Detection of Occult Hepatitis C Virus Infection in Egyptian Patients Who Achieved a Sustained Virologic Response to Direct-Acting Antiviral Agents.

BACKGROUND: Occult hepatitis C virus (HCV) infection (OCI) is diagnosed based on the detection of HCV-RNA in non-serum reservoirs, such as peripheral blood mononuclear cells (PBMCs) and/or hepatocytes with undetectable HCV-RNA in the serum. The current study was designed to shed more light on the presence of occult HCV in a population of cases who achieved an SVR after receiving treatments for HCV-infection and its significance. METHODS: This cross-sectional study evaluated 111 chronic HCV patients treated at Theodor Bilharz Research Institute, Egypt and achieved a sustained virological response (SVR) 12 -24 weeks after treatment with Direct acting antiviral drugs (DAAs). The treatment lasted 12 or 24 weeks using generic medications including Sofosbuvir (SOF) 400 mg/day and Daclatasvir (DCV) 60 mg/day ± weight-based Ribavirin (RBV) 600-1000 mg/day. After achieving the SVR 12 -24 weeks, all patients were subjected to clinical examination and full laboratory investigations. All the candidates were assessed for fibrosis pre/post-treatment by transient elastography (Fibroscan©). Eighty-seven patients (78.4%) received dual therapy (SOF/DCV) and 24 patients (21.6%) received triple therapy (SOF/DCV/RBV). One hundred and seven patients received the regimen for 12 weeks (96.4%) and only four patients received the regimen for 24 weeks (3.6%). All patients were examined in terms of HCV RNA in plasma and PBMCs. RESULTS: Nine patients (8.1%) were positive for PBMCs HCV RNA. The presence of Occult HCV infection (OCI) was significantly correlated with age, level of AFP, and the degree of liver stiffness. CONCLUSION: The OCI was present in 8.1% of the patients who achieved an SVR 12 - 24 weeks. These patients were mostly aged and with elevated AFP and advanced fibrosis. Monitoring and follow-up of those patients may help to assess the outcomes.

Eosinophilic ascites as an uncommon presentation of eosinophilic gastroenteritis: A case report.

BACKGROUND: Eosinophilic gastroenteritis (EGE) is defined by the presence of gastrointestinal symptoms, with an abnormal eosinophilic infiltrate of the intestine wall and exclusion of other causes of secondary eosinophilia. EGE has three clinical presentations, depending on the depth of eosinophilic infiltration of the bowel wall. It individualizes into three types, namely mucosal, muscular, and subserosal. Eosinophilic ascites, which is caused by edema and eosinophilic inflammation of the serosal layer of the small bowel wall, is the most uncommon presentation of EGE. CASE SUMMARY: A 30-year-old Egyptian woman presented with pain in the epigastrium and diffuse abdominal distension. Past medical history comprised allergy to iron injections (for iron deficiency anemia). Clinical examination showed moderate abdominal distention (palpation) and shifting dullness (percussion) suggestive of moderate ascites; mild right pleural effusion was also suspected, but findings were otherwise unremarkable. Abdominal and pelvic examinations by ultrasound and contrast-enhanced computed tomography showed moderate ascites, mild right pleural effusion, and diffuse thickening of the antrum and small bowel loops. Endoscopy of the upper gastrointestinal tract revealed mild diffuse hyperemia of the esophagus, stomach and duodenum, with no relevant findings in the histopathology of biopsy specimens taken from these sites. Laboratory results showed eosinophilia in the peripheral blood and marked increase of eosinophils in the ascitic fluid. Treatment with corticosteroids resulted in normalization of the laboratory test results, and the ascites resolved within a week of initiation of therapy. CONCLUSION: Eosinophilic ascites, characterized by increased eosinophils in peripheral blood and ascitic fluid, showed dramatic response to steroid therapy.

Characterizing a cohort of Egyptian patients with acute-on-chronic liver failure.

BACKGROUND AND AIM: Several studies performed in Western countries and Asia have shown that acute-on-chronic liver failure (ACLF) is an acute decompensation of cirrhosis characterized by organ system failures and high short-term mortality. However, the characteristics of Egyptian patients with ACLF have not yet been described. The aim of this study was to assess Egyptian patients with cirrhosis hospitalized for an acute decompensation using criteria and scores developed by the EASL-CLIF Consortium. PATIENTS AND METHODS: One hundred and twenty patients with acutely decompensated cirrhosis nonelectively admitted to two tertiary hospitals were prospectively included. Ninety-three percent of patients had hepatitis C virus-related liver disease. RESULTS: Of the 120 patients, 40 had ACLF; of these 45% had ACLF-1, 33% ACLF-2, and the remaining 22% had ACLF-3. None of the patients with ACLF had received direct-antiviral agents (DAAs) while 30% of patients without ACLF were treated with these agents. The prevalence of prior episodes of decompensation was significantly higher in patients with ACLF (60% vs. 28%). The prevalence of precipitating events such as bacterial infection alone or combined with gastrointestinal hemorrhage was higher in patients with ACLF than in those without. Systemic inflammation, assessed with white blood-cell count and plasma C reactive levels, was more intense in ACLF. CONCLUSION: Among Egyptian patients with acutely decompensated cirrhosis nonelectively admitted to the hospital, those with ACLF were distinct from those without ACLF, not only by the presence of organ failures, but also the absence DAA therapy, more frequent prior episodes of decompensation, more frequent bacterial infections as a precipitant, and more intense systemic inflammation.

Serum anandamide level as a potential indicator for nonalcoholic fatty liver disease severity.

INTRODUCTION AND AIM: Nonalcoholic fatty liver disease (NAFLD) is a very common disease, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) and is considered the hepatic expression of metabolic syndrome. Liver biopsy is currently considered the gold standard in diagnosis of NAFLD; however, it is an invasive technique and carries many risks. The serum anandamide level is recently discovered to play an important role as the potential indicator for NAFLD severity. The purpose of the study is to determine the association of endocannabinoid metabolite anandamide and NAFLD severity and to investigate its association with anthropometric and metabolic features in NAFLD patients. METHODOLOGY: A case-control study on 36 NAFLD biopsy-proven NAFLD patients and 15 healthy volunteers. They were subjected to full clinical history and examination, laboratory tests, abdominal ultrasound and serological testing of anadamide. RESULTS: The anadamide level was significantly higher among NAFLD subgroups (simple steatosis and NASH) vs. the normal group (1.1, 0.29 vs. 0.2 P value = 0.00085), with cutoff 0.58 in the NASH group (accuracy 89%; sensitivity 66% and specificity 100%) (P value < 0.01). CONCLUSION: Anandamide could be a specific serum marker for NASH and can be used to detect NAFLD severity.

Urinary Neutrophil Gelatinase-Associated Lipocalin in Cirrhotic Patients with Acute Kidney Injury.

INTRODUCTION AND AIM: It is well known that development of acute kidney injury (AKI) increases mortality in hospitalized cirrhotic patients; therefore many novel markers have been studied for early detection, differential diagnosis and prognosis in cirrhotic patients with AKI. The aim of the current work is to evaluate urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL) as a diagnostic biomarker for different causes of acute kidney injury in liver cirrhosis and to assess it as a prognostic marker. MATERIAL AND METHODS: Out of 83 cirrhotic patients with AKI admitted between October 2015 and June 2016; 70 patients were included in this prospective study. Routine laboratory tests, uNGAL and fractional excretion of Na were obtained on admission. End points were death or improvement of kidney function and discharge. RESULTS: The patients included in our study were 41 males and 29 females with mean age 54.27 ± 6.08 years. HCV was the etiology of cirrhosis in 69 cases while one had combined HBV and HCV infection. More than 50% of patients were classified as Child C. Causes of kidney injury were prerenal, hepatorenal syndrome (HRS) and intrinsic tubular injury (iAKI) in 39 patients (55.7%), 17 patients (24.3%) and 14 patients (20%) respectively. mean value of uNGAL in prerenal, HRS and iAKI was 21.70 ± 7.31, 115.53 ± 68.19 and 240.83 ± 116.94 ng/mg creatinine respectively. MELD above 20 and uNGL above 32 were predictors of mortality. CONCLUSION: A single baseline measurement of uNGAL level has the ability to determine type of kidney dysfunction in cirrhotic patients, perhaps accelerating management decisions and improving outcomes.

NON-INVASIVE PREDICTORS FOR THE PRESENCE, GRADE AND RISK OF BLEEDING FROM ESOPHAGEAL VARICES IN PATIENTS WITH POST-HEPATITIC CIRRHOSIS.

Variceal bleeding is the last step of a chain of events initiatedby an increase in portal pressure, followed by the development and progressive dilation ofvarices until these finally rupture and bleed. The ideal method to diagnose portal hypertension should be accurate, noninvasive, objective, and reproducible. The study evaluated the predictive value of two non-invasive parameters for the diagnosis of esophageal varices (EV): 1-Right liver lobe diameter/serum albumin ratios (RLLD/S. albumin), and 2-Platelet count/splenic bipolar diameter ratios (Platelets count/SBPD). This study included eighty Egyptian patients with post-hepatitic cirrhosis (45 males and 35 females). They underwent laboratory ultrasono-graphic and endoscopic examinations within one week. RLLD/S. albumin and Platelets count/SBPD ratios were calculated. The results showed that EV were not detected by upper digestive endoscopy in 25%, while grade I of EV was found in 17.5%, grade II in 17.5%, grade III in 20%, & grade IV in 20%. RLLD/S. albumin concentration ratio diagnosed the varices at cut off value of 3.43 with 95% sensitivity and 80% specificity. Also, it was positively correlated with grading of E.V, when this ratio increased the grading of E.V increases and vice versa. Besides, it predicted bleeding from E.V. at cut off value of 5.096 with 63% sensitivity and 73% specificity. Platelet count/SBPD ratio predicted the presence of varices at cut off value 1847 with 95% sensitivity and 93% specificity, and negatively correlated with grading of EV, when this ratio decreased grading of E.V increase and vice versa. It also predicted bleeding from E.V. at cut off value of 4809 with 50% sensitivity and 93% specificity.

Predictors of In-Hospital Mortality in patients with hepatocellular carcinoma and Acute Variceal bleeding.

INTRODUCTION: Detection of hepatocellular carcinoma (HCC) in cirrhotic patients remains a serious, unsolved problem, and the risk factors for acute variceal bleeding (AVB) in HCC patients remain unclear. This study aimed to determine the in-hospital mortality (IHM) and factors influencing the clinical outcomes of AVB in patients with liver cirrhosis and HCC. METHODS: This was a retrospective, non-randomized, clinical study that was conducted in 2014. The study was conducted on 70 patients with liver cirrhosis and HCC presenting by acute upper gastrointestinal bleeding (AUGIH). All patients were examined endoscopically within 24 hours from presentation and bleeding varices accounted for AUGIH. Full medical history, clinical examination, and laboratory and radiologic data were collected from admission charts, and hospital medical records were statistically analyzed with SSPS version 22. RESULTS: Thirty-two patients (45.7%) survived and 38 died (54.3%). Survivors are more likely to be Child-Pugh class A or B, and the non-survivors were class C. The Model for End-Stage Liver Disease (MELD) was highly predictive of IHM at an optimized cut-off value of ≥ 12.9. Higher esophageal varices grades and presence of active bleeding on index endoscopy were significant (p < 0.01) in the non-survivors compared to survivors. Complications of liver cirrhosis and associated major comorbidity were significantly higher (p < 0.01) in the non-survivors than the survivors. Univariate logistic regression analysis identified higher Grade Esophageal Varices and number of transfused packed red blood cells units as two independent predictors of IHM. CONCLUSIONS: IHM was particularly high (54.3%) among HCC patients with AVB who had MELD score > 12.9, higher grade Esophageal Varices, active bleeding on index endoscopy, more increased needs for blood transfusion, longer hospital stay, decompensated liver disease with major comorbidity.

Insulin resistance: a major factor associated with significant liver fibrosis in Egyptian patients with genotype 4 chronic hepatitis C.

BACKGROUND AND AIMS: The role of insulin resistance (IR) in chronic hepatitis C genotype 4 (CHC-4) patients is still under assessment. The aims of this study are to assess the prevalence and predictors of IR and its influence along with clinical, metabolic, virological, and histological factors on the severity of liver fibrosis in 100 Egyptian patients with CHC-4. PATIENTS AND METHODS: In 100 untreated patients with CHC-4, IR was assessed using the Homeostasis Model Assessment and defined greater than 3. By logistic regression (LR), independent factors associated with IR and significant fibrosis (SF=fibrosis, Metavir score≥F2) were assessed in nondiabetic and noncirrhotic patients. RESULTS: One hundred patients were included; 54% were men and 46% were women. The mean age of the patients was 40.46±9.41 years. Of the total patients, 55% were overweight and 28% were obese. Metabolic syndrome was observed in 26% of patients; five of them were known to be diabetic. All patients were genotype 4. Most of our patients had mild viremia (<2 00 000 IU/ml), whereas only 16% had higher viral load (>2 00 000 IU/ml). There was no correlation between IR and hepatitis C virus viremia (r=-0.069; P=0.492). Necroinflammation was moderate-severe (A2-A3) in 25% of patients. SF (F2-F4) was found in 46% of patients and 11% had cirrhosis (F4). Most of our patients, 54%, had moderate steatosis and 21% had severe steatosis. IR was present in 46% of patients; 39 (42.9%) were nondiabetic, which is correlated significantly with BMI (r=0.395; P<0.01). IR was found to increase significantly with the fibrosis stage (P=0.001), insignificant fibrosis, 18.5%, SF (F2-F4), 71.4%, and cirrhosis (F4), 100%. By LR, IR was independently and significantly associated with age more than 40 years, obesity (BMI>30 kg/m), SF, and severe steatosis (>30%). IR was also significantly associated with metabolic syndrome. SF was present in 46 patients (46%). It was associated with IR, moderate-severe necroinflammation, and severe steatosis. By LR, in noncirrhotic patients, SF was associated with age more than 40 years, obesity (BMI>30 kg/m), moderate/severe liver inflammation, and severe steatosis. CONCLUSION: In CHC-4 patients, IR is highly prevalent and independently associated with age, obesity, SF, and severe steatosis. Management of IR might significantly improve the prognosis of CHC-4 patients.

IL28B polymorphism is associated with treatment response in patients with genotype 4 chronic hepatitis C.

BACKGROUND & AIMS: Polymorphisms in the region of the interleukin (IL)28B gene have been associated with pegylated-interferon (PEG-IFN) and ribavirin treatment response mainly in genotype 1 HCV infections. However, there are few data on HCV genotype 4 (HCV-4) infection. We evaluated, in a unique well-characterized cohort of HCV-4 patients, the association of IL28B polymorphism with response to treatment or liver disease severity. METHODS: This study included 164 HCV-4 patients from different ethnic groups (Egyptian, European, and Sub-Saharan African). Among these patients, 82 were studied for response and 160 for disease severity. Free DNA extracted from all the 164 patient's serum samples was analyzed by direct sequencing of the SNP rs12979860 of IL28B. Genetic and bio-clinical features from patients having sustained virological response (43 SVR patients) and from those who did not respond to treatment or had a relapse after the end of the treatment (39 NR patients) were compared. IL28B polymorphism was compared between the 78 patients with mild fibrosis (Metavir score F0-F1) and the 82 with advanced fibrosis (F2-F4). RESULTS: Our data showed a better treatment response rate of the C allele of the IL28B gene SNP rs12979860 (p=0.0008). The response rates were 81.8%, 46.5%, and 29.4% for genotype CC, CT, and TT, respectively. No significant relationship was found between rs12979860 and the severity of the disease. CONCLUSIONS: The SNP rs12979860 is strongly associated with SVR in patients infected with HCV-4, but not with liver disease severity. Analysis of IL28B genotype might be used to guide treatment for these patients.

Twelve weeks posttreatment follow-up is as relevant as 24 weeks to determine the sustained virologic response in patients with hepatitis C virus receiving pegylated interferon and ribavirin.

UNLABELLED: A sustained virologic response (SVR) in patients with chronic hepatitis C receiving pegylated interferon (PEG-IFN) plus ribavirin is defined as undetectable serum HCV-RNA at 24 weeks (W+24) posttreatment follow-up. Viral load outcome in patients with virological relapse (VR) has not been explored. This study evaluated whether the assessment of serum HCV-RNA 12 weeks (W+12) after the end of treatment was as relevant as W+24 to evaluate SVR in 573 patients who received combination PEG-IFN and ribavirin and had a virological response at the end of treatment. Serum HCV-RNA was measured, using a new assay based on transcription-mediated amplification (TMA) with a lowest detection limit of 5-10 IU/mL, at W+12 and W+24 after the end of treatment. VR was defined as reappearance of detectable HCV-RNA at W+24 posttreatment follow-up. The positive predictive value (PPV) of undetectable serum HCV-RNA at W+12 was evaluated to identify patients with SVR, and the viral load outcome was measured in relapse patients. At the W+24 posttreatment follow-up, 408 (71%) patients had an SVR, 181 (71.2%) were treated with PEG-IFNalpha-2a and ribavirin, and 227 (71.1%) were treated with PEG-IFNalpha-2b and ribavirin. At W+12, serum HCV-RNA was undetectable in 409 patients, and 408 patients were SVR (PPV 99.7%, 95% confidence interval 99.1-100). In relapse patients, serum HCV-RNA levels were 5.623 +/- 0.748, 4.979 +/- 0.870, and 5.216 +/- 0.758 log(10) IU/mL at baseline, W+12, and W+24, respectively. CONCLUSION: Our results show that the assessment of serum HCV-RNA 12 weeks after the end of treatment, using the highly sensitive TMA assay (PPV 99.7%), is as relevant as after 24 weeks to predict SVR and make decisions on the management of treated patients, suggesting a new definition for SVR.

High predictive value of early viral kinetics in retreatment with peginterferon and ribavirin of chronic hepatitis C patients non-responders to standard combination therapy.

BACKGROUND/AIMS: To evaluate the efficacy of peginterferon alfa-2b and ribavirin in unselected consecutive patients with chronic hepatitis C, treated outside of trials, who were relapsers or non-responders to interferon and ribavirin combination. METHODS: One hundred and fifty-four patients were evaluated. There were 101 non-responders and 53 relapsers to standard combination therapy. Patients were retreated with peginterferon alfa-2b 1.5 microg/kg/wk plus ribavirin 1000-1200 mg/day during 48 weeks. RESULTS: Forty-four patients (28.6%) achieved sustained virological response (SVR). Rapid (week 4) and early (week 12) virological response had high negative predictive values of SVR (94% and 97%, respectively); however positive predictive values were relatively low (52% and 49%, respectively). Relapsers had higher SVR rates (58.5%) than non-responders (13%) p<0.0001. In non-responders, SVR raised to 50% in patients with genotype non-1 and mild or moderate fibrosis. In multivariate analysis, predictors of SVR were: relapse after interferon plus ribavirin combination, mild or moderate fibrosis, genotype non-1 and baseline viral load <2 million copies/ml. CONCLUSIONS: Relapsers to interferon plus ribavirin therapy, and non-responders with genotype non-1 and mild or moderate fibrosis, achieved a relatively high SVR rate following retreatment with peginterferon plus ribavirin. Early viral kinetics had a high negative predictive value of SVR.