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We report a case series of three HBeAg positive and five HBeAg negative patients (7 males, mean age 50.6±14.6 years) with chronic HBV infection experiencing seroconversion after treatment with entecavir (0.5 mg/day or 1 mg/day), initiated in 2007. Overall, the mean time to HBsAg clearance was 9.4±4.5 months. Seroconversion occurred in all patients, after a mean time of 8.0±3.7 months. In HBeAg negative patients, mean time to HBsAg clearance and to seroconversion were 9.2±5.9 and 6.8±4.0 months, respectively. In HBeAg positive patients, mean time to HBsAg clearance and to seroconversion were 9.7±0.6 months and 10.0±2.6 months, respectively. In this case series, seroconversion was maintained and was observed both in HBeAg positive patients and in HBeAg negative patients. Therefore, it may be preliminarily suggested that treatment with entecavir could be associated to HBsAg seroconversion in a short period of time, in both HBeAg positive and HBeAg negative HBV patients. [ABSTRACT FROM AUTHOR]

We determined whether triple therapy comprising amantadine (AMA), ribavirin (RBV) and either peginterferon (PEG-IFN)α-2a or conventional IFNα-2a would improve sustained virological response (SVR) rates over dual therapy with IFNα-2a and RBV in patients with chronic HCV infection. A total of 362 treatment-naïve patients were randomized to 48 weeks of treatment with: PEG-IFNα-2a 180 μg/week (group A) or IFNα-2a 3 MU tiw (groups B and C). All patients received RBV 1000 or 1200 mg/day and those in groups A and B received AMA 200 mg/day. SVR was defined as an undetectable HCV RNA after 24 weeks of untreated follow-up. At the end of therapy, 74.4% (95% CI 0.66–0.82) of patients in group A were HCV RNA-negative compared with 42.5% (95% CI 0.33–0.50) of those in group B (P = 0.0001) and 48.8% (95% CI 0.40–0.56) of those in group C. SVR was achieved in a significantly greater proportion of patients in group A compared with groups B and C: 65.3% (95% CI 0.53–0.56), 33.3% (95% CI 0.25–0.41) and 44.6% (95% CI 0.36–0.53;P = 0.0001) respectively. In patients with genotype 1, SVR rates were 55.2, 22.8 and 28.8% with the three regimens respectively. Factors independently associated with SVR were HCV genotype 2 or 3, therapy with PEG-IFN, female gender and age. In treatment-naïve patients with chronic hepatitis C, triple therapy with PEG-IFNα-2a, RBV and AMA produces higher SVR than dual or triple therapy with conventional IFNα-2a. [ABSTRACT FROM AUTHOR]

We tested the hypothesis that serum factors present in Crohn's disease interfere with the process of lymphocyte activation. The mitogen-induced proliferation and the expression of early activation antigens by normal lymphocytes cultured in the presence of either Crohn's disease sera or sera from different controls were evaluated. The mitogen-induced proliferation was significantly impaired in the presence of Crohn's disease sera. These sera markedly inhibited the mitogen-induced interleukin-2 receptor (IL-2R) expression (48% inhibition), while the effect of sera on the expression of the transferrin receptor and the 4F2 antigen was much less pronounced. Diafiltration experiments showed that the inhibitory effect was confined to a 30-50-kD serum fraction. Such a serum property was not related to the patients' disease activity and disappeared after surgical removal of the affected bowel. The capability of inhibiting the mitogen-induced IL-2R expression was not restricted to Crohn's disease and was observed with sera from other inflammatory and neoplastic gastrointestinal disorders. This study indicates that a marked inhibition of the IL-2R is a mechanism underlying the immunosuppressive property of the serum in Crohn's disease and in other gastrointestinal conditions. [ABSTRACT FROM AUTHOR]

Increasing amounts of porcine secretion (0.05 to 2.00 clinical units/h/100 g body wt) given to rats during a continuous infusion of bilirubin, increased bile flow and the apparent maximal biliary excretion of bilirubin ('Tm'). This increment was caused by an enhanced biliary output of bilirubin monoconjugates. The effect was dose dependent but maximal at a secretin infusion of 0.80 CU. Somatostatin 0.2 and 0.8 microgram/h/100 g body wt caused a dose related inhibition of the hepatic effects of secretin both on bile flow and on biliary output of bilirubin conjugates. As secretin elicits the release of somatostatin, a feed-back system could be envisaged whereby the somatostatin released stops the effects of secretin. [ABSTRACT FROM PUBLISHER]

Presents a letter to the editor about the case of antibodies anti-parvovirus B19 in chronic hepatitis C virus infection.

Cytological analysis of microsporogenesis in 72 popcorn plants, comprising nine from the original population (CMS-43, S(0)) and 63 from seven cycles of self-fertilization (S(1) to S(7)), one plant of S(0) generation (plant 2) was identified with B chromosomes. The number of B chromosomes varied from two to three in the same anther. The pattern of chromosome pairing and meiotic behavior of Bs were similar to those found in other plant species. The presence of B chromosomes did not affect chiasma frequency and chiasma distribution in A chromosomes. This is the first report of B chromosomes in popcorn.

The amount of copies of HCV-RNA and count of CD8(+) lymphocytes was retrospectively evaluated in 326 patients: sampling was performed in basal condition, during treatment with alpha-IFN (n=232) and post-treatment follow-up, and at the same time points in untreated patients (n=94). In the treated group the difference between CD8(+) lymphocytes in the patients successfully treated (n=65) and those with an unfavourable outcome (n=176) is statistically significant (898+/-172 vs., 440+/-176 CD8(+) lymphocytes per mm(3) P<0.005 ANOVA). Also, in the untreated patients the average count of CD8(+) cells is statistically higher in patients with a favourable outcome (P<0.01 ANOVA). The present data show that the count of CD8(+) lymphocyte is of clinical value in order to predict the outcome of HCV infection and may be used together with the viral load and genotype, already established predictors.

Finding one major hepatotropic virus may not be enough to identify the aetiology of liver disease when risk factors are present, particularly in patients with past or present infection with other viral agents, or chronic liver disease. The pathogenic process in these cases is often complex. In the five cases we report, acute hepatitis (initiated by halothane, cytomegalovirus or Epstein-Barr virus) preceded the reactivation of hepatitis B infection, and these events occurred in patients with chronic hepatitis C infection. Each case demonstrates how several viruses can be implicated in the development of hepatitis, either as single agents or via cross-activation of T cells. The nosography of hepatitis, therefore, and the optimum therapeutic choices, can puzzle the clinical team.

Many different aetiological agents stimulate alanine aminotransferase (ALT) production. Viral markers and other aetiologies were investigated in 2166 individuals, randomly selected from 10,000 consecutive blood donors. Elevation of ALT was found in 10.8% of subjects. Grouping donors according to ALT level and correlating with, respectively, hepatitis B core antibody (HBcAb), cytomegalovirus antibody alone, or associated with HBcAb, showed similar findings (high ALT 11.1%, normal 11.6%; high 85.4%, normal 81.4%; high 10.2%, normal 11.0%, respectively). Hepatitis C virus (HCV) antibody was found to be significantly associated with elevated ALT levels (high 1.7%, normal 0.26%). Other causes of ALT elevation were alcohol abuse (17%), obesity (25%) and dyslipidaemia (38%), but in 11% there was no obvious aetiology. Although HCV is a rare cause of elevated ALT in blood donors, it seems to be the only virus, among those tested, to account for liver damage. This may be due to the non-protective role of HCV antibody, the low specificity of ALT, or the pathogenic role of uninvestigated viruses.

The aim of the study was to investigate whether the immunoblot pattern for HCV is a predictor of the response to interferon treatment. In a group of 60 patients with persistent rise of aminotransferase, all were treated with 3-6MU of Alfa-IFN from normal leucocytes every other day for 6 months, followed by one weekly dose of 1-3 MU for 3 months. HCV serum markers were detected before treatment and every three months thereafter. In 22 out of 60 (36.6%) patients aminotransferase normalized and remained so for 3 months after therapy; 12 patients (54.5%) relapsed during a follow-up of 9-12 months. The most frequent pattern in responders and non responders was the positivity to four antibodies (55%). The pattern did not change during or after IFN therapy, nor was it related to the variation of aminotransferases. Three patients lost antibodies linked to viral replication (c100-3, 5-1-1) and 3 others became positive to the same antigens. No changes were observed during the follow-up of patients who had an initial normalization of ALT/AST levels and who then relapsed (either during the maintenance dose or during the whole follow-up:n = 19 pts). Therefore neither the antibody clearance of viral replication (c100-3 and 5-1-1) nor the antibody pattern is a valid predictor as to the efficacy of interferon therapy.

The pattern of individual bilirubin pigments during a 24 hour caloric restriction (400 Kcal) was investigated in three groups of patients: one group with constitutional hyperbilirubinaemia (n = 29), another with microcytaemia and signs of haemolysis (n = 15) and the third consisting of patients without signs of hepatic disease (n = 11). The different bilirubin fractions (unconjugated, mono- and di-conjugated) were separated as methylated tetrapyrroles by t.l.c. following alkaline methanolysis. In all patients fasting induced an enhancement of the unconjugated bilirubin while the concentration of mono- and di-methyl esters of conjugated bilirubins remained within the normal range. When a pre-fasting concentration of total bilirubin equal to 1.2 mg/dl was used as a discriminating point, two different patterns in the fasting-induced increase in unconjugated bilirubin were identified. An increase of more than 1 mg/dl was found in 30 patients and 28 of these had constitutional hyperbilirubinaemia as diagnosed by exclusion of other disorders. The group with an increase of less than 1 mg/dl was composed of 25 patients, only one of whom had constitutional hyperbilirubinaemia: 14 were affected by microcytaemia and 10 were outpatients without signs of disease. The "fasting-induced increase in unconjugated bilirubin" has a specificity of 78%, a sensitivity of 84% and a positive and negative predictive value of 85 and 76%, respectively, for the diagnosis of constitutional hyperbilirubinaemia.

Intravenous infusion of glucagon (100 micrograms/hr/100 g body weight) in rats produces a 20 to 35% increase in bile flow and enhances the activity of hepatic bilirubin uridine diphosphate-glucuronyltransferase to 132% after a 90 min infusion. When a bilirubin load is given to produce a constant and apparently maximal biliary bilirubin excretion rate (or transport maximum) the administration of glucagon increased the bilirubin transport maximum. The excretion rate of bilirubin monoglucuronides was more enhanced than that of diglucuronide. The enhanced rate of glucuronidation, assayed in vitro, correlated with the augmented biliary output and inversely with the plasma unconjugated bilirubin levels. It is concluded that glucagon, at the dosage used, leads to a higher formation rate of bilirubin monoconjugates and that the choleresis, also induced by the hormone, enhances the biliary secretion of the monoconjugates formed. The enhanced conjugation results in a decreased plasma concentration of unconjugated bile pigment and the associated choleresis leads to a decreased di- to monoconjugate ratio, opposite to what has been observed during bilirubinostasis and cholestasis. The secretory efficacy, as assessed from the bile-to-plasma concentration ratio, is enhanced for all bilirubin pigments after glucagon administration.

The clinical and laboratory findings of 37 patients with primary sclerosing cholangitis (PSC) were reviewed. Mean age was 43.8 years, sex ratio between males and females was 3:1; IBD was present in 91% of patients with 51% having ulcerative colitis, 23% unclassified colitis and 17% Crohn's disease. Twenty-seven patients (73%) were symptomatic presenting most commonly with fatigue, pruritus and hepato-splenomegaly. Cholangiography revealed abnormalities affecting both extrahepatic and intrahepatic biliary ductal systems in 51.8% of cases, and only the intrahepatic or extrahepatic biliary tree, respectively in 11.1% and in 37% of cases. The last prevalence was very high compared with that previously known. Clinical and biochemical data, when compared between asymptomatics and symptomatics, demonstrated a significant difference only for alkaline phosphatase which increased in the symptomatic group and for prothrombin activity which decreased among symptomatic patients. Nevertheless, predictive value of sALP for the presence of PSC was high when pts were pooled together with a randomly selected group of 36 non-affected persons that underwent ERCP for suspected primary sclerosing cholangitis: sensitivity was 94% and specificity 78%.

The aim of the present investigation was to define the role of the synthetic terpenoid epomediol on biliary secretion in rats recovered from anaesthesia, in stabilized conditions and receiving an intravenous infusion of Na+ taurocholate (120 or 240 nmol.min-1 per 100 g body wt.) or physiologic saline (NaCl 0.16 M). Epomediol was administered at the rate of 20 and 50 mg.kg-1 per h, through a second syringe connected to the same vein catheter. Bile flow was increased up to 67% according to the model. The effect of epomediol is dose-dependent, associated with enhanced Na+ transport into bile and with an increased anionic gap. The extent of epomediol action also changes according to the different rates of bile acid secretion. At low secretory rates a greater choleretic action was observed with epomediol. The effect was negligible for a secretion of bile acids above 350 nmol.min-1 per 100 g body wt. Excretion into bile of the epomediol glucuronide was not hampered by high Na+ taurocholate output. This suggests that there is no competition of the two anions for a common excretory pathway at the studied rates. The effect of epomediol seems due to a mechanism of action both independent and additive to the mechanism for bile acids. The presence of additivity of the two choleretic mechanisms at low flow and bile acid secretion and the loss of action at high secretory rates, suggests that the maximal capacity of passage for water into bile was reached.

Fifty-one patients with signs of past HBV infection were investigated for the HCV virus antibody. All patients were at least HBsAb, HBcAb positive. Two groups were selected: patients with increased serum AST activity (32/51) and patients with normal serum AST activity (19/51). Prevalence of HCV infection was higher (81.2%) in the group with high serum aminotransferases as compared to that found in the second group (31.6%) (p less than 0.002). Furthermore, histological findings showed higher prevalence of HCV infection in patients with cirrhosis as compared to patients with hepatic fibrosis. Results show that lack of clinical remission in patients with past HBV infection could be due to the presence of HCV, thus representing an unrecognized cause of "cryptogenetic" liver diseases.

We tested the hypothesis that serum factors present in Crohn's disease interfere with the process of lymphocyte activation. The mitogen-induced proliferation and the expression of early activation antigens by normal lymphocytes cultured in the presence of either Crohn's disease sera or sera from different controls were evaluated. The mitogen-induced proliferation was significantly impaired in the presence of Crohn's disease sera. These sera markedly inhibited the mitogen-induced interleukin-2 receptor (IL-2R) expression (48% inhibition), while the effect of sera on the expression of the transferrin receptor and the 4F2 antigen was much less pronounced. Diafiltration experiments showed that the inhibitory effect was confined to a 30-50-kD serum fraction. Such a serum property was not related to the patients' disease activity and disappeared after surgical removal of the affected bowel. The capability of inhibiting the mitogen-induced IL-2R expression was not restricted to Crohn's disease and was observed with sera from other inflammatory and neoplastic gastrointestinal disorders. This study indicates that a marked inhibition of the IL-2R is a mechanism underlying the immunosuppressive property of the serum in Crohn's disease and in other gastrointestinal conditions.

Treatment of both male and female rats with 5 IU/day mepartricin for 7-10 days administered by gastric tubing resulted in an increased faecal excretion of some steroids. Mean rate of elimination of total oestrogens was enhanced by 45% in male rats and by 14% in female rats, and the average excretion of conjugated oestrogen was also increased in the female animals. Faecal elimination of cholesterol was 37% and 42% higher in male and female rats, respectively, after mepartricin treatment, and in male rats plasma concentrations of cholesterol were reduced following treatment. It is suggested mepartricin acts either by changing the intestinal flora or by acting directly on the steroid moieties, and it is speculated that a similar mechanism may occur in man.

Sulfate glycolithocholic acid (SGLC) has been shown to be highly cholestatic in the rat. This study was performed in order to gain understanding of the mechanisms of SGLC-induced cholestasis and the aim of the investigation was to explore the hypothesis that SGLC could cause a precipitation of calcium in bile. We studied the effects of intravenously administrated SGLC on bile flow, biliary lipids secretion and calcium excretion in the female bile fistula hamster. We also performed in-vitro studies with a Ca2(+)-selective electrode in order to measure the calcium binding capacity of SGLC. The results showed that after 1 h of infusion of 8 mumol/100 g body weight [14C]SGLC bile flow dropped to zero. During the infusion period a fine white sludge was visible in the test tube used for bile collection. TLC and HPLC analysis of both the supernatant and the precipitate showed that unchanged SGLC was excreted into bile. Up to 20% of biliary SGLC and more than 50% of the total Ca2+ present in bile was precipitated. The SGLC/Ca2+ molar ratio in the precipitate was 1.12 +/- 0.3 (mean +/- S.D. of four experiments). Light and electron microscopy of the liver did not show any specific abnormalities. The Ca2+ binding activity of SGLC in vitro, was highest among the bile acids tested at a concentration of 0.1 mM, when almost 100% of bile acids are in the monomeric (non-micellar) form. This suggests that among the bile acids, SGLC exerts the strongest binding activity on free calcium ions.(ABSTRACT TRUNCATED AT 250 WORDS)

A steady maximal biliary secretion of bilirubin has been produced in male Wistar rats, recovered from anesthesia, by continuous infusion of 256 nmol of unconjugated bilirubin per hour per 100 gm body weight, after priming with 3.4 mumols. The administration of somatostatin (2 micrograms/hr/100 gm body weight) produced a reversible decrease of bile flow and bile acid excretion while bilirubin output was unchanged. After discontinuation of somatostatin, a slight increase in the output of bilirubin conjugates was observed with the rapid recovery of bile flow. Administration of Na+ taurocholate at increasing rates (30 to 480 nmol/min/100 gm body weight) progressively enhanced bile flow and bile acid secretion. The rate of secretion of bilirubin conjugates increased to 18% above the values in controls at a taurocholate dose of 120 nmol/min/100 gm body weight and remained at that level with higher amounts, in spite of further increases in flow. Under Na+ taurocholate, somatostatin failed to reverse the enhancement of bilirubin output, although it still inhibited the secretion of bile acids and bile flow. A mechanism linked to osmotic flow induced by taurocholate would appear to serve as a component of the total capacity of the hepatocyte to transfer bilirubin conjugates into the canaliculus. At low bile-acid secretory rates this component seems of minor quantitative importance, whereas a major (specific) pathway seems not yet saturated.

To test the hypothesis that the presence of food in the intestine plays a role in the control of serum bilirubin levels, the effect of a 1674 kJ (400 kcal) diet, including non-absorbable material able to produce an intestinal bulk, was compared with the effect of caloric restriction alone. In normal individuals (n = 10) the rise of plasma bilirubin was comparable after the two trials. In patients with Gilbert's syndrome (n = 18), bilirubin concentration rose to a much greater extent during the caloric restriction as compared with controls, and to a lesser extent (P less than 0.001) after the bulky diet, as compared with caloric restriction alone in the same patient. It is proposed that a factor originating from the intestine, perhaps a hormone, the release of which is dependent on the presence of food-bulk, plays a role in the control of hyperbilirubinaemia associated with caloric restriction.

A study of 108 patients with acute or acute relapsing gallstone pancreatitis was carried out in order to evaluate the incidence of biliary lithiasis and microlithiasis. The severity of pancreatic damage associated with both clinical states and the physicochemical characteristics of the minute stones were also evaluated. The results suggest that the risk of acute pancreatitis is increased in patients with microlithiasis and that in patients with acute pancreatitis due to microlithiasis the lesions are more severe. These results warrant the conclusion that cholecystectomy should be performed upon all patients with echographically detected microlithiasis, even in the absence of symptoms. Early surgical treatment must be performed whenever pancreatitis develops.

The apparent maximal transport capacity (Tm) of the liver for bilirubin was studied in rats after oral treatment for two weeks with the two flavonoids (+)-cyanidanol-3 and palmitoyl-catechin in order to investigate a possible mechanism of action on jaundice described in humans. (+)-Cyanidanol-3 produces no changes in bilirubin-Tm, and the analysis of bilirubin and its conjugates in the different compartments reveals a decreased amount of the whole bilirubin taken up by the liver. Palmitoyl-catechin, a more lipophilic derivative of catechin, produces a slight increase in bilirubin-Tm. This appears related to the increased conjugation rate demonstrated in vitro for bilirubin. A multicompartimental analysis shows a different distribution of bilirubins as compared to controls. It is likely that physicochemical changes of the membrane environment, where the enzyme is buried, have modified the capacity of the hepatocyte to dispose bilirubin.

The effect of secretin (0.4 C.U. per hr per 100 gm body weight) on bile flow and the apparent maximal hepatic transport of bilirubin (Tm) was investigated in the rat. When secretin was administered during an already established bilirubin-Tm condition, it increased bile flow and bilirubin-Tm by 15 to 20% over a 30- to 50-min period. Enhancement of bilirubin output correlated with augmented flow and was sustained by an increased rate of excretion of monoglucuronides. When secretin was given for 90 min before bilirubin loading, it enhanced biliary bilirubin concentration and output, largely as diglucuronides. Bilirubin-Tm correlated positively with glururonyltransferase activity in liver homogenates. In the isolated perfused rat liver, injection of secretin in the portal cannula failed to produce choleresis. Bilirubin uridine diphosphate-glucuronyltransferase activity was lower than in intact rats and higher after treatment than in controls. The effect of secretin had an early effect on hepatocytic bile flow and a later effect on conjugation. Maximal hepatic bilirubin output was modulated both by flow and conjugation rate; the two mechanism may act independently.

Mepartricin was given to cirrhotic patients in order to evaluate its effect on the imbalance of sex steroids which is typical of this disorder. Patients were divided into two group: one group received placebo (n = 19) and the other received 150,000 IU/day mepartricin for 30 days (n = 19). The patients were evaluated by separate medical staff who were unaware of the treatment. Mepartricin significantly decreased the plasma concentration of testosterone, oestradiol and prolactin as compared with the values at the start of the trial, while no significant changes were seen in the occurrence of gynaecomastia. No relevant changes were seen in patients receiving the control, except for a slight increase in the peripheral concentration of androstenedione, aldosterone and follicle stimulating hormone.

In the present study 54 cirrhotic patients were investigated in order to compare the clinical effects of spironolactone (100-200 mg/d) and potassium canrenoate (50-200 mg/d). Diagnosis was established on clinical and laboratory findings for at least 12 months and/or on liver biopsy: no patients had signs of hepatic decompensation. Patients entering the study without previous treatment, after a basal period of observation, were randomly allocated to one of the spirolactones (spironolactone or potassium canrenoate); those already under antialdosteronic treatment underwent a first observation period and were then all shifted to the other drug. After completing a second observation all patients underwent a second cross-over and a new assessment of clinical and laboratory parameters after the third period of observation. 31 patients completed all observations (3.5 months each, overall mean). No differences in liver function tests were present during follow-up. Maintenance of body weight was achieved with a dose of potassium canrenoate half that of spironolactone. Serum K+ was increased in each patient after spironolactone and potassium canrenoate as compared to the basal period. The 24-h urinary excretion of K+ was significantly decreased in each patient after both drugs. No significant changes were observed in both Na+ and Cl- plasmatic concentration and urinary excretion. Gynaecomastia was present in 3/11 patients during the basal observation, in 13/30 patients under spironolactone and in 5/25 patients under potassium canrenoate; this finding, however, was not correlated to changes in the basal serum concentration of prolactin.(ABSTRACT TRUNCATED AT 250 WORDS)