Tracheal resection anastomosis for rare tracheal inflammatory lesions mimicking malignancy: report of 2 cases.

BACKGROUND: Tumor-like lesions of the trachea are rare and challenging in diagnosis and management. Inflammatory myofibroblastoma, also known as Inflammatory pseudo tumors (IPTs), as well as Rosai Dorfman Disease (RDD) are inflammatory lesions that may involve the central airways with variable non-specific clinical features mimicking tumors. CASE PRESENTATION: In this study 2 cases with tumor-like lesions are presented. One case with an inflammatory pseudotumor and the other one with Rosai-Dorfman disease affecting the upper trachea. Both cases were successfully managed with tracheal resection anastomosis. CONCLUSION: Tracheal Inflammatory myofibroblastoma, and Rosai-Dorfman diseases are rare tumor like lesions that present with upper airway obstruction. Despite being benign, these lesions may have features suggestive of malignancy, requiring prompt management. Complete surgical excision by segmental resection and primary anastomosis (if feasible) is the treatment of choice with an optimum outcome.

Pathologic approach to Neonatal cholestasis with a simple scoring system for biliary atresia.

A liver biopsy is essential for the diagnostic workup of persistent neonatal cholestasis (NC). The differential diagnosis of NC is broad, including obstructive and non-obstructive causes. In addition, histologic features of certain disorders may be non-specific in the early course of the disease. To evaluate liver biopsies using a practical histopathologic approach for NC and to define a simple scoring system for biliary atresia (BA) for routine clinical practice. From June 2006 to December 2021, liver biopsy specimens from infants with persistent NC were examined by two independent pathologists. The cases diagnosed as BA were correlated with clinical, radiologic, and laboratory data to calculate the final score. Four hundred and fifty-nine cases were enrolled in the study. They had a mean age of 63.94 ± 20.62 days and were followed for a median time of 58 (1-191) months. They included 162 (35.3%) cases of BA. On multivariate analysis, portal edema, ductular proliferation, cholangiolitis, and bile duct/ductular plugs were the histopathologic predictors of BA. A liver biopsy did perform well with a 95.1% sensitivity, 91.6% specificity, 86% PPV, and 97.1% NPV. At a cutoff of 5 of the scoring system, diagnosis of BA could be done with a sensitivity of 95.1% and a specificity of 100%. We have shown detailed histopathologic features of BA with more depth to infants aged ≤ 6 weeks. We have developed a simple scoring system using a combination of liver biopsy with non-invasive methods to increase the diagnostic accuracy of BA.

Molar pregnancy with a coexisting living fetus: a case series.

BACKGROUND: Coexistence of molar pregnancy with living fetus represents a challenge in diagnosis and treatment. The objective of this study to present the outcome of molar pregnancy with a coexisting living fetus who were managed in our University Hospital in the last 5 years. METHODS: We performed a retrospective analysis of patients who presented with molar pregnancy with a coexisting living fetus to our Gestational Trophoblastic Clinic, Mansoura University, Egypt from September, 2015 to August, 2020. Clinical characteristics of the patients, maternal complications as well as fetal outcome were recorded. The patients and their living babies were also followed up at least 6 months after delivery. RESULTS: Twelve pregnancies were analyzed. The mean maternal age was 26.0 (SD 4.1) years and the median parity was 1.0 (range 0-3). Duration of the pregnancies ranged from 14 to 36 weeks. The median serum hCG was 165,210.0 U/L (range 7662-1,200,000). Three fetuses survived outside the uterus (25%), one of them died after 5 months because of congenital malformations. Histologic diagnosis was available for 10 of 12 cases and revealed complete mole associated with a normal placenta in 6 cases (60%) and partial mole in 4 cases (40%). Maternal complications occurred in 6 cases (50%) with the most common was severe vaginal bleeding in 4 cases (33.3%). There was no significant association between B-hCG levels and maternal complications (P = 0.3). CONCLUSION: Maternal and fetal outcomes of molar pregnancy with a living fetus are poor. Counseling the patients for termination of pregnancy may be required. TRIAL REGISTRATION: The study was approved by Institutional Research Board (IRB), Faculty of Medicine, Mansoura University (number: R.21.10.1492).

De novo Portal Vein Thrombosis in Non-Cirrhotic Non-Alcoholic Fatty Liver Disease: A 9-Year Prospective Cohort Study.

Background and Aims: Approximately 30-40% of portal vein thrombosis (PVT) remains of unknown origin. The association between non-alcoholic fatty liver disease (NAFLD) and PVT is a matter of debate. This study aimed to investigate the association between PVT and NAFLD. Methods: We included 94 out of 105 consecutive NAFLD patients in this prospective cohort study in addition to 94 from the healthy control group. We evaluated biochemical, clinical, immunological, and histopathological parameters; waist circumference (WC); leptin; adiponectin; and leptin/adiponectin ratio (LAR) for all participants at baseline and every 3 years thereafter. We described the characteristics of participants at baseline and showed individual WC, LAR, and PVT characteristics. Potential parameters to predict PVT development within 9 years were determined. Results: PVT developed in eight (8.5%) patients, mainly in the portal trunk. Univariate analysis showed three PVT-associated factors: diabetes mellitus (P = 0.013), WC (P < 0.001), and LAR (P = 0.002). After adjusting multiple confounding variables, the multivariate model showed that the only significant variables were WC and LAR. By applying the receiver operating characteristic curve, WC had 98.8% specificity, 87.5% sensitivity, and 0.894 area under the curve (AUC) for prediction of PVT (P < 0.001) at cutoff values of > 105 cm. In comparison, LAR had 60.5% specificity, 87.5% sensitivity, and 0.805 AUC for PVT prediction (P < 0.001) at cutoff values of >7.5. Conclusions: This study suggests that increased central obesity and LAR were independently associated with PVT development in non-cirrhotic NAFLD patients, and they should be considered risk factors that may participate in PVT multifactorial pathogenesis.

Histopathologic ─ Endoscopic Concordance of Pediatric Duodenal Biopsy; How to Be Improved?

OBJECTIVE: Few studies have correlated pediatric endoscopic and histologic impressions of duodenal biopsies. Method: This is a retrospective study on children undergoing upper gastrointestinal endoscopy over a period of 11 years. We investigated concordance between the gross endoscopic and histopathologic characteristics of pediatric duodenal biopsies. Results: Of 1793 children enrolled in the study, duodenal pathology was observed in 72.3%. The gross endoscopic findings showed a low sensitivity of 38.9%, specificity of 99.2%, PPV of 99.2%, and NPV of 38.3%. Concordance between the gross endoscopic and histopathologic analysis was 55.6%. Conclusion: This study showed a higher rate of pediatric duodenal pathologies than gross assessment. This emphasizes the value for acquiring routine duodenal biopsies from grossly normal mucosa.

Diffusion-weighted magnetic resonance imaging and micro-RNA in the diagnosis of hepatic fibrosis in chronic hepatitis C virus.

BACKGROUND: Diffusion-weighted magnetic resonance imaging has shown promise in the detection and quantification of hepatic fibrosis. In addition, the liver has numerous endogenous micro-RNAs (miRs) that play important roles in the regulation of biological processes such as cell proliferation and hepatic fibrosis. AIM: To assess diffusion-weighted magnetic resonance imaging and miRs in diagnosing and staging hepatic fibrosis in patients with chronic hepatitis C. METHODS: This prospective study included 208 patients and 82 age- and sex-matched controls who underwent diffusion-weighted magnetic resonance imaging of the abdomen, miR profiling, and liver biopsy. Pathological scoring was classified according to the METAVIR scoring system. The apparent diffusion coefficient (ADC) and miR were calculated and correlated with pathological scoring. RESULTS: The ADC value decreased significantly with the progression of fibrosis, from controls (F0) to patients with early fibrosis (F1 and F2) to those with late fibrosis (F3 and F4) (median 1.92, 1.53, and 1.25 × 10-3 mm2/s, respectively) (P = 0.001). The cut-off ADC value used to differentiate patients from controls was 1.83 × 10-3 mm2/s with an area under the curve (AUC) of 0.992. Combining ADC and miR-200b revealed the highest AUC (0.995) for differentiating patients from controls with an accuracy of 96.9%. The cut-off ADC used to differentiate early fibrosis from late fibrosis was 1.54 × 10-3 mm2/s with an AUC of 0.866. The combination of ADC and miR-200b revealed the best AUC (0.925) for differentiating early fibrosis from late fibrosis with an accuracy of 80.2%. The ADC correlated with miR-200b (r = - 0.61, P = 0.001), miR-21 (r = - 0.62, P = 0.001), and miR-29 (r = 0.52, P = 0.001). CONCLUSION: Combining ADC and miRs offers an alternative surrogate non-invasive diagnostic tool for diagnosing and staging hepatic fibrosis in patients with chronic hepatitis C.

Potential Role for a Panel of Immunohistochemical Markers in the Management of Endometrial Carcinoma.

BACKGROUND: In order to improve the efficacy of endometrial carcinoma (EC) treatment, identifying prognostic factors for high risk patients is a high research priority. This study aimed to assess the relationships among the expression of estrogen receptors (ER), progesterone receptors (PR), human epidermal growth factor receptor 2 (HER2), Ki-67, and the different histopathological prognostic parameters in EC and to assess the value of these in the management of EC. METHODS: We examined 109 cases of EC. Immunohistochemistry for ER, PR, HER2, and Ki-67 were evaluated in relation to age, tumor size, International Federation of Gynecology and Obstetrics (FIGO) stage and grade, depth of infiltration, cervical and ovarian involvement, lymphovascular space invasion (LVSI), and lymph node (LN) metastasis. RESULTS: The mean age of patients in this study was 59.8 ± 8.2 years. Low ER and PR expression scores and high Ki-67 expression showed highly significant associations with non-endometrioid histology (p = .007, p < .001, and p < .001, respectively) and poor differentiation (p = .007, p < .001, and p <. 001, respectively). Low PR score showed a significant association with advanced stage (p = .009). Low ER score was highly associated with LVSI (p = .006), and low PR scores were associated significantly with LN metastasis (p = .026). HER2 expression was significantly related to advanced stages (p = .04), increased depth of infiltration (p = .02), LVSI (p = .017), ovarian involvement (p = .038), and LN metastasis (p = .038). There was a close relationship between HER2 expression and uterine cervical involvement (p = .009). Higher Ki-67 values were associated with LN involvement (p = .012). CONCLUSIONS: The over-expression of HER2 and Ki-67 and low expression of ER and PR indicate a more malignant EC behavior. An immunohistochemical panel for the identification of high risk tumors can contribute significantly to prognostic assessments.

Adrenalectomy for solitary recurrent hepatocellular carcinoma five years after living donor liver transplantation: A case report.

INTRODUCTION: The adrenal gland is a rare site for hepatocellular carcinoma (HCC) recurrence after living-donor liver transplantation (LDLT). Solitary adrenal recurrence can be managed by surgical excision, with expected better survival outcomes. We describe a rare case of successful left adrenalectomy of solitary recurrent HCC in the left adrenal gland 5 years after LDLT. PRESENTATION: 59 years male patient with HCC complicating chronic HCV infection received a right hemi-liver graft from his son. The actual graft weight was 1208 g and GRWR was 1.5. The patient started oral direct acting antiviral drugs for recurrent HCV 2 years after LDLT. A left adrenal mass was detected on follow up radiology. No other metastatic lesions were detected on metastatic workup. Left adrenalectomy was done by an anterior approach. The postoperative course was uneventful and was discharged a week after operation. Postoperative pathological and immune-histochemical examinations confirmed the metastatic HCC nature of the mass. The patient is under regular follow up with no recurrences 6 month after resection. DISCUSSION: There is no consensus regarding the management of HCC recurrence after LDLT. Most patients had multi-organ recurrences and usually offered palliative or supportive care. Solitary HCC recurrence offers a better chance for more aggressive therapy, offering better prognosis. CONCLUSION: Solitary adrenal recurrence of HCC after LDLT is extremely rare. Strict follow up protocol is necessary to allow early detection of tumor recurrence. Curative surgical resection is a safe option associated with low morbidity and expected to have a good long-term survival.

Rifaximin in nonalcoholic fatty liver disease: hit multiple targets with a single shot.

BACKGROUND/AIMS: The pathogenesis of nonalcoholic fatty liver disease (NAFLD) may include increased insulin resistance, upregulation of proinflammatory cytokines, lipopolysaccharide, and BMI. Rifaximin is a minimally absorbable antibiotic that might act against a broad spectrum of gut bacteria. This study aimed to investigate the effects of rifaximin on NAFLD. PATIENTS AND METHODS: Fifty participants with biopsy-proven nonalcoholic steatohepatitis (NASH) were registered in this multicentric, double-blind, randomized, placebo-controlled study. BMI, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, lipid profile, serum endotoxin, homeostatic model assessment, toll-like receptor-4, interleukin-10 (IL-10), IL-6, tumor necrosis factor-α, and cytokeratin-18 (CK-18) levels were evaluated at baseline and at 1, 3, and 6 months of rifaximin therapy (1100 mg/day). RESULTS: Patients were randomized into two groups (rifaximin group; n=25 and placebo group; n=25). After 6 months of rifaximin therapy, patients with NASH showed a significant reduction in homeostatic model assessment, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, endotoxin, toll-like receptor-4, IL-6, tumor necrosis factor-α, CK-18, and NAFLD-liver fat score (all P<0.05), but no changes in the lipid profile; moreover, there was a mild nonstatistically significant reduction of BMI. However, in the placebo group, there was no significant difference in these variables at baseline and after therapy. CONCLUSION: Rifaximin therapy appears to be effective and safe in modifying NASH through reduction of serum endotoxin and improvement of insulin resistance, proinflammatory cytokines, CK-18, and NAFLD-liver fat score.

Chronic Hepatitis C Patients with Obesity: Do we Need two Operators for Accurate Evaluation of Liver Stiffness?

INTRODUCTION AND AIM: Transient elastography is gaining popularity as a non-invasive method for predicting liver fibrosis, but inter observer agreement and factors influencing reproducibility have not been adequately assessed. MATERIAL AND METHODS: This cross-sectional study was conducted at Specialized Medical Hospital and the Egyptian Liver Foundation, Mansoura, Egypt. The inclusion criteria were: age older than 18 years and chronic infection by hepatitis C. The exclusion criteria were the presence of ascites, pacemaker or pregnancy. Three hundred and fifty-six patients participated in the study. Therefore, 356 pairs of exams were done by two operators on the same day. RESULTS: The overall inter observer agreement ICC was 0.921. The correlation the two operators was excellent (Spearman's value q = 0.808, p < 0.001). Inter-observer reliability values were κ = 0.557 (p < 0.001). A not negligible discordance of fibrosis staging between operators was observed (87 cases, 24.4%). Discordance of at least one stage and for two or more stages of fibrosis occurred in 60 (16.9%) and 27 cases (7.6%) respectively. Obesity (BMI ≥ 30 kg/m2) is the main factor associated with discordance (p = 0.002). CONCLUSION: Although liver stiffness measurement has had an excellent correlation between the two operators, TE presented an inter-observer variability that may not be negligible.

Diagnosis of cirrhosis in patients with chronic hepatitis C genotype 4: Role of ABCB11 genotype polymorphism and plasma bile acid levels.

BACKGROUND/AIMS: Chronic hepatitis C (CHC)-related mortality generally results from cirrhosis and subsequent complications. We aimed to investigate the potential role of plasma bile acid levels and ABCB11 1331T > C (V444A, rs2287622) (ATP-binding cassette subfamily B, member 11) gene polymorphism in fibrosis prediction in CHC genotype 4 patients. MATERIALS AND METHODS: This case control study included 85 healthy control and the following 225 subjects: 170 adult patients infected with hepatitis C virus (HCV) and categorized into three groups according to liver biopsy; no fibrosis group (F0) (n=33), early fibrosis group (F1-F2) (n=61), and advanced fibrosis group (F3-F4) (n=76). Fasting bile acid levels, hepatitis C virus (HCV) genotyping, and ABCB11 1331T > C gene polymorphism were assessed. RESULTS: The frequency of the variant homozygote genotype CC in advanced fibrosis was significantly higher than that in early fibrosis (48.7% vs. 36.1%) (odd ratio, OR =2.58; 95% confidence interval, CI=1.07-6.20; p=0.03). C allele was significantly represented in advanced fibrosis (65.8%) compared with that in early fibrosis (51.6%) (OR=1.80, 95% CI=1.10-2.93, p=0.01). A significant elevation of plasma bile acid levels in advanced fibrosis was observed compared with those in early fibrosis (p≤0.001). Receiver operating characteristic curve for plasma bile acid levels at cutoff value of 75.5 µmol/L had a 59% specificity and 97.4% sensitivity as a predictor of advanced hepatic fibrosis (AUROC=0.78%). CONCLUSION: We concluded that Egyptian patients having chronic hepatitis C genotype 4 with CC genotype of ABCB11 SNP 1331T > C and high plasma bile acid levels at cutoff value of 75.5 µmol/L were associated with advanced hepatic fibrosis.

Correlation between testicular mast cell count and spermatogenic epithelium in non-obstructive azoospermia.

Although there is emerging evidence that mast cells are involved in infertility, their exact role has not been elucidated clearly. Here we carried out a retrospective case-control study to find out whether there is a correlation between mast cell (MC) count and proliferation (Ki67 index) of the spermatogenic epithelium as well as of the Sertoli cells (vimentin-positive) in non-obstructive azoospermia (NOA). We assessed MCs, Ki67 and vimentin expression in Sertoli cells in testicular biopsies of germ cell aplasia (GCA, n = 14) and maturation arrest (MA, n = 14) vs. normal spermatogenesis (n = 14) cases. There was a significant decrease in the spermatogonial Ki67 index (1.25 ± 0.91, 4.21 ± 1.81 vs. 39.57 ± 3.92) and Johnsen score (2.48 ± 0.65, 4.89 ± 1.05 vs. 9.75 ± 0.30) as well as a significant increase (P < 0.001) in MC count (29.00 ± 4.11, 7.57 ± 1.95 vs. 3.00 ± 1.30) in seminiferous tubules of infertile cases with GCA and MA vs. controls. On the other hand, the percentage of vimentin-expressing Sertoli cells was significantly decreased (P < 0.001) in biopsies of cases with MA (35.50 ± 15.62) compared to those of cases with GCA and controls (72.64 ± 10.67 and 98.57 ± 1.45 respectively). Additionally, a significant negative correlation was detected between MC count and Ki67 index as well as Johnsen score in the MA group which became more significant in the GCA group. The significant increase in MC count in the GCA group and to a lesser extent in the MA group indicates their possible role in NOA particularly at the spermatogonial proliferation level and this is supported by the significant negative correlation with the Ki67 index.

Blastic Plasmacytoid Dendritic Cell Neoplasm: A Case Report and Clinicopathological Review.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is aggressive hematopoietic malignancy derived from the precursors of plasmacytoid dendritic cells. The present study reported a case of a 35-year-old BPDCN patient, who presented with scalp lesions without extracutaneous involvement of the lymph nodes (LNs), peripheral or bone marrow. Histopathological examination of scalp lesion revealed monomorphous diffuse infiltrate of small to medium-sized cells with irregular nuclear contours, pleomorphic nuclei, finely dispersed chromatin, inconspicuous nucleoli and scant amount of cytoplasm. Immunohistochemical staining showed diffuse positivity for CD45, CD4, CD 56, CD45 and negative for CD3, CD5, CD7, CD8, CD19, CD20, CD30, CD33, CD34, CD79a, CD99, CD117, TDT, and myeloperoxidase. Patient started treatment with acute lymphoblastic lymphoma protocol (Hyper-CVAD). Reevaluation after the second course showed marked regression of scalp lesion. The patient continued Hyper-CVAD protocol and planned for allogeneic stem cell transplant.

New predictive factors of poor response to therapy in autoimmune hepatitis: role of mean platelet volume.

BACKGROUND AND OBJECTIVES: The response to immunosuppressive therapy in autoimmune hepatitis (AIH) is a matter of debate. The aim of this work is to identify the histological, biochemical, and clinical predictive factors of incomplete response/treatment failure to the standard treatment (prednisone with or without azathioprine) in a well-characterized series of AIH Egyptian patients. PATIENTS AND METHODS: Of 49 AIH patients, only 36 patients completed this retrospective cohort study. The immunological, biochemical, histopathological, and clinical characteristics of patients were evaluated at diagnosis and during follow-up. RESULTS: Patients were classified into two groups; group A showed a complete response to therapy (n=22; 61%) and group B showed partial response/treatment failure (n=14; 39%). In a multivariate analysis, we observed that age at diagnosis up to 22 years [odds ratio (OR): 23.22; confidence interval (CI): 3.978-135.549; P<0.001], serum albumin up to 3.2 g/dl (OR: 5.36; CI: 1.237-23.209; P=0.025), mean platelet volume (MPV) of at least 10.75 fl (OR: 16.5; CI: 3.093-88.037; P<0.001), and presence of cirrhosis at diagnosis (OR: 8.44; CI: 1.682-42.392; P=0.001) were independent variables that can predict partial response/treatment failure. MPV correlated positively with stages of fibrosis/cirrhosis and grades of activity in liver biopsy at diagnosis and correlated inversely with serum albumin and age at presentation. During therapy, group B showed a fluctuation in MPV levels, however, group A showed a progressive decline until the end point. CONCLUSION: Our study confirmed that younger age, hypoalbuminemia, increased MPV, and cirrhosis at diagnosis were all independent predictors of incomplete response/treatment failure in AIH patients. MPV may reflect the response to therapy.

Does steatosis affect the performance of diffusion-weighted MRI values for fibrosis evaluation in patients with chronic hepatitis C genotype 4?

BACKGROUND/AIMS: To evaluate the effect of hepatic steatosis on the apparent diffusion coefficient (ADC) of hepatic fibrosis in patients with HCV genotype 4-related chronic hepatitis. MATERIALS AND METHODS: Overall, 268 chronic hepatitis C patients (164 males and 104 females) underwent liver biopsy for fibrosis assessment by the METAVIR score and grading for hepatic steatosis. They were classified into early fibrosis stage (F1, F2) and advanced fibrosis stage (F3, F4). Diffusion-weighted MRI (DWI) of the liver was performed using 1.5-Tesla scanners, and the ADC value of the patients with and without steatosis in different stages of fibrosis was estimated and compared. RESULTS: In patients with early fibrosis, the ADC value significantly decreased in patients with steatosis (1.52±0.17×10-3 mm2/s) compared to that in patients without steatosis (1.65±0.11×10-3 mm2/s) (p<0.001). In those with an advanced stage of fibrosis, the ADC value was also significantly decreased in patients with steatosis (1.07±0.16×10-3 mm2/s) compared with that in patients without steatosis (1.35±0.11×10-3 mm2/s) (p≤0.001). The cutoff value for ADC for steatosis prediction in the early fibrosis group was 1.585 according to the AUROC curve, with a sensitivity of 76.8% and a specificity of 73.5%. The cutoff value for ADC for steatosis prediction in patients with an advanced stage of fibrosis was 1.17×10-3 mm2/s, with a sensitivity of 97% and a specificity of 88.5%. CONCLUSION: Histologically detected hepatic steatosis should always be considered when assessing hepatic fibrosis using diffusion-weighted MRI to avoid the underestimation of the ADC value in patients with chronic hepatitis C genotype 4.

Short-term effects of extracorporeal graft rinse versus circulatory graft rinse in living donor liver transplantation. A prospective randomized controlled trial.

Living donor liver transplantation has shorter cold ischemia time, less preservative volume, and lower metabolic load compared to transplantation from deceased donors. We investigated the impact of rinsing the graft contents into the systemic circulation on operative course and postoperative outcomes. Donors had right hepatectomy, and grafts were preserved with cold histidine-tryptophan-ketoglutarate solution. On ending portal vein anastomosis, grafts were flushed by patient's portal blood either through incompletely anastomosed hepatic vein (extracorporeal rinse group, EcRg, n = 40) or into systemic circulation (circulatory rinse group, CRg, n = 40). The primary outcome objective was the lowest mean arterial blood pressure within 5 min after portal unclamping as a marker for postreperfusion syndrome (PRS). Secondary objectives included hemodynamics and early graft's and patient's outcomes. Within 5 min postreperfusion, mean arterial blood pressure was significantly lower in the CRg compared to the EcRg, yet this was clinically insignificant. Postoperative graft functions, early biliary and vascular complications, and three-month survival were comparable in both groups. Rinsing the graft into the circulation increased the incidence of PRS without significant impact on early graft or patient outcome in relatively healthy recipients.

Prediction of Fibrosis Progression Rate in Patients with Chronic Hepatitis C Genotype 4: Role of Cirrhosis Risk Score and Host Factors.

The rate of liver fibrosis progression in chronic hepatitis C (CHC) patients is highly variable and affected by different factors. This study aimed to assess the role of cirrhosis risk score (CRS) based on 7 genetic variants (7 single-nucleotide polymorphisms [SNPs]) and host factors (age and sex) in the prediction of the rate of fibrosis progression in CHC. Duration of infection was determined in 115 patients. The fibrosis progression rate (FPR) per year was calculated as the ratio between fibrosis stage and the duration of infection. SNP genotyping were performed and CRS was determined based on it. FPR was significantly elevated in patients who acquired infection at age >40 years versus those who acquired infection at 30-40 years and those who acquired infection at <30 years. Median FPR was significantly higher in males than females (0.17 vs. 0.15) with P = 0.001. CRS value ≥0.8 is predictive of patients with high risk for cirrhosis, and CRS value <0.5 is predictive of patients with low risk for cirrhosis. There was significant positive correlation between CRS and FPR (P ≤ 0.001). CRS based on 7 SNPs at cutoff value ≥0.8, age at infection >40 years, and male sex are predictors of higher FPR.

Pegylated interferon α/ribavirin therapy enhances bone mineral density in children with chronic genotype 4 HCV infection.

BACKGROUND: The impact of chronic hepatitis C (CHC) on bone mineral density (BMD) has been well studied in adults with a relative paucity of data in children, especially concerning effect of treatment with pegylated interferon (PEG-IFN) plus ribavirin (RV). In the current work, we assessed prospectively changes in BMD in children with CHC before, during, and after treatment. METHODS: Forty-six consecutive children with noncirrhotic genotype 4 CHC were subjected to dual-energy X-ray absorptiometry at baseline, 24 weeks, 48 weeks of therapy and 24 weeks after treatment. BMD, bone mineral content (BMC), and Z score of lumbar spine (L2-L4) were reported. Tanner pubertal stage, viral load, liver function tests, serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone, and liver histopathology were assessed in all included children. RESULTS: Thirty (65.2%) patients had normal BMD, 10 (21.7%) were at risk for low BMD, and 6 (13.1%) had low BMD for chronological age. Patients with low BMD were significantly older (P=0.001), with higher frequency of delayed puberty than other groups (P=0.002). Baseline densitometric parameters (BMD & BMC) were significantly positively correlated with patients' age, weight, height, body mass index and hemoglobin level; while they were insignificantly correlated with basal viral load, histopathology activity index and fibrosis score. Densitometric parameters improved significantly on PEG-IFN plus RV treatment, this improvement was found to be sustainable 24 weeks after therapy. CONCLUSIONS: Low BMD is detectable in a proportion of CHC children. Antiviral therapy leads to a sustainable increase in BMD.

Increased Proliferative Activity Accompanies the Local Inflammatory Response of Gastric Mucosa After Intragastric Balloon Insertion.

BACKGROUND AND AIM: The use of BioEnterics intragastric balloon (BIB) is progressively increasing, owing to the fact that morbid obesity becomes a global epidemic together with risks of bariatric surgery. Yet, the possible local BIB effect on gastric mucosa is not clearly elucidated. The aim of the current study was to assess the histological changes occurring in the gastric mucosa post-BIB insertion. METHODS: Gastric mucosa biopsy was obtained from 87 cases of morbid obesity both pre-BIB and 6 months post-BIB insertion to compare the local changes by histological and immunohistochemical analysis. RESULTS: An inflammatory reaction was detected in the post-BIB mucosa which displayed a positive CD20, CD3 (p < 0.05), and the proliferation index (Ki67) increased significantly compared with that of the pre-BIB cases. The Ki67 index showed a significant positive correlation with CD20 and CD3 immunoexpression in the post-BIB gastric mucosae. CONCLUSION: Our results demonstrated a possible increase in the gastric proliferative activity after BIB insertion accompanied with a remarkable local inflammatory reaction. Although these findings may be reactive and transient, endoscopic follow-up is recommended for early detection of further pathological changes.

Effect of tranilast in comparison with beclomethasone in chronic murine model of asthma.

AIM OF THE STUDY: The current investigation was taken to scrutinize the action of tranilast on the airway remodeling in chronic asthma in mice. MATERIALS AND METHODS: Intraperitoneal injection of ovalbumin was applied to mice for sensitization and subsequent inhalation of 1% ovalbumin three times week for 10 weeks for challenge. Beclomethasone or tranilast were given daily for the 10 week challenge period. At the end of the study, lung weight index, total collagen content, bronchoalveolar lavage level of total and differential cell counts, interleukin-13, in addition to lung tissue nitrate/nitrite and transforming growth beta-1 were measured. Also, histological analysis was done. RESULTS: Asthmatic mice demonstrated apparent fibrotic changes. Significant airway fibrosis was demonstrated by hyperplasia of goblet cells and thickening of airway epithelium, increased content of lung collagen, lung and bronchoalveolar lavage of transforming growth factor beta-1 and interleukin-13 mutually accompanied by reduction in nitrate/nitrite generation. CONCLUSIONS: Beclomethasone influence on airway remodeling was mediated mainly via suppression of eosinophilic recruitment into the airways and reduction of interleukin-13 cytokine levels. Whereas, tranilast effects on airway remodeling was found to be mainly mediated via its inhibitory effect on transforming growth beta-1. Both beclomethasone and tranilast influence airway remodeling by different degrees and mechanisms.