Antonio Linares

Characterization and clinical impact of antinuclear antibodies in primary biliary cirrhosis.

OBJECTIVES:The clinical impact of antinuclear antibodies in primary biliary cirrhosis is uncertain. We analyzed in detail the antinuclear antibodies reactivity of primary biliary cirrhosis patients and correlated the fine specificities observed with clinical, biochemical, and immunologic parameters.METHODS:A total of 96 consecutive primary biliary cirrhosis patients and 283 pathologic controls were studied. To dissect the fine antinuclear antibodies specificities we used different techniques, such as indirect immunofluorescence on cryostat tissue sections and cell culture (HEp-2 cells), counterimmunoelectrophoresis with thymus and spleen extracts, ELISA assays with recombinant Sp100 and purified gp210 and Lamin B receptor, and immunoblot with several recombinant nuclear and cytoplasmic antigens.RESULTS:Antinuclear antibodies were detected in 53% of patients, with the following hierarchy of specificities: 27% anti-Sp100, 16% ldquo;multiple nuclear dots,” 16% anti-gp210, 16% anti-centromere, 7% XR1, 6% anti-lamin B receptor, 5% anti–SS-A/Ro, 5% anti-ribonucleoprotein, 4% XR2, 2% anti–SS-B/La, 2% perinuclear antineutrophil cytoplasmic antibodies, and 1% anti–double-stranded deoxyribonucleic acid. Several patients showed multiple specificities. The “multiple nuclear dots” pattern was detected more often in antimitochondrial antibodies negative patients. In particular, primary biliary cirrhosis specific antinuclear antibodies (anti-Sp100, anti-gp210, and anti-lamin B receptor) were detected in nine of 13 antimitochondrial negative primary biliary cirrhosis cases. Anti-gp210 was more frequent in patients with more pronounced cholestasis and more impaired liver function.CONCLUSIONS:Antinuclear antibodies reactivities are present in more than half of primary biliary cirrhosis patients and target diverse autoantigens located in distinct subnuclear structures. Anti-gp210 identifies a subgroup of primary biliary cirrhosis patients with more serious liver disease. Positivity for anti-Sp100, anti-gp210, and anti-lamin B receptor, either alone or in combination, may act as a serologic marker of antimitochondrial antibodies negative primary biliary cirrhosis.

Celiac disease in autoimmune cholestatic liver disorders

OBJECTIVES:In this study, serological screening for celiac disease (CD) was performed in patients with autoimmune cholestasis to define the prevalence of such an association and to evaluate the impact of gluten withdrawal on liver disease associated with gluten sensitive enteropathy.METHODS:Immunoglobulin A endomysial, human and guinea pig tissue transglutaminase antibodies, and immunoglobulin A and G gliadin antibodies were sought in 255 patients with primary biliary cirrhosis, autoimmune cholangitis, and primary sclerosing cholangitis.RESULTS:Immunoglobulin A endomysial and human tissue transglutaminase antibodies were positive in nine patients (seven primary biliary cirrhosis, one autoimmune cholangitis, and one primary sclerosing cholangitis), whose duodenal biopsy results showed villous atrophy consistent with CD. Two of these patients had a malabsorption syndrome, and one had iron-deficiency anemia. Clinical and biochemical signs of cholestasis did not improve after gluten withdrawal in the three patients with severe liver disease. A longer follow-up of the six celiac patients with mild liver damage is needed to clarify whether gluten restriction can contribute to slow down the progression of liver disease.CONCLUSIONS:The high prevalence of CD (3.5%) in autoimmune cholestasis suggests that serological screening for CD should be routinely performed in such patients by immunoglobulin A endomysial or human tissue transglutaminase antibodies.

Presence of Bacterial Infection in Bleeding Cirrhotic Patients Is Independently Associated with Early Mortality and Failure to Control Bleeding

Bacterial infection is strongly associated with gastrointestinal bleeding in cirrhotic patients and seems to be related with the failure to control bleeding. The aims of this study were to assess the influence of infections on the failure to control bleeding and death in cirrhotic patients without antibiotic prophylaxis. Ninety-one consecutive bleeding cirrhotic patients were analyzed. Bleeding was managed using somatostatin with sclerotherapy for active bleeding. Screening for bacterial infection (analysis and culture of blood, urine, ascitic and other fluids, together with chest radiography) was made at time 0 and when clinical signs suggested infection. The cause of bleeding was variceal in 72 (79%) patients. Failure to control bleeding occurred in 24 (26%) patients, and 10 (11%) of the patients died. Compared with the group without infection, failure to control bleeding (65% vs 15%; P < 0.001) and mortality (40% vs 3%; P < 0.001), were observed more frequently in patients with infection. Multivariate analysis showed that bacterial infection (OR = 9.7; P < 0.001) and the presence of shock (OR = 3.5; P < 0.05) were independently associated with failure to control bleeding. Bacterial infection (OR = 12.6; P < 0.01), encephalopathy (OR = 6.9; P < 0.05), and shock (OR = 5.8; P < 0.05) were identified as predictive of death. In conclusion, in bleeding cirrhotic patients bacterial infection is associated with failure to control bleeding as well as mortality.

HFE gene mutations in alcoholic and virus-related cirrhotic patients with hepatocellular carcinoma

OBJECTIVE:The increased risk of developing hepatocellular carcinoma in hereditary hemochromatosis has been associated with cirrhosis and hepatic iron overload. The aim of this study was to investigate the association between HFE gene mutations (C282Y, H63D) and hepatocellular carcinoma in patients with alcoholic and virus-related cirrhosis.METHODS:Serum markers of iron status and HFE mutations were determined in 179 patients with alcoholic cirrhosis and 98 patients with hepatitis B and/or hepatitis C virus-related cirrhosis. A total of 43 patients with alcoholic cirrhosis and 34 patients with virus-related cirrhosis had hepatocellular carcinoma. The control group consisted of 159 healthy bone marrow donors.RESULTS:No differences were found in the frequencies of mutations among patients with alcoholic cirrhosis, those with virus-related cirrhosis, and the control subjects. However, nine (20.9%) of the 43 patients with alcoholic cirrhosis and hepatocellular carcinoma were heterozygous for the C282Y mutation, compared with six (4.4%) of the 136 patients without tumor (p = 0.002). This difference was not found in patients with virus-related cirrhosis, with or without hepatocellular carcinoma, or the H63D mutation. The transferrin saturation was the only serum iron marker the value of which was significantly higher among C282Y heterozygotes with alcoholic cirrhosis compared to those without mutation.CONCLUSIONS:The high frequency of heterozygosity for the C282Y mutation in patients with alcoholic cirrhosis plus hepatocellular carcinoma suggests that the presence of this mutation could be associated with an increased risk of developing hepatocellular carcinoma in these patients.

Stress and contingency management in the treatment of irritable Bowel syndrome

Ninety patients with irritable bowel syndrome (IBS) who did not respond to medical treatment were randomly assigned to four treatment conditions - two experimental groups: stress management and contingency management; and two control groups: medical treatment and placebo. The subjects underwent 12 individual sessions which were specific for each condition. All the subjects completed symptom-monitoring diaries. Thirty-three dropped out during the assessment or treatment. The subjects who received training in contingency management experienced significant reductions in all the characteristic digestive symptoms: abdominal pain (p < 0.001), diarrhoea (p < 0.05), constipation (p < 0.05) and dyspepsia (p < 0.001). At the end of the treatment, 50 per cent of the patients remained asymptomatic and 37.5 per cent reduced their symptoms by at least 50 per cent. Among the patients assigned to the condition stress management, 33 per cent got rid of their symptomatology and the subjects showed significant reductions in the following digestive symptoms: abdominal pain (p < 0.05), diarrhoea (p < 0.05) and dyspepsia (p < 0.05). The changes in the placebo group are not representative. The subjects assigned to this condition showed a high dropout rate. Significant changes were not observed in symptomatology in the medical treatment group. The results are maintained after a year of follow-up. Possible predictive parameters of the progress of the patients are explored.

Hepatitis C virus infection in patients with acute hepatitis B

The prevalence of antibodies to hepatitis C virus (anti-HCV) was studied using a second-generation ELISA test in 121 patients with self-limiting acute hepatitis B, including 63 intravenous drug addicts (IVDA). Within the first month after the onset of illness, 47.1% of the patients were anti-HCV positive, this figure reaching 52.1% six months later. The prevalence in the sixth month was significantly higher in the IVDA (93.6%) than in the non-IVDA (6.9%) (p<0.00001). Among the IVDA, anti-HCV was more frequent in those with (100%) than in those without hepatitis delta virus (HDV) coinfection (84.6%) (p=0.004). Of the 63 anti-HCV positive patients, 36 (57.1%) continued to exhibit abnormal transmainase levels for more than six months, while this was not observed in anti-HCV negative patients. These results show a high prevalence of infection by hepatitis C virus (HCV) in IVDA with acute B hepatitis. As a rule, infection by HCV occurred prior to the hepatitis B infection, although occasionally simultaneous infections were observed. HCV appears to be the agent responsible for chronic liver disease in patients with acute B hepatitis who become HBsAg negative. Bei 121 Patienten mit akuter, spontan heilender Hepatitis B, unter denen auch 63 intravenös Drogenabhängige waren, wurden mit einem ELISA-Test der zweiten Generation auf Hepatitis C-Virus-Antikörper untersucht. Im ersten Monat nach Krankheitsbeginn waren 47,1% der Patienten anti-HCV-positiv, sechs Monate später 52,1%. Bei den intravenös Drogenabhängigen war die Antikörperprävalenz nach sechs Monaten mit 93,6% signifikant höher als bei den nicht Drogenabhängigen (6,9%; p=0,00001). Drogenabhängige mit Koinfektion durch Hepatitis Delta-Virus waren zu 100% anti-HCV-positiv, ohne Delta Virus-Infektion zu 84,6% (p=0,004). Bei 36 der 63 anti-HCV-positiven Patienten (57,1%) waren länger als sechs Monate pathologisch erhöhte Transaminasenspiegel festzustellen. Bei anti-HCV- negativen Patienten war dies nicht der Fall. Diese Ergebnisse belegen, daß bei intravenös Drogenabhängigen mit akuter Hepatitis B häufig eine HCV- Infektion vorliegt. Bei den meisten war die HCV-Infektion vor der B-Hepatitis aufgetreten, in einigen Fällen war eine simultane Infektion festzustellen. HCV scheint für die chronische Lebererkrankung bei Patienten mit akuter B- Hepatitis, die HBsAg-negativ werden, verantwortlich zu sein.SummaryThe prevalence of antibodies to hepatitis C virus (anti-HCV) was studied using a second-generation ELISA test in 121 patients with self-limiting acute hepatitis B, including 63 intravenous drug addicts (IVDA). Within the first month after the onset of illness, 47.1% of the patients were anti-HCV positive, this figure reaching 52.1% six months later. The prevalence in the sixth month was significantly higher in the IVDA (93.6%) than in the non-IVDA (6.9%) (p<0.00001). Among the IVDA, anti-HCV was more frequent in those with (100%) than in those without hepatitis delta virus (HDV) coinfection (84.6%) (p=0.004). Of the 63 anti-HCV positive patients, 36 (57.1%) continued to exhibit abnormal transmainase levels for more than six months, while this was not observed in anti-HCV negative patients. These results show a high prevalence of infection by hepatitis C virus (HCV) in IVDA with acute B hepatitis. As a rule, infection by HCV occurred prior to the hepatitis B infection, although occasionally simultaneous infections were observed. HCV appears to be the agent responsible for chronic liver disease in patients with acute B hepatitis who become HBsAg negative.ZusammenfassungBei 121 Patienten mit akuter, spontan heilender Hepatitis B, unter denen auch 63 intravenös Drogenabhängige waren, wurden mit einem ELISA-Test der zweiten Generation auf Hepatitis C-Virus-Antikörper untersucht. Im ersten Monat nach Krankheitsbeginn waren 47,1% der Patienten anti-HCV-positiv, sechs Monate später 52,1%. Bei den intravenös Drogenabhängigen war die Antikörperprävalenz nach sechs Monaten mit 93,6% signifikant höher als bei den nicht Drogenabhängigen (6,9%; p=0,00001). Drogenabhängige mit Koinfektion durch Hepatitis Delta-Virus waren zu 100% anti-HCV-positiv, ohne Delta Virus-Infektion zu 84,6% (p=0,004). Bei 36 der 63 anti-HCV-positiven Patienten (57,1%) waren länger als sechs Monate pathologisch erhöhte Transaminasenspiegel festzustellen. Bei anti-HCV- negativen Patienten war dies nicht der Fall. Diese Ergebnisse belegen, daß bei intravenös Drogenabhängigen mit akuter Hepatitis B häufig eine HCV- Infektion vorliegt. Bei den meisten war die HCV-Infektion vor der B-Hepatitis aufgetreten, in einigen Fällen war eine simultane Infektion festzustellen. HCV scheint für die chronische Lebererkrankung bei Patienten mit akuter B- Hepatitis, die HBsAg-negativ werden, verantwortlich zu sein.