Relationship between hepatitis C virus infection and extrahepatic malignancies.

Aim of the study: Hepatitis C virus (HCV) is one of the most common causes of liver-related deaths worldwide. Non-hepatic cancers such as lung and pancreatic cancers have been linked to HCV infection. This study aimed to determine whether HCV seropositivity was related to the development of extrahepatic malignancies and whether this had an impact on patients' survival. Material and methods: This retrospective case control study included 1476 patients with lung, colorectal, pancreatic and breast cancers compared to 1550 age- and sex-matched controls regarding HCV seropositivity. In the cancer group, HCV seropositive and seronegative subjects were compared for TNM staging, histologic grading and survival. Results: There was no significant difference between cancer patients and controls regarding age and sex. The percentage of HCV seropositivity was significantly higher in the total cancer group compared to that in the control group (11.6% vs. 7.3%) [OR = 1.67, p < 0.001] and in cancer types: lung (20.1%) [OR = 3.20, p < 0.001], colorectal (11.8%) [OR = 1.70, p = 0.025], pancreatic (25.4%) [OR = 4.33, p < 0.001] and breast cancer (8.1%) [OR = 1.47, p = 0.03]. There was a significant decrease in survival among HCV seropositive subjects compared to seronegatives in colorectal [HR = 2.77, p = 0.002] and pancreatic cancer [HR = 2.2, p = 0.004], a non-significant decrease in lung cancer [HR = 1.02, p = 0.93] and a non-significant increase in breast cancer [HR = 0.79, p = 0.51]. Conclusions: HCV seropositivity was associated with increased risk of lung, colorectal, pancreatic and breast cancer development; it was also associated with reduced survival in colorectal and pancreatic but not in lung and breast cancers.

Clinical study on the efficacy of hepatitis B vaccination in hepatitis C virus related chronic liver diseases in Egypt.

BACKGROUND: Chronic hepatitis B (HBV) and C virus (HCV) infections represent significant public health issues internationally. HBV vaccination has high sero-conversion rates in patients with mild to moderate chronic liver disease but has reduced efficacy in advanced stages. AIM: to evaluate the efficacy of hepatitis B vaccination in HCV-related chronic liver disease and identify possible factors that may contribute to hypo-responsiveness in those patients. METHODS: Our study was a retrospective observational clinical study carried out at the tropical medicine department. It was conducted on 500 individuals (400 chronic HCV patients and 100 healthy controls). Individuals were divided into 5 groups: A (control group), B (cirrhotic patient not receiving treatment), C (chronic hepatitis patients receiving treatment), D (cirrhotic patients receiving treatment), and E (HCC patients receiving treatment). All individuals were subjected for comprehensive history taking, clinical examination, laboratory investigations, and assessment of anti-HBs titer. RESULTS: There is an inverse relationship between the level of anti-HBs Abs and the duration of vaccine. Diabetes and presence of cirrhosis have statistically significant relationship with serum anti-HBs Abs titer (P = 0.007). Oral DAAs therapy is associated with reduced response to HBV vaccine (only 31.75% of the patients were protected). CONCLUSION: HCV infection and its complications significantly impair HBV vaccine response. Levels of anti-HBs Abs decline progressively with increasing duration from the last dose in immunization schedule of HBV vaccine. Diabetes and presence of cirrhosis being the main risk factors for vaccine hypo-responsiveness, also oral DAAs therapy is associated with reduced response to HBV vaccine.

Impact of COVID-19 on endoscopic follow-up of gastroesophageal varices.

Background: Portal hypertension is considered as a major complication of liver cirrhosis. Endoscopy plays a main role in managing of gastrointestinal complications of portal hypertension. Endoscopists are at increased risk for COVID-19 infection because upper gastrointestinal (GI) endoscopy is a high-risk aerosol-generating procedure and may be a potential route for COVID-19. Objectives: To compare the outcome between cirrhotic patients who underwent classic regular endoscopic variceal ligation after primary bleeding episode every 2-4 weeks, and those presented during the era of COVID-19 and their follow-up were postponed 2 months later. Methods: This retrospective study included cross-matched 238 cirrhotic patients with portal hypertension presented with upper GI bleeding, 112 cirrhotic patients presented during the era of COVID19 (group A) underwent endoscopic variceal ligation, another session after 2 weeks and their subsequent follow-up was postponed 2 months later, and 126 cirrhotic patients as control (group B) underwent regular endoscopic variceal band ligation after primary bleeding episode every 2-4 weeks. Results: Eradication of varices was achieved in 32% of cases in group A, and 46% in group was not any statistically significant (p > 0.05); also, there was no any statistical significant difference between both groups regarding occurrence of rebleeding, post endoscopic symptoms, and mortality rate (p > 0.05). Conclusion: Band ligation and injection of esophageal and gastric vary every 2 months were as effective and safe as doing it every 2 to 4 weeks after primary bleeding episode for further studies and validation.

COVID-19 in Cirrhotic Patients: Is Portal Vein Thrombosis a Potential Complication?

Introduction: Several studies have demonstrated that thromboembolic events increased in patients with coronavirus infection, usually occurring in elderly patients with severe illness, associated with comorbid diseases such as diabetes and hypertension. Portal vein thrombosis (PVT) is a rare venous thromboembolic disease occurring typically in patients with an underlying disease such as decompensated cirrhosis with or without hepatocellular carcinoma (HCC). Aim: To evaluate incidence of occurrence of acute PVT in cirrhotic patients infected with 2019 coronavirus disease (COVID-19). Methods: This cross-sectional, observational study involved 70 patients of the liver cirrhosis: (group A) 28 patients with liver cirrhosis infected with COVID-19, and 42 patients with liver cirrhosis as the control group matched for age and sex (group B). All patients were subjected to thorough medical history, routine investigations (complete blood count, liver, and renal function tests), imaging in the form of abdominal and Doppler ultrasonography to assess the presence of acute PVT, serum ferritin, D-dimer, C-reactive protein, and PCR of COVID-19 for group A only. Results: There was a significant difference between the two groups regarding Doppler ultrasound findings as 3 of the patients in group A had PVT (10.7%), 2 of them had HCC diagnosed by triphasic CT abdomen, and only 1 patient in group B had PVT (2.3%) (p < 0.05). Conclusion: In cirrhotic patients infected with COVID-19, portal vein thrombosis may be a potential complication even in the absence of hepatocellular carcinoma; further prospective studies with longer follow-up may be needed.

Distribution of naturally -occurring NS5B resistance-associated substitutions in Egyptian patients with chronic Hepatitis C.

BACKGROUND: NS5B polymerase inhibitors represent the cornerstone of the present treatment of Hepatitis C virus infection (HCV). Naturally occurring substitution mutations to NS5B inhibitors have been recorded. The current study intended to demonstrate possible natural direct acting antiviral (DAA)-mutations of the HCV NS5B region in HCV patients in Minia governorate, Egypt. METHODS: Samples were collected from 27 treatment-naïve HCV patients and 8 non-responders. Out of 27 treatment-naïve patients, 17 NS5B sequences (amino acids 221-345) from treatment-naïve patients and one sample of non-responders were successfully amplified. Nucleotide sequences have been aligned, translated into amino acids, and compared to drug resistance mutations reported in the literature. RESULTS: NS5B amino acid sequence analysis ensures several novel NS5B mutations existence (more than 40 substitution mutations) that have not been previously documented to be correlated with a resistant phenotype. It was found that K304R (82.4%), E327D and P300T (76.5% each) substitutions were the most distributed in the tested samples, respectively. S282T, the major resistance mutation that induces high sofosbuvir-resistance level in addition to other reported mutations (L320F/C) and (C316Y/N) were not recognized. Q309R mutation is a ribavirin-associated resistance, which was recognized in one strain (5.9%) of genotype 1g sequences. Besides, one substitution mutation (E237G) was identified in the successfully amplified non-responder sample. CONCLUSION: Our study showed various combinations of mutations in the analyzed NS5B genes which could enhance the possibility of therapy failure in patients administered regimens including multiple DAA.

Isotretinoin Induced Hyperlipidemia and Impact of Leptin Gene rs 7799039 Polymorphism in Safety of Acne Patients.

BACKGROUND: Acne vulgaris (AV) is a chronic inflammatory disease that affects the pilosebaceous unit. Leptin (LEP) gene polymorphisms is associated with higher risk of multiple disorders. Insulin-like growth factor-1 (IGF-1) exerts comedogenic effect by stimulating the sebaceous glands. Isotretinoin is an effective oral therapy for AV with many side effects including hyperlipidemia and increased serum levels of liver enzymes. PURPOSE: To evaluate the impact of LEP gene rs7799039 polymorphism in acne patients' clinical response lipid profile and liver enzymes following 6 months oral isotretinoin therapy in Egyptian AV patients. METHODS: One hundred eligible AV patients received 0.5 mg/kg oral isotretinoin for 6 months. Patients' demographics and clinical data were obtained. Body mass index (BMI), lipid profile, liver enzymes and IGF-1 were measured at baseline and after 6 months of therapy. Genotyping was done for LEP gene rs 7799039. RESULTS: Six month administration of oral isotretinoin in Egyptian AV patients is associated with significantly elevated aspartate transaminase (AST) in CC and AC genotypes (P<0.001). Significant alanine aminotransferase (ALT) elevation was observed in CC, AC and AA genotypes (P <0.001, 0.004, 0.002, respectively). Total cholesterol (TC), triglycerides (TG) and low density lipoprotein (LDL) were elevated significantly P<0.001) in the three genotypes. IGF-1 was decreased significantly in CC and AC genotypes (P<0.001). CC genotype is associated with highest response (P<0.001). CONCLUSION: LEP rs7799039 gene had an impact on the clinical response, lipid profile and liver enzymes in AV patients treated with oral isotretinoin. LEP rs7799039 CC genotype is predicted to be the treatment candidate for 6 month oral isotretinoin.

Efficacy of antiviral therapy in patients with post-hepatitis C liver cirrhosis: is hyperuricaemia a potential adverse effect?

Hepatitis C virus (HCV) related liver cirrhosis is considered a major health problem; sofosbuvir (SOF)/ledipasvir (LDV) and SOF/daclatsvir (DACLA) are very promising direct antiviral agents (DAAS) especially in treating HCV genotype 4 which is the main genotype in Egypt. Uric acid elevation was reported in many systemic diseases and might be elevated during direct antiviral therapy. The aim is to evaluate efficacy and safety of SOF/LDV and SOF/DACLA plus ribavirin in treating HCV related child A liver cirrhosis and assess hyperuricaemia as a potential adverse effect to this regimen. METHODS: This prospective observatinal study included 128 HCV naive child A cirrhotic patients divided into two groups (77 patients were treated with SOF 400 mg, DACLA 60 mg and ribavirin 600 mg and 51 patients were treated with SOF 400 mg, LDV 90 mg and ribavirin 600 mg) for 12 weeks, during the treatment complete blood count, creatinine, bilirubin, alanine transaminase, aspartate transaminase and serum uric acid were monitored, HCV RNA quantitative PCR at 12 weeks after the end of treatment was done. RESULTS: Response to treatment in SOF/LDV (sof/led) group is about (98%), response to treatment in SOF/DACLA (sof/dacla) group is about (96%). Hyperuricaemia was noticed in 17.6% of patients received sof/led and in 15.5% of those received sof/dacla. CONCLUSION: SOF+LDV and SOF+DACLA plus ribavirin regimens are highly effective in treating chronic HCV patients with compensated liver cirrhosis. Hyperuricaemia is considered a potential adverse effect to DAAS containing ribavirin and may lead to serious side effects such as renal impairment.

RAS Pathway Mutation Patterns in Patients With Juvenile Myelomonocytic Leukemia: A Developing Country Single-center Experience.

INTRODUCTION: Juvenile myelomonocytic leukemia (JMML) is a rare clonal myelodysplastic/myeloproliferative neoplasm of early childhood. Historically, it was difficult to diagnose clinically, as patients present with manifestations shared with other hematologic malignancies or viral infections. It is now clear that JMML is a disease of hyperactive RAS signaling. PATIENTS AND METHODS: We examined the bone marrow of 41 Egyptian children with JMML by direct sequencing for mutations in the RAS pathway genes. RESULTS: Mutations were detected in 33 (80%) of 41 patients. We identified 12 (29%) of 41 patients with PTPN11 mutation; 18 (44%) of 41 with RAS mutation; 9 (22%) of 41 with NRAS mutation; 9 (22%) of 41 with KRAS mutation; and 3 (7%) of 41 with CBL mutation. Eleven (92%) of the PTPN11 mutations were detected in exon 3 and 1 (8%) in exon 13. Seven of the NRAS mutations were in exon 2, and 2 were in exon 3. All KRAS mutations were in exon 2. The 3 cases with CBL mutation were homozygous mutations in exon 8. All the mutations detected in PTPN11, NRAS/KRAS, and the CBL genes were previously reported missense mutations in JMML. CONCLUSION: Our results demonstrate that Egyptian children diagnosed with JMML have high frequency of NRAS/KRAS mutations and lower frequency of PTPN11 mutations as compared with previous studies. The concept of mutually exclusive RAS pathway mutations was clearly observed in our patients. All cancer centers in our region should start implementing molecular diagnostic methods before confirming the diagnosis of JMML and before offering hematopoietic stem cell transplantation.

Effects of genistein on pentylenetetrazole-induced behavioral and neurochemical deficits in ovariectomized rats.

Estrogenic compounds have been documented in literature to exert neuroprotective effects. This study investigated the potential neuroprotective effect of genistein; a phytoestrogen at doses of 5, 10, 20, and 40 mg/kg p.o. in ovariectomized rats challenged with pentylenetetrazole (PTZ) 90 mg/kg i.p. Systemic acute administration of PTZ induced seizures, increased oxidative stress, and caused apoptosis and histological abnormalities. Pretreatment with genistein delayed seizure onset, reduced the seizure duration, improved oxidative stress profile, decreased estrogen receptor expression, reduced apoptosis, and improved the histopathological pattern. Overall, the genistein doses (10 and 20 mg/kg) showed the strongest protective effects. In conclusion, the current study suggests that genistein exhibits neuroprotective effects against PTZ-induced seizures. Such effects might be attributed to its estrogenic, antioxidant, and/or anti-apoptotic properties.

Proposed Parent Vessel Geometry Based Classification of Anterior Communicating Artery-Located Aneurysms.

BACKGROUND AND OBJECTIVES: The present study is focused on correlation of parent vessels and neck diameters with anterior communicating artery (AComA) aneurysmal depth and growth direction. The study principally aims to suggest a new classification of AComA-located aneurysms based on the physical characteristics of parent vessels. METHODS: A retrospective analysis was performed of 155 patients with ruptured AComA-located aneurysms. The percentage of difference between both A1 arteries was measured on computed tomography angiography images and neck locations were determined. Accordingly, AComA-located aneurysms were classified into 2 groups. In both groups, A1 and A2 arteries and neck size diameters were measured and their relation with aneurysmal depth was studied. The aspect ratio was calculated. RESULTS: Eleven patients in which the aneurysm neck originates from the AComA proper with almost equal A1s were classified as the true AComA aneurysm group whereas 144 patients in whom the aneurysm neck originates at the dominant A1 bifurcation into the AComA and A2 with the average difference between both A1s of about 84.44% were classified as the dominant A1-bifurcation group. There is significant correlation between aneurysmal depth and neck diameter in both groups (P ≤ 0.05, P < 0.001). The aspect ratio was calculated as equal to 1.166. CONCLUSIONS: The dominant A1 bifurcation type is the most common type of AComA-located aneurysm. The present classification provides clinical value in understanding how AComA aneurysms grow and behave. It helps to understand the geometry of multilobulated aneurysms such as ruptured blebs locations during treatment procedures respecting the direction of the dominant A1 axis in group II. Multiple anatomic variations of this complex AComA area can clarify future subtypes of these 2 groups. Thus, further investigation of more patients is needed.

The use of a locked plate in the treatment of ununited femoral shaft fractures.

BACKGROUND: Sixteen patients with ununited fractures of the femur were treated by locked plate. There were 14 men and 2 women. The youngest patient was 18 years old and the oldest was 48 years (average, 32.9 years). Two fractures were infected and 14 were noninfected. METHODS: Time between injury and operation varied from 4 to 26 months (average, 8.2 months). A standard broad dynamic compression plate and AO washers and nuts were used to construct a locked plate. Follow-up ranged from 6 to 24 months. RESULTS: All fractures have healed after this operation; bone graft was not used in any of them. Time until healing ranged from 4 to 6 months (average, 4.9 months). Shortening after surgery ranged from 0 to 5 cm (average, 1.8 cm). There was no metal failure or recurrence of infection. Two patients were readmitted 1 year after operation for metal removal, knee arthrolysis, and quadricepsplasty to improve the range of motion of the knee. CONCLUSION: Locked plate fixation is rigid enough for bone healing and to allow early postoperative mobilization, with good functional outcome.