Ehab E. Abdel-Khalek

Systemic inflammatory response syndrome in patients with liver cirrhosis.

BACKGROUND AND STUDY AIMS Patients with liver cirrhosis present an increased susceptibility to the systemic inflammatory response syndrome (SIRS), which is considered the cause of hospital admission in about 10% of patients and is present in about 40% of those admitted for ongoing complications. We tried to assess the prevalence of the SIRS with the possible effects on the course of the disease during hospital stay. PATIENTS AND METHODS Two hundred and three patients with liver cirrhosis were examined and investigated with close monitoring during hospital stay. The main clinical endpoints were death and the development of portal hypertension-related complications. RESULTS Eighty-one patients met the criteria of SIRS (39.9%). We found significant correlations between SIRS and jaundice (p=0.005), bacterial infection (p=0.008), white blood cell count (p<0.001), low haemoglobin concentration (p=0.004), high serum creatinine levels (p<0.001), high alanine aminotransferase levels (p<0.001), serum bilirubin levels (p<0.001), international normalised ratio (p<0.001), serum albumin levels (p=0.033), high Child-Pugh score (p<0.001). During the follow-up period, 26 patients died (12.8%), 15 developed portal hypertension-related bleeding (7.3%), 30 developed hepatic encephalopathy (14.7%), and 9 developed hepatorenal syndrome type-1 (4.4%). SIRS showed significant correlations both to death (p<0.001) and to portal hypertension-related complications (p<0.001). CONCLUSION The systemic inflammatory response syndrome occurs in patients with advanced cirrhosis and is associated with a bad prognosis.

Paraoxonase1 55 and 192 gene polymorphisms in an Egyptian population with diabetic complications

Type 2 diabetes is a polygenic disease characterized by interaction of environmental and genetic factors. The paraoxonase 1 gene (PON1) 55 and 192 polymorphisms have been reported to be associated with type 2 diabetes and its complications. Our aim is to study the PON1 55, 192 gene polymorphisms and enzyme activity in type 2 diabetic Egyptian population with complications. 100 type 2 diabetic patients with complications (34 with cardiac and 66 with microvascular complications (neuropathy, retinopathy and/or nephropathy)). This was in addition to 100 healthy control subjects of matched age and sex were taken. PON1 55 L⁄M and 192 Q⁄R gene polymorphisms and PON1 enzyme activity serum levels were detected. The LL genotype of PON1 55 polymorphism and QR and QQ genotypes of PON1 192 polymorphism were more frequent among the patients with diabetic complications. The PON1 enzyme activity levels were lower among the diabetic patients than in control subjects. PON1 55 and 192 polymorphisms and enzyme activity seems to be related to diabetic complications in this population.

Circadian pattern of acute variceal bleeding among cirrhotic Egyptian patients

BackgroundLiver cirrhosis is the most common cause of portal hypertension which may end in serious bleeding from gastro-esophageal varices. Recent studies have demonstrated a daily pattern of acute upper gastrointestinal bleeding in patients with liver cirrhosis evidenced by one or two peaks throughout the day.AimThe assessment of the circadian rhythm of acute variceal bleeding with the possible participation of circadian changes of the fibrinolytic parameters.Patients and methodsThe study included 264 patients with liver cirrhosis and upper gastrointestinal bleeding in addition to 20 healthy subjects as a control group. A series of hemostatic tests and parameters including prothrombin (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib), Factors II, V, VII, IX, X, XI, platelets counts and fibrinolytic parameters assessement were completed in 60 patients in addition to the control group. The fibrinolytic activity was assessed by estimation of plasminogen, tissue plasminogen activator antigen (tPA: Ag) and plasminogen activator inhibitor antigen (PAI-1: Ag) at hour 09:00 and hour 17:00. The hemostatic tests and liver function tests were assessed once at hour 09.00.ResultsWe observed statistically significant two time peaks of upper gastrointestinal bleeding at hour 04:00 and hour 17:00 with a peak of the fibrinolytic parameter, tissue plasminogen activator antigen, with the night peak of bleeding. A significant correlation between the levels of fibrinolytic parameters and hemostatic factors as well as liver function tests were detected.ConclusionThere are two time peaks of upper gastrointestinal bleeding with a temporal association between the night peak and a relative hyperfibrinolytic state.

Predictors of hepatitis C virus recurrence after living donor liver transplantation: Mansoura experience

BACKGROUND AND STUDY AIMS Hepatitis C virus (HCV)-related cirrhosis is the leading cause of liver transplantation (LT). All patients who undergo LT with detectable serum HCV-RNA experience graft reinfection, which is the most frequent cause of graft loss and death in these patients. We estimated the rate of HCV recurrence and evaluated the current therapeutic regimens. PATIENTS AND METHODS The records of consecutive 325 living donor LT (LDLT) surgeries performed between May 2004 and August 2014 were retrospectively analysed; 207 of them were followed-up throughout the study. Clinical, laboratory, radiological and histopathological examinations were performed thoroughly. Patients received treatment in the form of either pegylated interferon (PEG-IFN) or sofosbuvir, both in combination with ribavirin. RESULTS In total, 90.3% of recipients who were transplanted because of HCV-related end-stage liver disease experienced recurrence due to the virus. The donor age was older in the HCV recurrent group versus the non-recurrence group (28.7±7.1 versus 22.6±2.6years: p≤0.001), warm ischaemia time was prolonged (46.1±18.1 versus 28.6±4.1min: p≤0.001), median cold ischaemia time was 40.0 (10-175) versus 22.5 (15-38) min (p≤0.001) and basal PCR was 414000 (546-116000000) versus 10766 (1230-40000) (p≤0.001). Sustained virological response was achieved in 95.4% of patients treated with a combination of a fixed daily dose of 400mg sofosbuvir with ribavirin and in 65.1% of those who were treated with PEG-IFN with ribavirin. CONCLUSIONS Older donor age and prolonged warm ischaemia time are independent predictors of HCV recurrence after LDLT, and early treatment with the direct-acting sofosbuvir is helpful in resolving the problem of post-LT HCV recurrence.

Evaluation of transarterial chemoembolization in treating hepatocellular carcinoma: a single center experience

Background Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death, and its increasing incidence worldwide is a reason for concern. The evolving field of locoregional therapies continues to provide novel therapeutic options that can be used in place of, or in addition to, surgical approaches. Aim The aim of this study was to determine the efficacy and safety and evaluate the clinical outcome and survival benefits of transarterial chemoembolization (TACE) in patients with HCC. Methods A total of 64 patients with unresectable HCC met the inclusion criteria for the study, which was carried out at a single tertiary medical center. All patients underwent TACE and 59 of them completed the study. Results HCC was more frequently encountered among men compared with women. The mean age for diagnosis was 56.6±6.8 years. A total of 33 patients showed complete response (55.9%) and partial response was reported in 12 patients (20.3%), whereas a lack of response was reported in 14 patients (23.7%). The initial median serum &agr; fetoprotein level was lower among complete responders compared with partial responders. Moreover, there was a greater reduction in the level of &agr; fetoprotein in complete responders compared with partial responders. The negative impact on the liver function tests was in the form of a significant decrease in the levels of serum albumin (P=0.005), a significant elevation in the levels of serum bilirubin (P=0.038), and a prolongation of prothrombin time (P=0.015). The overall survival rate was 69% during the first year, 15.5% during the second year, 8.6% during the third year, and 6.9% during the fourth year. Conclusion TACE can be performed safely and may improve the overall survival for palliative treatment of patients with unresectable HCC.

Predictive value of the adiponectin to leptin ratio for diagnosis of steatohepatitis in patients with nonalcoholic fatty liver disease

Background Differentiation between nonalcoholic steatohepatitis (NASH) and simple steatosis (SS) is critical for proper management. The adiponectin to leptin ratio (A/L) might be of value for the diagnosis of NASH. Aim The aim of this study was to assess the serum levels of adiponectin and leptin and to determine their ratio (A/L) for the diagnosis of steatohepatitis in patients with nonalcoholic fatty liver disease (NAFLD). Materials and methods A total of 46 patients with biopsy-proven NAFLD (25 with NASH and 21 with SS) and 22 controls with matched age, sex, and BMI were included in this study. In all participants, the fasting serum insulin, glucose, liver transaminases, triglycerides, cholesterol, leptin, and adiponectin levels were measured and the Homeostasis Model Assessment (HOMA) index was determined. Results The leptin levels were significantly higher in patients with NASH and in those with SS compared with controls (P1<0.0001). The adiponectin levels were significantly lower in NASH patients compared with controls (P1<0.001). No significant difference in adiponectin levels was found between patients with NASH and those with SS (P>0.05), and there was no difference between those with SS and controls (P>0.05). The mean A/L ratio was significantly lower in NASH patients compared with those with SS and controls (P<0.001 and P<0.0001, respectively). The area under the receiver-operating characteristic curve for the A/L ratio to distinguish between patients with NASH and those with SS was 0.85. At a cutoff value of 0.71, the sensitivity was 80%, specificity was 77%, positive predictive value was 78%, negative predictive value was 79%, and accuracy was79%. In multivariate analysis, both an A/L ratio less than 0.71 and a HOMA index greater than 3 were independently associated with NASH. The leptin levels positively correlated with the HOMA index (r=0.51 and P<0.003) and BMI (r=0.32 and P<0.02). The A/L ratio negatively correlated with the HOMA index (r=−0.6 and P<0.001) and BMI (r=−0.4 and P<0.002). In univariate analysis, fibrosis was significantly associated with age, BMI, hyperglycemia, and serum leptin levels. In the multivariate analysis, age and BMI were independent factors associated with fibrosis. Conclusion The A/L ratio has a good predictive value for the diagnosis of NASH and could be utilized as a noninvasive test for the assessment of liver injury in patients with NAFLD.

Alanine aminotransferase levels in citizens of Nile Delta infected with the chronic hepatitis C virus

Background Approximately 30% of patients with chronic hepatitis C have persistently normal serum alanine aminotransferase (ALT) levels. In most previous studies, the follow-up period of ALT levels did not exceed 12 months. Aims Our objective was to redefine the terms persistently normal alanine aminotransferase (PNALT), persistently elevated alanine aminotransferase (PEALT), and fluctuating alanine aminotransferase (FLUXALT) and to determine the proportion of each group among Nile Delta patients. Methods A total of 348 patients with chronic hepatitis C infection were included. Hepatitis C virus infection was proved by a PCR. We studied an average of 19 ALT measurements for each participant between 2004 and 2007 with a 2-month interval between successive measurements. We defined a patient as having PNALT, PEALT, or FLUXALT when all the 19 ALT levels were normal (<40 IU/l), elevated (>40 IU/l), or did not fit either of the above two categories, respectively, during the 36-month follow-up period. Results Seventy-three patients had PNALT, 157 had PEALT, and 118 had FLUXALT (P<0.001). There were no significant differences between the three groups in age, sex, or BMI. Patients with PNALT were more likely to have Ishak fibrosis scores of equal to or less than 2, whereas those with PEALT were likely to have a score of 2–6 and a third group with FLUXALT a score of 1–5 (P<0.001). Conclusion Twenty-one percent of patients infected with chronic hepatitis C had PNALT and 45% had PEALT, whereas 34% had FLUXALT. Patients with PEALT were significantly more likely to have higher degrees of fibrosis than patients with FLUXALT and both groups had higher fibrosis scores than patients with PNALT.