cases than in healthy controls which confers an increased risk of ITP development (OR: 2.349, 95%CI: 1.271-4.339, P = 0.006). CONCLUSIONS: CD40 gene SNP rs1883832 is associated with an increased risk of ITP development in the Egyptian population, while the SNP rs4810485 has no association. Moreover, T-G haplotype is a risk genetic model for ITP.

Intermittent versus Daily Eltrombopag Dosage Protocols for the Treatment of Primary Immune Thrombocytopenia: Real-Life Experience.

INTRODUCTION/AIM: Eltrombopag is recommended for the treatment of refractory immune thrombocytopenia (ITP). Based on its half-life, it may be practical to use an intermittent dosage. Our aim was to compare the effectiveness and safety of intermittent vs daily eltrombopag dosage protocols for the treatment of primary ITP refractory to prior therapies. PATIENTS AND METHODS: This was a retrospective study, and 34 adult primary ITP patients refractory to prior therapies were included in our analysis. Eltrombopag was used in this study. The patients were divided into daily eltrombopag dosage and intermittent eltrombopag dosage groups. Eltrombopag effectiveness was assessed regarding platelet count and bleeding resolution. Safety was assessed via adverse events reporting. RESULTS: In the daily eltrombopag dosage group, overall response (OR), complete response (CR), partial response (PR), and relapse rates were 69.23%, 53.85%, 15.38%, and 30.77%, respectively. In the intermittent eltrombopag dosage group, OR, CR, PR, and relapse rates were 68.75%, 50%, 18.75%, and 31.25%, respectively. Comparison between daily and intermittent eltrombopag dosage groups as regards CR, PR, relapse, relapse-free survival and adverse events showed insignificant differences. CONCLUSION: Intermittent eltrombopag dosage is safe and effective in patients with ITP refractory to prior therapies and comparable to the daily eltrombopag dosage.

Predictors for eltrombopag response in patients with hepatitis C virus-associated thrombocytopenia.

BACKGROUND AND AIMS: Thrombocytopenia is a common hematological abnormality observed in patients infected with hepatitis C virus (HCV). The use of eltrombopag has been approved for HCV-associated thrombocytopenia. This is the first study aiming to determine the predictive factors of response to eltrombopag therapy in patients with HCV-associated thrombocytopenia. PATIENTS AND METHODS: This prospective study was carried out on 130 patients with chronic HCV-associated thrombocytopenia (<50,000×109/L) that precludes the initiation of HCV therapy. Eltrombopag was initiated at a dose of 25 mg once daily; the dose was adjusted with 25 mg increments every 2 weeks to achieve the target platelet count. The primary end point was to achieve stable target platelet count (50,000-100,000×109/L) required to initiate antiviral therapy. RESULTS: Treatment response was achieved in 111 (85.38%) patients. This prospective study showed that megakaryocyte hypoplasia or aplasia and splenectomy were independent risk factors for eltrombopag nonresponse in chronic HCV-associated thrombocytopenic patients. CONCLUSION: Eltrombopag is safe and effective for patients with HCV-associated thrombocytopenia. Bone marrow examination should be considered before initiating treatment with eltrombopag in chronic HCV-associated thrombocytopenic patients, especially in patients with splenectomy.

Comparative study to evaluate the effect of l-carnitine plus glimepiride versus glimepiride alone on insulin resistance in type 2 diabetic patients.

AIM: Insulin resistance (IR) is predominant in type 2 diabetic patients. This study aimed to investigate benefits from adding l-carnitine to ongoing glimepiride compared to glimepiride monotherapy on IR in diabetic patients who failed to achieve their glycemic goals on glimepiride monotherapy. METHODS: 58 patients were recruited from Internal Medicine Department, Tanta University Hospital, Egypt then prospectively randomized to receive their glimepiride dose 2 mg twice daily (group 1) or glimepiride 2 mg twice daily + l-carnitine 1 g m twice daily (group 2) for 6 months. Fasting blood samples were collected at baseline, 3 and 6 months after treatment for analysis of fasting and postprandial blood glucose [FBG &PPBG], glycated hemoglobin [HbA1c %], fasting insulin, extracellular part of insulin regulated aminopeptidase [IRAPe] as a novel marker, tumor necrosis factor-alpha [TNF-α], visfatin and lipid panel. Body mass index [BMI] and homeostasis model assessment of insulin resistance [HOMA-IR] were calculated. Data were statistically analyzed by SPSS using unpaired Student's t-test and one way analysis of variance; p ≤ 0.05 was considered statistically significant. RESULTS: The obtained data suggested that adding l-carnitine to glimepiride has a significantly beneficial effect on FBG, PPBG, HbA1c, fasting insulin, HOMA-IR index, IRAPe, TNF-α, visfatin and lipid panel parameters but doesn't have effect on BMI and blood pressure. CONCLUSION: The co-administration of l-carnitine with glimepiride represents a new therapeutic strategy for better controlling diabetic patients as it resulted in more beneficial effects on direct and indirect biomarkers of insulin resistance than glimepiride alone.

Predictors of in-hospital mortality in a cohort of elderly Egyptian patients with acute upper gastrointestinal bleeding.

Acute upper gastrointestinal bleeding (UGIB) affects large number of elderly with high rates of morbidity and mortality. Early identification and management of the factors predicting in-hospital mortality might decrease mortality. This study was conducted to identify the causes of acute UGIB and the predictors of in-hospital mortality in elderly Egyptian patients.286 elderly patients with acute UGIB were divided into: bleeding variceal group (161 patients) and bleeding nonvariceal group (125 patients). Patients' monitoring was done during hospitalization to identify the risk factors that might predict in-hospital mortality in elderly.Variceal bleeding was the most common cause of acute UGIB in elderly Egyptian patients. In-hospital mortality rate was 8.74%. Increasing age, hemodynamic instability at presentation, co-morbidities (especially liver cirrhosis associated with other co-morbidity) and failure to control bleeding were the predictors of in-hospital mortality.Increasing age, hemodynamic instability at presentation, co-morbidities (especially liver cirrhosis associated with other co-morbidity) and failure to control bleeding should be considered when triaging those patients for immediate resuscitation, close observation, and early treatment.

MicroRNAs and clinical implications in hepatocellular carcinoma.

AIM: To assess the role of some circulating miRNAs (miR-23a, miR-203, miR338, miR-34, and miR-16) as tumor markers for diagnosis of hepatocellular carcinoma (HCC). METHODS: One hundred and seventy-one subjects were enrolled, 57 patients with HCC, 57 patients with liver cirrhosis (LC) and 57 healthy subjects as control group. Severity of liver disease was assessed by Child Pugh score. Tumor staging was done using Okuda staging system. Quantification of Micro RNA (miR-23a, miR-203, miR338, miR-34, and miR-16) was performed. RESULTS: All studied miRNA showed significant difference between HCC and cirrhotic patients in comparison to healthy control. miR-23a showed statistically significant difference between HCC and cirrhotic patients being higher in HCC group than cirrhotic. miR-23a is significantly higher in HCC patients with focal lesion size equal or more than 5 cm, patients with multiple focal lesions and Okuda stage III. At cutoff value ≥ 210, miR-23a showed accuracy 79.3% to diagnose HCC patients with sensitivity 89.47% and specificity about 64.91%. At cut off level ≥ 200 ng/mL, serum alpha fetoprotein had 73.68% sensitivity, 52.63% specificity, 43.75% PPV, 80% NPV for diagnosis of HCC. CONCLUSION: MicroRNA 23a can be used as a screening test for early detection of HCC. Also, it is related to larger size of tumour, late Okuda staging and multiple hepatic focal lesions, so it might be a prognostic biomarker.

Hepatitis C virus: A global view.

Hepatitis C virus (HCV) is a global challenge; 130-175 million are chronically infected. Over 350000 die each year from HCV. Chronic HCV is the primary cause of cirrhosis, hepatocellular carcinoma (HCC), and end-stage liver disease. Management of chronic HCV is aimed at preventing cirrhosis, reducing the risk of HCC, and treating extra hepatic complications. New treatments for chronic HCV has been devoted based on direct-acting antivirals, as pegylated interferon (peginterferon) is responsible for many side effects and limits treatment access. Sofosbuvir is the first compound to enter the market with Peginterferon-free combination regimens.

Prevalence and chemotherapy-induced reactivation of occult hepatitis B virus among hepatitis B surface antigen negative patients with diffuse large B-cell lymphoma: significance of hepatitis B core antibodies screening.

BACKGROUND: Occult hepatitis B infection (OBI) is characterized by negative hepatitis B surface antigen (HBsAg) and detectable hepatitis B virus (HBV)-DNA in the liver and/or serum, with or without hepatitis B core antibody (anti-HBc). Anti-HBc is the most sensitive marker of previous HBV. HBV reactivation in patients under immunosuppressive treatment is life-threatening, occurring in both overt and occult HBV especially in hematological malignancies. AIM OF THE WORK: To evaluate the prevalence and chemotherapy-induced reactivation of OBI among hepatitis B surface antigen negative patients with diffuse large B-cell lymphoma (DLBCL) patients and to determine the significance of anti-HBc screening among this group of patients before receiving chemotherapy. PATIENTS AND METHODS: This cross-sectional study included 72 DLBCL patients negative for HBsAg, HBsAb and hepatitis C virus antibodies (anti-HCV). Patients were subjected to investigations including anti-HBc. All patients underwent alanine transaminase (ALT) monitoring before each cycle of chemotherapy and monthly for 12 months after the end of chemotherapy. Patients with suspected OBI were tested for HBV-DNA using real-time polymerase chain reaction (PCR). RESULTS: Anti-HBc was detected in 10 of 72 HBsAg negative sera (13.89%) (95% confidence interval 6.9-22.2%). Five of the 10 anti-HBc positive patients in this study had OBI reactivation. CONCLUSION: The study concluded that anti-HBc screening is mandatory before chemotherapy. HBsAg-negative/anti-HBc-positive patients should be closely observed for signs of HBV reactivation through the regular monitoring of ALT. Prophylaxis lamivudine is recommended for anti-HBc positive patients before chemotherapy.