Biomedical subjects

G Mazzella

Publications and source records attributed to G Mazzella.

At least 19 recordsLinked to original sources

PubMed2006

Ursodeoxycholic acid improves gastrointestinal motility defects in gallstone patients.

AIM: To simultaneously evaluate the presence of defects in gallbladder and gastric emptying, as well as in intestinal transit in gallstone patients (GS) and the effect of chronic ursodeoxycholic acid (UDCA) administration on these parameters and on serum bile acids and clinical outcome in GS and controls (CTR). METHODS: After a standard liquid test meal, gallbla-dder and gastric emptying (by ultrasound), oroileal transit time (OITT) (by an immunoenzymatic technique) and serum bile acids (by HPLC) were evaluated before and after 3 mo of UDCA (12 mg/kg bw/d) or placebo administration in 10 symptomatic GS and 10 matched healthy CTR. RESULTS: OITT was longer in GS than in CTR (P < 0.0001); UDCA significantly reduced OITT in GS (P < 0.0001), but not in CTR. GS had longer gastric half-emptying time (t(1/2)) than CTR (P < 0.0044) at baseline; after UDCA, t(1/2) significantly decreased (P < 0.006) in GS but not in CTR. Placebo administration had no effect on gastric emptying and intestinal transit in both GS and CTR. CONCLUSION: The gallstone patient has simultaneous multiple impairments of gallbladder and gastric emptying, as well as of intestinal transit. UDCA administration restores these defects in GS, without any effect in CTR. These results confirm the pathogenetic role of gastrointestinal motility in gallstone disease and suggest an additional mechanism of action for UDCA in reducing bile cholesterol supersaturation.

Adult↗

PubMed2006

A statistical model predicting high hepatocyte proliferation index and the risk of developing hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis.

BACKGROUND: Incidence of hepatocellular carcinoma in hepatitis C virus-related cirrhosis is 4% per year. Although cost-effective, current screening could be improved. AIM: To develop a statistical model including non-invasive parameters able to identify patients at high risk of developing hepatocellular carcinoma. METHODS: One hundred and fifty-eight patients (73F:85M) with compensated chronic hepatitis C virus liver disease underwent evaluation, including argyrophilic nucleolar organizer regions proliferation index, and were followed up for 56.18 +/- 1.44 months. RESULTS: Fifty-six patients had chronic hepatitis without cirrhosis and low argyrophilic nucleolar organizer regions proliferation index (< or =25%), 65 had hepatitis C virus-related cirrhosis and low argyrophilic nucleolar organizer regions proliferation index and 37 had hepatitis C virus-related cirrhosis and high argyrophilic nucleolar organizer regions proliferation index (>25%). Groups were similar for gender and viral genotype distribution. None of the patients with chronic hepatitis without cirrhosis developed hepatocellular carcinoma, compared with 6.1% of low argyrophilic nucleolar organizer regions proliferation index and 30.6% of high argyrophilic nucleolar organizer regions proliferation index (P = 0.002). By multivariable logistic regression analysis, the following parameters were independently associated with hepatocellular carcinoma development and used for the development of the statistical model: platelets (OR 0.98), gamma-globulins (OR 0.111), alanine aminotransferase/aspartate aminotransferase ratio (OR 0.07), serum ferritin (OR 1.0) and ultrasonographic pattern (coarse OR 2.9, coarse nodular OR 10.12). The statistical model properly allocated 95.9% of patients with low argyrophilic nucleolar organizer regions proliferation index and 72.2% of patients with high argyrophilic nucleolar organizer regions proliferation index. CONCLUSIONS: The model, to be validated in large prospective studies, may help tailoring screening according to the risk of hepatocellular carcinoma development.

Adult↗

PubMed2006

High incidence of allograft dysfunction in liver transplanted patients treated with pegylated-interferon alpha-2b and ribavirin for hepatitis C recurrence: possible de novo autoimmune hepatitis?

BACKGROUND: Interferon may trigger autoimmune disorders, including autoimmune hepatitis, in immunocompetent patients. To date, no such disorders have been described in liver transplanted patients. METHODS: 9 of 44 liver transplanted patients who had been receiving pegylated-interferon alpha-2b and ribavirin for at least 6 months for hepatitis C virus (HCV) recurrence, developed graft dysfunction despite on-treatment HCV-RNA clearance in all but one case. Laboratory, microbiological, imaging and histological evaluations were performed to identify the origin of graft dysfunction. The International Autoimmune Hepatitis scoring system was also applied. RESULTS: In all cases infections, anastomoses complications and rejection were excluded, whereas the autoimmune hepatitis score suggested a "probable autoimmune hepatitis" (score from 10 to 14). Three patients developed other definite autoimmune disorders (overlap anti-mitochondrial antibodies (AMA)-positive cholangitis, autoimmune thyroiditis and systemic lupus erythematosus, respectively). In all cases, pre-existing autoimmune hepatitis was excluded. Anti-lymphocyte antibodies in immunosuppressive induction treatment correlated with the development of the disorder, whereas the use of granulocyte colony-stimulating factor to treat interferon-induced neutropenia showed a protective role. Withdrawal of antiviral treatment and treatment with prednisone resulted in different outcomes (five remissions and four graft failures with two deaths). CONCLUSIONS: De novo autoimmune hepatitis should be considered in differential diagnosis along with rejection in liver transplanted patients developing graft dysfunction while on treatment with interferon.

Aged↗

PubMed2006

Intrahepatic cholestasis of pregnancy: three novel MDR3 gene mutations.

BACKGROUND: The aetiology of intrahepatic cholestasis of pregnancy is unknown, but more than 10 different MDR3 gene mutations have recently been identified. AIM: To evaluate the genetic contribution of the MDR3 gene in the pathogenesis of intrahepatic cholestasis of pregnancy in Italian subjects. METHODS: We performed a multicentre prospective case-control study, enrolling 80 women with intrahepatic cholestasis of pregnancy at the third trimester of pregnancy and 80 pregnant women without intrahepatic cholestasis of pregnancy. Genomic DNA was extracted from peripheral venous blood leucocytes using standard procedures. The polymerase chain reaction was used to amplify exon 14 of the MDR3 gene and the polymerase chain reaction products were sequenced using a Big Dye Terminator Cycle Sequencing kit. RESULTS: Three novel non-synonymous heterozygous mutations in exon 14 were found (4%; E528D, R549H, G536R) among the 80 intrahepatic cholestasis of pregnancy patients, whereas the pregnant controls were all negative for exon 14 polymorphisms. The three patients involved had normal GGT and bilirubin, but high levels of both ALT and serum bile acids. One had cholesterol bile stones. The outcome of pregnancy was normal for two (with vaginal delivery), while foetal distress was recorded in the third. CONCLUSIONS: These three novel mutations add further information on the involvement of the MDR3 gene in intrahepatic cholestasis of pregnancy. As in other studies, we found only heterozygous mutations that could cause an impaired transport protein function, not its absence (which is responsible for more severe liver disease). Different genetic backgrounds might justify the presence of novel MDR3 gene mutations.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2005

Measurement of hepatic functional mass by means of 13C-methacetin and 13C-phenylalanine breath tests in chronic liver disease: comparison with Child-Pugh score and serum bile acid levels.

AIM: To evaluate and compare the clinical usefulness of 13C-phenylalanine and 13C-methacetin breath tests in quantitating functional hepatic mass in patients with chronic liver disease and to further compare these results with those of conventional tests, Child-Pugh score and serum bile acid levels. METHODS: One hundred and forty patients (50 HCV-related chronic hepatitis, 90 liver cirrhosis patients) and 40 matched healthy controls were studied. Both breath test and routine liver test, serum levels of cholic and chenodeoxycholic acid conjugates were evaluated. RESULTS: Methacetin breath test, expressed as 60 min cumulative percent of oxidation, discriminated the hepatic functional capacity not only between controls and liver disease patients, but also between different categories of chronic liver disease patients. Methacetin breath test was correlated with liver function tests and serum bile acids. Furthermore, methacetin breath test, as well as serum bile acids, were highly predictive of Child-Pugh scores. The diagnostic power of phenylalanine breath test was always less than that of methacetin breath test. CONCLUSION: Methacetin breath test represents a safe and accurate diagnostic tool in the evaluation of hepatic functional mass in chronic liver disease patients.

Acetamides↗

PubMed2005

Higher doses of peginterferon alpha-2b administered twice weekly improve sustained virological response in difficult-to-treat patients with chronic hepatitis C: results of a pilot randomized study.

SUMMARY: Beside substantial progress in treatment of chronic hepatitis C (CHC) particular patients (genotype 1/4, high viral load, previous nonresponse, cirrhosis) remain difficult to treat. The aim of our pilot randomized study was to compare efficacy and tolerability of standard doses of Peginterferon alpha-2b + ribavirin with higher doses of Peginterferon alpha-2b administered twice weekly + ribavirin. Sixty-five outpatients with CHC were subsequently enrolled. Group A (n = 22) received recommended doses of Peginterferon alpha-2b and group B (n = 43), received high doses twice weekly. Groups were comparable for baseline characteristics. All genotype 1/4 patients had high baseline viraemia. Sustained virological response (SVR) was significantly higher in group B among naïve patients (72%vs 25%, P = 0.024). A significantly higher rate of SVR was observed in group B both considering only genotype 1/4 patients, (46%vs 13%, P = 0.03) and grouping together genotype 1/4 naive and relapsers (57%vs 11%, P = 0.039). Discontinuation rate was 32% (7 of 22) in group A and 21% (9 [corrected] of 43) in group B. Our response rates are the highest reported for genotype 1/4 with high viraemia. Our pilot study supports the need of randomized studies to evaluate both viral kinetics and efficacy of high dose and twice weekly administration of Peginterferon alpha-2b in genotype 1/4 patients with high viraemia who may need personalized treatment schedules.

Adult↗

PubMed2004

Safety of interferon beta treatment for chronic HCV hepatitis.

Hepatitis C is a major cause of liver-related morbidity and mortality worldwide. In fact, chronic hepatitis C is considered as one of the primary causes of chronic liver disease, cirrhosis and hepatocellular carcinoma, and is the most common reason for liver transplantation. The primary objectives for the treatment of HCV-related chronic hepatitis is to eradicate infection and prevent progression of the disease. The treatment has evolved from the use of alpha-interferon (IFNalpha) alone to the combination of IFNalpha plus ribavirin, with a significant improvement in the overall efficacy, and to the newer PEG-IFNs which have further increased the virological response, used either alone or in combination with ribavirin. Despite these positive results, in terms of efficacy, concerns are related to the safety and adverse events. Many patients must reduce the dose of PEG-IFN or ribavirin, others must stop the treatment and a variable percentage of subjects are not suitable owing to intolerance toward drugs. IFNbeta represents a potential therapeutic alternative for the treatment of chronic viral hepatitis and in some countries it plays an important role in therapeutic protocols. Aim of the present paper was to review available data on the safety of IFNbeta treatment in HCV-related chronic hepatitis. The rates of treatment discontinuation and/or dose modification due to the appearance of severe side effects during IFNbeta are generally low and in several clinical studies no requirements for treatment discontinuation and/or dose modifications have been reported. The most frequent side effects experienced during IFNbeta treatment are flu-like syndromes, fever, fatigue and injection-site reactions. No differences in terms of side-effect frequency and severity between responders and non-responders have been reported. A more recent study, performed to compare IFNbeta alone or in combination with ribavirin, confirmed the good safety profile of both treatments. Similar trends of adverse event frequency have been observed in subpopulations such as patients with genotype-1b HCV hepatitis unresponsive to IFNalpha treatment or with HCV-related cirrhosis and patients with acute viral hepatitis. If further studies will confirm the efficacy of combined IFNbeta and ribavirin treatment, this regimen could represent a safe and alternative therapeutic option in selected patients.

Antiviral Agents↗

PubMed2003

Gallbladder motility and functional gastrointestinal disorders.

Functional gastrointestinal disorders can be defined as 'a variable combination of chronic or recurrent gastrointestinal symptoms not explained by structural or biochemical abnormalities'. Motor disorders are considered to be one of the pathogenetic mechanisms of these symptoms; in fact, it has been hypothesized that the smooth muscle of the whole gastrointestinal tract could be involved. Gallbladder motility has been evaluated in patients with dysmotility-like dyspepsia, irritable bowel syndrome and biliary disorders without gallstones; results of these observations are often inconclusive, conflicting and not always useful from a clinical point of view. The aim of this review is to explore the relationship between gallbladder motility and functional gastrointestinal disorders from pathogenetic and physiopathological points of view, and also to define the possible impact of these observations on clinical practice.

Acalculous Cholecystitis↗

PubMed2003

Ten year incidence of HCV infection in northern Italy and frequency of spontaneous viral clearance.

BACKGROUND: Little is known of the incidence of hepatitis C virus (HCV) infection, and the frequency of spontaneous viral clearance in the general population is unknown. We conducted an epidemiological study in two Apennine towns in northern Italy. METHODS: Anti-HCV (ELISA and RIBA third generation) and HCV-RNA by polymerase chain reaction were tested in thawed sera from an adult general population of Loiano-Monghidoro in 1986 and 1996, obtained in the context of the MICOL (Multicenter Italian Study on Cholelithiasis). In 1999, anti-HCV positive subjects and sex and age matched controls were recalled in order to identify risk factors for acquiring HCV infection and to assess the family composition of anti-HCV+ subjects. RESULTS: For 1646 subjects, sera were available from both 1986 and 1996 (mean age in 1986 43 (0.39) years). In 1986, 57 (3.46%) subjects were HCV antibody positive (HCV-Ab+). Eight new cases were recorded in 1996: adult incidence was 50.3 cases/100 000 inhabitants/year. Fifty three of 63 (84.1%) HCV-Ab+ sera were also HCV-RNA+. Genotype 2a/2c accounted for 44% and 1b for 47.0% of cases. HCV-Ab+ subjects had higher serum levels of alanine aminotransferase with respect to controls (p<0.005), as did subjects infected with genotype 1 with respect to those with genotype 2 (p<0.05). Eleven of 65 (16.9%) HCV-Ab+ subjects spontaneously cleared HCV-Ab; 7/11 also lost HCV-RNA- in both serum and leucocytes. Sixteen anti-HCV+ subjects belonged to families containing more than one infected member. Married couples accounted for 10 of these 16 subjects. In four of these five married couples, HCV genotype was identical in the two spouses. CONCLUSIONS: In rural northern Italy, the adult incidence of HCV is approximately 50 cases/100 000 inhabitants/year. Our findings suggest that as many as 17% of infected subjects may spontaneously clear HCV-Ab. Interfamilial transmission seems to have a role in the spread of infection.

Adolescent↗

PubMed2003

Gallbladder cholesterol polyps and cholesterolosis.

Cholesterolosis of the gallbladder consists in an accumulation of cholesterol esters and triglycerides in the macrophages at gallbladder wall level and may be either diffuse or polypoid in form. A prevalence of 4-8% has been reported, particularly in the male sex; results concerning a relationship between cholesterolosis and lifestyle are controversial (alcohol intake, smoking habit), as well as the clinical and laboratory parameters, such as serum cholesterol and body mass index. Even more controversial is the relationship with gallstones which has been associated with the presence of cholesterol polyps only in a few surgical series. An increase in the activity of the cholesterol ester enzyme has been observed, in cholesterolosis patients, at gallbladder mucosa level which has led to the hypothesis of an increase in cholesterol ester deposit at this level; the hypothesis of an alteration in bile composition, in these patients, still remains to be elucidated. Ultrasonography is a sensitive tool in the diagnosis of cholesterolosis even if the use of echoendoscopy is becoming increasingly important in the differential diagnosis between benign and malignant polypoid lesions. Even if, in a few series, patients with polyps present a clinical pattern characterized by specific biliary symptoms, both in our experience and in that of others, symptoms are aspecific, the frequency of dyspeptic symptoms being comparable to that in the general population. The natural history of this lesion is, in general, benign and for polyps with size ranging from 6 mm to 10 mm a yearly follow-up with ultrasonography is advisable.

Journal Article↗

PubMed2002

Improved liver tests and greater biliary enrichment with high dose ursodeoxycholic acid in early stage primary biliary cirrhosis.

BACKGROUND: Ursodeoxycholic acid is currently used for the treatment of primary biliary cirrhosis at 13-15 mg/kg/day, but liver tests of some patients do not return to normal at this dose. Studies reported here were designed to test whether a higher dose of ursodeoxycholic acid than is currently used would induce still greater biliary enrichment of ursodeoxycholic acid and whether such enrichment would lead to still further improvement in liver tests in patients with early primary biliary cirrhosis. METHODS: A total of 20 patients with histologically proven primary biliary cirrhosis were enrolled. Patients had early stage primary biliary cirrhosis as serum bilirubin levels were normal and the Mayo risk score 4.2 +/- 0.5. Group 1 received 600, 1200 and 1800 mg/day of ursodeoxycholic acid; group 2 received 900, 1500 and 2100 mg/day. The order of periods was randomized. Each treatment period lasted 3 months followed by a further 3 months during which a standard dose of ursodeoxycholic acid was given. At the end of each treatment period, liver tests were evaluated, and biliary bile acid pattern of duodenal bile was determined using high pressure liquid chromatography. RESULTS: Biliary bile acid became enriched in ursodeoxycholic acid in direct relationship to dosage [r = 0.84, p < 0.001). At doses of 1800 mg/day (25-35 mg/kg/day), biliary ursodeoxycholic acid averaged 69 +/- 6.6%. A progressive decrease of alanine aminotransferase [p < 0.0001), aspartate aminotransferase [p < 0.001) and alkaline phosphatase [p < 0.02) was observed with increasing concentrations of ursodeoxycholic acid in bile. Biochemical liver tests showed a stronger correlation with biliary concentrations of ursodeoxycholic acid than with the administered dose. CONCLUSIONS: In early primary biliary cirrhosis, higher dose ursodeoxycholic acid appears to be more effective than doses currently recommended.

Alkaline Phosphatase↗

PubMed2001

Serum alpha-fetoprotein for diagnosis of hepatocellular carcinoma in patients with chronic liver disease: influence of HBsAg and anti-HCV status.

BACKGROUND: It is not established whether virological status affects the efficiency of alpha-fetoprotein (AFP) as a hepatocellular carcinoma (HCC) marker among patients with chronic liver disease (CLD). METHODS: We enrolled in a case-control study 170 HCC and 170 CLD patients, matched for age, sex, CLD and HBsAg/anti-HCV status. The AFP sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were calculated. PPV and NPV were evaluated for three additional HCC prevalences (5, 10, and 20%). RESULTS: The best discriminating AFP value was 16 ng/ml. A value of 20 ng/ml (above which investigations for HCC are recommended) had equivalent sensitivity (60.0 vs. 62.4%) and specificity (90.6 vs. 89.4%). PPV of 20 ng/ml was 84.6% but decreased to 25.1% at 5% tumor prevalence. NPV was 69.4% and rose to 97.7% at 5% prevalence. In the different groups of infected patients PPV ranged from 80.0 to 90.9%, falling to 17.4-34.5% at 5% prevalence. In noninfected patients PPV was 100% at any HCC prevalence. NPV ranged from 59.0 to 73.0%, reaching 96.5-98.1% at 5% prevalence. CONCLUSIONS: In CLD patients, AFP monitoring misses many HCCs and inappropriately arouses suspicion of malignancy in many patients. Its usefulness is barely affected by the infection responsible for CLD. An AFP elevation could be more indicative of HCC in non-infected patients.

Aged↗

PubMed2001

Ursodeoxycholic acid administration in patients with cholestasis of pregnancy: effects on primary bile acids in babies and mothers.

Little is known about the effects on the fetus of ursodeoxycholic acid (UDCA) treatment for intrahepatic cholestasis of pregnancy (ICP). Twenty ICP patients were given UDCA at 1.5 to 2 g/d, to our knowledge the highest dosage yet reported. Effects were evaluated on conjugated bile acids (BA) in amniotic fluid (15 of 20 patients) and umbilical cord serum obtained at delivery (20 of 22 newborns), as compared with 10 untreated patients (amniotic fluid, 9 of 10 patients; cord serum, 9 of 10 newborns). Liver function tests, serum BA and UDCA were evaluated on enrollment and then weekly until 1 week after delivery. Maternal serum conjugated cholic (CCA) and chenodeoxycholic (CCDCA) acids levels fell (18.5 +/- 1.9 to 10.5 +/- 1.9 micromol/L, and 5.8 +/- 0.8 to 2.97 +/- 0.7 micromol/L, respectively [P <.01]) in treated patients, and remained unaffected (20.0 +/- 3.1 vs. 20.3 +/- 2.3, and 5.6 +/- 0.6 vs. 5.4 +/- 0.5, respectively [P = not significant]) in untreated ones. Serum conjugated UDCA levels rose to 16.5 +/- 1.8 micromol/L (P<.001). Median values of CCA and CCDCA in amniotic fluid around delivery were 4.9 +/- 12.4 and 4.8 +/- 7.7 micromol/L, respectively, in treated patients, as against 17.9 +/- 27.5 and 18.5 +/- 20.9 micromol/L in untreated ones. In treated mothers, CCA and CCDCA concentrations in cord blood were 6.0 +/- 0.9 and 5.2 +/- 0.95 micromol/L, respectively, as against 21.9 +/- 5.6 and 18.9 +/- 2.1 micromol/L in untreated ones. In treated patients, median UDCA values in amniotic fluid and cord blood were 0.8 +/- 2.4 and 0.9 +/- 0.14 micromol/L, respectively. We conclude that increasing the dose of UDCA more effectively controls ICP and improves maternal clinical outcome after delivery.

Adult↗

PubMed2000

Review: low caloric intake and gall-bladder motor function.

Cholelithiasis is the primary expression of obesity in the hepatobiliary system. In obese subjects the risk of developing gallstones is increased due to a higher cholesterol saturation of gall-bladder bile. During weight reduction with very low calorie diets (VLCD) the incidence of gallstones increases, but the mechanism for gallstone formation is not completely understood and several pathogenetic mechanisms have been suggested: increased saturation of bile, increased gall-bladder secretion of mucin and calcium, increased presence of prostaglandins and arachidonic acid. Alterations in gall-bladder motility may contribute to gallstone formation, but few studies have addressed the issue of gall-bladder motility during rapid weight loss and its possible role in gallstone formation. VLCD have been associated with a gall-bladder stasis, as a consequence of reduced gall-bladder stimulation by low fat content of the diets. A threshold quantity of fat (10 g) has been documented to obtain efficient gall-bladder emptying. Ursodeoxycholic acid administered during VLCD seems to have a protective role in developing a biliary cholesterol crystals. Gall-bladder emptying was lower in response to low fat meals with respect to relative higher fat meals, before as well as during the VLCD. This may account the possibility of an adaptative response of the gall-bladder motility to a given diet regimen. Adequate fat content of the VLCD may prevent gallstone formation, maintaining adequate gall-bladder motility and may be more economic and physiologically acceptable than administration of a pharmacological agent.

Bile Acids and Salts↗

PubMed2000

Efficacy of ursodeoxycholic acid in association with alpha-interferon for chronic hepatitis C in alpha-interferon non-responder patients.

BACKGROUND: The aim of the present study was to evaluate the effect of combined treatment with alpha-interferon (alpha-IFN) and ursodeoxycholic acid (UDCA) on liver function tests and serum HCV-RNA in patients with chronic hepatitis C who had not responded to alpha-IFN alone. METHOD: One hundred and three patients (60 men, 43 women, mean age 49 +/- 1.3 years) who had not responded (both HCV-RNA positive and increased serum ALT levels) to 4 consecutive months of treatment with alpha-IFN (3 MU three times weekly) were randomly assigned to receive UDCA (IFN-UDCA, 53 patients, 600 mg/day) in addition to the same alpha-IFN dose, or to continue alpha-IFN alone (IFN-controls, 50 patients). After stopping alpha-IFN, patients who had received UDCA continued to receive UDCA for an additional 6-month period. The two groups were comparable for sex, basal ALT, basal yGT, genotype distribution and liver histology, while mean age was lower in controls (53 +/- 1.8 vs 46 +/- 1.8 years; P< 0.01). RESULTS: Twenty (38%) out of 53 IFN-UDCA patients had normal ALT, compared with only six (12%) out of 50 IFN-control patients (P < 0.01). HCV-RNA became undetectable in four IFN-UDCA patients. Three months after withdrawal of alpha IFN, 15 IFN-UDCA responders, but none of the IFN-controls, had normal ALT values (P< 0.01); 6 months after withdrawal, nine IFN-UDCA responders still had normal ALT (P= NS) and HCV-RNA was still undetectable in four of them. Portal and periportal inflammation showed a statistically significant improvement (Fisher's exact test P< 0.01) in IFN-UDCA patients as compared with IFN-controls, while no effect was observed on portal fibrosis. CONCLUSIONS: These data demonstrate that UDCA improves the response rate to alpha-IFN. Furthermore, in 8% of IFN-UDCA patients the response rate was sustained and associated with HCV-RNA clearance.

Analysis of Variance↗

PubMed1999

Clinical manifestations of gallstone disease: evidence from the multicenter Italian study on cholelithiasis (MICOL).

Despite the many efforts to delineate the clinical manifestations of gallbladder disease, the precise symptom complex associated with gallstones is still a matter of debate, and even the existence of gallstone-specific symptoms has been questioned. We carried out a large population-based cross-sectional study (MICOL) to identify symptoms significantly related to gallstones. Fourteen centers throughout Italy enrolled 29,504 subjects aged 30 to 69 years. All subjects were administered an ultrasonographic examination of the upper abdomen and a precoded questionnaire. All subjects were divided into 4 groups: 25,374 (86.0%) gallstone-free subjects (GF), 1,832 (6.2%) patients with gallstones not previously diagnosed (GNPD), 638 (2.2%) patients with gallstones previously diagnosed (GPD), 1,660 (5.6%) patients with a history of cholecystectomy for gallstones (CC). In logistic regression analysis, pain at epigastrium and, even more, pain at right hypocondrium were significantly associated with gallstones. For pain at right hypocondrium, this association progressively increased from GNPD (OR = 1.60, 95% CI = 0.97-2.65) to GPD (OR = 8.77, 95% CI = 5.27-14.61) to CC (OR = 59.40, 95% CI = 43.87-80.42). Absence of heartburn combined with right hypocondrium or epigastrium pain and intolerance to fried or fatty food were also significantly related to gallstones. We also found some pain characteristics significantly associated with gallstones, i.e., pain radiated to the right shoulder, forcing the patient to rest, occurring soon after meals or unrelated to meals, not relieved by bowel movements, and frequently accompanied by gallstone-related morbidities. We developed a probability tree reporting the cumulative probability of having gallstones for each combination of those symptoms and characteristics of pain significantly associated with gallstones. In conclusion, we have identified symptoms and signs significantly associated with gallstones. We have shown that there is an increase in frequency and severity of these symptoms and signs across the different stages of gallstone disease. We have proposed a complex of symptoms and signs significantly associated with gallstones that might help physicians in clinical decision making.

Adult↗

PubMed1999

Methylprednisolone administration in primary biliary cirrhosis increases cholic acid turnover, synthesis, and deoxycholate concentration in bile.

As immunosuppressive agents, corticosteroids may be considered an appropriate treatment for primary biliary cirrhosis, even if bone loss and other side effects may occur. We studied biliary lipid metabolism in 10 nonicteric patients, with histologically proven primary biliary cirrhosis (stage I-IV). We administered methylprednisolone (24 mg daily) for 30 days to ascertain its effects on biliary lipid metabolism, which are largely still unknown. All patients underwent a 30-day drug-washout period before entering the trial. The following parameters were studied before and after methylprednisolone treatment: serum biochemistry; cholic acid pool size, kinetics and synthesis; biliary lipid secretion; biliary bile acid pattern; biliary lipid molar percentage; and cholesterol saturation index. Methylprednisolone induced a statistically significant (Wilcoxon rank test) increase in cholic acid turnover (from 0.26+/-0.04 to 0.50+/-0.05 K/day, P = 0.005) and synthesis (from 0.42+/-0.12 to 0.78+/-0.11 mmol/day, P = 0.04), and in bile deoxycholic acid molar percentage (from 19.4+/-2.7 to 30.6+/-4.4% molar, P = 0.01). On the other hand, a significant decrease in biliary cholesterol molar percentage (from 7.9+/-0.7 to 6.4+/-0.5% molar, P = 0.005), cholesterol saturation index (from 1.11+/-0.11 to 0.95+/-0.07, P = 0.05), and biliary cholesterol secretion (from 64.7+/-5.4 to 53.0+/-4.5 micromol/hr, P = 0.005) was observed. These findings show that short-term administration of methylprednisolone in patients with primary biliary cirrhosis does not induce expansion of the cholic acid pool but increases cholic acid synthesis and turnover, as well as intestinal production of deoxycholic acid. If long-term treatment is considered, the beneficial immunosuppressive effects of corticosteroids have to be weighed against the hepatotoxic properties of deoxycholic acid.

Adult↗

PubMed1999

Effect of ursodeoxycholic acid administration in patients with acute viral hepatitis: a pilot study.

BACKGROUND: Ursodeoxycholic acid (UDCA) is able to improve biochemical markers of cholestasis, with a parallel decrease in transaminases, in various cholestatic liver diseases. AIM: To evaluate the effects of UDCA administration on acute viral hepatitis-related cholestasis and the course of acute viral hepatitis. METHODS: Seventy-nine consecutive patients with acute viral hepatitis (HBV: 43, HCV: 11, HAV: 15, HEV: 3, Non A-E: 7) were randomized to receive either UDCA for 3 weeks or no treatment. Liver biochemistry and serum bile acid determinations were run at weekly intervals. RESULTS: No significant differences were observed in mean percentage decreases in transaminases between treated and untreated patients. By contrast, cholestatic indexes decreased significantly more quickly in patients treated with UDCA than in controls, and this effect was more evident in patients with increasing alanine transaminase levels at admission. After a peak at the end of the first week of therapy, serum levels of conjugated ursodeoxycholic acid (CUDCA) showed a gradual decrease. Conjugated cholic acid (CCA) and chenodeoxycholic acid (CCDCA) showed a progressive decrease with the resolution of viral hepatitis, but no influence of UDCA administration was observed. CONCLUSIONS: Our study demonstrates that UDCA significantly improves cholestatic indices in patients with acute viral hepatitis, but this effect does not seem to affect the course of the illness.

Acute Disease↗