The prevalence of functional dyspepsia using Rome IV questionnaire among chronic kidney disease patients.

Background: Symptoms of dyspepsia are usually encountered by chronic kidney disease patients. Abdominal discomfort is commonly seen in CKD patients with no other causes of organic affection. Aim: to determine the prevalence of functional dyspepsia in CKD patients, and which subtype is predominant in them. Materials and patients: This observational study included 150 CKD patients. Clinical and laboratory data were recorded for every patient. All the patients were interviewed using the ROME IV questionnaire of functional dyspepsia. Patients fulfilling criteria for functional dyspepsia were exposed to upper GI endoscopy. Results: Overall, 73 (48.7%) of CKD patients were males and 77 (51.3%) were females with mean age of (45.71 ± 9.59) and mean BMI (26.58 ± 5.39). The frequency of functional dyspepsia among CKD patients was determined to be 14.7% (22 out of 150 patients). Among those affected by functional dyspepsia, the most prevalent subtype was found to be Epigastric Pain Syndrome (EPS), accounting for 59% (13 out of 22 cases). The most common predictor of FD in CKD patients was chronic HCV infection, hemodialysis, stage of CKD and eGFR as revealed by Univariate regression analysis. Conclusion: The prevalence of FD amongst CKD patients is 14.7% with EPS the predominant subtype. Male patients, HCV patients, patients with higher CKD stages and highly impaired eGFR (low eGFR) are more probable to have FD.

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.

Down-regulation of hepatic expression of GHR/STAT5/IGF-1 signaling pathway fosters development and aggressiveness of HCV-related hepatocellular carcinoma: Crosstalk with Snail-1 and type 2 transforming growth factor-beta receptor.

BACKGROUND AND AIMS: So far, few clinical trials are available concerning the role of growth hormone receptor (GHR)/signal transducer and activator of transcription 5 (STAT5)/insulin like growth factor-1 (IGF-1) axis in hepatocarcinogenesis. The aim of this study was to evaluate the hepatic expression of GHR/STAT5/IGF-1 signaling pathway in hepatocellular carcinoma (HCC) patients and to correlate the results with the clinico-pathological features and disease outcome. The interaction between this signaling pathway and some inducers of epithelial-mesenchymal transition (EMT), namely Snail-1 and type 2 transforming growth factor-beta receptor (TGFBR2) was studied too. MATERIAL AND METHODS: A total of 40 patients with HCV-associated HCC were included in this study. They were compared to 40 patients with HCV-related cirrhosis without HCC, and 20 healthy controls. The hepatic expression of GHR, STAT5, IGF-1, Snail-1 and TGFBR2 proteins were assessed by immunohistochemistry. RESULTS: Compared with cirrhotic patients without HCC and healthy controls, cirrhotic patients with HCC had significantly lower hepatic expression of GHR, STAT5, and IGF-1proteins. They also displayed significantly lower hepatic expression of TGFBR2, but higher expression of Snail-1 versus the non-HCC cirrhotic patients and controls. Serum levels of alpha-fetoprotein (AFP) showed significant negative correlations with hepatic expression of GHR (r = -0.31; p = 0.029) and STAT5 (r = -0.29; p = 0.04). Hepatic expression of Snail-1 also showed negative correlations with GHR, STAT5, and IGF-1 expression (r = -0.55, p = 0.02; r = -0.472, p = 0.035, and r = -0.51, p = 0.009, respectively), whereas, hepatic expression of TGFBR2 was correlated positively with the expression of all these proteins (r = 0.47, p = 0.034; 0.49, p = 0.023, and r = 0.57, p<0.001, respectively). Moreover, we reported that decreased expression of GHR was significantly associated with serum AFP level>100 ng/ml (p = 0.048), increased tumor size (p = 0.02), vascular invasion (p = 0.002), and advanced pathological stage (p = 0.01). Similar significant associations were found between down-regulation of STAT5 expression and AFP level > 100 ng/ml (p = 0.006), vascular invasion (p = 0.009), and advanced tumor stage (p = 0.007). Also, attenuated expression of IGF-1 showed a significant association with vascular invasion (p < 0.001). Intriguingly, we detected that lower expression of GHR, STAT5 and IGF-1 were considered independent predictors for worse outcome in HCC. CONCLUSION: Decreased expression of GHR/STAT5/IGF-1 signaling pathway may have a role in development, aggressiveness, and worse outcome of HCV-associated HCC irrespective of the liver functional status. Snail-1 and TGFBR2 as inducers of EMT may be key players. However, large prospective multicenter studies are needed to validate these results.

Pro-Neurotensin as a Potential Novel Diagnostic Biomarker for Detection of Nonalcoholic Fatty Liver Disease.

Background and Aims: Currently, liver biopsy is the gold standard method for diagnosis of non-alcoholic fatty liver severity. It is critical to develop non-invasive diagnostic method to diagnose nonalcoholic fatty liver rather than invasive techniques. Our case-control study was to address the value of circulating miRNA-122 and serum pro-neurotensin as a potential non-invasive biomarker for the diagnosis of non-alcoholic fatty acid diseases. Methods: Clinical assessment, laboratory investigations, and anthropometric measurements were reported for 157 patients with proven NAFLD. Apparently, healthy participants (n=100) were enrolled as a control group. Serum samples were tested for micro-RNAs-122 and pro-neurotensin. Results: Compared with the control subjects, both mi-RNA-122 and serum proneurotensin levels were increased in NAFLD (p<0.001) and at a cut-off ≥6.83, mi-RNA-122 had 51.0% sensitivity, 70.0% specificity to differentiate NAFLD from healthy controls, while serum proneurotensin had 80.0% sensitivity and 80.0% specificity at a cutoff ≥108. Conclusion: The circulating pro-neurotensin might be used as a novel biomarker for diagnosis of patients with NAFLD, wherefore the integration of a circulating mi-RNA-122 and serum pro-neurotensin could be beneficial to diagnose NAFLD cases. Large-scale studies are needed to investigate the possible role of mi-RNA-122 and pro-neurotensin in the development, progression, and prognosis of NAFLD and NASH.

Colonic mucosal eosinophilia and immunohistochemical expression of COX-2 and NF-kB in patients with irritable bowel syndrome.

BACKGROUND: There is growing evidence that eosinophilic infiltration can release mediators which are harmful to the intestinal epithelium in patients with irritable bowel syndrome (IBS). Although cyclooxygenase 2 (COX-2) and nuclear factor-kappa beta (NF-kB) expression had been previously reported to increase in many inflammatory conditions, there is a paucity in data investigating their expressions in IBS. Our aim was to evaluate colonic mucosal eosinophilia and immunohistochemical expression of COX-2 and NF-kB in patients with irritable bowel syndrome. METHODS: A total of 80 patients who met the inclusion criteria of IBS based on Rome IV symptoms questionnaire were subjected to abdominal ultrasound, laboratory investigations, serum immunoglobulin E (IgE) level assessment and colonoscopic examination. Immunohistochemistry was performed to detect COX-2 and NF-kB expression in colonic biopsies obtained from IBS patients. RESULTS: Histopathological examination showed that 60 colonic biopsy specimens (75%) showed few mixed inflammatory cells ≤3 cells/ HPF, 12 biopsy specimens (15%) showed eosinophilic infiltration ≥25 eosinophils/HPF and 8 biopsy specimens (10%) showed severe lymphocytic infiltration and aggregation. Colonic eosinophilic infiltrate was significantly higher among patients presented with IBS-D subtype. Serum IgE was significantly higher among patients with colonic eosinophilic infiltrate than the others. In IBS-D patients, colonic mucosa showed positive expression of COX-2 and NF-kB in 52.1% and 81.25% of cases, respectively. CONCLUSION: Patients with IBS -particularly IBS-D subtype- should undergo colonoscopy and biopsy to exclude underlying inflammatory pathology. Moreover, patients with positive COX-2 and NF-kB need further evaluation and follow-up.

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.

Rome IV Diagnostic Criteria for Functional Gastrointestinal Disorders in Patients with Chronic Hepatitis C Virus.

BACKGROUND: Patients with chronic hepatitis C virus (HCV) usually have different abdominal complaints without any organic lesions. The functional cause of these complaints is claimed in most patients. This study aimed to evaluate functional gastrointestinal disorders (FGIDs) in patients with chronic hepatitis C using Rome IV diagnostic criteria. METHODS: This study included 1506 participants (1006 patients with chronic HCV, and 500 controls). All individuals were subjected to taking thorough medical history, basic investigations (complete blood counts, liver and renal functions tests), international normalized ratio (INR), alpha-fetoprotein, HCV RNA PCR (polymerase chain reaction), abdominal ultrasonography, and upper gastrointestinal tract (GIT) endoscopy for patients only), and Rome IV diagnostic questionnaire. RESULTS: Patients with HCV had symptoms of FGIDs including functional dyspepsia (FD) (P=0.009), early satiety (P=0.002), postprandial distress (P=0.02), epigastric pain (P=0.03), Inflammatory bowel syndrome (IBS) (P<0.001), IBS predominant constipation (P<0.001), IBS predominant diarrhea (P<0.001), and IBS mixed (P<0.001). There were multiple factors for the prediction of FD in patients with HCV, including high body mass index (BMI), education level, positive polymerase chain reaction (PCR), and fibrosis stage. Also, there were multiple factors for the prediction of IBS in patients with HCV, including male gender, high BMI, urban residence, education level, positive PCR, and fibrosis stage. CONCLUSIONS: FD is a prevalent finding in obese patients with HCV and with higher fibrosis scores. IBS is also prevalent in male patients with HCV.

NAFLD mark: an accurate model based on microRNA-34 for diagnosis of non-alcoholic fatty liver disease patients.

BACKGROUND: It remains essential for non-alcoholic fatty liver (NAFLD) patients, to develop a sensitive and specific diagnostic model. Data regarding the use of micro (mi)RNA-34 for NAFLD diagnosis are few. Routine clinical assessment, laboratory tests were done for Egyptian individuals (n = 314) were included (100 healthy individuals and 214 NAFLD patients). Quantification of miRNA-34 was done using real-time PCR. Extremely significant variables were entered into stepwise logistic regression. The diagnostic power of variables was estimated by the area under the ROC (AUC). RESULTS: MiRNA-34 levels were higher in NAFLD patients than healthy individuals with a significant difference (P< 0.0001). The multivariate analysis was used to evaluate the NAFLD-associated variables (CRP, cholesterol, body mass index (BMI), ALT had p< 0.0001 while mRNA-34 had (p=0.0004). The AUCs (CI) of candidate NAFLD markers were in the order of miRNA-34 0.72 (0.66-0.77) < ALT 0.73 (0.67-0.79) < BMI 0.81 (0.76-0.86) < cholesterol < 0.85 (0.79-0.90) < CRP 0.88 (0.84-0.92). We developed a novel index for discriminating patients with NAFLD named NAFLD Mark. AUC was jumped to 0.98 (0.93-0.99) when five markers were combined. The AUC of NAFLD mark for NAFLD detection was higher than the AUCs of seven common NAFLD indexes (0.44-0.86). CONCLUSIONS: The NAFLD mark is a non-invasive and highly sensitive and specific model for NAFLD diagnosis.

Quality of Life after Transcatheter Arterial Chemoembolization Combined with Radiofrequency Ablation in Patients with Unresectable Hepatocellular Carcinoma Compared with Transcatheter Arterial Chemoembolization alone.

AIM: The aim of this study was to assess quality of life (QoL) in patients with unresectable hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE) compared to TACE plus radiofrequency ablation (RFA) done at the same sitting, and to assess tumor therapy response after these 2 palliative interventions. METHODS: 73 patients with unresectable HCC (BCLC-B) were included. Patients with tumor ≤ 5 cm were subjected to TACE (N = 45) while patients with tumors > 5 cm were subjected to TACE followed immediately by RFA (N = 28). QoL was evaluated with two validated questionnaires (EORTC QLQ-30 and EORTC HCC18). These questionnaires were filled out before intervention, 2 weeks and 2 months after intervention. Pre/post interventional changes were analyzed. The modified response evaluation criteria in solid tumor (mRECIST) were employed for the evaluation of therapeutic efficacy. RESULTS: Baseline global health status/QoL was significantly higher in TACE group (64.1%) compared to TACE-RFA group (51.2%). Two weeks after intervention: the absolute decrease in global health state was higher in TACE-RFA (- 12.1%) compared to TACE (- 6.3%, p = 0.411). Less impairment was found in TACE group compared to TACE-RFA group for physical/social functioning, fatigue and pain but it was statistically insignificant. Two months after intervention; TACE-RFA group showed significant improvement in global health score, social and physical functioning scores, as well as significant improvement in pain and fatigue compared to TACE group. The therapeutic efficacy of TACE-RFA was better than TACE alone: complete remission, partial remission, stable disease and progressive disease were 17.9%, 32.1%, 42.9% and 7.1% Vs11.1%, 22.2%, 48.9% and 17.8%, respectively). CONCLUSION: Neither TACE nor TACE-RFA showed a significant decrease in QoL in patients with unresectable HCC two weeks after intervention. However, two months after intervention; TACE-RFA showed significant improvement in global health score compared to TACE monotherapy. TACE-RFA appeared safe, effective and more favorable than TACE monotherapy.
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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.