Mucosal immunity and primary biliary cirrhosis: presence of antimitochondrial antibodies in urine.

We have shown that IgA-class antimitochondrial autoantibodies (AMA) can be detected in the bile and saliva of patients with PBC, suggesting that AMA are secreted into the luminal fluid across bile ducts and salivary glands. These data prompted us to determine whether AMA of the IgA isotype may be transported across other epithelial mucosa. Therefore, we tested for the presence of AMA in the urine specimens of 83 patients with PBC and 58 non-PBC controls including healthy individuals and patients with other liver diseases. Patients enrolled in this study had no history of renal disease, and we confirmed there was less than 50 microgram/mL of protein in each of the urine specimens. Interestingly, we found that AMA were present in the urine of 71/83 (86%) of all patients with PBC and in 71/78 (91%) of patients with PBC that were serum AMA positive. In contrast, AMA were not detected in any of the 58 control urine specimens. Of particular interest, AMA of the IgA isotype was present in 57/83 (69%) of patients with PBC, and in 52 of these 57, we found secretory-type IgA. In a nested random subgroup of urine samples, the prevalence of the IgA2 AMA was 6/18 (33%), significantly lower than in matched serum samples, 13/16 (81%, P =.007). These data show that AMA of the IgA isotype is secreted into urine from the uroepithelium of patients with PBC, and support the thesis that PBC originated from either a mucosal challenge or a loss of mucosal tolerance.

[Distribution of the genotypes of hepatitis C virus in intravenous drug addicts in Argentina]. / Distribución de los genotipos del virus de la hepatitis C en una población Argentina de drogadictos endovenosos.

Intravenous drug addiction (IVD) is an unfrequent risk factor in Argentina, representing less than 10% of patients (pts) with chronic HCV infection seen in our Unit. In order to study the genotypes (Gt) in IVD and compare them with a non drug addicted control population, 68 pts with a history of IVD were enrolled in this study and compared with 68 non drug addict (NDA) pts with chronic HCV, with similar age and gender distribution. In all pts a liver biopsy was performed. Genotyping was done by INNO LiPA (Innogenetics, Belgium). Mean age in both groups was 35 +/- 7.8 years and 50 were males. No difference was observed between both groups in the prevalence of Gt1a, Gt2a/c and in those with mixed infections. The prevalence of Gt1b in IVD was 19.1% and in NDA 38.2% (p = 0.0228). A highly significant difference was also observed in the prevalence of Gt3a, of 42.6% in IVD and only 11.8% in NDA (p = 0.0001). Gt1a was the second most frequent genotype in IVD pts (26.5%). Simultaneous HIV infection was present in 8 IVD pts (11.8%) and in none of NDA group. Liver biopsies showed a higher prevalence of mild chronic hepatitis in NDA (57.3%) than in IVD (32.4%) (p = 0.0058). Severe chronic hepatitis with advanced fibrosis or cirrhosis was more frequent in the Gt3 of the group with IVD when compared with Gt3 of the NDA group. It can be concluded that in accordance with other geographical areas, Gt3a is far more prevalent in intravenous drugs addicts than in the general population in Argentina where Gt1b is more frequent. Mild forms of chronic hepatitis are less frequent in IVD. In spite of the relatively small group with HCV co-infection with HIV, it seems important to note that 2/8 (25%) showed severe hepatitis C or cirrhosis.

Distribución de los genotipos del virus de la hepatitis C en una población Argentina de drogadictos endovenosos. / [Distribution of the genotypes of hepatitis C virus in intravenous drug addicts in Argentina]

Intravenous drug addiction (IVD) is an unfrequent risk factor in Argentina, representing less than 10

of patients (pts) with chronic HCV infection seen in our Unit. In order to study the genotypes (Gt) in IVD and compare them with a non drug addicted control population, 68 pts with a history of IVD were enrolled in this study and compared with 68 non drug addict (NDA) pts with chronic HCV, with similar age and gender distribution. In all pts a liver biopsy was performed. Genotyping was done by INNO LiPA (Innogenetics, Belgium). Mean age in both groups was 35 +/- 7.8 years and 50 were males. No difference was observed between both groups in the prevalence of Gt1a, Gt2a/c and in those with mixed infections. The prevalence of Gt1b in IVD was 19.1

and in NDA 38.2

(p = 0.0228). A highly significant difference was also observed in the prevalence of Gt3a, of 42.6

in IVD and only 11.8

in NDA (p = 0.0001). Gt1a was the second most frequent genotype in IVD pts (26.5

). Simultaneous HIV infection was present in 8 IVD pts (11.8

) and in none of NDA group. Liver biopsies showed a higher prevalence of mild chronic hepatitis in NDA (57.3

) than in IVD (32.4

) (p = 0.0058). Severe chronic hepatitis with advanced fibrosis or cirrhosis was more frequent in the Gt3 of the group with IVD when compared with Gt3 of the NDA group. It can be concluded that in accordance with other geographical areas, Gt3a is far more prevalent in intravenous drugs addicts than in the general population in Argentina where Gt1b is more frequent. Mild forms of chronic hepatitis are less frequent in IVD. In spite of the relatively small group with HCV co-infection with HIV, it seems important to note that 2/8 (25

) showed severe hepatitis C or cirrhosis.

Ketoconazole-induced liver damage.

Five cases (four females, one male) of ketoconazole-related liver damage are presented, two of whom died. All patients received ketoconazole (400 mg/day) for various mycoses. In the four women the first signs of hepatotoxicity appeared after four weeks of therapy. One fatal case developed massive necrosis with fulminant liver failure and the other, submassive necrosis. In four cases cholestasis was a prominent finding. Biochemical evidence of biliary stasis may persist for several months, as occurred in the three surviving patients of our series. The two fatal cases continued receiving the drug in spite of its adverse effects. Consequently, repeated evaluation is recommended to detect early signs of liver environment.

[Cholestasis associated with ticlopidine]. / Colestasis asociada a ticlopidina.

The case of a 56-years-old male with cholestasis associated with ticlopidine is presented. Cholestasis is an infrequent adverse effect of this drug. The patient was admitted to hospital because of jaundice, choluria, and itching of one month of evolution. The patient had taken ticlopidine twice a day for 3 months up to one week prior to admission for peripheral arteriopathy. Biopsy was performed showing acinar cholestasis and portal inflammatory infiltrate compatible with cholestasis due to hypersensitivity. Ticlopidine was discontinued by the patient himself one week prior to admission. The drug was not readministered and the evolution of the clinical and biochemical parameters of cholestasis decreased. The patient was asymptomatic and laboratory data were normal 4 months later.

[Non alcoholic steatohepatitis]. / Esteatohepatitis no alcohólica.

A prospective study of 21 patients with the diagnosis of non-alcoholic steatohepatitis (NASH) was carried out. All patients had hepatomegaly and in 10 (48%) image studies were consistent with steatosis and/or fibrosis. Biochemically, there was increase of AST, ALT and cholesterol in 48%, of GGT in 52% and of alkaline phosphatase in 38%. 18 patients were obese, 2 of them diabetic, 2 others had a history of exposure to drugs (amiodarone and isopropilic alcohol) and the last one presented hypothyroidism. Liver biopsies were studied using a semiquantitative scale to evaluate the degree of steatosis, inflammation and fibrosis in a scale from 1 to 3. Results showed a medium score of 2.6 for steatosis, 1.5 for inflammation and 1.8 for fibrosis. Four patients had cirrhosis and Mallory bodies were found in 11 cases (52%). NASH is an oligosymptomatic disease that can be found in different clinical conditions, mainly obesity, and is more frequent in women. It is histologically indistinguishable from alcoholic steatohepatitis. It is frequently underdiagnosed clinically and must be taken into account as a possible cause of cryptogenetic cirrhosis.

Esteatohepatitis no alcoholica / Non alcoholic steatohepatitis

Se estudiaron prospectivamente 21 pacientes con el diagnóstico de esteato-hepatitis no alcohólica (EHNA). Clínicamente todos los pacientes tenían hepatomegalia y 10 (48 por ciento) tenían estudios por imágenes compatibles con esteatosis o fibrosis. Bioquímicamente se comprobó aumento de AST, ALT e hipercolesterolemia en el 48 por cento, de GGT en el 52 por ciento y de FA en el 38 por ciento. Dieciocho pacientes eran obesos, 2 de ellos diabéticos, 2 con antecedentes de tóxicos y el restante hipotiroideo. Morfológicamente las biopsias fueron evaluadas semicuantitativamente para evaluar el grado de esteatosis, infiltración inflamatoria y fibrosis en una escala de 1 a 3. Se obtuvo un puntaje medio de 2,6 para esteatosis, 1,5 para la inflamación y 1,8 para la fibrosis. Cuatro pacientes presentaban una cirrosis ya constituida y se halló hialina de Mallory en 11 casos (52 por ciento). La EHNA es una enfermedad oligosintomática que puede hallarse en diferentes condiciones clínicas siendo más frecuente en la obesidad, con mayor prevalencia en mujeres e histologicamente indeferenciable de la estatohepatitis alcohólica

Esteatohepatitis no alcohólica. / [Non alcoholic steatohepatitis]

A prospective study of 21 patients with the diagnosis of non-alcoholic steatohepatitis (NASH) was carried out. All patients had hepatomegaly and in 10 (48

) image studies were consistent with steatosis and/or fibrosis. Biochemically, there was increase of AST, ALT and cholesterol in 48

, of GGT in 52

and of alkaline phosphatase in 38

. 18 patients were obese, 2 of them diabetic, 2 others had a history of exposure to drugs (amiodarone and isopropilic alcohol) and the last one presented hypothyroidism. Liver biopsies were studied using a semiquantitative scale to evaluate the degree of steatosis, inflammation and fibrosis in a scale from 1 to 3. Results showed a medium score of 2.6 for steatosis, 1.5 for inflammation and 1.8 for fibrosis. Four patients had cirrhosis and Mallory bodies were found in 11 cases (52

). NASH is an oligosymptomatic disease that can be found in different clinical conditions, mainly obesity, and is more frequent in women. It is histologically indistinguishable from alcoholic steatohepatitis. It is frequently underdiagnosed clinically and must be taken into account as a possible cause of cryptogenetic cirrhosis.

Esteatohepatitis no alcoholica / Non alcoholic steatohepatitis

Se estudiaron prospectivamente 21 pacientes con el diagnóstico de esteato-hepatitis no alcohólica (EHNA). Clínicamente todos los pacientes tenían hepatomegalia y 10 (48 por ciento) tenían estudios por imágenes compatibles con esteatosis o fibrosis. Bioquímicamente se comprobó aumento de AST, ALT e hipercolesterolemia en el 48 por cento, de GGT en el 52 por ciento y de FA en el 38 por ciento. Dieciocho pacientes eran obesos, 2 de ellos diabéticos, 2 con antecedentes de tóxicos y el restante hipotiroideo. Morfológicamente las biopsias fueron evaluadas semicuantitativamente para evaluar el grado de esteatosis, infiltración inflamatoria y fibrosis en una escala de 1 a 3. Se obtuvo un puntaje medio de 2,6 para esteatosis, 1,5 para la inflamación y 1,8 para la fibrosis. Cuatro pacientes presentaban una cirrosis ya constituida y se halló hialina de Mallory en 11 casos (52 por ciento). La EHNA es una enfermedad oligosintomática que puede hallarse en diferentes condiciones clínicas siendo más frecuente en la obesidad, con mayor prevalencia en mujeres e histologicamente indeferenciable de la estatohepatitis alcohólica (AU)

Hepatitis toxoplásmica / Hepatic toxoplasmic

Con el objeto de valorar el compromiso hepático en el curso de una toxoplasmosis aguda adquirida, se efectúo punción biopsia hepática a 9 pacientes adultos: 8 con linfadenitis y con meningoencefalitis el caso restante. Todos los pacientes alcanzaron títulos de Sabin-Feldman de 1:64.0000 y con la reacción de fijación de complemento superaron la dilución de 1:80. Presentaron hepatomegalia 7 de 9 pacientes. El hepatograma mostró una ASAT con una media de 30 UI/L (VR:20), una ALAT de 51 UI/L (VR:20), fosfatasa alcalina de 68 UI/L (VR:10-50) y GGT de 75 UI/L (VR:5-35). El cuadro histológico consistió en una hiperplasia e hipertrofia kupfferiana difusa con tendencia a conformar acúmulos focales en dos casos. No se observaron granulomas ni colestasis. La necrosis hepatocítica fue muy frecuente (6 de 9 casos) siempre focal y de poca monta y mostró en algún caso tendencia a localizarse en la zona centrolobulillar. El infiltrado portal fue constante en todos los casos a predominio neto de células mononucleares, pero sin tendencia a la destrucción de la lámina hepatocítica limitante. En tres casos se observaron francos signos de regeneración con abundantes hepatocitos binucleados y en un caso mitosis. La imagen histológica resultante es la de una hepatitis reactiva inespecífica. El sustrato morfológico explica la escasa repercución clínica y bioquímica que se observa en estos pacientes. La necrosis focal parece ser el hallazgo más constante junto a la hiperplasia kupfferiana difusa o focal

Hepatitis toxoplásmica / Hepatic toxoplasmic

Con el objeto de valorar el compromiso hepático en el curso de una toxoplasmosis aguda adquirida, se efectúo punción biopsia hepática a 9 pacientes adultos: 8 con linfadenitis y con meningoencefalitis el caso restante. Todos los pacientes alcanzaron títulos de Sabin-Feldman de 1:64.0000 y con la reacción de fijación de complemento superaron la dilución de 1:80. Presentaron hepatomegalia 7 de 9 pacientes. El hepatograma mostró una ASAT con una media de 30 UI/L (VR:20), una ALAT de 51 UI/L (VR:20), fosfatasa alcalina de 68 UI/L (VR:10-50) y GGT de 75 UI/L (VR:5-35). El cuadro histológico consistió en una hiperplasia e hipertrofia kupfferiana difusa con tendencia a conformar acúmulos focales en dos casos. No se observaron granulomas ni colestasis. La necrosis hepatocítica fue muy frecuente (6 de 9 casos) siempre focal y de poca monta y mostró en algún caso tendencia a localizarse en la zona centrolobulillar. El infiltrado portal fue constante en todos los casos a predominio neto de células mononucleares, pero sin tendencia a la destrucción de la lámina hepatocítica limitante. En tres casos se observaron francos signos de regeneración con abundantes hepatocitos binucleados y en un caso mitosis. La imagen histológica resultante es la de una hepatitis reactiva inespecífica. El sustrato morfológico explica la escasa repercución clínica y bioquímica que se observa en estos pacientes. La necrosis focal parece ser el hallazgo más constante junto a la hiperplasia kupfferiana difusa o focal (AU)

[Hepatitis B (HBV) and C (HBC) virus infections in Down's syndrome and in neuropsychiatric patients without Down's syndrome]. / La infección por el virus de la hepatitis B (VHB) y C (VHC) en el síndrome de Down y pacientes neuropsiquiátricos sin síndrome de Down.

UNLABELLED: Hepatitis B virus (HBV) markers are found with high frequency in immunocompromised individuals. In order to find out if this is also true for the hepatitis C virus (HCV), we have analyzed a group (G.1) of 46 patients (pts.) with Down syndrome, situation known to be associated with immunodepression G. 1. We compared them with a G. of 310 mentally retarded pts. without Down syndrome G. 2 and without evidence of immunological disfunction. All of them were studied for infection with HBV. All pts. in G. 1 and G. 2 were also tested for HCV. The pts. have been hospitalized in a specialized medical institution for mentally retarded on a long term basis and were followed during 1 year. Finally G 3 was composed of 5454 voluntary blood donors. MATERIAL AND METHODS: In all pts. search for HBV infection markers (anti-HBc, HBsAg, HBeAg by EIA test and HBV-DNA by nucleic acids hybridization) were performed. Search for HCV markers was done by a second generation EIA kit (Abbott Hepatitis C (rDNA) (Antigen). RESULTS: HBsAg was found to be positive in 12/46 (26%) of G. I and 25/310 (8%) of G. II (p < 0.001). HBeAg was positive in 8/12 (67%) of G. I and in 2/25 (8%) of G. II (p < 0.001). All HBeAg positive pts. had elevated values of DNA-HBV. In G. I, 4/12 (33%) pts. lost HBeAg during the observation period, one of them remained HBV-DNA positive and none become HBsAg negative.(ABSTRACT TRUNCATED AT 250 WORDS)