FibroScan, APRI, FIB4, and GUCI: Role in prediction of fibrosis and response to therapy in Egyptian patients with HCV infection

Background and study aims: Multiple noninvasive methods have been used successfully in the prediction of fibrosis. However, their role in the prediction of response to hepatitis C virus [HCV] antiviral therapy is debatable. The aim of this study was to validate and compare the diagnostic performance of FibroScan, APRl [aspartate aminotransferase [AST]-to-platelet ratio index], FIB4, and GUCI [Goteborg University Cirrhosis Index] for the prediction of hepatic fibrosis and treatment outcome in HCV-infected patients receiving pegylated interferon and ribavirin [PEG-IFN/ribavirin]

Patients and methods: this study included 182 Egyptian patients with chronic HCV infection. They were classified into two groups based on the stages of fibrosis: mild to significant fibrosis [F1-F2] and advanved fibrosis [F3-F4]. The APRI, FIB4, and GUCI scores were calculated before the antiviral treatment. The FibroScan was performed for all patients before treatment

Results: stiffness and FIB4 have greater sensitivity and specificity in detecting advanced fibrosis of 80%, 77% and 88%, 84%, respectively. Based on multivariate regression analysis, FIB4, body mass index [BMI], and alpha-fetoprotein [AFP] level were found to be statistically significant predicators of advanced fibrosis [p-value: 0.000, 0.011, and 0.001, respectively] with odds ratio [OR: 3.184, 1.170, and 1.241, respectively]. With respect to virological response, the stiffness, APRI, FIB4, and GUCI were significantly lower in sustained virological responders. However, these are not good predictors of response to PEG-IFN/ribavirin therapy. AFP was the only statistically significant predictor of response [p = 0.002] with OR of 1.141 in multivariate regression analysis

Conclution: FibroScan and noninvasive scores such as APRI, FIB4, and GUCI can be used as good predictors of liver fibrosis in chronic hepatitis C. However, they are not good predictors of response to PEG-IFN/ribavirin therapy

Effect of androgen and schistosoniicide in murine schistomiasis mansoni: an experimental study

Impotence is aconsistent inability to sustain an erection sufficient for sexual intercourse. Testosterone administration in men with liver cirrhosis improves the sense of well-being, increase serum proteins and reduces edema without serious adverse effects. Oral, alkylated forms of testosterone can create a situation of liver toxicity. There is little evidence that other methods of administration cause liver dysfunction. Most doctors be indecisive on prescribing androgen preparations in patients with liver disease, so this work was designed to study the effect of androgen replacement [injectable form] on the murine diseased liver, and subsequently whether it can be used safely in men with chronic liver disease or not. To evaluate the effect of exogenous injectable androgen and praziquantel on the diseased liver of mice. National Hepatology and Tropical Medicine Research Institute [NHTMRI]. Materials and methods: Forty male mouse [weighing 25-30 g] were infested subcutaneously with Schistosoma mansoni [100 cercariae/animal], and then they were divided into four groups. Mice in the first group were infected only and used as infected control group. Mice of group II and IV were given the Schistosomicide, praziquantel in a dose of 0.3 mg/mouse. Androgen [Sustarion] was injected intramuscularly in a "dose of 0.125 mg/mouse, [three doses, 3 weeks apart] in group III and IV. At the end of the trial all animals were then sacrificed to study histopathologically the possible effects of androgen on the liver tissue. Liver function tests were done in animals of group I, III, and IV, first prior to study and finally by the end of study. Results of assayed liver function tests and histopathological examination were tested for statistical significant association. there were marked elevation of the liver enzymes in mice of group IV compared to the corresponding control [p<0.01] and mice of the third group [p<0.01], which reflect deterioration of hepatic function in those mice received the antibilharzial drug praziquantel. On the other hand there was statistical difference between control group [group I] and androgen treated group III [P<0.05]. Histological examination of liver sections of mice in all groups revealed the presence of typical bilharzial granulomas. The mean diameter of bilharzial granulomas clearly dropped to 283.20 micrometer in group II compared to 392.55 in corresponding control. The difference between these two groups was statistically significant [p=0.0001]. In group III there was no statistical difference in the number of egg granulomas [P>0.05] compared to group I. There was a reduction of granulomas diameter in group III and IV [animals injected with androgen] in comparison to group I [P>0.05 and P<0.01] respectively. Also comparison between the four groups as regards the type of bilharzial granulomas, it is clearly evident that the predominant type of granulomas in the androgen treated groups is the cellular type [38% and 57.1%] in group III and IV respectively and this may reflect the possible beneficial effect of androgen on the diseased liver. Our results clearly indicate that androgen have no deleterious effects on tissues of the diseased liver and hence on liver functions. In conclusion androgen therapy [injectabi form] appears to be safe in the clinical management of erectile dysfunction patients with chronic liver disease

Promising early results for keloid treatment with intralesional colchicine: a clinical and histopathological study

To evaluate the effect ofcolchicine local infiltration in the treatment of keloids. Prospective study. National Hepatology and Tropical Medicine Research Institute [NHTMRI]. In a clinical trial, 14 cases with keloids were treated by local infiltration ofcolchicine. The results were evaluated objectively and subjectively. Lesional biopsy was obtained before and after treatment and examined by light microscopy. Marked reduction of the size of the lesions and decrease of such complaints as itching and erythema were noted. Favorable results were obtained according to the patients in 83.4% and according to the opinion of the medical examiner in 91.7% of cases. Systemic complications of colchicine absorption, i.e. nausea, did not occur in any patient. Histopathological examination of the lesions after colchicine infiltration reveled marked reduction in the density of collagen bundles, which are widely dispersed through out the dermis. intralesional infiltration of colchicine is safe and effective treatment, of keloids

Reproductive effects of human interferon-alpha-2b administration on male albino mice testes. An experimental study

Recombinant human interferon alpha [rh-IFN-alpha] is used therapeutically in malignant disorders and chronic hepatitis. The phenotypic effects of this drug at the structural levels on testicular tissue were hardly ever addressed. Hence, this work was designed in adult male albino mice to study the phenotypic effects of rh-INF-alpha-2b on testicular tissue as well as assessing its effects on serum testosterone and gonadotropins levels. This research was planned to through light on the effects of interferon-alpha-2b [IFN-alpha-2b] on the hypothalamic-pituitary-testicular [HPT] axis of the adult male albino mice. Experimental study. National Hepatology and Tropical Medicine Research Institute [NHTMRI]. The study was conducted from November [2004] to February [2005]. Thirty sexually mature male mice were divided into three groups [10 mice in each group], namely: the control, the experimental and the recovery groups. Mice in the experimental and recovery groups were administered recombinant human interferon alpha intraperitoneally at a dose of 3000 U / mouse weekly for 12 weeks in a volume of 1.0-microliter isotonic normal' saline, then animals in the recovery group were left to recover for a further period of two months. At the end of the experiment, serum concentrations of gonadotropins and testosterone were measured and then all animals were then sacrificed to study histopathologically the possible effects of interferon on the testicular tissue. rh-IFN-alpha-2b induced remarkable decline in the serum levels of both follicle stimulating hormone [FSH] and luteinizing hormone [LH] in mice of the experimental group compared to the corresponding control and mice of recovery group. At the same time, testosterone was moderately increased in the experimental group, and then returned to its normal levels within 2 months after cessation of treatment. Histopathologically, in the experimental group, there were focal thickening of the basement membrane, degenerative changes and clumping of the germinal epithelial cells in the center of seminiferous tubules, partial desquamation of the germinal epithelium from basement membrane, reduction in the germ cell height, partial arrest of maturation and increased number of Sertoli cells. Increased number of leydig's cells and hypervascularity were detected in the interstitial spaces. In the recovery group, there was lessening of the germ cell hypoplasia manifested by restoration of spermatogenic cells and accidental disruption in the basement membrane. Most of the spermatogenic and Sertoli cells restored their polarity, height and maturation. Our results suggest that rh-INF-alpha-2b temporally affects the hypothalamic-pituitary-testicular axis [HPT], both centrally and peripherally [at the testicular level], through the lessening of FSH, LH, raise of testosterone serum levels and direct phenotypic effect on the testicular tissue

Reproductive effects of human interferon-Alpha-2b administration on male albino mice testes. An experimental study

Background: recombinant human interferon alpha [rh-IFN-alpha] is used therapeutically in malignant disorders and chronic hepatitis. The phenotypic effects of this drug at the structural levels on testicular tissue were hardly ever addressed. Hence, this work was designed in adult male albino mice to study the phenotypic effects of rh-INF-alpha-2b on testicular tissue as well as assessing its effects on serum testosterone and gonadotropins levels

Objective: this research was planned to through light on the effects of interferon-alpha-2b [IFN-alpha-2b] on the hypothalamic-pituitary-testicular [HPT] axis of the adult male albino mice

Design: experimental study

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

Materials and methods: thirty sexually mature male mice were divided into three groups [10 mice in each group], namely: the control, the experimental and the recovery groups. Mice in the experimental and recovery groups were administered recombinant human interferon alpha intraperitoneally at a dose of 3000 U / mouse weekly for 12 weeks in a volume of 1.0-microliter isotonic normal saline, then animals in the recovery group were left to recover for a further period of two months. At the end of the experiment, serum concentrations of gonadotropins and testosterone were measured and then all animals were then sacrificed to study histopathologically the possible effects of interferon on the testicular tissue

Results: rh-IFN-alpha-2b induced remarkable decline in the serum levels of both follicle stimulating hormone [FSH] and luteinizing hormone [LH] in mice of the experimental group compared to the corresponding control and mice of recovery group. At the same time, testosterone was moderately increased in the experimental group, and then returned to its normal levels within 2 months after cessation of treatment. Histopathologically, in the experimental group, there were focal thickening of the basement membrane, degenerative changes and clumping of the germinal epithelial cells in the center of seminiferous tubules, partial desquamation of the germinal epithelium from basement membrane, reduction in the germ cell height, partial arrest of maturation and increased number of Sertoli cells. Increased number of Leydig's cells and hypervascularity were detected in the interstitial spaces. In the recovery group, there was lessening of the germ cell hypoplasia manifested by restoration of spermatogenic cells and accidental disruption in the basement membrane. Most of the spermatogenic and Sertoli cells restored their polarity, height and maturation

Conclusion: our results suggest that rh-INF-alpha-2b temporally affects the hypothalamic-pituitary-testicular axis [HPT], both centrally and peripherally [at the testicular level], through the lessening of FSH, LH, raise of testosterone serum levels and direct phenotypic effect on the testicular tissue

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

Effect of anti - cox -z on tumor proliferation, angiogenesis and metastatic potential in induced colon cancer in adult albino rats: an immunohistopathological study

In this study, 60 male albino rats [average weight 100-150 g] were used. They were randomly divided into four groups, each comprised 15 rats: The first group served as a control; rats in the second and third groups were subcutaneously injected with 1,2 dimethylhydrazine [DMH] 20 mg/kg b.w. once a week for 20 weeks as well as rats in the third and fourth groups were orally administered celecoxib 20 mg/kg b.w. daily for 20 weeks. At the end of the trial, all animals were sacrificed to study the possible effects of selective cox-2 inhibitor on induced colon cancer tumor cell proliferation, angiogenesis and migration in the experimental animals. Colons, livers and lungs were taken, put in 10% neutral formalin, processed and stained for histopathological and immunohistopathological study. The tumor incidence in DMH treated group [2nd group] was 100%. Celecoxib + DMH treated group had fewer tumors and less angiogenesis compared with DMH treated group and control group [4th and 1st group]. Also, liver and lung metastasis were less in celecoxib + DMH treated group than the DMH treated group

Protective effect of Allium sativum and Nigella sativa against no-mediated alterations in dimethylhydrazine- induced colon cancer rats

Plasma levels of nitric oxide [NO] and alpha-tocopherol as well as catalase activities in colon and liver tissues were assessed in 1, 2 dimethylhydrazine-induced colon cancer rats. Five groups of male Sprague-Dawley rats were fed the experimental diets supplemented with Allium sativum powder and Nigella sativa seeds [2.5%, 5%] or a mixed dose of both plants [5% of each] for 24 weeks, experimental period. At the fifth week rats were subcutaneously injected with dimethylhydrazine dihydrochloride [DMH] at a dose of 20mg/kg body weight for 20 weeks. Another two groups of rats were fed the basal diet for the same period, the first group designed as negative control group and injected with saline solution while the second group was injected with DMH at the same dose and designed as positive control group. Colon carcinogenesis was accompanied by a significant increase in the level of NO as well as catalase activity and significant decrease in plasma levels of alpha-tocopherol. Only the 5% Allium sativum powder fed group exhibited a significant decrease in NO level. Administration of Allium sativum powder and the mixed dose caused significant decrease in colonic and hepatic catalase activities and significant increase in alpha-tocopherol levels. On the other hand, the effects of Nigella sativa seeds on the measured parameters were non significant. These results were confirmed by the histopathological results that showed low incidence of colon tumors in rats fed 5% Allium sativum powder [17%] and the mixed dose [56%] fed groups. It could be concluded that the promising effect of garlic in DMH-induced colon cancer rats may be mediated through modulation of plasma levels of nitric oxide and alpha-tocopherol as well as tissue catalase activity

Effect of androgen and schistosomicide in murine schistomiasis mansoni: an experimental study

Background: Impotence is a consistent inability to sustain an erection sufficient for sexual intercourse. Testosterone administration in men with liver cirrhosis improves the sense of well-being, increase serum proteins and reduces edema without serious adverse effects. Oral, alkylated forms of testosterone can create a situation of liver toxicity. There is little evidence that other methods of administration cause liver dysfunction. Most doctors be indecisive on prescribing androgen preparations in patients with liver disease, so this work was designed to study the effect of androgen replacement [injectable form] on the murine diseased liver, and subsequently whether it can be used safely in men with chronic liver disease or not

Objective: To evaluate the effect of exogenous injectable androgen and praziquantel on the diseased liver of mice

Setting: National Hepatology and Tropical Medicine Research Institute [NHTMRI]

Materials and methods: Forty male mouse [weighing 25-30 g] were infested subcutaneously with Schistosoma mansoni [100 cercariae/animal], and then they were divided into four groups. Mice in the first group were infected only and used as infected control group. Mice of group II and IV were given the Schistosomicide, praziquantel in a dose of 0.3mg/mouse. Androgen [Sustanon] was injected intramuscularly in a dose of 0.125 mg/mouse, [three doses, 3 weeks apart] in group III and IV. At the end of the trial all animals were then sacrificed to study histopathologically the possible effects of androgen on the liver tissue. Liver function tests were done in animals of group I, III, and IV, first prior to study and finally by the end of study. Results of assayed liver function tests and histopathological examination were tested for statistical significant association

Results: there were marked elevation of the liver enzymes in mice of group IV compared to the corresponding control [p<0.01] and mice of the third group [p<0.01], which reflect deterioration of hepatic function in those mice received the antibilharzial drug praziquantel. On the other hand there was statistical difference between control group [group I] and androgen treated group III [P < 0.05]. Histological examination of liver sections of mice in all groups revealed the presence of typical bilharzial granulomas. The mean diameter of bilharzial granulomas clearly dropped to 283.20 micrometer in group II compared to 392.55 in corresponding control. The difference between these two groups was statistically significant [p = 0.000].]. In group III there was no statistical difference in the number of egg granulomas [P> 0.05] compared to group I. There was a reduction of granulomas diameter in group III and IV [animals injected with androgen] in comparison to group I [P>0.05 and P<0.01] respectively. Also comparison between the four groups as regards the type of bilharzial granulomas, it is clearly evident that the predominant type of granulomas in the androgen treated groups is the cellular type [38% and 57.1%] in group III and IV respectively and this may reflect the possible beneficial effect of androgen on the diseased liver