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.

Correlations between Cytokine Levels, Liver Function Markers, and Neuropilin-1 Expression in Patients with COVID-19.

Aim: The study evaluated the correlations between cytokine levels, liver function markers, and neuropilin-1 (NRP-1) expression in patients with COVID-19 in Egypt. The study also aimed to evaluate the accuracy sensitivity, specificity, and area under the curve (AUC) of the tested laboratory parameters in identifying COVID-19 infection and its severity. Patients and Methods: Fifty healthy subjects and 100 confirmed patients with COVID-19 were included in this study. COVID-19 patients were separated into two groups based on the severity of their symptoms. Serum ALT, AST, albumin, C-reactive protein (CRP), interleukin (IL)-1ß, IL-4, IL-6, IL-18, IL-35, prostaglandin E2 (PGE2), and thromboxane A2 (TXA2) were estimated. We measured the gene expression for nuclear factor-kappa B p50 (NF-κB p50) and nuclear factor-kappa B p65 (NF-κB p65) and NRP-1 in blood samples using quantitative real-time polymerase chain reaction (qRT-PCR). AUC and sensitivity and specificity for cytokine levels and NF-κB p50 and NF-κB p65 and NRP-1 in identifying COVID-19 infection were also determined in both moderate and severe patient groups using receiver-operating characteristic curve (ROC) analysis. Results: All patients with COVID-19 showed higher serum activities of liver enzymes, levels of CRP, IL-1ß, IL-4, IL-6, IL-18, IL-35 PGE2, and TXA2, and mRNA expression of NF-κB p50, NF-κB p65, and NRP-1 than healthy subjects. The severe group exhibited a significant increase in serum ALT, AST and IL-6 and a significant decrease in albumin, IL-1ß, TXA2, and NF-κB p65 levels compared to the moderate group. In all patients (moderate and severe), all cytokines were positively correlated with NF-κB p50, NF-κB p65 and NRP-1 expression levels. Serum ALT and AST were positively correlated with CRP, cytokines (IL-4, IL-6, IL-18, IL-35 and TXA2), and NF-κB p50 and NF-κB p65 expression levels in both moderate and severe groups. They were also positively correlated with serum IL-1ß level in the severe COVID-19 patient group and with NRP-1 expression in the moderate group. Using the logistic regression analysis, the most important four statistically significant predictors associated with COVID-19 infection in the study were found to be IL-6, TAX2, NF-κB p50 and NF-κB p65. ROC analysis of these variables revealed that three of them had AUC > 0.8. In moderate cases, AUC of the serum TXA2 level and NF-κB p65 expression were 0.843 (95% CI 0.517−0.742, p < 0.001) and 0.806 (95% CI 0.739−0.874, p < 0.001), respectively. In the severe group, AUC of serum IL-6 level was 0.844 (95% CI 0.783−0.904, p < 0.001). Moreover, Il-6 had a sensitivity of 100% in both moderate and severe groups. Conclusions: This study concluded that liver injury in patients with COVID-19 may be strongly attributed to the cytokines storm, especially IL-6, which was positively correlated to NF-κB p50, NF-κB p65 and NRP-1 mRNA expression levels. Moreover, ROC analysis revealed that IL-6, TXA2, and NF-κB p65 could be useful in predicting the possibility of infection with COVID-19, and IL-6 could be of possible significance as a good predictor of the severity and disease progress. However, RT-qPCR for SARS-CoV-2 detection is essential to confirm infection and further clinical studies are required to confirm this elucidation.

Relation between Cytokine Levels and Pulmonary Dysfunction in COVID-19 Patients: A Case-Control Study.

Aim: The study aimed to assess the relationships between serum cytokine levels and pulmonary dysfunctions in individuals with COVID-19. These correlations may help to suggest strategies for prevention and therapies of coronavirus disease. Patients and methods: Fifty healthy participants and one hundred COVID-19 patients participated in this study. COVID-19 participants were subdivided into moderate and severe groups based on the severity of their symptoms. In both patients and healthy controls, white blood cells (WBCs) and lymphocytes counts and serum C-reactive protein (CRP), interleukin (IL)-1, IL-4, IL-6, IL-18, and IL-35 levels were estimated. All the patients were examined by chest computed tomography (CT) and the COVID-19 Reporting and Data System (CO-RADS) score was assessed. Results: All COVID-19 patients had increased WBCs count and CRP, IL-1ß, IL-4, IL-6, IL-18, and IL-35 serum levels than healthy controls. Whereas WBCs, CRP, and cytokines like IL-6 showed significantly higher levels in the severe group as compared to moderate patients, IL-4, IL-35, and IL-18 showed comparable levels in both disease groups. Lymphocytes count in all patient groups exhibited a significant decrease as compared to the heathy controls and it was significantly lower in severe COVID-19 than moderate. Furthermore, CO-RADS score was positively connected with WBCs count as well as CRP and cytokine (IL-35, IL-18, IL-6, IL-4 and IL-1ß) levels in both groups. CO-RADS score, also demonstrated a positive correlation with lymphocytes count in the moderate COVID-19 patients, whereas it demonstrated a negative correlation in the severe patients. The receiver operator characteristic (ROC) curve analysis indicated that IL-1ß, IL-4, IL-18, and IL-35 were fair (acceptable) predictors for COVID-19 in moderate cases. Whereas IL-6 was good predictor of COVID-19 in severe cases (AUC > 0.800), IL-18 and IL-35 were fair. Conclusion: Severe COVID-19 patients, compared to individuals with moderate illness and healthy controls, had lower lymphocyte counts and increased CRP with greater WBCs counts. In contrast to moderate COVID-19 patients, severe COVID-19 patients had higher levels of IL-6, but IL-4, IL-18, and IL-35 between both illness categories were at close levels. IL-6 level was the most potent predictor of COVID-19 progress and severity. CO-RADS 5 was the most frequent category in both moderate and severe cases. Patients with a typical CO-RADS involvement had a higher CRP and cytokine (IL-1ß, IL-6, IL-4, IL-18, and IL-35) levels and WBCs count with a lower lymphocyte number than the others. Cytokine and CRP levels as well as WBCs and lymphocyte counts were considered surrogate markers of severe lung affection and pneumonia in COVID 19 patients.

Detection of hepatitis C virus core antigen as an alternative method for diagnosis of hepatitis C virus infection in blood donors negative for hepatitis C virus antibody.

BACKGROUND: Screening of blood donors in many countries is based on the use of serologic assays to detect specific anti-HCV antibodies (HCV Ab), but it lacks detection sensitivity. So, HCV RNA detection using the current gold standard real-time PCR is a must to rule out HCV infection with the main disadvantage being of high cost. HCV core antigen (HCV-c-Ag) immunoassay is proposed as a more cost efficient alternative to HCV RNA detection with PCR. AIM: To evaluate the effectiveness of HCV-c-Ag detection as a cheap alternative to HCV RNA (PCR) in diagnosis of HCV infection in blood donors who are HCV Ab negative. METHODS AND RESULTS: One hundred eighty-six volunteer blood donors who tested negative for HCV Ab were examined for HCV-c-Ag. Seven cases out of these 186 cases were HCV-c-Ag positive (4%). HCV RNA detection (PCR technique) was done to 30 cases (seven cases who test positive for HCV-c-Ag and 23 cases who test negative). Six out of the seven cases who were HCV-c-Ag positive (86%) were HCV RNA positive. Twenty-two cases out of the 23 cases who were HCV-c-Ag negative (96%) were HCV RNA negative. CONCLUSION: HCV-c-Ag detection is an efficient method for diagnosis of HCV infection during screening of blood donors with high specificity (95.6%) and high negative predictive value (95.6%).

Efficacy and safety of sofosbuvir plus simeprevir therapy in Egyptian patients with chronic hepatitis C: a real-world experience.

BACKGROUND: Simeprevir plus sofosbuvir (SIM/SOF) regimen was recommended by professional guidelines for certain patients with HCV genotype 1 infection and there is lack of data about this regimen in patients with genotype 4 infection. AIM: To evaluate the efficacy and safety of this regimen in Egyptian patients with chronic HCV genotype 4 infection in the real world. METHODS: Multicentre observational study included 583 patients with HCV genotype 4 infection who began 12 weeks of treatment with SIM plus SOF. Demographic, clinical and virological data as well as adverse outcomes were collected. Treatment naïve patients were 342 (59%) of all included patients, 45% of patients had severe fibrosis (F3 and F4) while 55% had mild fibrosis (F1 and F2) and the primary outcome was sustained virological response (SVR). RESULTS: The overall SVR rate was 95.7% (558 out of 583 patients). In total, SVR12 in naïve patients with mild fibrosis score (F1 and F2) was achieved in 98.9% (94/95) for F1 and 98.1% (105/107) for F2, while naïve patients with severe fibrosis (F3 and F4) achieved SVR of 97.7% (86/88) for F3 and (42/52) 80.8% for F4. SVR in patients with previous interferon treatment achieved in 100% (45/45) for patients with F1 and 98.7% (74/75) for F2. While 94.7% (72/76) in experienced patients with F3; and 88.9% (40/45) for F4 achieved SVR12. Notable side effects included rash in 21 patients, photosensitivity in 18 patients, pruritus in 44 patients and hyperbilirubinemia in 42 patients. CONCLUSIONS: A 12-week regimen of simeprevir/sofosbuvir was efficacious and well tolerated by treatment-naïve and treatment-experienced patients with chronic HCV genotype 4.

Clinical significance and diagnostic value of serum dickkopf-1 in patients with hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide. It has been widely established that the early detection of HCC enables more treatment options and translates to improved survival. AIM: To assess the diagnostic accuracy of DKK1 as a serum protein marker for HCC by examining its diagnostic sensitivity and specificity in HCC. METHODS: We analyzed data for 50 patients with hepatitis C virus (HCV) related HCC as the studied group. Twenty patients with chronic hepatitis C and 20 patients with HCV-related liver cirrhosis will serve as control group. DKK1 was measured in serum by ELISA. We used receiver operating characteristics (ROC) to calculate its diagnostic accuracy. RESULTS: We assessed serum DKK1 in 90 participants: 50 with HCC (studied group), 20 with chronic HCV infection, and 20 with liver cirrhosis (as control group). Serum concentration of DKK1 was significantly higher in HCC group and values did not differ significantly between the two control groups. We performed multivariate regression analysis using AFP level, number of focal lesions, focal lesion size and Portal vein thrombosis as an independent variable. ROC curves showed the optimum diagnostic cut off was 1.5 ng/mL (sensitivity 67.5%, specificity 89.3%). CONCLUSION: Serum DKK1 could potentially be used for early diagnosis of HCC and complement measurement of AFP in the diagnosis of HCC.

Chronic hepatitis C-associated thrombocytopenia: aetiology and management.

Thrombocytopenia is perhaps the most common haematological abnormality in patients with chronic hepatitis C virus (HCV) infection. In these patients, the presence of thrombocytopenia may be a limiting factor when considering antiviral therapy and may be associated with decreased sustained virological response rates. Thrombocytopenia may interfere with diagnostic procedures such as liver biopsy, because of risk of bleeding. Pathogenetic mechanisms include hypersplenism secondary to portal hypertension, bone marrow suppression resulting from either HCV itself or interferon treatment, and aberrations of the immune system resulting in the formation of anti-platelet antibodies and/or immune-complexes that bind to platelets and facilitate their premature clearance. The ability to increase platelet levels could significantly reduce the need for platelet transfusions and facilitate the use of interferon-based antiviral therapy and other medically indicated treatments in patients with liver disease. Therapeutic options include pharmacological and non-pharmacological therapies. This review summarizes the available data on these therapeutic options.

Hematopoietic stem cell mobilization into the peripheral circulation in patients with chronic liver diseases.

OBJECTIVE: The present study was aimed to investigate and compare the kinetics of bone marrow-derived hematopoietic stem cells (BMHSC) migration in the peripheral blood and liver in response to liver injury in patients with chronic liver disease (CLD). METHODS: In all, 45 CLD patients staged with Child-Pugh A, B and C and 15 healthy participants were evaluated for the concentration of circulating BMHSC by a flow cytometric analysis of CD133(+) /CD34(+) cells. In addition, homing BMHSC and hepatic progenitors were assessed by the immunohistochemical detection of CD133(+) and OV6(+) cells in liver biopsy specimens from Child-Pugh A and B patients. RESULTS: No significant difference in the percentage of circulating CD133(+) /CD34(+) cells was observed among all groups of patients. In liver tissues, OV6(+) cells increased significantly in Child-Pugh B cases (P < 0.05), while CD133(+) cells were distributed sparsely in the periportal region in Child-Pugh A and B patients. OV6(+) cells were significantly correlated with CD34(+) cells but not with CD133(+) cells in Child-Pugh A and B patients (P < 0.01 and P < 0.05, respectively). CONCLUSIONS: Various degrees of severity in CLD neither evoked the mobilization of BMHSC into the circulation nor triggered their homing into liver tissue, thus excluding extrahepatic stem cell-mediated repair. The recovery process seems to be dependent on proliferating endogenous liver progenitors (OV6(+) cells).

A randomized trial of 24 versus 48 weeks of peginterferon alpha-2a plus ribavirin in Egyptian patients with hepatitis C virus genotype 4 and rapid viral response.

BACKGROUND AND AIM: Little data is available regarding the 24-week therapy with pegylated interferon and ribavirin in Egyptian patients with hepatitis C virus (HCV) genotype 4 infection. We aimed to investigate the efficacy of 24-week versus 48-week peginterferon alpha-2a plus ribavirin therapy in patients with HCV genotype 4 infection with with rapid virological response. METHODS: This trial included 102 patients with HCV genotype 4 infection and low viral load. They were treated with peginterferon alpha-2a (180 microg/week) plus ribavirin. Patients (87/102) with a rapid virological response were randomized for a total treatment duration of 24 weeks (group A: 43) or 48 weeks (group B:44). Virological responses (EVR: early virological response, EOTR: end of treatment response, and SVR: sustained virological response) were assessed for each group. RESULTS: In group A, EVR was achieved in 37/43 (84%) patients, while EOTR was achieved in 34/43 (79%) patients and SVR in 30/43 (70%) patients. In group B, on the other hand EVR was achieved in 38/44 (84%) patients, while EOTR was achieved in 35/44 (80%) patients and SVR in 32/44 (73%) patients. No significant difference in SVR rates was observed between the two groups. The rate of adverse events was higher in group B, with lower adherence rates than group A. CONCLUSIONS: In patients with chronic HCV genotype 4 infection with rapid virological response and low viral loads, a 24-week peginterferon alpha-2a plus ribavirin therapy is as effective as a 48-week therapy with lower rate of adverse events.

Incidence and risk factors of retinopathy in Egyptian patients with chronic hepatitis C virus treated with pegylated interferon plus ribavirin.

BACKGROUND: Data are scarce on ocular complications in Egyptian patients with chronic hepatitis C treated with pegylated interferon and ribavirin therapy. The aim of this study was to investigate the development of retinal lesions induced by interferon therapy for chronic hepatitis C. METHODS: We prospectively analyzed 84 patients with chronic hepatitis C (total 168 eyes), who underwent combination pegylated interferon and ribavirin therapy for 48 weeks. Visual acuity, color vision, and visual field were measured, and a fundus assessment was made at baseline, at 12, 24, and 48 weeks post the commencement of treatment, and at follow-up, 1 month after treatment. Past medical and ocular histories, visual symptoms, and the results of a full ophthalmologic assessment were recorded for each patient. RESULTS: Twenty-two patients (26%) developed retinopathy. Retinal hemorrhage was observed in eight patients. Four patients complained of visual disturbance. Retinopathy disappeared in 16 patients (73%) despite the continuation of combination therapy. However, retinopathy persisted in six patients with retinal hemorrhage and three of them stopped treatment. A comparison of the clinical backgrounds between the patients with and without retinopathy showed no significant differences with regard to gender, HCV RNA level, white blood cell count, platelet count, hemoglobin level, or fibrosis score. However patients with retinopathy were of older age, had a higher prevalence of hypertension and diabetes mellitus, and more often did not respond to therapy. Multiple logistic regression analysis revealed that hypertension and diabetes were factors predicting retinopathy. CONCLUSION: Retinopathy associated with interferon α-2a and ribavirin combination therapy tends to develop in patients of older age with hypertension and diabetes.

Bile aspiration cytology in diagnosis of bile duct carcinoma: factors associated with positive yields.

BACKGROUND/PURPOSE: In bile duct carcinoma (BDC) patients, bile aspiration cytology (BAC) is an established method for cytodiagnosis. However, almost all previous reports investigated the biliary strictures caused not only by BDC but also by gallbladder and pancreatic carcinomas. Therefore, BAC in BDC patients only has not yet been investigated sufficiently. The aim of this study was to evaluate the actual sensitivity of BAC and to evaluate the factors that affect positive yields of BAC in patients with defined BDC. METHODS: Data on 47 consecutive patients with definite BDC, who underwent BAC via endoscopic nasobiliary drainage (ENBD) or percutaneous transhepatic cholangiodrainage (PTCD), were retrospectively collected. Fourteen factors were studied for association with positive BAC. RESULTS: The number of cytological samplings ranged from 1 to 14 times. The cumulative diagnostic yield was 72.3% (34/47), and 32 positive results were obtained at a maximum of six samplings. Independent factors associated with positive BAC were perihilar location, stricture length ≥ 2 cm, and macroscopic papillary type. CONCLUSION: In BDC patients with ENBD or PTCD, repeated BAC is useful, and six times was the optimum number of repeat samplings. Although the sensitivity of BAC is not sufficient for the preoperative diagnosis of malignant biliary stricture, the three independent factors noted above predict positive yields and indicate whether or not BAC should be repeated up to six times.

Hepatitis C virus (genotype 4)-associated mixed cryoglobulinemia vasculitis: effects of antiviral treatment.

OBJECTIVE: Type II mixed cryoglobulinemia (MC) is a systemic vasculitis usually associated with hepatitis C virus (HCV). The present trial was performed to investigate the efficacy of therapy with pegylated interferon alfa-2a (PEG-IFN alfa-2a) plus ribavirin in patients with HCV-related MC vasculitis and evaluate the factors associated with clinical remission of MC. METHODS: A total of 46 consecutive patients with HCV-related Type II MC received PEG-IFN alfa-2a (standard dose 180 mg/week) subcutaneously plus oral ribavirin (800-1,200 mg/day) for 48 weeks. The response to treatment was analyzed by comparing clinical, immunologic, and virologic parameters at the initial evaluation with those observed at the end of follow-up. Logistic regression was used to assess the factors associated with clinical remission. RESULTS: A total of 22 patients (48%) had a sustained virologic response and were complete clinical responders. Serum cryoglobulin disappeared in 26 of 46 patients (56%), and complement levels normalized in 70% of the patients. In univariate analysis, factors associated with complete clinical response were early virologic response at 4 weeks [OR 1.4 (95% CI 0.1-17.1)], proteinuria [OR 1.4 (95% CI 0.2-8.2)] and the fibrosis score [OR 1.09 (95% CI 0.6-1.9)], peripheral neuropathy [OR 0.9 (95% CI 0.1-6.5)], arthralgia [OR 0.7 (95% CI 0.1-3.9)], sicca syndrome [OR 0.6 (95% CI 0.1-3.2)], cryoglobulin [OR 0.2 (95% CI 0.07-1.09)], and purpura [OR 0.1 (95% CI 0.01-1.3)]. In multivariate analysis, only cryoglobulinemia was independently associated with complete clinical response. No patient had side effects for which discontinuation of therapy was required. CONCLUSION: The results indicated that treatment with PEG-IFN alfa-2a plus ribavirin can achieve a complete clinical response in patients with HCV-related MC. Complete clinical response correlates with the eradication of HCV.

Cystatin C: a predictor of hepatorenal syndrome in patients with liver cirrhosis.

BACKGROUND: Recent studies suggest that serum cystatin C (CysC) is a more sensitive marker of renal functions than serum creatinine (Cr). AIM: Evaluation of the clinical significance of cystatin C as a predictor of hepatorenal syndrome (HRS) in patients with liver cirrhosis, ascites, and normal serum Cr level. METHODS: Eighty patients with cirrhotic ascites were enrolled in this study (53 men and 27 women; age: 59.5 ± 7.5 years). All patients were subjected to full clinical assessment and laboratory investigations focussing on renal functions, glomerular filtration rate, and measurement of serum cystatin level. RESULTS: The Serum Cr and CysC levels were 1.04 ± 0.1 and 1.8 ± 0.8 mg/L, respectively. HRS developed in 18 patients during the follow-up period (6 months). Type 1 HRS was found in 5 patients and type 2 HRS was found in 13 patients with no significant difference between both types regarding baseline characteristics. Age (p < 0.001), albumin (p < 0.001), sodium (p < 0.005), cystatin C (p < 0.001), and e-GFRMDRD (estimated glomerular filtration rate-modification of the diet in renal disease) (p < 0.007) were significant dependent predictive factors for the development of HRS. The CysC level was the most independent predictive factor for HRS (OR, 2.1; 95% CI, 0.75-0.97; p < 0.002). Eighteen patients died during the follow-up period. Age (p < 0.001), INR (p < 0.001), e-GFRMDRD (p < 0.03), sodium (p < 0.01), MELD score (p < 0.05), albumin (p < 0.001), and CysC (p < 0.001) levels were significant dependent factors for predicting mortality. CysC (OR, 5.3; p < 0.006) level and INR (OR, 1.01; p < 0.006) were the most independent factors for predicting mortality. CONCLUSION: Serum CysC level may be considered a predictor of HRS and mortality in patients with liver cirrhosis and ascites.

Nitric oxide levels and sustained virological response to pegylated-interferon alpha2a plus ribavirin in chronic HCV genotype 4 hepatitis: A prospective study.

BACKGROUND: The role of nitric oxide (NO) in infectious diseases is gaining attention because of its antiviral effects. AIM: To evaluate whether serum and hepatic NO levels are predictors of the outcome of treatment in patients with chronic hepatitis C genotype 4. METHODS: Fifty six patients with chronic HCV genotype 4 treated with pegylated interferon (IFN) alpha-2a plus ribavirin underwent blood tests, assessment of serum level of NO and hepatic tissue expression of NO synthase (iNOS) before and during treatment. RESULTS: The pre-treatment serum NO level was significantly higher in sustained responders (SR) [39.583 (35-43.8)] compared to relapsers [36.25 (26-43.8)], and non responders (NR) [35.417 (25.0-43.8)]. During treatment, the serum NO level was significantly higher in SR [58.125 (47.9-60.6)] compared to relapsers [53.854 (47.9-59.4)] and NR [50 (42.9-59.4)]. The pre-treatment iNOS expression was significantly higher in SR [37.5 (15-75)] compared with either relapsers [25 (15-45)] and or NR [20 (2-45)]. In multivariate logistic regression analysis, the serum NO was correlated with the virological response to pegylated interferon alpha-2a plus ribavirin therapy. CONCLUSION: In patients with chronic hepatitis C, nitric oxide levels may be associated with the outcome of pegylated-IFN-α 2a plus ribavirin treatment.

Portal hypertensive enteropathy before and after variceal obliteration: an endoscopic, histopathologic and immunohistochemical study.

AIM: To study portal hypertensive enteropathy (PHE) before and after the obliteration of esophageal varices. METHODS: 30 patients with portal hypertension and esophageal varices were included. Band ligation was performed for every patient until the obliteration of esophageal varices. Enteroscopy and biopsies from gastric, duodenal and jejunal mucosa were taken at the beginning of the study and after variceal obliteration. Morphometric measurement of mean vascular areas and estimation of tissue vascular endothelial growth factor (VEGF) were also completed. RESULTS: The number of patients with enteropathy increased from 6.6% before obliteration to 46.7% after variceal obliteration (p< 0.001). Angiogenesis, vascular ectasia and blood extravasation were the main histopathological findings and all increased significantly after variceal obliteration. The mean vascular area of ectatic vessels in the gastric, duodenal and jejunal biopsies also increased after variceal obliteration. The mean VEGF in the gastric, duodenal and jejunal biopsies increased after variceal obliteration. The mean corpuscular volume (MCV) and hemoglobin (Hb) concentration were significantly lower after variceal obliteration. CONCLUSION: the portal hypertensive enteropathic changes increased in frequency and severity after esophageal variceal obliteration with a probability of causing anemia.

Is irritable bowel syndrome associated with chronic hepatitis C?

BACKGROUND AND AIM: Hepatitis C virus (HCV) is a common chronic infection that is widely associated with symptoms of fatigue and abdominal pain. The aim of the present study was to determine the prevalence of irritable bowel syndrome (IBS) among patients with hepatitis C compared to controls. METHODS: This study included 258 patients with chronic hepatitis C, 36 patients with chronic hepatitis B, and 160 healthy volunteers. Clinical and laboratory data were recorded for every patient. All patients and controls were administered a questionnaire of IBS according to Rome III criteria. RESULTS: The percentage of patients with IBS was significantly higher in patients with chronic HCV (66%, 170/258) than chronic hepatitis B virus (HBV; 22%, 8/36) and normal controls (18%, 28/160 patients; P < 0.001 and P < 0.001, respectively). There was no significant difference between chronic HBV and normal controls. In chronic HCV patients, IBS with constipation was the predominant type (51%, 86/170) followed by mixed IBS (73/170, 43%). In patients with chronic HCV, the percentage of females with IBS (91%) was significantly higher than those without IBS (9%; P < 0.001), and the percentage of patients with a high fibrosis score (F2-3) was significantly higher in patients with IBS (45%) than in patients without IBS (6%; P < 0.001). There was no difference regarding age, alanine aminotransferase level, or HCV viremia. A multivariate regression analysis revealed a significant association between sex, fibrosis score, and IBS. CONCLUSION: IBS is more prevalent in patients with chronic hepatitis C. Female patients with chronic HCV and those with higher fibrosis scores are more likely to have IBS.

Barrett's esophagus: prevalence and risk factors in patients with chronic GERD in Upper Egypt.

AIM: To determine the prevalence and possible risk factors of Barrett's esophagus (BE) in patients with chronic gastroesophageal reflux disease (GERD) in El Minya and Assuit, Upper Egypt. METHODS: One thousand consecutive patients with chronic GERD symptoms were included in the study over 2 years. They were subjected to history taking including a questionnaire for GERD symptoms, clinical examination and upper digestive tract endoscopy. Endoscopic signs suggestive of columnar-lined esophagus (CLE) were defined as mucosal tongues or an upward shift of the squamocolumnar junction. BE was diagnosed by pathological examination when specialized intestinal metaplasia was detected histologically in suspected CLE. pH was monitored in 40 patients. RESULTS: BE was present in 7.3% of patients with chronic GERD symptoms, with a mean age of 48.3 +/- 8.2 years, which was significantly higher than patients with GERD without BE (37.4 +/- 13.6 years). Adenocarcinoma was detected in eight cases (0.8%), six of them in BE patients. There was no significant difference between patients with BE and GERD regarding sex, smoking, alcohol consumption or symptoms of GERD. Patients with BE had significantly longer esophageal acid exposure time in the supine position, measured by pH monitoring. CONCLUSION: The prevalence of BE in patients with GERD who were referred for endoscopy was 7.3%. BE seems to be associated with older age and more in patients with nocturnal gastroesophageal reflux.

Renal duplex Doppler ultrasound in patients with HCV related liver cirrhosis.

AIM: To study the renal resistive index (RI) and pulsatility index (PI) measured by renal Doppler in various stages of liver cirrhosis and their values to detect cirrhotic patients at risk for developing the hepatorenal syndrome. METHODS: This study included 60 cirrhotic patients divided into 4 groups (15 patients each): compensated liver cirrhosis (group A), diuretic responsive ascites (group B), refractory ascites (group C), hepatorenal syndrome (group D) and ten healthy persons as the control group (E). All patients were subjected to detailed history taking and clinical examination. Laboratory investigations included simple urine analysis, complete blood picture, liver function tests, blood urea and serum creatinine, serum sodium and serum potassium, 24-hour urine collection for sodium concentration, creatinine concentration and protein concentration. Ultrasonographic examination and renal duplex Doppler ultrasonography were undertaken to assess the RI and PI. RESULTS: The RI of both interlobar and arcuate arteries was significantly higher in all patient groups than in the control group (p<0.01). The RI was significantly higher in patients with refractory ascites than in patients with diuretic responsive ascites, and also in patients with diuretic responsive ascites than in patients with compensated cirrhosis (p<0.01); in patients with hepatorenal syndrome than in patients with diuretic responsive ascites and patients with compensated cirrhosis (p<0.0001). The PI was significantly higher in all patients groups than in the control group (p<0.01) and in patients with refractory ascites than in patients with diuretic responsive ascites and was also higher in patients with responsive ascites than in patients with compensated cirrhosis (p<0.0001). Also, the PI was significantly higher in patients with hepatorenal syndrome than in patients with responsive ascites and patients with compensated cirrhosis (p<0.0001). Creatinine clearance in patients with the hepatorenal syndrome was significantly lower than that of other different groups (p<0.0001) but there was no significant change in creatinine clearance between patients with compensated cirrhosis and control group. While creatinine clearance in patients with diuretic responsive ascites was significantly higher than that in patients with compensated cirrhosis (p<0.05) there was no significant change between patients with diuretic responsive ascites and patients with refractory ascites. CONCLUSION: Both renal resistive index and pulsatility index increase with the degree of hepatic decompensation. Renal duplex ultrasound which is a non-invasive, simple and easy method to study intrarenal hemodynamics in patients with liver cirrhosis may predict patients at risk of hepatorenal impairment.