Inhibition of renin-angiotensin system in experimental acute pancreatitis in rats: a new therapeutic target?

OBJECTIVE: Pancreatic renin-angiotensin system has been implied to play a role in the regulation of pancreatic functions and could be a new therapeutic target in acute pancreatitis. The aim of this study was to evaluate the therapeutic potential of angiotensin-converting-enzyme inhibition by captopril and angiotensin II type 1 receptor inhibition by L-158809 and losartan experimentally in acute pancreatitis. DESIGN: Rats were randomly divided into 15 groups. Acute edematous pancreatitis was induced by injection of cerulein 20microg/kg SC four times at hourly intervals. Severe necrotizing pancreatitis was induced by retrograde injection of 3% taurocholate into the biliary-pancreatic duct. INTERVENTIONS: Captopril, L-158809 and losartan were given intraperitoneally. Main outcome features: pancreatic pathology, pancreatic myeloperoxidase activity and serum amylase activity were assessed. RESULTS: Captopril decreased serum amylase (10,809+/-1867 vs. 4085+/-1028U/L, p<0.01), myeloperoxidase activity (3.5+/-0.5 vs. 1.5+/-0.1, p<0.05) and histopathological score (5.0+/-0.4 vs. 1.1+/-0.5, p<0.01) in acute edematous pancreatitis. In taurocholate induced severe necrotizing pancreatitis captopril ameliorated histopathological score (10.1+/-1.2 vs. 3.4+/-0.5, p<0.01), pancreatic parenchymal necrosis (4.5+/-0.6 vs. 0.0+/-0.0, p<0.001), fatty necrosis (2.8+/-0.9 vs. 0.1+/-0.1, p<0.01) and edema (2.1+/-0.3 vs. 1.4+/-0.3, p<0.05). However, L-158809 did not have similar beneficial effects on acute pancreatitis in rats while losartan decreased pancreatic parenchymal necrosis and neutrophil infiltration. CONCLUSIONS: This study not only demonstrated the differential effects of captopril, losartan and L-158809 in acute pancreatitis but also showed that there is still much to investigate about pancreatic renin-angiotensin system. Inhibition of angiotensin-converting enzyme should be evaluated carefully as a potential new therapeutic target in acute pancreatitis.

Serum procalcitonin and CRP levels in non-alcoholic fatty liver disease: a case control study.

BACKGROUND: Both C reactive protein (CRP) and procalcitonin (PCT) are well known acute phase reactant proteins. CRP was reported to increase in metabolic syndrome and type-2 diabetes. Similarly altered level of serum PCT was found in chronic liver diseases and cirrhosis. The liver is considered the main source of CRP and a source of PCT, however, the serum PCT and CRP levels in non-alcoholic fatty liver disease (NAFLD) were not compared previously. Therefore we aimed to study the diagnostic and discriminative role of serum PCT and CRP in NAFLD. METHODS: Fifty NAFLD cases and 50 healthy controls were included to the study. Liver function tests were measured, body mass index was calculated, and insulin resistance was determined by using a homeostasis model assessment (HOMA-IR). Ultrasound evaluation was performed for each subject. Serum CRP was measured with nephalometric method. Serum PCT was measured with Kryptor based system. RESULTS: Serum PCT levels were similar in steatohepatitis (n 20) and simple steatosis (n 27) patients, and were not different than the control group (0.06 +/- 0.01, 0.04 +/- 0.01 versus 0.06 +/- 0.01 ng/ml respectively). Serum CRP levels were significantly higher in simple steatosis, and steatohepatitis groups compared to healthy controls (7.5 +/- 1.6 and 5.2 +/- 2.5 versus 2.9 +/- 0.5 mg/dl respectively p < 0.01). CRP could not differentiate steatohepatitis from simple steatosis. Beside, three patients with focal fatty liver disease had normal serum CRP levels. CONCLUSION: Serum PCT was within normal ranges in patients with simple steatosis or steatohepatitis and has no diagnostic value. Serum CRP level was increased in NAFLD compared to controls. CRP can be used as an additional marker for diagnosis of NAFLD but it has no value in discrimination of steatohepatitis from simple steatosis.

The effect of 1alpha,25(OH)2D3 vitamin over oxidative stress and biochemical parameters in rats where Type 1 diabetes is formed by streptozotocin.

INTRODUCTION: The 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] plays an essential role in mineral balance but has also been recognized as a powerful modulator of immune response. We aimed to examine the effect of the 1alpha,25(OH)(2)D(3) treatment on insulin/c-peptide, catalase, superoxide dismutase (SOD), and blood glucose in rats that take streptozotocin (STZ). METHODS: Forty pieces of male rats of Albino family whose average weights were 261.00+/-07.62 g were used in the study. Rats were made diabetic by giving STZ of 40 mg/kg during 5 days through intraperitoneal path. Some of the diabetic group and nondiabetic group were received 1alpha,25(OH)(2)D(3). The levels of SOD, insulin, c-peptide, glucose, SOD, and catalase were measured at the zero, second, fourth, and sixth weeks. RESULTS: Erythrocyte SOD levels didn't show a significant difference at the end of the sixth week in all groups when compared to the beginning. While erythrocyte catalase levels didn't show a significant difference in nondiabetic control and nondiabetic with vitamin D, and diabetic with vitamin D groups at the end of sixth week when compared to the beginning, a significant measurement was made in diabetic without vitamin D group. Maximal insulinitis scoring values were observed in diabetic without vitamin D that didn't receive 1alpha,25(OH)(2)D(3) treatment. CONCLUSION: The highness of insulin and c-peptide levels in the group that received treatment when compared to other groups and the lowness of oxidative markers such as SOD, catalase in this study can be explained by the fact that 1alpha,25(OH)(2)D(3) treatment prevents the intervention of apoptosis mechanism.

Use of activated protein C has no avail in the early phase of acute pancreatitis.

OBJECTIVES: Sepsis and acute pancreatitis have similar pathogenetic mechanisms that have been implicated in the progression of multiple organ failure. Drotrecogin alfa, an analogue of endogenous protein C, reduces mortality in clinical sepsis. Our objective was to evaluate the early therapeutic effects of activated protein C (APC) in a rat model of acute necrotizing pancreatitis. SUBJECTS AND METHOD: Acute necrotizing pancreatitis was induced by intraductal injection of 5% Na taurocholate. Hourly bolus injections of saline or recombinant human APC (drotrecogin alfa) was commenced via femoral venous catheter four hours after the induction of acute pancreatitis. The experiment was terminated nine hours after pancreatitis induction. Animals in group one (n=20) had a sham operation while animals in group two (n=20) received saline and animals in group three (n=20) received drotrecogin alfa boluses after acute pancreatitis induction. Pancreatic tissue for histopathologic scores and myeloperoxidase, glutathione reductase, glutathione peroxidase, and catalase activities were collected, and blood for serum amylase, urea, creatinine, and interleukin-6 measurements was withdrawn. RESULTS: Serum amylase activity was significantly lower in the APC treated group than the untreated group (17,435+/-432 U/L vs. 27,426+/-118 U/L, respectively). While the serum interleukin-6 concentration in the APC untreated group was significantly lower than the treated group (970+/-323 pg/mL vs. 330+/-368 pg/mL, respectively). CONCLUSION: In the early phase of acute pancreatitis, drotrecogin alfa treatment did not result in a significant improvement in oxidative and inflammatory parameters or renal functions.

The role of heme in hemolysis-induced acute pancreatitis.

BACKGROUND: The aim was to reveal the mechanism of hemolysis-induced acute pancreatitis and to evaluate the role of heme and heme oxygenase activity in inducing pancreatic inflammation in an experimental hemolysis model. MATERIAL/METHODS: Hemolytic anemia was induced in rats by intraperitoneal injection of 60 mg/kg acetylphenylhydrazine (APH). To evaluate the toxic effect of free heme after hemolysis, heme oxygenase inhibitor (HOI) was used to inhibit the enzyme which decreases the free heme concentration after hemolysis. One hundred and fifty rats were divided into two treatment and three control groups. Rats in the hemolysis group were given APH intraperitoneally. Rats in the HOI+hemolysis group were given Cr(III)mesoporphyrin IX chloride as HOI and then APH intraperitoneally. Serum amylase and lipase levels as well as pancreatic tissue cytokine content were determined and histological examination performed. RESULTS: No hemolysis or pancreatitis was seen in the control groups. Massive hemolysis was seen in 22 of the 30 rats of the hemolysis group and 20 of the 30 rats of the HOI+hemolysis group. The total pancreatitis rates were 60% and 76.6% in the hemolysis and HOI+hemolysis groups, respectively (p<0.05). Pancreatic cytokine levels were significantly higher in the HOI+hemolysis and hemolysis groups than in all control groups. The highest ICAM-1 and MCP-1 levels were in the HOI+hemolysis group. Histological signs of acute pancreatitis were also more severe in this group. CONCLUSIONS: Acute massive hemolysis can induce acute pancreatitis. Excess of free vascular heme seems to be an inducer of inflammation by modulating ICAM-1 and MCP-1.

Two-year interferon therapy with or without ribavirin in chronic delta hepatitis.

UNLABELLED: The only beneficial agent for the treatment of chronic delta hepatitis (CDH) is interferon (IFN). However, there is no consensus on the best dosage or duration of IFN therapy. As ribavirin (RBV) increases the sustained response when added to IFN in chronic hepatitis C, probably because of its immunomodulatory effect, we aimed to investigate the efficacy of 2-year IFN treatment and whether RBV had any additive effect to IFN in CDH. METHODS: Patients (n = 31) with CDH were randomized with a 1:2 ratio as 10 patients (3 females/7 males, age 39 +/- 9) receiving IFN monotherapy (9 MU IFN-alpha2a three times weekly) and 21 patients (8 females/13 males, age 38 +/- 11) receiving IFN plus RBV for 2 years (IFN at the same dosage and RBV at 1000-1200 mg/day). Alanine transferase normalization and hepatitis delta virus (HDV) RNA negativity at the end of treatment and at the end of the follow-up period (at least 6 months following 2-year treatment) were primary endpoints of the study. In addition, virological response and biochemical response were determined separately. RESULTS: Eight of 31 patients (25%) had cirrhosis in liver biopsies. Six patients from the IFN monotherapy group and 12 patients from the combination group had biochemical response. Five patients from the IFN monotherapy group and 11 patients from the combination group had virological response at the end of therapy. Two patients from the IFN group and five patients from the combination group had sustained biochemical response at the end of the follow-up period. Hepatitis B virus (HBV) activations with HBV DNA positivity were observed in two patients (one from the IFN monotherapy group, one from the combination group). Two patients (20%) in the IFN group and five patients (23.5%) in IFN plus RBV group remained as virological responders at the end of the follow-up period (P > 0.05). None of the patients with liver cirrhosis were responsive at the end of the follow-up period. CONCLUSION: Almost 20% of the patients with CDH were responsive to 2-year IFN treatment at the end of the follow-up period and no additional effect of RBV was observed. Patients with advanced liver disease failed to respond to treatment.

Recipient-derived hepatocytes in sex-mismatched liver allografts after liver transplantation: early versus late transplant biopsies.

BACKGROUND: The presence of microchimerism in transplanted tissues is well defined; however, the timeframe of appearance and disappearance of engraftment in liver allograft is unknown. The aims of this study were to analyze for the presence of "recipient-derived cells" in sex-mismatched individuals after liver transplantation, comparing the frequency of "recipient-derived cell repopulation" in early versus late transplant biopsies and to evaluate the relationship between "recipient-derived cell repopulation" and the severity of graft injury. METHODS: Paraffin-embedded liver biopsy samples of 18 recipients were reviewed. Sixteen of them were obtained from recipients with sex-mismatched donors. The remaining two were obtained from recipients with sex-matched donors and were used as controls. Immunohistochemistry and fluorescence in situ hybridization double-labeling method were performed on pretreated slides using anti-human hepatocyte antibody to identify hepatocytes, a mouse anti-human cytokeratin-7 to identify ductal epithelial cells, and using CEPX/Y DNA probes for visualizing X and Y chromosomes. The double-labeled slides were examined systematically using an image analyzer system. RESULTS: The mean time from transplantation to biopsy was 8.1 months. Eleven of the 16 samples obtained from recipients with sex-mismatched grafts demonstrated "recipient-derived hepatocyte repopulation," comprising a mean of 2.1% of the hepatocytes. In the control biopsies, none of the cells demonstrated different nuclear signals from the donor's sex origin. The presence and proportion of "recipient-derived hepatocyte repopulation" rate were significantly higher in early transplant biopsies than in late transplant biopsies (P < 0.05). CONCLUSION: Some hepatocytes of sex-mismatched liver grafts were replaced by "recipient-derived cells" during injury. Such repopulation is more common in the early liver-graft biopsies. The severity of acute cellular rejection appears to have no effect on the rate of recipient-derived repopulation.

Low plasma apolipoprotein A-I level is not a reliable marker of fibrosis in children with chronic hepatitis B.

AIM: To evaluate the clinical value of plasma apolipoprotein A-I (Apo A-I) as a marker of fibrosis in children with chronic hepatitis B (CHB). METHODS: Liver biopsy specimens from 49 children with CHB were evaluated by using Knodell index. Plasma Apo A-I level was measured after 12-h fasting. Student's t test, Spearman's correlation test and receptor-operating characteristic (ROC) curve were used for statistical evaluation. RESULTS: Mean Apo A-I level of the patients was not different from that of controls (P>0.05). Six (8.7%) children had fibrosis score of more than 2 (severe fibrosis). No difference in the level of mean plasma Apo A-I was found among children with and without severe fibrosis (P>0.05). No correlation between Apo A-I level and fibrosis scores was found (P>0.05). The area under the ROC curve was 0.407+/-0.146 (P>0.05). CONCLUSION: Severe fibrosis is not common in children with CHB and plasma Apo A-I level is not a reliable indicator of fibrosis.

Interferon-lamivudine combination is no better than lamivudine alone in anti-HBe-positive chronic hepatitis B.

BACKGROUND AND AIMS: Results of studies using lamivudine and interferon combination in the treatment of chronic hepatitis B are not consistent or conclusive. This study aimed to evaluate the efficacy of interferon plus lamivudine use versus single lamivudine in anti-HBe-positive chronic hepatitis B. METHODS: Eighty patients were treated with either lamivudine or lamivudine plus simultaneously started interferon. Patients were assigned in groups according to random allocation rule. Lamivudine was given 150 mg/day for 96 weeks in each group; interferon was administered 10 MU three times a week for 24 weeks in the combination therapy group. RESULTS: Alanine aminotransferase (ALT) normalization was achieved earlier in patients treated with lamivudine alone. At the end of treatment, there was no difference between the groups with respect to HBV DNA negativity, ALT normalization and breakthrough rate. Histological improvement was remarkable in each group, but fibrosis score and necro-inflammatory activity were much lower in lamivudine-treated patients. CONCLUSIONS: Addition of interferon to the lamivudine regimen does not increase the effectiveness of the treatment. Considering the side effects of interferon treatment, this combination seems not to be convenient for anti-HBe-positive chronic hepatitis B.

Is procalcitonin a reliable marker for the diagnosis of infected pancreatic necrosis?

BACKGROUND: Infected necrosis in acute pancreatitis is the main factor in determining the prognosis of the disease. Early and accurate diagnosis of infected pancreatic necrosis might decrease mortality. The aim of the present study is to identify a reliable marker for the onset infection in three different experimentally induced pancreatitis models. METHODS: Ninety female Wistar albino rats were randomly divided into nine groups. In three different experimental models, including cerulein induced acute oedematous pancreatitis (AEP), sterile pancreatic necrosis due to taurocholate-induced acute pancreatitis (SPN) and infected pancreatic necrosis taurocholate-induced acute pancreatitis (IPN). Serum levels of procalcitonin (PCT), C-reactive protein (CRP), tumour necrosis factor a (TNF-alpha), interleukin 6 (IL-6) and interleukin 8 (IL-8), amylase were measured. The degree of pancreatic damage also evaluated pathologically. RESULTS: Procalcitonin levels were increased significantly in AEP, SPN and IPN compared to control groups (P < 0.05). PCT and IL-6 level were the highest in the IPN group (P < 0.05). Serum amylase, CRP, TNF-alpha, IL-2, and IL-8 levels were similar between IPN and SPN groups (P > 0.05), but higher than in other groups. The results of histological evaluation also correlated with the advent of the disease. CONCLUSION: Procalcitonin and IL-6 acts as reliable acute phase reactant in an experimental model of AEP, SPN and IPN in the rat. PCT and IL-6 combination might be surrogate marker of infected pancreatic necrosis and should be preferred to other markers assay especially in severe pancreatitis.

Regenerative nodule mimicking hepatocellular carcinoma in a cirrhotic child due to hepatitis B: an imaging dilemma.

Viral hepatitis B, post-hepatitic cirrhosis and hepatocellular carcinoma (HCC) is the classical sequence of events in hepatitis B virus (HBV) infected children and serum Alpha-fetoprotein (AFP) and ultrasound (USG) screening is recommended during follow up. We present a 13-yr-old girl with cirrhosis related to chronic HBV infection with normal AFP level and a 4 cm mass appearance by USG. Contrast spiral evaluation computed tomography (CT) study demonstrated a single mass located at 8th segment of the liver. Pre-contrast CT and portal venous phase studies showed heterogeneous liver parenchyma without mass appearance. HCC was suspected based on strong arterial enhancement. Two mediastinal lymphadenopathies, 1 cm under the xyphoid and 2 cm above the pericardium, were detected by thorax CT. Mediastinal exploration was undertaken with living related liver transplant donor in a second operating room. She was transplanted with the right lobe of her ABO compatible mother after evaluation of the lymph nodes revealed reactive histology by frozen section. Histologic evaluation of the explant liver documented cirrhosis with a cirrhotic nodule without histologic malignant evidence. False negative results from screening methods are familiar in the literature; however false positivity of a contrast CT study is rare. The significance of screening methods is discussed.

Leiomyosarcoma of the inferior vena cava: report of a case.

We report a case of leiomyosarcoma of the inferior vena cava, which was successfully treated by surgical en bloc resection and reconstruction of the inferior vena cava, followed by adjuvant radiation therapy. A 39-year-old man presented with nausea, vomiting, epigastric pain, and weight loss. Radiologic examinations showed a mass originating from the inferior vena cava and surgical resection was performed. Histopathological examination of the specimen revealed a moderately differentiated (grade II) leiomyosarcoma arising from the inferior vena cava. We believe that radical resection with clear surgical margins followed by adjuvant radiation therapy is a good curative strategy for achieving any chance of long-term survival.

Leukotriene receptor antagonism in experimental acute pancreatitis in rats.

OBJECTIVES: Acute pancreatitis is a multifactorial disease caused by activation of several inflammatory mediators. Leukotrienes, beside other mediators, may be involved in acute pancreatitis. The aim of this study was to investigate the effects of 'zafirlukast', a leukotriene receptor antagonist, in acute pancreatitis and its relation with prostaglandin synthesis. METHODS: Eighty rats were randomly divided into eight groups. Acute pancreatitis was induced by subcutaneous injection of cerulein (20 microg/kg), four times at 1-h intervals. Zafirlukast (20 mg/kg) was applied intraperitoneally as a pretreatment. Prostaglandin synthesis was inhibited by low-dose indomethacin (5 mg/kg subcutaneously). Pancreatic histopathology, serum amylase activity and pancreatic myeloperoxidase activity were determined to assess the severity of pancreatitis. RESULTS: Zafirlukast pretreatment alone did not induce any inflammation and fatty necrosis in pancreatic tissue. However, it increased the histopathological score from 3.70 +/- 0.57 to 6.62 +/- 0.53 in rats with acute pancreatitis (P < 0.001). Fatty necrosis was especially prominent in the zafirlukast-treated acute pancreatitis group compared with the untreated group (2.62 +/- 0.26 versus 0.40 +/- 0.22, respectively; P < 0.001). Inhibition of prostaglandin synthesis by indomethacin partially suppressed the harmful effects of zafirlukast in acute pancreatitis. It decreased the pathological score (4.62 +/- 0.73) and fatty necrosis (1.50 +/- 0.32) in that group. CONCLUSION: Interestingly, leukotriene receptor antagonism by zafirlukast increased the pancreatic histopathological score and fatty necrosis in rats with acute pancreatitis. Blocking of cysteinyl leukotriene receptors might cause an induction of mediator synthesis via other pathways. Effects of leukotriene receptor antagonism on the pancreas must be evaluated extensively in further studies.

Infliximab: a new therapeutic agent in acute pancreatitis?

PURPOSE: Tumor necrosis factor alpha (TNF-alpha) has a central role in the pathogenesis of acute pancreatitis and related systemic complications. The aim of this study is to investigate the therapeutic effectiveness of monoclonal TNF antibody (infliximab) in acute edematous and severe necrotizing pancreatitis models in rats. METHODS: One hundred rats were randomly divided into 10 groups. Acute edematous pancreatitis (AEP) was induced by injection of cerulein 20 microg/kg 4 times subcutaneously at hourly intervals. Severe necrotizing pancreatitis (SNP) was induced by retrograde injection of 3% taurocholate into the common biliopancreatic duct. Infliximab 8 mg/kg was given via intravenous infusion. Serum amylase activity, pancreatic histopathology, myeloperoxidase enzyme activity (MPO), and pulmonary changes were assessed. RESULTS: Infliximab treatment significantly decreased serum amylase activity (11939 +/- 1914 U/L versus 3458 +/- 915 U/L, P < 0.001) and histopathologic score (4.1 +/- 0.5 versus 1.5 +/- 0.3, P < 0.001) in AEP. It also suppressed neutrophil infiltration and MPO activity of the pancreatic tissue. In SNP, infliximab treatment was found to decrease pathologic score (9.4 +/- 1.2 versus 3.6 +/- 0.8, P < 0.001) and serum amylase activity (20442 +/- 2375 versus 8990 +/- 1730, P < 0.01). It ameliorated both parenchymal and fatty tissue necrosis of the pancreas. Infliximab also alleviated alveolar edema and acute respiratory distress syndrome like pulmonary complications, but the difference was not significant. CONCLUSIONS: Chimeric TNF antibody, infliximab, should be evaluated for treatment of acute pancreatitis.

Detection of mutant p53 in hepatocellular cancer from Turkey and its correlation with clinicopathologic parameters.

The samples of hepatocellular carcinoma from Turkey, a country with a high prevalence of hepatitis B virus and hepatitis C virus, but low dietary exposure to aflatoxin B1, were examined in order to detect the frequency of mutant p53 and its association with clinical and pathological data. Fifty-two samples of hepatocellular cancer from the patients who were diagnosed in our clinic were included in this study. The mutant p53 protein was searched for by specific enzyme-linked immunosorbent assay. Of 52 patients with hepatocellular carcinoma, 26 (50%) had the mutant p53. The incidence of p53 mutation in hepatocellular cancer patients with chronic liver disease due to hepatitis B virus infection was significantly higher than in those with chronic liver disease due to alcohol, indicating that not alcohol but hepatitis B virus, in fact induces the mutations in p53 gene. In addition, it has been shown that the p53 mutation was significantly associated with the diameter of tumor nodule and the degree of cellular differentiation in hepatocellular cancer. The p53 mutation rate found in our study is concordant for a geography where hepatitis B virus and hepatitis C virus are common. Hepatitis B virus and possibly hepatitis C virus, but not alcohol, should be responsible, to a degree, for the mutational change in p53 protein in hepatocellular cancer patients with chronic liver disease. The p53 mutation is a late event in hepatocarcinogenesis because it is related with cellular differentiation and tumor diameter. The specific ELISA can be a useful screening test in future studies to select the patients for gene therapy using wild-type p53.

Effects of methimazole pretreatment on cerulein induced acute pancreatitis in rats.

BACKGROUND: Many interrelationships exist between the thyroid gland and the gastrointestinal tract. Several past and recent studies have shown that the thyroid gland profoundly influences the structure and function of the exocrine pancreas in the rat. In the present study we investigated the effect of methimazole (METZ), an antithyroid drug, on cerulein induced acute pancreatitis (AP) in rats. METHODS: Rats were divided into 3 groups (10-12 weeks age, 200-250 g weight, n: 10). Group B was made hypothyroid with methimazole 5 mg/kg daily for 10 days and the others were untreated euthyroid groups. After 10 days, acute pancreatitis was induced with four doses of 20 microg/kg body weight of cerulein administered s.c at hourly intervals in group A and B while the control group C was given 4 doses of I ml saline. Pancreas wet weight (mg), plasma amylase activity (IU/l) and pancreatic histology were used as endpoints to quantify the severity of the AP. RESULTS: Plasma tri-iodothyronine (T3) (ng/dl) and thyroxine (T4) (microg/dl) levels were significantly reduced after METZ treatment for 10 days (p < 0.01). METZ pretreatment reduced significantly the cerulein induced increase in pancreatic weight (1,205 +/- 12 mg in METZ treated AP group versus 1,617 +/- 14 mg in AP group, p < 0.05) and the rise in amylase activity (7,078 +/- 816 IU/l in METZ treated AP group versus 8,611 +/- 830 IU/l in AP group p < 0.05). CONCLUSION: METZ reduces the severity of cerulein induced AP in rats. This effect might be through its antithyroid property.

Clinical and biochemical features and therapy responses in primary biliary cirrhosis and primary biliary cirrhosis-autoimmune hepatitis overlap syndrome.

BACKGROUND/AIMS: Primary biliary cirrhosis and autoimmune hepatitis are two main immune-mediated liver diseases. Some patients display characteristics of both diseases, so called overlap syndrome. The aims of this study were to investigate and to compare the clinical and laboratory features and responses to therapy in primary biliary cirrhosis and overlap syndrome. METHODOLOGY: Twenty-three patients with primary biliary cirrhosis (21 females, 2 males; median age: 50 years) and 20 with primary biliary cirrhosis-autoimmune hepatitis overlap syndrome (18 females, 2 males; median age: 44 years) were included in the study. All patients with primary biliary cirrhosis were treated with ursodeoxycholic acid. Of patients with overlap syndrome, 16 were treated with ursodeoxycholic acid and 4 with ursodeoxycholic acid plus prednisolone. Histological findings laboratory and clinical data were compared at the baseline and at the 2nd year of treatment. RESULTS: Fatigue and pruritus were the most frequent and comparable symptoms in each group. Serum ALT, AST, gamma-glutamyl transpeptidase, total protein, globulin and gammaglobulin levels were higher in patients with overlap syndrome than those in patients with primary biliary cirrhosis. At the end of the 2nd year of the treatment, ALT normalization was achieved in 12 (52%), alkaline phosphatase in 7 (30%) patients with primary biliary cirrhosis. One of the non-responders to ursodeoxycholic acid therapy had the histological findings of overlap syndrome in her control biopsy. Fibrosis score deteriorated in 50% of the patients. Of ursodeoxycholic acid-treated overlap syndrome patients, 11 completed 2 years of treatment. Three patients were biochemically non-responsive and prednisolone was added to their regimen. Of the remaining 8 patients, 7 (64% of total patients) had normal ALT. Three patients had worse fibrosis score comparing the onset of the treatment. Six of 7 (86%) patients who were given ursodeoxycholic acid plus prednisolone including ursodeoxycholic acid-non-responsives had normal ALT and 2 of 6 biopsy-controlled patients display deterioration of their fibrosis score. CONCLUSIONS: Biochemical tests tended to be higher in patients with overlap syndrome comparing to those with primary biliary cirrhosis. Response to ursodeoxycholic acid treatment in patients with overlap syndrome was comparable with that obtained in primary biliary cirrhosis. Therefore it should be the first-line treatment. Non-responsive patients may benefit from the use of ursodeoxycholic acid plus prednisolone combination.

Alpha interferon and lamivudine combination therapy for chronic hepatitis B in children.

BACKGROUND: Lamivudine is a new alternative therapeutic agent for chronic hepatitis B, in which alpha interferon (IFN-alpha) monotherapy is not successful enough. Published reports have revealed no satisfactory data on IFN-alpha and lamivudine combination therapy in children. The aim of this study is to investigate the efficacy and safety of this combination therapy in children with chronic hepatitis B. METHODS: Children with chronic hepatitis B were given either IFN-alpha and lamuvidine (group 1, n = 47) or IFN-alpha alone (group 2, n = 30). Alpha interferon was administered as 5 million U/m2 s.c., thrice a week for 6 months and lamivudine 4 mg/kg per day p.o., maximum 100 mg, for 1 year. Clinical examination was performed; blood cell counts and serum alanine aminotransferase (ALT) and amylase were studied at each visit. At the third, sixth and twelfth month, serological markers were determined. RESULTS: End of therapy response was achieved in 19 (40.4%) patients in group 1 and in 14 (46.7%) children in group 2 (P > 0.05). In group 1, pretreatment serum ALT and hepatic activity index (HAI) were statistically higher in children who responded to therapy (P < 0.005). In group 2, mean serum ALT was higher and hepatitis B virus (HBV) DNA was lower in responders. Sustained response rate was 40.4 versus 43.3% in two groups. CONCLUSION: The response rate of IFN-alpha and lamivudine combination therapy in children with chronic hepatitis B was similar to that of IFN-alpha monotherapy. High ALT level and HAI, rather than low HBV-DNA level were found to be important predictors of response.

Clinicopathological features of hepatitis C virus infection in dialysis and renal transplantation.

BACKGROUND: Liver biopsy (LB) gives an accurate picture of the severity of hepatitis C virus (HCV) infection in end-stage renal disease. The aim of this study was to find out whether clinical and histopathological course of HCV infection in renal transplant (RT) patients (pts) is different from dialysis (Dx) pts. METHODS: Forty Dx and 46 RT pts underwent LB. Clinical and biochemical data were retrospectively collected from medical charts. ALT level above the upper limit was described as elevated. LB was done regardless of the ALT level. LB specimens were examined using a semiquantitative scoring system locally modified from Scheuer. Histological activity (grade) and fibrosis (stage) were scored separately. RESULTS: ALT was elevated in 65% of Dx pts. At the time of LB 30% of Dx pts had elevated ALT and 95% were viremic. Normal/minimal inflammation was detected in 25% of LBs, chronic hepatitis in 72.5%, cirrhosis in 2.5%. Stage and grade were respectively 1.08 +/- 1.02 and 4.30 +/- 2.98. Normal/minimal inflammation was detected in 9% of the 46 RT pts, chronic hepatitis in 84%, cirrhosis in 7%. Stage and grade were respectively 1.74 +/- 1.1 and 5.39 +/- 2.21. Although there was no significant difference in the histological grade between Dx and RT pts, histological stage was significantly higher in RT pts than Dx. The frequency of cirrhosis, hepatitis and normal inflammation was similar in the two groups. CONCLUSION: Histopathological liver injury due to HCV infection seems to be more severe in RT than Dx pts but this does not seem to be clear at the clinical and biochemical level. Sequential histopathological assessment and longer follow-up will be required to clarify this issue.