HBV vaccination in liver transplant recipients: not an effective strategy in the prophylaxis of HBV recurrence.

Anti-HBs immunoglobulins (HBIG) and lamivudine are main options to prevent hepatitis B virus (HBV) reinfection after liver transplantation. Although they are very effective, development of mutant viruses and high cost of treatment are main limitations for their application. Additionally there is an uncertainity for the duration of that prophylaxis regimen and its mostly applied indefinitely. Recently, post-transplant HBV vaccination is reported to be a cheaper alternative prophylaksis strategy, that enables discontinuation of HBIG. To investigate the efficacy of HBV vaccination in patients transplanted for HBV cirrhosis, we administered double course of double dose recombinant HBV vaccine (Genhavac B; containing HBV pre-S1, pre-S2, and S gene products). Vaccination has been started 1 month after HBIg discontinuation, and lamivudine (100 mg/day) was given throughout the study. The first cycle consisted of 0, 1- and 6-month schedule, and, in nonresponders, second cycle 0, 1-, 2-month schedule. Fourteen patients included into the study. Only one patient seroconverted (an anti-HBs titre of 37 IU/L) after the first cycle. No other patient responded to second cycle. HBV vaccination in the post-transplantation setting does not seems like an effective strategy in the prophylaxis of HBV recurrence.

Impact of pretransplant MELD score on posttransplant outcome in living donor liver transplantation.

It is not clear whether pretransplantation MELD (model for End-Stage Liver Disease) score can foresee posttransplant outcome. We retrospectively evaluated 80 adult patients (55 men, 25 women) who underwent living donor liver transplantation between September 1998 and March 2003. Five other patients with fulminant hepatitis were excluded. The UNOS-modified MELD scores were calculated to stratify patients into three groups: group 1) MELD score less than 15 (n = 13); group 2) MELD score 15 to 24 (n = 36); and group 3) MELD score 25 and higher (n = 26). The patients were predominantly men (n = 52, 69.3%) with overall mean age of 43.9 years (range, 17-62 years). The mean follow-up was 15.7 months (range, 1-47; median = 14 months). The mean MELD score was 22.7 (range, 9-50; median = 21). The overall 1- and 2-year patient survivals were 87% and 78.7%, respectively. The 1-year patient survivals for groups 1, 2, and 3 were 100%, 87%, and 79%; respectively. 2-year survivals, 100%, 79%, and 61%, respectively. Survivals stratified by MELD showed no statistically remarkable differences in 1-year and 2-year patient survival (P = .08). In contrast, 1-year and 2-year patient survival rates for UNOS status 2A, 2B, and 3 were 73%-50%, 95%-91%, and 91%-91%, statistically significant difference (P = .002). Finally, to date preoperative MELD score showed no significant impact on 1- and 2-year posttransplant outcomes in adult-to-adult living donor liver transplantation recipients, but we await longer-term follow-up with greater numbers of patients.

Serum leptin levels in patients with liver cirrhosis and chronic viral hepatitis.

BACKGROUND: The aim of the present study was to investigate serum leptin levels in relation to anthropometric features in patients with liver cirrhosis (LC) and chronic viral hepatitis (CVH), and to determine the effect of the severity and aetiology of the LC on serum leptin levels. METHODS: Forty-nine patients with LC, 32 patients with CVH and 69 control subjects were age, body mass index (BMI) and sex-matched and included in the study. Plasma glucose, serum leptin and insulin levels were determined. Insulin resistance was assessed using homoeostasis model assessment (HOMA). Body composition was estimated by skinfold thickness. RESULTS: Female patients with Child-A LC had higher levels of leptin, and female and male patients with Child-A LC had higher absolute leptin (leptin/BFM) levels compared to patients with Child-C LC and control subjects. Serum leptin levels of the patients with alcohol LC were higher than the control subjects, but the absolute leptin levels were comparable. When alcoholic and post-viral hepatitis cirrhotic patients were compared with each other on an aetiologic basis, there was no significant difference between them in leptin and absolute leptin levels. There were significant correlations between leptin and BMI, body fat percentage (BFP), BFM (body fat mass) in all three groups in both sexes. CONCLUSIONS: These data suggest that the physiologic correlations among serum leptin level, sex, BMI and BFM were well preserved in patients with chronic liver disease. Patients with alcohol LC had higher leptin levels. In early stages of liver disease, leptin levels and absolute leptin levels are higher than in normal subjects. However, in advanced stages of the disease the significant decline in leptin levels and similar levels of leptin expressed in relation to BFM compared to control subjects predominantly represent the expression of fat mass.

TT virus infection and genotype distribution in blood donors and a group of patients from Turkey.

BACKGROUND: TT virus (TTV) DNA has been found in a large proportion of patients with different forms of non-A-G hepatitis, however the clinical importance is unclear. We aimed to determine the genotypes of TTV isolates found in blood donors and different patient groups from the western part of Turkey. MATERIALS AND METHODS: TT DNA was investigated in serum samples of 91 volunteer blood donors (BD), 105 thalassemia (TH) patients, ten patients with fulminant hepatitis (FH) and 16 hemodialysis (HD) patients by heminested PCR using primers NG059, NG061 and NG063 from the ORF1 region. 39 isolates were genotyped by analyzing the partial sequence of ORF1. RESULTS: TTV DNA was found in 75% of HD, 80% of FH, 61% of TH patients and in 51.6% of BD. Among the sequenced isolates, 14 (35.9%) belonged to genotype 1 (G1) and 25 (64.1%) belonged to genotype 2 (G2). Among the G2 sequences, 22 were grouped as G2c. CONCLUSION: TTV infection was common in the population studied, even with moderately sensitive primers. G2 was the major genotype of the studied population without any significant differences in distribution between various patient groups and BD.

Salycylate--induced pancreatic injury in the cat: a preliminary study.

The effect of intravenous aspirin on the exocrine pancreatic secretion was investigated in a feline isolated pancreaticoduodenal preparation. The study group received a 500 mg/kg bolus dose of aspirin intravenously. Duodenal washouts were collected for six hours. The serum and perfusate aspirin content increased significantly after aspirin administration (p = 0.01). However, the pH, bicarbonate, sodium, potassium and calcium content in the duodenal outflow did not show significant changes between 0 and 6 hours. A significant difference in the perfusate calcium content was present between ASA treated and control cats starting at the end of the first hour of the experiment (p=0.005). Histopathological examination of the pancreas revealed marked erythrocyte extravasation in the ASA treated animals. It is suggested that the ASA- related increase in the calcium secretion of the pancreas should be regarded as an indication of aspirin induced pancreatic damage.

Nitroimidazole-induced chronic hepatitis.

Drug-induced chronic hepatitis is a rare pathological condition. There is no reported case with chronic hepatitis secondary to nitroimidazole use. We report a patient who developed nitroimidazole-induced chronic hepatitis following acute exacerbation of hepatitis three times after nitroimidazole use.

Severe toxic hepatitis associated with amoxycillin and clavulanic acid.

Toxic hepatitis secondary to amoxycillin-clavulanic acid is an infrequent clinical picture. Most of the cases are reported to have a benign course. We report two cases of severe hepatic failure following amoxycillin-clavulanic acid use. One of the cases had cholestatic features primarily, and the other had hepatocellular injury prominently. The first case had also findings of trombotic trombositic purpura and had a fatal course.

The effects of chronic hepatitis C and B virus infections on liver reduced and oxidized glutathione concentrations.

The aim of this study was to evaluate the effects of hepatitis B and C virus infections on liver glutathione status. Reduced and oxidized glutathione levels were determined in liver biopsy specimens obtained from patients with chronic liver disease including chronic active hepatitis and cirrhosis. In patients with hepatitis B virus infections, GSH and GSH/GSSG levels were significantly low compared with those in controls (P<0.01). There was a significant negative correlation between histological activity indices (HAI) and hepatic GSSG levels only in patients with chronic HCV infection (P<0.01; r=-0.895). In addition to this, we also found a positive correlation between indices (HAI) and GSH/GSSG of the same group (r=0.915; P<0.05). These observations suggest that HBV and HCV infections have different effects on liver glutathione status based on diverse mechanisms.

Effects of trimetazidine on oxidant/antioxidant status in trinitrobenzenesulfonic acid-induced chronic colitis.

Trimetazidine (TMZ), an anti-ischemic agent with proposed antioxidant properties, was used in a chronic colitis model in order to evaluate its effectiveness as a therapeutic agent in chronic colitis. Treatment of male Swiss Albino rats with ethanol (50%) and trinitrobenzenesulfonic acid (TNBS) (30 mg/kg) produced colitis as evidenced by histopathologic damage and inflammatory alterations, lipid peroxidation [increased malondialdehyde (MDA) levels], and enhanced neutrophil infiltration [increased myeloperoxidase (MPO) activity] without marked change in glutathione status. Administration of TMZ (5 mg/kg) to TNBS-treated rats failed to affect the TNBS-induced changes in histopathology and MPO activities. Unexpectedly, intrarectal (i.r.) administration of TMZ significantly elevated colonic MDA levels to a greater extent than TNBS alone. Intraperitoneal (i.p.) TMZ treatment seemed to increase total glutathione (tGSH), GSH, and GSH/GSSG values. In conclusion, our results demonstrated that (a) i.r. administration of ethanol and TNBS is an effective way of inducing a chronic colitis model, (b) inflammation and lipid peroxidation augment tissue damage in the chronic colitis model, (c) i.p. TMZ treatment significantly inhibits MDA production in the chronic colitis model, (d) TMZ treatment is more effective via the i.p. compared to i.r. route, and (e) TMZ seems to show its antioxidant effect via preserving the tissue's GSH/GSSG ratios.

Is administration of n-3 fatty acids by mucosal enema protective against trinitrobenzene-induced colitis in rats?

We investigated the protective role of fish oil (FO-source of n-3 FA) enriched diet (in the first protocol) in 20 rats and FO administration intrarectally (in the second protocol) in 40 rats with trinitrobenzene (TNB) colitis. All colonic specimens were pathologically evaluated, myeloperoxidase enzyme activities were measured, leukotriene B4 (LTB4) and LTC4 levels were determined by radioimmunoassay. In the first protocol 10 rats (group A1) were fed with 8% sunflower and cotton oil enriched diet and (group A2) with 8% FO enriched diet for 6 weeks. At the end of this period, TNB (30 mg in 0.25 ml of 30% ethanol) were intrarectally administered. After 2 weeks, rats were sacrificed. MPO activities (2.47 versus 30.17), LTB4 (34.5 versus 903.3) and LTC4 (77.7 versus 456.0) levels were significantly reduced in group A2 compared with group A1 (P<0.005). There was also a significant difference in pathologic scores (1.55 versus 2.12, P<0.002) between two groups. In the first part of the second protocol, 20 male rats were randomized into two equal groups (B1 and B2) and TNB colitis was induced. After 1 day, 1 ml of saline (group B1) or n-3 FA enemas (group B2) were administered every day for 2 weeks. At the end of this period, rats were sacrificed and evaluated as done for previous groups. Although there was no significant difference between the two groups in comparison with MPO enzyme activities and pathologic scores, the LTB4 (130.1 versus 971.0) and LTC4 (126.0 versus 532.0) levels of FO group were significantly reduced (P<0.005). In the second part of the second protocol, 20 male rats were randomized into two groups. One millilitre of saline (group B3) or FO enemas (group B4) were administered to rats every day for 3 days. At the fourth day, TNB-colitis was induced and after 24 h rats were sacrificed. We could not find any significant difference in MPO activities, pathologic scores, LTB4 and LTC4 levels between groups B3 and B4. In conclusion, FO enriched diet decreased both pathologic damage and tissue LT levels. The second protocol of our study revealed that the long-term FO enemas decreased the LTB4 and LTC4 levels; however, did not have any beneficial effect on the tissue lesions. Short periods of FO enemas did not have a protective role in the occurrence of experimental colitis. The present study showed that FO enemas significantly decreased LT levels. The protective effect of FO (oral and enema) in TNB colitis may open a new insight into the treatment of inflammatory bowel disease.

The effect of interferon therapy on erythrocyte membrane Na+,K+ ATP activity in patients with chronic hepatitis B and C virus infections.

In order to evaluate the effect of alpha interferon on erythrocyte membrane Na+,K+ ATPase (EC 3.6.1.37) activity, 10 patients with chronic hepatitis B virus (HBV) infection and 8 patients with chronic hepatitis C virus (HCV) infection were investigated. Erythrocyte membrane Na+,K+ ATPase activity was determined in controls and in patients with HBV and HCV infection. Na+,K+ ATPase activity was significantly less in untreated patients with (HBV) infection (n = 20; 0.134 +/- 0.073 mumol of phosphate produced per milligram of protein per hour) and (HCV) infection (n = 11; 0.144 +/- 0.049) when compared to the controls (n = 10; 0.219 +/- 0.055). Among these subjects patients were treated with interferon and following treatment, significant elevation of Na+,K+ ATPase activity was seen in patients with HCV (n = 8; 0.183 +/- 0.044; P = 0.049) and HBV (n = 10, 0.213 +/- 0.095, P = 0.0069) infections when compared with the pre-treatment values (n = 8; 0.152 +/- 0.050) and (n = 10, 0.131 +/- 0.083), respectively. Normalization of serum alanin amino transferase levels (ALT) at treatment cessation was seen in 8 of 10 (%80) HBV infected patients of whom 2 of 8 (%25) had sustained ALT responses within three months after the end of treatment. In HCV infected patients 1 of 8 (%12.5) had sustained response following treatment. At the end of treatment, although Na+,K+ ATPase was restored in both of the patients groups, relative changes in enzyme activity in relation to relative reduction in ALT levels as a response to IFN therapy were not correlated.

Possible role of glutathione in prevention of acetaminophen-induced hepatotoxicity enhanced by fish oil in male Wistar rats.

It has been reported that fish oil protects the rat liver against acetaminophen (APAP) induced toxicity; however, this finding is controversial. The present study was undertaken to investigate the effects of fish oil-enriched diet on APAP-induced liver injury in Wistar rats. Rats were fed a diet supplemented with either 8% fish oil or 8% corn oil, or standard rat feed for 6 wk. After an overnight fast, rats in each group were given either 2 g/kg APAP or saline orally. Our findings showed that APAP increased serum alanine aminotransferase (ALT) and that this rise was potentiated in the presence of dietary fat. Further fish oil ingestion increased the glutathione (GSH) content in rat liver; however, this was not effective in protecting liver from APAP-induced toxicity. Data suggest that GSH may be necessary to detoxify APAP metabolites, which are known to induce hepatotoxicity but are increased by dietary fat.

Long-term efficacy of interferon-alpha and ursodeoxycholic acid in treatment of chronic type C hepatitis.

Interferon-alpha (IFN) and ursodeoxycholic acid (UDCA) combined have a controversial role in the treatment of chronic type C hepatitis. We studied the long-term efficacy of both drugs alone or in combination. In a three-year period, 108 patients were randomized into three treatment arms: (1) IFN alone 3 MU three times a week (N = 49), (2) IFN 3 MU three times a week + UDCA 250 mg twice a day (N = 45), and (3) UDCA alone 250 mg twice a day (N = 14). Response was defined as complete normalization of serum ALT. For the responders at the end of six months, the treatment was run to 12 months. Nonresponders (NRs) of the first group were crossed over to combination and NRs of the combination received 6 MU three times a week IFN+UDCA for the next six months. The enrollment to the UDCA alone arm was stopped early, since only 1/14 normalized serum ALT at the end of third month. However, 12/14 completed six months and 11 NRs received IFN 3 MU three times a week alone for the next six months. Twelve discontinued treatment due to side effects. Responders were followed-up untreated for 18 months. Sustained response (SR) was defined as persistence of normal serum ALT levels in this period. At the end of six months, 22/45 (48%) from the IFN-alone and 23/39 (58%) from the combination group responded. Twenty NRs from former and 15 of latter group were crossed over. While none of the 20 from the IFN-alone group responded to the combination, 1/15 NRs of the combination group responded to dose escalation. SR was achieved in 9/45 (20%) of the IFN alone and 7/39 (18%) of the combination group. The mean time form the end of the treatment to the relapse was not different between the groups. Five of 11 UDCA NRs responded to IFN with SR in 2. It was concluded that UDCA as a single agent is ineffective in achieving response in the treatment of chronic type C hepatitis. Combined with IFN, it increases response rate insignificantly although this is not sustained.

Erythrocyte membrane Na+,K+ ATP ase activity can be a marker of liver histopathology.

Erythrocyte membrane Na+,K+: Ca2+ ATP ase activities, cholesterol (CH) phospholipid (PL) composition and erythrocyte glutathione (GSH) contents were determined in controls, in patients with chronic active hepatitis and liver cirrhosis. NA+,K+ ATP ase activities were significantly (P < 0.0001) less in patients with chronic active hepatitis and liver cirrhosis (n = 8, 0.102 +/- 0.02 mumol P/mg protein/hour; n = 8, 0.081 +/- 0.02 mumol P/mg protein/hour) than in controls (n = 10, 0.219 +/- 0.05). Histopathological analysis of liver sections obtained from patients with chronic active hepatitis (n = 3) and liver cirrhosis (n = 2) correlated well with erythrocyte biochemical findings. There was a significant negative correlation between Na+,K+ ATP ase activity and portal fibrosis (P < 0.05, r = -8680). However, further experiments performed on larger study populations are needed to better elucidate this correlation. Therefore, NA+K+ ATP ase activity measurement can be reliable assessment of liver fibrosis.

The endogenous scavengers in cerulein-induced acute pancreatitis.

Studies in animal models suggest that oxygen radicals are important in the pathogenesis of acute pancreatitis. Cerulein, a decapeptide isolated from the skin of the frog, Hyla caerula, is closely related to the C-terminus of cholecystokinin and it is a potent stimulant of pancreatic exocrine secretion. The aim of the present study was to measure the activity of endogenous scavengers, superoxide dismutase, catalase and glutathione levels in cerulein-induced acute pancreatitis in rats. We found that the plasma amylase and ribonuclease levels in the pancreatitis group were both significantly high (p < 0.01, p < 0.05, respectively) when compared with the control group. Although superoxide dismutase and glutathione levels of pancreatic tissue were decreased significantly (p < 0.01, p < 0.01 respectively), we observed a significant increase (p < 0.01) in catalase activity in the cerulein treated group compared to the control group. Therefore, we concluded that the profound alteration of the activities of endogenous scavengers (superoxide dismutase, catalase) and glutathione depletion occurring after cerulein-induced pancreatitis seemed to be important in tissue injury and may provide the basis for successful therapy of the disease.

Pancreatitis as a complication of a hydatic liver cyst--a case report.

A 56 year old patient who developed acute pancreatitis following intrabiliary rupture of a hydatic cyst of the liver is reported herein. Hepatic hydatic disease is a very rare cause of acute pancreatitis for which the surgical treatment consists of evacuation of the cyst material and biliary drainage. Cystoenteric drainage is not mandatory.

The effect of bile on the gastric mucosal barrier in the presence and after blockade of normal gastric acidity.

Induced physiologic changes in the gastric mucosa was investigated both in the presence of normal gastric acidity and after parietal cell vagotomy (PCV), in dogs. Cholecystogastrostomy and common bile duct ligation was performed in eleven and PCV was added to this procedure in five dogs. During histopathological examination, 70 days after the procedure, both groups proved to have superficial gastritis. The most prominent changes occurred at the anastomotic site and at the gastric antrum. Bile had broken down the gastric mucosal barrier and the Na+ flux roughly paralleled the H+ back diffusion. Potassium had taken part in the bi-directional movement of ions in the gastric mucosa, as well as the sodium flux, and in the late phase it accompanied the action of sodium ions. The destruction of the K+-H+ pump, possibly located in the plasma membrane, may be the responsible mechanism of this flux.