Efficacy and safety of oral naltrexone treatment for pruritus of cholestasis, a crossover, double blind, placebo-controlled study.

BACKGROUND/AIMS: To assess the efficacy and safety of naltrexone for the short and long term treatment of pruritus of cholestasis. METHODS: Twenty patients with pruritus and cholestasis were included. A baseline pruritus score was obtained over 1 week. Patients were then randomized to receive 50 mg/day of naltrexone or placebo for 2 weeks. Subsequently, a 1-week washout period ensued and patients were crossed over to the other therapy for 2 additional weeks. Pruritus was assessed daily with a visual analogue scale (VAS) from 0 to 10. Patients whose pruritus decreased >50% of basal with naltrexone received naltrexone 50 mg/day for 2 additional months. RESULTS: Mean basal VAS was similar in both groups. VAS showed greater and more significant changes with naltrexone than with placebo (P<0.0003). In nine out of 20 patients (45%) receiving naltrexone, pruritus decreased >50% compared to basal value, including five whose pruritus disappeared completely. No significant changes were observed in serum biochemistry. Most of the adverse events that occurred during the first 48 h of naltrexone therapy were consistent with opioid withdrawal-like phenomena and spontaneously disappeared 2 days after starting treatment. CONCLUSIONS: Naltrexone can be considered as an alternative option to treat pruritus of cholestasis. In the current study, side effects were transient and did not require specific medication.

Familial association in autoimmune liver disease.

The occurrence of autoimmune liver disease in members of the same family is hardly a frequent observation in clinical practice. In a group of 204 cases of primary biliary cirrhosis (PBC) (196 women) and 219 of type 1 autoimmune hepatitis (AIH) (183 women), seen from 1985 to 2000, family occurrence of autoimmune liver disease was investigated. Diagnosis of both entities was based on clinical criteria, immunological studies and liver biopsy. Six families were identified with 2 members each presenting with autoimmune liver disease. In 4 of them the index case had an AIH. This association was observed between mother and daughter in 3 instances. In the remaining AIH index case the association found was with a PBC in her sister. In the other two families the index cases were PBC. In one of them, PBC and AIH association were observed in sisters. Lastly, in another case, an antimitochondrial (AMA) negative variant of PBC was detected in mother and her daughter. The low frequency of family association observed in this cohort could be due to the fact that only symptomatic cases were included. Concurrent autoimmune manifestations were confirmed in 5 members of 6 families (42%). Our results, given the concurrence of both liver diseases in the same family, suggest a link among diverse entities of the autoimmune lineage. The frequency of AIH family association seems to be more prominent in this series than that of PBC. It is also shown that family association in the case of an AMA-negative variant of PBC is feasible, thus confirming that no substantial differences exist between the latter and AMA-positive PBC.

Primary biliary cirrhosis and hepatocellular carcinoma.

The findings by epidemiological studies on the link between PBC and HCC are in general agreement with the notion that cirrhosis is a risk factor for HCC development. From the clinical perspective, this implies that in PBC patients with cirrhosis, the screening for HCC should be considered for evaluating prognosis as well as therapeutic options. At this time, it is not possible to determine whether any PBC-specific risk factors other than cirrhosis per se exist for the development of HCC. Identification of such risk factors may point to new mechanisms involved in the carcinogenesis of HCC. In order to answer the question whether the underlying mechanisms for PBC are risk factors for HCC, more aggressive clinical studies with larger patient populations are needed. Such studies should include patients with PBC as well as patients with cirrhosis of other etiologies, both have to be carefully matched for patient characteristics including race, gender, age, disease stage and period of follow-up. On the other hand, the resolution of this issue also relies on a better understanding of the molecular pathogenesis of PBC itself.

Familial association in autoimmune liver disease

The occurrence of autoimmune liver disease in members of the same family is hardly a frequent observation in clinical practice. In a group of 204 cases of primary biliary cirrhosis (PBC) (196 women) and 219 of type 1 autoimmune hepatitis (AIH) (183 women), seen from 1985 to 2000, family occurrence of autoimmune liver disease was investigated. Diagnosis of both entities was based on clinical criteria, immunological studies and liver biopsy. Six families were identified with 2 members each presenting with autoimmune liver disease. In 4 of them the index case had an AIH. This association was observed between mother and daughter in 3 instances. In the remaining AIH index case the association found was with a PBC in her sister. In the other two families the index cases were PBC. In one of them, PBC and AIH association were observed in sisters. Lastly, in another case, an antimitochondrial (AMA) negative variant of PBC was detected in mother and her daughter. The low frequency of family association observed in this cohort could be due to the fact that only symptomatic cases were included. Concurrent autoimmune manifestations were confirmed in 5 members of 6 families (42). Our results, given the concurrence of both liver diseases in the same family, suggest a link among diverse entities of the autoimmune lineage. The frequency of AIH family association seems to be more prominent in this series than that of PBC. It is also shown that family association in the case of an AMA-negative variant of PBC is feasible, thus confirming that no substantial differences exist between the latter and AMA-positive PBC. (AU)

Familial association in autoimmune liver disease

The occurrence of autoimmune liver disease in members of the same family is hardly a frequent observation in clinical practice. In a group of 204 cases of primary biliary cirrhosis (PBC) (196 women) and 219 of type 1 autoimmune hepatitis (AIH) (183 women), seen from 1985 to 2000, family occurrence of autoimmune liver disease was investigated. Diagnosis of both entities was based on clinical criteria, immunological studies and liver biopsy. Six families were identified with 2 members each presenting with autoimmune liver disease. In 4 of them the index case had an AIH. This association was observed between mother and daughter in 3 instances. In the remaining AIH index case the association found was with a PBC in her sister. In the other two families the index cases were PBC. In one of them, PBC and AIH association were observed in sisters. Lastly, in another case, an antimitochondrial (AMA) negative variant of PBC was detected in mother and her daughter. The low frequency of family association observed in this cohort could be due to the fact that only symptomatic cases were included. Concurrent autoimmune manifestations were confirmed in 5 members of 6 families (42). Our results, given the concurrence of both liver diseases in the same family, suggest a link among diverse entities of the autoimmune lineage. The frequency of AIH family association seems to be more prominent in this series than that of PBC. It is also shown that family association in the case of an AMA-negative variant of PBC is feasible, thus confirming that no substantial differences exist between the latter and AMA-positive PBC.

Familial association in autoimmune liver disease.

The occurrence of autoimmune liver disease in members of the same family is hardly a frequent observation in clinical practice. In a group of 204 cases of primary biliary cirrhosis (PBC) (196 women) and 219 of type 1 autoimmune hepatitis (AIH) (183 women), seen from 1985 to 2000, family occurrence of autoimmune liver disease was investigated. Diagnosis of both entities was based on clinical criteria, immunological studies and liver biopsy. Six families were identified with 2 members each presenting with autoimmune liver disease. In 4 of them the index case had an AIH. This association was observed between mother and daughter in 3 instances. In the remaining AIH index case the association found was with a PBC in her sister. In the other two families the index cases were PBC. In one of them, PBC and AIH association were observed in sisters. Lastly, in another case, an antimitochondrial (AMA) negative variant of PBC was detected in mother and her daughter. The low frequency of family association observed in this cohort could be due to the fact that only symptomatic cases were included. Concurrent autoimmune manifestations were confirmed in 5 members of 6 families (42

). Our results, given the concurrence of both liver diseases in the same family, suggest a link among diverse entities of the autoimmune lineage. The frequency of AIH family association seems to be more prominent in this series than that of PBC. It is also shown that family association in the case of an AMA-negative variant of PBC is feasible, thus confirming that no substantial differences exist between the latter and AMA-positive PBC.

Distribucion de los genotipos del virus de la hepatitis C en una poblacion argentina de drogadictos endovenosos / Distribution of the genotypes of Hepatitis C virus in a Argentine population of intravenous drug addicts

El antecedente de drogadicción endovenosa constituye un factor de riesgo poco frecuente en pacientes (pts) con infección crónica por el virus C (HCV) en la Argentina, representando en nuestro servicio menos del 10 por ciento. Nos propusimos determinar la prevalencia de los diferentes genotipos (Gt) del HCV en un grupo de pts con hepatitis crónica por HCV con antecedentes de drogadicción endovenosa. Un total de 68 pts con antecedentes de drogadicción endovenosa y hepatitis crónica HCV fueron comparados con 68 pts de igual edad y sexo pero sin el antecedente de drogadicción. La biopsia hepática fue realizada en todos los pts. La genotipificación del HCV fue efectuada por INNO LiPA (Innogenetics). Para el análisis estadístico se empleó el test de Student. La edad media en ambos grupos fue de 35 + 7.8 años correspondiendo 50 pts al sexo masculino. No se observaron diferencias entre ambos grupos en la prevalencia de los GT 1a, 2a/c e infecciones mixtas. El Gt 1b fue más frecuente en el grupo control 26/68 (38,2 por ciento) que en el de drogadictos 13/68 (19.1 por ciento) (p = 0.0228). También fue observada una diferente prevalencia en el GT3, presente en 29/68 (42.6 por ciento) de los drogadictos y en 8/68 (11.8 por ciento) del grupo control (p = 0.0001). El Gt1a fue el segundo más frecuente en el grupo con antecedentes de drogadicción 18/68 (26.5 por ciento). La infección simultánea con el HIV fue observada en 8 pts con antecedentes de drogadicción y en ninguno del grupo control. La biopsia hepática mostró una mayor prevalencia de lesiones leves en el grupo control 39/68 (57.3 por ciento) que en los pts con antecedentes de drogadicción 22/68 (32.4 por ciento) (p = 0.0058). En los pts infectados con el Gt3 la hepatitis crónica severa y cirrosis fueron más frecuentes en los pts con antecedentes de drogadicción. Se concluye que en nuestro medio el Gt 3 es el más prevalente en los pts con antecedentes de drogadicción endovenosa. Las formas de hepatitis leves son menos frecuentes en los pts con antecedentes de drogadicción. A pesar del pequeño número de pts coinfectados con el HIV es importante notar que el 25 por ciento de ellos presentaron hepatitis crónica severa o cirrosis. (AU)

Distribucion de los genotipos del virus de la hepatitis C en una poblacion argentina de drogadictos endovenosos / Distribution of the genotypes of Hepatitis C virus in a Argentine population of intravenous drug addicts

El antecedente de drogadicción endovenosa constituye un factor de riesgo poco frecuente en pacientes (pts) con infección crónica por el virus C (HCV) en la Argentina, representando en nuestro servicio menos del 10 por ciento. Nos propusimos determinar la prevalencia de los diferentes genotipos (Gt) del HCV en un grupo de pts con hepatitis crónica por HCV con antecedentes de drogadicción endovenosa. Un total de 68 pts con antecedentes de drogadicción endovenosa y hepatitis crónica HCV fueron comparados con 68 pts de igual edad y sexo pero sin el antecedente de drogadicción. La biopsia hepática fue realizada en todos los pts. La genotipificación del HCV fue efectuada por INNO LiPA (Innogenetics). Para el análisis estadístico se empleó el test de Student. La edad media en ambos grupos fue de 35 + 7.8 años correspondiendo 50 pts al sexo masculino. No se observaron diferencias entre ambos grupos en la prevalencia de los GT 1a, 2a/c e infecciones mixtas. El Gt 1b fue más frecuente en el grupo control 26/68 (38,2 por ciento) que en el de drogadictos 13/68 (19.1 por ciento) (p = 0.0228). También fue observada una diferente prevalencia en el GT3, presente en 29/68 (42.6 por ciento) de los drogadictos y en 8/68 (11.8 por ciento) del grupo control (p = 0.0001). El Gt1a fue el segundo más frecuente en el grupo con antecedentes de drogadicción 18/68 (26.5 por ciento). La infección simultánea con el HIV fue observada en 8 pts con antecedentes de drogadicción y en ninguno del grupo control. La biopsia hepática mostró una mayor prevalencia de lesiones leves en el grupo control 39/68 (57.3 por ciento) que en los pts con antecedentes de drogadicción 22/68 (32.4 por ciento) (p = 0.0058). En los pts infectados con el Gt3 la hepatitis crónica severa y cirrosis fueron más frecuentes en los pts con antecedentes de drogadicción. Se concluye que en nuestro medio el Gt 3 es el más prevalente en los pts con antecedentes de drogadicción endovenosa. Las formas de hepatitis leves son menos frecuentes en los pts con antecedentes de drogadicción. A pesar del pequeño número de pts coinfectados con el HIV es importante notar que el 25 por ciento de ellos presentaron hepatitis crónica severa o cirrosis.

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 involvement.

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 involvement. (AU)