Nermine Ahmed Ehsan

Khat-induced liver injuries: A report of two cases.

Khat is consumed for recreational purposes in many countries, including Yemen, where >50% of adults chew khat leaves regularly. A wide spectrum of khat-induced liver injuries has been reported in the literature. Herein, we report two patients with khat-induced liver injury. Both patients clinically presented with acute hepatitis, one of whom showed radiological evidence of hepatic outflow obstruction. Based on the histological tests, both patients had acute hepatitis, which indicated drug-induced liver injury (DILI) on a background of chronic hepatitis and portal fibrosis; of the two, one presented with symptoms of immune-mediated liver injury.

Impact of nitazoxanide on sustained virologic response in Egyptian patients with chronic hepatitis C genotype 4: a double-blind placebo-controlled trial.

Background Nitazoxanide, approved for the treatment of Cryptosporidium parvum and Giardia lamblia, was found to inhibit hepatitis C virus replication. Aim The aim of this study was to assess the impact of nitazoxanide as an add-on therapy to pegylated interferon &agr;-2a and ribavirin on sustained virologic response (SVR) in patients with chronic hepatitis C. Patients and methods A total of 200 patients with chronic hepatitis C were enrolled in the study, assigned randomly in a 1 : 1 ratio to two groups: group A (placebo group) and group B (nitazoxanide group). Five patients withdrew from the study after they signed the consent form. A total of 195 patients were evaluated: 97 patients in group A versus 98 patients in group B at a dose of 500 mg twice daily. Placebo and nitazoxanide were administered as an add-on therapy to pegylated interferon &agr;-2a plus ribavirin following a 12-week lead-in phase. SVR was evaluated. Statistical analysis was carried out using the SPSS software. Results The mean age of the patients in group A was 46.5 versus 45.7 years in group B. In group A, 85 out of 97 (87.6%) patients were men and in group B, 84 out of 98 (85.7%) patients were men. In group A, 59 out of 97 (60.82%) patients achieved an SVR versus 57 out of 98 (58.16%) patients in group B (P=0.70); this difference was not significant. Conclusion Our data did not show any significant impact of nitazoxanide on SVR.

The Role of Monocyte/Macrophage and CXCR3 in Differentiation between Recurrent Hepatitis C and Acute Cellular Rejection Postliver Transplantation

Objective Liver transplantation (LT) is the recommended treatment for patients with advanced liver disease and cirrhosis in all guidelines, mostly as a complication of HCV. The distinction between reinfection of the graft with HCV and acute cellular rejection (ACR) is essential because they are managed differently. Hepatic macrophages, which can either arise from circulating blood-derived monocytes (BDM) or from resident tissue Kupffer cells, are central in the pathogenesis of chronic liver injury. The aim of this work was to evaluate whether the origin of macrophages and the immune mediator CXCR3 could help in differentiating between acute recurrent HCV and ACR after liver transplantation. Methods Twenty-nine cases of recurrent hepatitis C and 26 cases of ACR were included in this study. The expression of CD 68 (macrophage marker), CD11b (BDM marker), and CxCR3 in the postliver transplant biopsy using immunohistochemistry was determined. Results CD11b expression highlighting macrophages of BDM origin was in favor of recurrent hepatitis C (P < 0.001) than in ACR (P = 0.44), while CXCR3 expression by hepatocytes was in favor of ACR (P = 0.001). Conclusion Macrophage infiltrating liver tissue post LT can distinguish between ACR by upregulation of CXCR3 and recurrent hepatitis C by predominant CD11b.

Sarcoidosis-Lymphoma Syndrome presenting by severe Cholestatic Hepatitis

Severe cholestatic hepatitis is an uncommon presentation of either sarcoidosis or Hodgkin lymphoma. Sarcoidosis lymphoma syndrome is a rare disorder with sarcoidosis heralding the onset of lymphoma. Here we report a case of coexisting sarcoidosis-Hodgkin’s lymphoma syndrome presenting with severe cholestatic hepatitis.

Congenital Hepatic Fibrosis (CHF): A Report of Two Cases and an Overview

Congenital hepatic fibrosis is a rare, mostly autosomal recessive disorder that belongs to the group of diseases known as fibrocystic hepatic disorders. The fibrocystic hepatic disorders include Caroli’s disease, Von Meyenburg complex (multiple biliary hamartomas) and polycystic liver diseases. Disordered maturation of the ductal plates representing the embryonic skeleton of the intrahepatic biliary ducts had been acknowledged as ductal plate malformations (DPMs). These DPMs are portraying the pathogenetic background for the fibrocystic hepatic disorders. CHF had mostly been described in the context of autosomal recessive polycystic kidney disease. Mutations of the polycystic kidney and hepatic disease 1 (PKHD1) gene have been documented in ARPKD/CHF. Fibrocystin; a transmembrane protein encoded by PKHD1 gene, is located in the renal tubular and bile duct epithelial cells and thought to be important in tubulogenesis and the three-dimensional ductal structure. Fibrocystin had been found to be lacking on the inheritable combined biliary-renal disorders.

Evaluation of the Role of Liver and Splenic Transient Elastography in Chronic Hepatitis C Related Fibrosis

Background: Liver fibrosis is common consequence of chronic HCV infection. Noninvasive assessment is still evolving. Aim: Evaluate role of liver stiffness measurement (LSM), spleen stiffness measurement (SSM) and their combination (CLSM) using FibroScanTM in assessment of liver fibrosis in CHC patients. Methods: 420 CHC patients and 40 healthy controls included.Liver, renal function tests, CBC and INR done. Liver biopsy done for all of them except if contraindicated. Fibrosis was graded by Metavir score. Abdominal ultrasonography was done before the FibroScanTM and the liver biopsy. LSM, SSM, and CLSM had doneusing FibroScanTM in the supine position after 6-8 hours fasting.The patient were classified into mild fibrosis (F1-F2, n=248) and significant fibrosis (F3-F4, n=172) group. Results: There were significant difference (p=0.001) between patients with mild fibrosis (F1-F2) versus patients with significant fibrosis (F3-F4) regarding; the age (35.06 ± 8.63 vs 43.71 ± 7.97 years), serum bilirubin (0.73 ± 0.25 vs 1.26 ± 0.73 mg/dL), serum albumin (4.42 ± 0.32 vs 3.84 ± 0.51 g/dL), platelets (206.81 ±50.55 vs 140.50 ± 53.77×103/μL), platelets spleen ratio (1762.20± 521.26 vs. 1014.64 ± 470.27). Furthermore a significant difference (p=0.001) detected with LSM (6.57 ± 2.62 vs. 23.04± 12.15 kPa), SSM (25.56 ± 5.36 vs 46.19 ± 16.29 kPa), and CLSS (32.13 ± 7.15 vs. 69.23 ± 25.43 kPa) respectively. Thecutoff values of significant fibrosis were 9.15 kPa by LSM (94.8% Sensitivity, 88.3% Specificity, 84.9% PPV, and 96.1.8% NPV), 27.5 kPa by SSM (94.8% Sensitivity, 70.2% specificity,68.8% PPV, and 95.1% NPV) and 40.85 kPa by CLSM (92.4% Sensitivity, 91.1% specificity, 87.8% PPV, and 94.6% NPV). Conclusion: The measurement of liver, spleen stiffness by FibroScanTM or their combination is convenient for liver fibrosis assessment.

Pathogenesis of HCV and Liver Fibrosis

Inspite of the oppressive research, hepatitis C virus (HCV) pathogenesis is still evolving. A new prospectives assembling pothgenic theories of HCV and its related liver fibrosis , would be an additionaladvocate. Reccurrent HCV induced iflamation, hepatic stellate cells activation, along with hepatic progenirator cells proliferation and apoptosis; all together might be portraying the most probable HCV pathogenic pathways.

Impact of clinicopathological parameters in differentiation between acute rejection and recurrent hepatitis C after liver transplantation

Objective The aim of the study was to investigate the impact of clinical and histopathological changes in the liver tissue of acute rejection and recurrent hepatitis C patients after liver transplantation and determine whether they could differentiate between them. Background Hepatitis C virus (HCV) is considered the most common cause of chronic liver disease and may require liver transplantation in advanced stages. Liver transplantation is today a well-established procedure for curative treatment of various inherited and acquired liver diseases, and in many conditions it is the only possible therapeutic strategy. Acute rejection and recurrent HCV infection are the major causes of graft failure in liver transplant patients and differentiation between them is necessary because of different treatment strategies. Patients and methods This retrospective study included liver biopsies from 51 post-transplant patients (25 acute rejection and 26 recurrent hepatitis C patients). Post-transplanted liver biopsies were histopathologically evaluated for portal tract inflammation as regards the extent and nature of the infiltrate, bile duct injury, venous injury, interface hepatitis, and lobular inflammation (spotty necrosis and confluent necrosis). Other pathological findings were also addressed. Demographic, laboratory, and histopathological results were subjected to statistical analysis. Results Clinically, high model for end-stage liver disease score (P < 0.01) and high viremia (P < 0.01) were in favor of recurrent hepatitis C compared with acute rejection. Histopathologically, the two groups differed with regard to the extent and nature of the inflammatory infiltrate, whereas dense infiltrate (grade II and III) was in favor of recurrent hepatitis C (P = 0.02). With regard to the nature of infiltrate, the mean number of eosinophils (P < 0.01), neutrophils (P < 0.05), macrophages (P < 0.01), and immunoblasts (P < 0.01) was higher in acute rejection compared with recurrent hepatitis C. Presence of bile duct injury(P = 0.001), vascular injury (P = 0.001), and perivenular necrosis(P = 0.001) was in favor of acute rejection, whereas the presence of interface hepatitis (P = 0.001), fibrosis (P = 0.001), and steatosis (P = 0.001) was in favor of recurrent hepatitis C. Conclusion The current study demonstrated that discrimination between acute rejection and recurrent hepatitis C in the setting of post-liver-transplantation could be possible on the basis of clinical data (the value of model for end-stage liver disease score and the degree of HCV viremia) and several histopathological parameters.

The impact of clinicopathological parameters in predicting response to pegylated interferon and ribavirin in chronic hepatitis C patients

Objectives This study aimed to investigate the impact of clinical and histopathological changes in liver tissue of responders and nonresponders to standard pegylated interferon (Peg-IFN) and ribavirin (RBV) therapy and to determine whether they could predict treatment outcome or not. Background Hepatitis C virus (HCV) infection is a major health problem worldwide. Combination therapy of Peg-IFN and RBV has been recognized as a standard treatment for HCV infection. Unfortunately, this standard therapy produces a sustained virological response in only 50% of HCV-infected patients. Clinical and histological findings may play a role in predicting response to standard Peg-IFN/RBV therapy. Patients and methods This retrospective study included 64 patients with chronic HCV who were treated with Peg-IFNa/RBV. According to their response to treatment, they were classified into responders ( n = 34) and nonresponders ( n = 30). Pretreatment liver biopsies were evaluated histopathologically for necroinflammatory grade and fibrosis stage according to the modified Ishak and Metavir scoring systems for chronic hepatitis. Other pathological findings were also reported. Demographic, laboratory, and histopathological results were subjected to a statistical analysis. Results The current study showed that the age of the patients ( P = 0.003), sex ( P = 0.027), and serum a-fetoprotein level ( P = 0.046) were the parameters that showed a statistically significant difference between responders and nonresponders to interferon therapy. However, the grade of necroinflammation, stage of fibrosis as well as other pathological changes did not show a statistically significant difference between both groups. Conclusion The current study showed that young age, female sex, and the baseline serum level of a-fetoprotein are the parameters that favored response to interferon and RBV therapy in chronic HCV Egyptian patients, whereas histopathological changes played no role in predicting response to treatment.