Entecavir 1 mg versus combined lamivudine/adefovir dipivoxil in chronic HBV Egyptian patients resistant to LAM monotherapy, non-randomised controlled study

The development of antiviral-resistant mutations with long-term treatment remains a major concern in the treatment of chronic hepatitis B virus [HBV] infection. The study aimed to compare the therapeutic efficacy of entecavir 1 mg versus combined lamivudine/adefovir dipivoxil [Lam/Adv] in chronic HBV patients resistant to lamivudine monotherapy. This study included two groups of lamivudine-resistant patients who received lamivudine 100 mg for 1-3 years. Group 1 was composed of 25 cases [52% HBeAg+ve] who received combined Lam/Adv, and group 2 was composed of 13 patients [30.8% HBeAg+ve] who received entecavir 1 mg. Pre-enrolment assessment included biochemical, serological and quantitative HBV-DNA testing as well as HBeAg and hepatitis B envelope antibody [HBeAb] assessment. Evaluation was done at 3, 6, 12, 24 and 36 months of treatment by the same parameters. Hepatitis B surface antigen and antibody [HbsAg and HBsAb] were assessed after each year of treatment. At the end of 36 months of treatment, 16 cases [69%] in group 1 completed the study period, versus 13 [100%] in group 2. Two cases in group 1 underwent HBeAg seroconversion, accompanied by HBV-DNA undetectability, at 6 and 12 months, respectively; no cases were seroconverted in group 2. Both treatments achieved improvement in alanine aminotransferase [ALT], bilirubin and alpha-foetoprotein equally at the end of the study. HBV-DNA undetectability was better achieved in group 2 when compared to group 1. HBeAg seroconversion was only achieved in two cases in group 1, whereas no cases lost HBeAg in group 2. None of our cases achieved HbsAg seroconversion or loss at the end of the study period. The entecavir I-mg monotherapy group achieved better HBV-DNA undetectability starting at 3 months of treatment when compared to the Lam/Adv group; however, both lines of treatment showed almost similar results over the rest of the study period. HBeAg seroconversion was only achieved in two cases in the combined Lam/Adv group, whereas no cases lost HBeAg in the other group

Response and seroconversion rates among HBeAg-positive chronic HBV Egyptian patients treated with peginterferon alpha 2a [Pegasys], a single-centre experience

We aimed to evaluate the therapeutic efficacy of pegylated interferon alpha- 2a 180 micro g as a treatment for hepatitis B 'e' antigen [HBeAg]-positive genotype D chronic hepatitis B patients. Thirty patients attending the outpatient clinic at the National Hepatology and Tropical Medicine Research Institute were treated with peg.interferon alpha-2a [180 micro g] weekly for a period of 48 weeks. Pre-enrolment assessment was performed through biochemical, serological and quantitative HBV DNA testing. Liver biopsy was performed in all patients. Evaluation was done at weeks 12, 24 and 48 of treatment by liver enzymes, complete blood count [CBC], HBeAg /HBeAb and quantitative HBV DNA testing. At the end of 48 weeks of treatment only three cases [10%] of the study population showed HBeAg seroconversion and an undetectable HBV DNA level. None of responders exhibited hepatitis B surface antigen [HbsAg] loss. There were five [16.7%] primary non-responders, four [13.3%] relapses, four [13.3%] cases flared at week 12, and 14 [46.6%] cases who were non-responders. No specific predictors of response could be identified among patients. One year of peg. interferon alpha-2a 180 microgm weekly led to HBeAg seroconversion and an undetectable HBV DNA level in 10% of cases. Considering the privilege of a finite duration of treatment, tailoring of treatment and proper patient selection is of great importance in considering this therapy as a first line of treatment among HBeAg-positive chronic HBV Egyptian patients

Hepatic expression of the proliferative marker Ki-67 and cell cycle p53 protein in chronic hepatitis C [a histopathological and immunohistochemical study]

To evaluate hepatic expression of the nuclear proliferative marker Ki-67 and the cell cycle marker p53 oncoprotein in chronic hepatitis C in relation to the advanced stages of liver fibrosis in HCV positive Egyptian patients. Paraffin-embedded liver biopsy specimens were studied from 21 untreated patients with chronic HCV infection. All patients were HCV antibody positive, as determined by a commercially available enzyme-linked immunosorbent assay kit. Patients having other etiologies for chronic liver disease including HBV infection were not included in this study. Liver biopsies were obtained percutaneous. All biopsies were fixed in formalin, embedded in paraffin, and sectioned by microtome with a thickness of 5 ?m. Routine specimen processing involved staining slides with hematoxylin and eosin [5 levels], Masson's trichrome stain [5 levels], for a total of 10 levels per specimen All levels were screened. All specimens were examined by two pathologists, and classified by consensus for all abnormal histological findings. The histological activity index [or histological grade] was determined using Ishak grading scheme22 expressed as a semiquantitative score for portal inflammation [0-4], lobular activity sporadic lytic foci [0-4] and parenchymal confluent necrosis [0-6], and piecemeal necrosis[0-4]. The extent of fibrosis [or histological stage] was determined using Ishak score [0-6]. Steatosis was scored according to Keliner et al 2005, from grade 0 to 3; where S0 = no steatosis or less than 5% [low or medium power evaluation] of parenchymal involvement by fatty changes, S1 [mild] = 5%-33%, S2 [moderate] = >33%-66% and S3 [severe] > 66% of the hepatocytes are involved by fatty changes. Expression of p53 and Ki67 were determined by immunohistochemistry, using avidin-biotin-peroxidase. Liver histology: The studied group [n = 21] involved 16 males and 5 females [male to female ratio 3.3:1]. The histopathological findings of HCV infection, including portal lymphoid infiltration, periportal piecemeal necrosis, lymphocyte infiltration of the lobules, hepatocellular necrosis, steatosis and fibrosis, were studies. The age ranged from 31 to 59 years old with mean of 44.86 +/- 8.74, males 76.2%, females 23.8% .P53 expression was positive in 52.4% and negative in 47.6%. cytoplasmic localization dominated over nuclear expression. Ki 67 was negative in 81% of cases and positive in19% of cases, all cases in stage 6 were positive for p53 while there were no difference in the other stages of fibrosis, and this relation was statistically significant. There was no relation between the grade of necro-inflammation and the expression of p53, and this result was statistically non significant.There was a relation between the percent of steatosis and the expression of p53 as percent of positivity increases with the increase of the percent of steatosis, and this result was statistically significant using independent sample t test and regression test.All negative cases for P53 have negative Ki67 but this rule is not applied on positive cases for P53, and this relation was not statistically significant. There was no relation between the grade of necro-inflammation and the expression of Ki67, and this result was statistically non significant. Hepatic expression of the nuclear proliferative marker Ki-67 and the cell cycle marker p53 oncoprotein in chronic hepatitis C in relation to advanced stages of liver fibrosis in HCV positive patients are expressed in a considerable present of cases which should be cansdidates for follow up for early detection of hepatocellular carcinoma

Study of IL-10 and Il-18 levels in relation to different stages of liver fibrosis in Egyptian chronic hepatitis C infected patients

Most acute and chronic liver diseases are characterized by inflammatory processes with enhanced expression of various pro-and anti-inflammatory cytokines in the liver. These cytokines are the driving force of many inflammatory liver disorders often resulting in fibrosis and cirrhosis. This work aimed to identify the role of serum IL-10 and IL-18 in the pathogenesis of chronic hepatitis C in different grades and stages of HCV patients and correlate their levels to the necroinflammatory grade and stage of fibrosis. A prospective study on [55] HCV infected patients 43 males and 12 females, their age ranged from 20 to 55 years with a mean of 41.3 year and [20] age and sex matched control [HCV-ve] from National Hepatology and Tropical Medicine Research Institute clinics, from whom consents were taken. The patients included in this study were those originally enrolled on protocol for treatment [interferon + ribavirin] where liver biopsy was required for eligibility of treatment according to the approved protocol. 5ml of blood was collected at the same day of biopsy for assessment of IL-10 and IL-18 levels in blood [ELISA technique]. Serum level of IL-18 was significantly higher in patients with chronic HCV [126.80 +/- 11.76 pg/ml] as compared to control group [45.97 +/- 5.26 pg/ml]; the level was even higher in cases with hepatocellular carcinoma [HCC]. IL-18 levels were significantly higher in patients with early fibrosis than in patients with advanced fibrosis., it was also higher in case with minimal to mild necro-inflammatory grade than in cases with moderate to severe grades, but that difference was not significant. As regards serum IL-10, the level was also higher in patients with chronic HCV [9.24 +/- 1.9 pg/ml] than control group [3.28 +/- 1.81 pg/ml]. Serum IL-10 level was significantly lower in early than advanced stages [P=0.04]. When classifying cases according to necro-inflammatory grade the IL-10 level was lower in minimal/mild cases than moderate /severe cases, but this difference wasn't statistically significant. Serum concentrations of IL-10 and IL18 could be correlated to the histopathological spoilage of the liver as they can predict the stage of fibrosis and hence can be used as indirect markers to assess the severity of liver disease in HCV infected patients. They can also be used as complementary markers in HCC patients

Laparoscopic cholecystectomy in liver cirrhosis patients: an Egyptian experience

Cirrhosis represents a common histologic pathway for a wide variety of chronic liver diseases. Hepatitis C virus [HCV] is the most important cause of liver cirrhosis in Egypt. Although cirrhosis has been regarded as a relative contraindication for laparoscopic cholecystectomy [LC] due to bleeding complications and subsequent liver failure, several reports support the safety of LC in selected patients. A prospective study to evaluate the efficacy and safety of laparoscopic cholecystectomy in cirrhotic patients. 177 hepatitis C positive patients with chronic calculus cholecystitis, scheduled for cholecystectomy, were included in this study between Jan. 2009 and Mar. 2010 where laparoscopic cholecystectomy was performed to them after fulfilling the inclusion criteria. Two risk stratifications schemes have been used to estimate the perioperative risk of patients with cirrhosis; the Child-Turcotte-Pugh [CTP] score and the Model for End-stage Liver Disease [MELD] score. 177 liver cirrhosis patients with chronic calcular cholecystitis scheduled for LC represented the population of this study. All patients were HCV positive patients with Child A class cirrhosis and MELD score < 9. Mean surgical time: 55 minutes, surgical difficulty varied between average in 64%, moderate in 28% and extensive in 8% where 3.4% needed conversion to open cholecystectomy. Postoperative follow up of all cases was multidisciplinary approached by both surgeons and hepatologists. All cases showed sound recovery confirmed by abdominal sonar to exclude intra-abdominal collections and application of both CTP and MELD scores, where all cases kept class A Child score and MELD score < 9. Laparoscopic cholecystectomy is a safe procedure for hepatitis C positive cirrhotic patients when established risk stratifications systems such as CTP and MELD scores are used for evaluation

Adult onset diabetes mellitus in hepatitis C virus infection

There is growing evidence to suggest an association between hepatitis C virus [HCV] infection and diabetes, two common disorders that cause devastating long-term complications in a signficant number of patients. Several reports have found a high prevelance of HCV infection among diabetic patients. Additionally, a high prevelance of diabetes has also been reported in HCV- infected patients in comparison with other liver diseases. On the other hand some authors have not observed an association between HCV infection and diabetes, while others found that diabetes mellitus type 2 occurred with increasing frequency among patients with hepatitis C and this was associated with family history of diabetes mellitus. HCV seropositivity among patients with type 2 diabetes mellitus is higher than in the general population. Aim of work: Is to study the association between HCV infection and diabetes mellitus. This study included 410 consecutive patients with chronic liver diseases. They were attending the outpatient clinic of the National Hepatol-ogy and Tropical Medicine Research Institute and Aswan Teaching Hospital in the period from May 2004 to July 2005. Their ages ranged from 20-60 years. They were 304 males and 106 females. Patients were classified into 3 groups. Group A consisted of 220 non cirrhotic patients with HCV +ve. Group B consisted of 110 cirrhotic patients with HCV +ve. Group C consisted of 80 patients all are -ve for HCV Ab. Type2 diabetes was diagnosed as a fasting plasma glucose level [7.0mmol/L [126 mg/L] or on treatment with oral hypoglycaemic agents. It was found that distribution of diabetes mellitus between group A and B [HCV +ve] and group C [HCV Ab -ve] were 21.21%, 27.27%, 12.5% in respect order. There were no significant difference between AST levels, ALT level, BMI and diabetes mellitus. we have found an association between diabetes mellitus and HCV infection. It remains to be determined whether an HCV infection leads to diabetes mellitus or vice versa

Effect of bifendate [DDB] on normal and diseased liver of adult male albino rats: an experimental study

Background: fructus Schizandrae Sinensis bail, a traditional Chinese medicine, has been shown to lower the elevated serum level of liver enzymes of patients suffering from chronic active hepatitis. A synthetic derivative compound of Schisandrian, Dimethyl Diphenyl Bicarboxylate [DDB] is now used widely in clinical fields as a hepatoprotective drug. Thus it is important to know whether DDB has a beneficial effect on damaged liver or not

Objective: to evaluate the protective effect of DDB on induced liver tissue injury in rats

Design: experimental study

Setting: national Hepatology and Tropical Medicine Research Institute. The study was conducted from October [2004] to February [2005]

Materials and methods: 120 male albino rats aged 6-8 weeks, weight 150-200g were grouped in six groups, 20 rats per group. Group 1 received food and water only, group 2 received food, water and DDB intragastric 6mg/kg daily for 12 weeks, group 3 received 20% ethanol instead of water, group 4 received 20% ethanol instead of water plus DDB, group 5 received thioacetamide [TAA] in a dose of 200mg/kg body weight intraperitoneal injection, group 6 received thioacetamide plus DDB at the same dose of the above group. At the end of the trial, blood samples were taken from all groups for biochemical analysis. Liver tissue excised from each rat was fixed in 10% neutral formalin, embedded in paraffin, and stained with Hematoxylin and Eosin, as well as Masson's trichome stain, for evaluation of hepatic injury and/or fibrosis

Results: statistical elevation of serum hepatic enzymes was noticed in rats received alcohol, Thioacetamide and alcohol + DDB [groups III, V and IV respectively] compared to the corresponding control [P= 0.000]. On the other hand, administration of DDB to TAA treated group [group VI] induced significant improvement of liver function tests compared to other groups [P= 0.000]. Histopathologically, the control livers showed normal lobular architecture without any pathological changes. Liver sections of animals administered alcohol, TAA respectively showed chronic inflammatory reaction, fat accumulation, hepatic parenchymal necrosis and/or hepatic fibrosis. Administration of DDB resulted in improvement of the pathological changes induced by TAA [group VI], but not that induced by alcohol [group IV]

Conclusion: our results revealed that DDB has antitoxic effect against TAA and ameliorates the dangerous effect on the liver parenchyma, while it has no beneficial effect on alcoholic liver disease

Study of pancreatic islet cell function in cirrhotic patients due to hepatitis C virus

The liver is of key importance in the proper functioning of most of the endocrine system. It is a major organ for metabolic degradation of many hormones. In chronic liver disease, there is a change in the concentrations of the main pancreatic hormones. Is to study the pancreatic islet cell secretory function of insulin, C-peptide, somatostatin and glucagon hormones in non ascitic non diabetic cirrhotic HCV patients by measuring these hormones basally and after intravenous glucose load with different concentrations at several intervals in order to evaluate the pattern of endocrine pancreatic hormonal response at increasing glucose concentration. The case-control study included 25 non ascitic non diabetic patients with cirrhosis due to HCV infection; their ages ranged from 28 to 60 years. They were selected from outpatient clinic of the National Hepatology and Tropical Medicine Research Institute [NHTMRI] in the period from June 2004 to January 2005. Fifteen age and sex matched apparently healthy control subjects from the same area were also included in the study. Assessment of pancreatic islet cell function was done by assaying insulin, C-peptide, somatostatin and glucagon hormones. All hormones were determined by radioimmunoassay [RIA] for both patients and controls. Basal serum insulin, basal plasma somatostatin and basal plasma glucagon levels were significantly higher than that of the control group [p<0.05], while basal serum C-peptide was significantly lower than that of the control group [p<0.05]. After intravenous glucose load with the different concentrations 5%, 10% and 25%, serum insulin level showed a significant increase than that of the controls [p<0.05]. while other hormones showed no significant difference as compared to the control group [p>0.05]. The study suggests pancreatic islet cell functional defects with liver cirrhosis due to HCV infection