Correlation between Serum Hyaluronic Acid with Steatosis, Non alcoholic Steato-hepatitis and Fibrosis in Patients with Chronic Hepatitis C Virus Infection.

Background: Hyaluronic acid (HA) is an attractive potential marker for noninvasive diagnosis of liver fibrosis instead of liver biopsy for both patients and physicians. Aim: To assess the role of HA for diagnosing the progression of steatosis to steato-hepatitis (SH) and fibrosis in patients with Chronic Hepatitis C virus (HCV) infection. Methods: 90 patients with chronic HCV infection, 77 (85.6%) males and 13 (14.4%) females, were included. Blood samples were collected for routine laboratory investigations, liver function tests and serum HA measurements. A liver biopsy was taken for histopathological examination. Results: Steatosis was found in 37 patients (41.1%), fibrosis in 29 patients (32.2%) and SH in 51 patients (56.7%). The mean serum HA for all patients was 86.4±48.2 ng/L. HA levels were significantly higher in patients with fibrosis (95.6±53 vs 54.5±3.5) and SH (88.7±52 vs 49.9±12) than those without (P value = 0.001and 0.001 respectively). HA levels were also significantly higher in patients with an advanced degree of fibrosis, SH and steatosis as compared to those with mild degrees (P value = 0.000, 0.001 and 0.01 respectively). Positive correlations were found between serum HA and the degree of fibrosis, SH and steatosis (P value =0.000 and r = + 0.758, 0.701and 0.727 respectively). The mean HA cut off value for the diagnosis of fibrosis and SH was taken to be 70 and 60 ng/L providing a diagnostic accuracy of 94.1% and 91.6% respectively. Conclusion: Serum HA level is a good noninvasive marker for the diagnosis of fibrosis and steato-hepatitis in patients with chronic HCV infection.

Possible Role of Helicobacter pylori in Ear Nose and Throat Diseases.

Background: Helicobacter pylori is assumed to cause many gastric and extragastric diseases. We aimed to assess the possible association role of H. pylori in Otitis media with effusion (OME), nasal polyps and adenotonsillitis. Patients and Methods: A total of 186 patients with various ear, nose and throat diseases were included. The study comprised 78 children with chronic adenotonsillitis, 43 children with nasal polyps and 65 children with OME. OME patients were assigned to two subgroups: those who have and those who did not have adenoid hyperplasia. Among the patients with bilateral nasal polyps, 20 individuals had recurrent nasal polyps and 23 had de novo nasal polyps. Patients who have chronic adenotonsillitis were divided into three groups: those with chronic tonsillitis and those who underwent tonsillitis, those with chronic adenoiditis and adenoidectomy was performed, and those with chronic adenotonsillitis and underwent adenotonsillectomy. In addition to examination of H. pylori antigen in stool samples of all included patients, real-time polymerase chain reaction (RT-PCR) for detection of H. pylori in the effusion fluid was performed, additionally, Giemsa stain was used for detection of H. pylori organism within the tissue samples when available. Results: Frequency of H. pylori in effusion fluid was 28.6% in patients with OME and adenoid hyperplasia, while in those with OME it was only 17.4% with a p value of 0.2. Nasal polyp biopsies were positive in 13% patients of denovo, and 30% patients with recurrent nasal polyps, p=0.2. De novo nasal polyps were more prevalent in the positive stools than recurrent ones, p=0.7. All adenoid samples were negative for H. pylori, only two samples of tonsillar tissue (8.3%) were positive for H. pylori, and stool analysis was positive in 23 patients with chronic adenotonsillitis. Conclusion: Lack of association between Helicobacter pylori and occurrence of OME, nasal polyposis or recurrent adenotonsillitis.

Fluoroquinolone-resistant strains in cirrhotic patients with spontaneous bacterial peritonitis: microbiological and molecular aspects.

OBJECTIVES: This study aimed to determine the causative bacterial agents of spontaneous bacterial peritonitis (SBP) in patients with cirrhosis and to define antibiotic-resistance patterns in addition to identifying the genetic mutations in the quinolone resistance determining regions (QRDRs). PATIENTS AND METHODS: Twenty milliliters of ascetic fluid was obtained from 51 patients with SBP. The antibiotic-sensitivity patterns of different strains were determined by the Kirby-Bauer method. Extracted bacterial DNA was used to determine the mutations in four different genes in QRDRs (gyrA, gyrB, parC, and parE) by sequencing after gene amplification by PCR. RESULTS: Gram-negative bacilli were detected in 60.7% of the patients. Escherichia coli was detected in 33.3% of the patients, and Staphylococcus aureus was detected in 21.6%. Gram-negative bacilli showed the best sensitivity to meropenem (90.3%), followed by amikacin (83.9%). Gram-positive cocci were sensitive to vancomycin and oxacillin at 90 and 80%, respectively. Fluoroquinolone resistance was detected in 27% of the bacterial strains. Mutations in the gyrA and parC genes were detected in quinolone-resistant strains (64.3 and 35.7%, respectively). Several mutations were found in the gyrA gene (Ser83Leu, Ser81Phe, and Ser-84Leu). Ser80Ile and Ser79Tyr mutations were detected in the parC gene. No mutation was detected in the parE gene. CONCLUSION: Frequent use of antibiotics as prophylaxis against SBP leads to an increase in antibiotic resistance and changes the microbial pattern of causative agents. The gyrA gene mutation was the most common mutation detected in fluoroquinolone-resistant strains.

Lactoferrin versus Long-Acting Penicillin in Reducing Elevated Anti-Streptolysin O Titer in Cases of Tonsillopharyngitis.

Background: Beta-Hemolytic streptococci are the most frequent bacteria causing tonsillitis. Lactoferrin may play a role in the treatment of chronic tonsillitis due to its direct antimicrobial activity. Objective: To assess the possible role of lactoferrin in reduction of raised serum Anti-Streptolysin O Titer (ASOT) in cases of chronic tonsillopharyngitis in comparison to long acting penicillin. Methods: This study included 117 children with tonsillopharyngitis with high ASOT randomly divided into three groups; group 1 treated with lactoferrin, group 2 treated with long acting penicillin and group 3 treated with both drugs. For all patients ASOT was measured after three and six months of starting treatment. Results: This study included 60 males and 57 females with the mean age (8.5 ± 2.4). There is statistically significant reduction in ASOT in all groups after three months of treatment. ASOT after 3 months was significantly lower in group1 (370±440) and group 3 (350±450) in comparison to group 2 (420±560) with p value 0.02, 0.004, respectively, with no significant difference in comparing group 1 to group 3 p value 0.4. Also, ASO titre after 6 months was significantly lower in group1 (350±420) and group 3 (340±440) in comparison to group 2 (420±550) with p value 0.02, 0.007, respectively, with no significant difference in comparing group 1 to group 3 p value 0.5. In comparing ASOT at three months and six months of treatment in the three studied groups; it decreased by 2% in group 1, and 1.6% in group 3 and no change in group 2. Conclusion: Lactoferrin alone or in combination with long acting penicillin is safe and more effective than long acting penicillin alone in reducing ASOT. Treatment for six months with lactoferrin alone or in combination with long acting penicillin could offer a better response.

Possible Role of Ivermectin Mucoadhesive Nanosuspension Nasal Spray in Recovery of Post-COVID-19 Anosmia.

Purpose: Anosmia or hyposmia, with or without taste changes, are common symptoms that occur in SARS-CoV-2 infection and frequently persist as post-COVID-19 manifestations. This is the first trial to assess the potential value of using local ivermectin in the form of a mucoadhesive nanosuspension nasal spray to treat post-COVID-19 anosmia. Methods: It is a controlled, randomized trial. Participants were recruited from South Valley University Hospitals in Qena, Upper Egypt, from the ENT and Chest Diseases Departments and outpatient clinics. Patients with persistent post COVID-19 anosmia were randomly divided into two groups, the first group "ivermectin group" included 49 patients treated by ivermectin nanosuspension mucoadhesive nasal spray (two puffs per day). The second group included 47 patients "placebo group" who received saline nasal spray. Follow- up of anosmia [using Visual analogue scale (VAS)] in all patients for three months or appearance of any drug related side effects was done. Results: The mean duration of pre-treatment post COVID-19 anosmia was 19.5± 5.8 days in the ivermectin group and 19.1± 5.9 days in the placebo group,p˃0.05. Regarding the median duration of anosmia recovery, the ivermectin group recovered from post COVID-19 anosmia in 13 days compared to 50 days in the placebo group, p˂ 0.001. Following the first week of ivermectin nanosuspension mucoadhesive nasal spray therapy, the ivermectin group had a significantly higher percentage of anosmia recovery (59.2%) than the placebo group (27.7%), p˂ 0.01, with no significant differences in recovery rates between the two groups at 1, 2, and 3 months of follow up, p˃0.05. Conclusion: In the small number of patients treated, local Ivermectin exhibited no side effects. In persistent post-COVID-19 anosmia, it could be used for one week at the most as the treatment was extended to one, two and three months, with no difference in recovery compared to the placebo treatment. Trial Registration No: NCT04951362.

Olfactory Disturbances as Presenting Manifestation Among Egyptian Patients with COVID-19: Possible Role of Zinc.

COVID-19 is a severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2). Deficiency of zinc has been supposed to contribute to loss of smell and taste in COVID-19 patients. Our study aimed to assess the serum zinc levels among patients with COVID-19 of various severities, with and without olfaction dysfunction, and to evaluate the effect of zinc therapy in recovery of smell dysfunction among such patients. This study included 134 patients; real-time reverse transcription-polymerase chain reaction (rRT-PCR) proved SARS-CoV-2. Serum zinc levels were measured for all infected patients. One hundred and five patients were detected to have anosmia and/or hyposmia and were categorized randomly into 2 groups; the first group included 49 patients who received zinc therapy and the second group included 56 patients who did not received zinc. All patients were followed up for the recovery duration of olfactory and gustatory symptoms and duration of complete recovery of COVID-19. Olfactory dysfunction was reported in 105 patients (78.4%). Serum zinc levels were not significantly different between the patient subgroups regarding disease severity or the presence or absence of olfactory and/or gustatory dysfunction (p ˃ 0.05). The median duration of recovery of gustatory and/or olfactory function was significantly shorter among patients who received zinc therapy than those who did not received zinc (p < 0.001), while the median duration of complete recovery from COVID-19 was not significantly different among the two groups (p ˃ 0.05). Although the zinc status of COVID-19 patients did not exhibit a significant role in development of anosmia and/or hyposmia or disease severity, zinc therapy may have a significant role in shortening the duration of smell recovery in those patients without affecting the total recovery duration from COVID-19.

Validity of serum amyloid A and HMGB1 as biomarkers for early diagnosis of gastric cancer.

BACKGROUND AND AIM: Gastric carcinomais a frequent neoplasm with poor outcome, and its early detection would improve prognosis. This study was designed to evaluate the possible use of new biomarkers, namely SAA and HMGB1, for early diagnosis of gastric cancer. METHODS: A total of 100 patients presenting with gastric symptoms were included. All patients underwent upper endoscopic evaluation, histopathological diagnosis and serum CEA, SAA, and HMGB1 measurements. RESULTS: Patients were classed endoscopically with neoplastic, inflammatory, and normal-appearing gastric mucosa: 50, 25, and 25 patients, respectively. Histologically, half the patients had chronic gastritis and the remaining cases gastric carcinoma of diffuse (n=28) or intestinal (n=22) type. SAA at cutoff of 18.5 mg/L had the best validity to differentiate gastritis from gastric carcinoma, with AUC, sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of 0.99, 98%, 100%, 100%, and 98%, respectively, followed by HMGB1 at cutoff of 14.5 pg/µL, with AUC, sensitivity, specificity, PPV, and NPV of 0.91, 70%, 96%, 94.6%, and 76.2%, respectively. Sensitivity, specificity, PPV, and NPV of serum CEA at cutoff of 2.9 ng/mL to differentiate gastritis from gastric carcinoma were 42%, 72%, 60%, and 55.4%, respectively, with AUC of 0.53. Nonetheless, higher serum levels of both SAA and HMGB1 reflected higher tumor grade (P=0.027 and P=0.016, respectively) and advanced tumor stage (P-OBrk-0.001 for both). CONCLUSION: Serum levels of both SAA and HMGB1 could be of great value for early diagnosis of gastric carcinoma, comparable to the diagnostic role of serum CEA, which is not valid for early diagnosis of gastric cancer.

Characteristics, Outcomes and Indicators of Severity for COVID-19 Among Sample of ESNA Quarantine Hospital's Patients, Egypt: A Retrospective Study.

BACKGROUND: The risk factors, disease characteristics, severity, and mortality of COVID-19 are unclear, particularly in Egypt. OBJECTIVE: The objective was to analyze the patients' characteristics, hematological, biochemical, and chest imaging findings among the cohort of patients with COVID-19 in Egypt and also to shed light on the predictors of COVID-19 severity. PATIENTS AND METHODS: A retrospective study was conducted on 66 patients with COVID-19 in Egypt. Medical history, imaging data (CT chest findings), and measured hematological and biochemical parameters at diagnosis were recorded in the form of complete blood counts and differential counts; CRP, ESR, serum ferritin, creatinine, and liver function tests . Results of real-time reverse transcription-polymerase chain reaction (rRT-PCR) for detection of SARS-CoV-2 RNA at diagnosis and during follow up of these patients were also recorded. RESULTS: The study included 36 patients with mild to moderate COVID-19 and 30 patients with severe/critical infection. There was a significant older age among severe (62.6 years old ±10.1SD) than mild to moderate infection (55.5 ± 10.1) (p˂0.05). Fever, dry cough, dyspnea, and sore throat malaise were highly frequent among COVID-19 patients, while headache and diarrhea were the least frequently occurring manifestations. All included cases (30 patients, 100%) with severe COVID-19 showed crazy-paving appearance (in the form of reticular and/or interlobular septal thickening) with or without GGO. There were significantly lower mean values of WBCs, lymphocytic count, total protein, and albumin among the severely infected than those who had mild to moderate COVID-19 infection, p˂0.05 for all. Additionally, there were significantly higher mean values of CRP, ESR, ferritin, ALT, and AST among patients with severe/critical COVID-19 when compared with those having mild to moderate COVID-19, p˂0.05 for all. CONCLUSION: Among the studied demographic, clinical, hematological, biochemical, and imaging data, dyspnea, diabetes mellitus, lymphopenia, raised CRP, ESR, ferritin, ALT, AST, low albumin, and presence of CT chest findings could be considered as predictors for COVID-19 severity using binary logistic regression analysis.

Reactivation of herpesvirus in patients with hepatitis C treated with direct-acting antiviral agents.

BACKGROUND: We performed a case-series analysis of reactivation of herpesvirus in patients with hepatitis C virus (HCV) infection treated with direct-acting antiviral (DAA) agents. METHODS: Eight cases were detected among 100 treated patients with DAA regimens in Qena University Hospital from June 2016 to June 2017. Herpesvirus was reactivated in eight patients who received DAA therapy. None of the cases had risk factor for herpes zoster reactivation. RESULTS: The DAA regimens used were sofosbuvir/daclatasvir in six cases and sofosbuvir/ledipasvir in two cases. Immune changes that follow HCV clearance might lead to reactivation of other viruses, such as herpesvirus. CONCLUSION: Patients with HCV infection suspected of having herpesvirus infection should be treated promptly.

Daclatasvir and Sofosbuvir Therapy Enhance Monocyte Phenotypic Changes in Naive Chronic Hepatitis C Patients: A Prospective Cohort Study.

BACKGROUND: Liver inflammation influences monocyte function, recruitment, and consequently inflammatory and fibrogenic responses. We aimed to investigate changes in the circulating monocyte phenotypes in response to Daclatasvir-Sofosbuvir (SOF/DCV) therapy in chronic hepatitis C (CHC) and relate findings to the viral kinetics and the fibrosis score. METHODS: A longitudinal study involving 100 treatment-naïve patients and 30 healthy controls, tested for liver function, fibrosis scores (AST to platelet ratio index, FIB-4), and blood monocyte subsets based on CD14/CD16 expression by flow cytometer. RESULTS: CHC patients had significantly lower albumin, higher ALT, AST, alkaline phosphatase, and increased fibrosis scores [Fib-4 (1.85±0.98) and AST to platelet ratio index (APRI) (0.6±0.35)], higher monocyte and eosinophil counts and lowered neutrophil to monocyte ratio (NMR), and lymphocyte to monocyte ratio (LMR) compared to week 12 and control. CHC patients had significantly increased median [classical (52.2% versus 25.8%, P=0.004) and inflammatory CD16+ monocytes (23.1% versus 13.58%, P=0.035)]. Therapy results in achievement of sustained virological response in 92% of cases, liver function improvement, and normalization of the inflammatory monocytes subsets. Monocyte counts showed positive correlation with viral load, calculated fibrosis scores (APRI and FIB-4 score), AST, ALT, ANC, and inverse correlations with serum albumin, leukocyte, eosinophil, NMR, and LMR. Multivariate regression found eosinophil count as predictors of CD16+ monocyte count in CHC patients. CONCLUSION: CHC infection promotes a proinflammatory and profibrotic monocytes profile. SOF/DCV therapy efficiently decreases viral load, reduces fibrosis potentials, attenuates monocyte activation, normalizes monocytes phenotypic abnormalities, and modulates monocyte subsets recruitment and differentiation later in the liver.

Management Of Patients With Hepatitis B Virus Reactivation Post-DAA Treatment Of Chronic Hepatitis C Virus Infection In HCV-HBV Coinfected Patients With Pretreatment HBeAg Seroconversion And Early Degree Of Hepatic Fibrosis.

BACKGROUND AND AIM: Hepatitis C virus (HCV)-HBV coinfection is a significant health problem with rapid progression of liver disease without precise diagnosis and treatment. We aimed in this study to identify if there were any role of HBV antiviral therapy in patients with HBV reactivation after direct-acting antiviral therapy in HCV-HBV coinfected patients. METHODS: A prospective random study was carried out on 140 patients presenting with chronic HCV and chronic HBV coinfection. All patients had pretreatment HBeAg seroconversion, HBV DNA <2,000 IU/mL, normal liver enzymes, and F0/F1 hepatic fibrosis. They treated with sofosbuvir 400 mg and daklatasvir 60 mg once daily for 3 months. All patients underwent pretreatment hepatic fibrosis assessment using Fibro Scan and laboratory investigations: platelet count, liver-function tests, quantitative HCV PCR, HBsAg, HBc IgG, HBeAg, and HBeAb. All patients were followed up at 1, 3, 6, and 12 months from the start of HCV therapy. RESULTS: The study enrolled 140 HCV-HBV coinfected patients: 55% were F0 and the rest F1. All our patients had negative HCV PCR at 1 month posttreatment and had achieved sustained virologic response with negative HCV PCR 3 months after treatment end. Four patients showed HBV reactivation with raised HBV DNA PCR and liver enzymes. Their mean age was 23.7±2.7 years, and three were male. Regarding patients with HBV reactivation, at 12 months posttreatment they showed significant decreases in liver enzymes, bilirubin, and INR, with increased platelet count (P=0.001), each with undetectable HBV PCR (P=0.001). CONCLUSION: HBV-HCV coinfected patients with no/mild hepatic fibrosis, HBeAg seroconversion, and HBV DNA <2,000 IU/mL can complete direct-acting antiviral therapy without HBV antiviral treatment with close monitoring.

Relative frequency of acute pancreatitis from dengue outbreaks as a late complication, in Egypt.

Patients with dengue virus infection have a different symptoms range from asymptomatic to sever form depending on primary and secondary immune status of host, infecting genotype and patient's age. The current study aimed to describe the clinical and laboratory profile of dengue fever outbreak and acute pancreatitis as a late complication, in Egypt, as two case reports only were available in literature regarding this issue. This prospective cohort study was carried out on 100 patients confirmed to have dengue disease out of 200 clinically suspected patients. Clinical, laboratory (serology for dengue specific IgM, real-time PCR for dengue virus, serum amylase and lipase) and abdominal multi-slice CT were done to all included patients. All patients presented with fever, headache and fatigue, which are the main clinical manifestations of dengue fever. The mean age of studied patients was 40.34 ± 15.74 years. Thirteen patients (13%), with their mean age 44.57 ± 11.53, presented after 3 months with typical clinical, laboratory and radiological manifestations of acute pancreatitis with positive serum dengue virus IgM, antibodies and negative serum dengue virus PCR. So, acute pancreatitis as a late complication of dengue fever disease should be keep in mind for its early diagnosis and management, thus minimize the morbidity and mortality from dengue fever.

Urinary 8-hydroxydeoxyguanosine in relation to XRCC1 rs25487 G/A (Arg399Gln) and OGG1 rs1052133 C/G (Ser326Cys) DNA repair genes polymorphisms in patients with chronic hepatitis C and related hepatocellular carcinoma.

Background and aim: DNA repair represents a protective mechanism against cell injury and cancer. 8-hydroxy-deoxyguanosine (8-OHdG) is the main ROS-induced DNA mutation. The current study aimed to evaluate urinary 8-OHdG levels in patients with chronic hepatitis C virus (HCV) and its related hepatocellular (HCC) and correlate its level to XRCC1 rs25487 G/A and OGG1 rs1052133 C/G gene polymorphisms. Materials and methods: Urinary 8-OHdG assays were performed using HPLC technique, and XRCC1 rs25487 G/A and OGG1 rs1052133 C/G gene polymorphisms were analyzed by PCR using confronting two-pair primer method (PCR-CTPP) in 200 subjects allocated into 50 chronic HCV patients, 50 HCV-related HCC patients, and 100 controls. Results: There were significantly increased urinary 8-OHdG levels in HCV-related HCC and chronic HCV patients when compared with the controls (P<0.05 for all). Urinary 8-OHdG was associated with the tumor spread. Regarding, XRCC1 (Arg399Gln), AA (Gln/Gln) genotype and A-allele were more frequent in HCC and chronic HCV patients than in the controls (P<0.05). ORs (95%CI) using the dominant and the recessive genetic models were; 2.1 (1.1-4.1), P=0.032 and 1.9 (1-3.6), P=0.043 respectively. For OGG1 (Ser326Cys), GG (Cys/Cys) genotype and G-allele were increased significantly in chronic HCV and HCC patients compared to the controls (P<0.05). ORs (95%CI) under the dominant and the recessive genetic models were; 2.1 (1.1-4.1), P=0.032 and 1.9 (1-3.8), P=0.049 respectively. Additionally, XRCC1 (AA) and OGG1 (GG) genotypes had significantly increased urinary 8-OHdG levels among patients (P<0.05). Conclusions: XRCC1 (AA) and OGG1 (GG) could be considered as possible genotypic risk factors for HCV- related HCC development which were associated with significantly high urinary 8-hydroxy-deoxyguanosine levels, thus urinary 8-OHdG could be considered as non-invasive marker in follow-up chronic HCV progression into HCC.