Javier Brahm

The combination of ursodeoxycholic acid and methotrexate for primary biliary cirrhosis is not better than ursodeoxycholic acid alone

BACKGROUND/AIMS Many therapies have been tried in primary biliary cirrhosis. It has been suggested that a combination of ursodeoxycholic acid and methotrexate may offer advantages. Because the benefit and safety of this combination is uncertain, we conducted this prospective, randomized, double-blind, controlled trial. METHODS Twenty-five patients with well-defined primary biliary cirrhosis were randomly assigned to receive either ursodeoxycholic acid (500 mg/day) plus methotrexate (10 mg/week) or ursodeoxycholic acid plus placebo for a period of 48 weeks. Clinical, biochemical and histologic evolution were assessed. RESULTS In both groups the clinical response was similar and heterogeneous. In patients of ursodeoxycholic acid alone group, biochemical and histologic changes were comparable to those of patients of ursodeoxycholic acid plus methotrexate at 48 weeks. The addition of methotrexate was not associated with substantial adverse affects. CONCLUSIONS The use of methotrexate in combination with ursodeoxycholic acid was not followed by an additive benefit over ursodeoxycholic acid alone, nor was substantial toxicity added. Unless larger and longer controlled trials with clinical, biochemical and histologic controls show it to be a safe and effective therapy for primary biliary cirrhosis, ursodeoxycholic acid+methotrexate should not be used as a proven and accepted treatment.

IL28B polymorphisms associated with therapy response in Chilean chronic hepatitis C patients

AIM To analyze the association of three IL28B single nucleotide polymorphisms with response to therapy in Chilean patients infected with hepatitis C virus (HCV). METHODS We studied two groups of patients with chronic HCV infection (genotype 1), under standard combined treatment with pegylated interferon plus ribavirin. One group consisted of 50 patients with sustained virological response, whereas the second group consisted of 49 null responders. In order to analyze the IL28B single nucleotide polymorphisms rs12979860, rs12980275 and rs8099917, samples were used for polymerase chain reaction amplification, and the genotyping was performed by restriction fragment length polymorphism. RESULTS The IL28B rs12979860 CC, rs12980275 AA and rs8099917 TT genotypes were much more frequently found in patients with sustained virological response compared to null responders (38%, 44% and 50% vs 2%, 8.2% and 8.2%, respectively). These differences were highly significant in all three cases (P < 0.0001). CONCLUSION The three IL28B polymorphisms studied are strongly associated with sustained virological response to therapy in Chilean patients with chronic HCV (genotype 1).

Phylogenetic analysis of hepatitis B virus genotype F complete genome sequences from Chilean patients with chronic infection

Molecular epidemiological data concerning the hepatitis B virus (HBV) in Chile are not known completely. Since the HBV genotype F is the most prevalent in the country, the goal of this study was to obtain full HBV genome sequences from patients infected chronically in order to determine their subgenotypes and the occurrence of resistance‐associated mutations. Twenty‐one serum samples from antiviral drug‐naive patients with chronic hepatitis B were subjected to full‐length PCR amplification, and both strands of the whole genomes were fully sequenced. Phylogenetic analyses were performed along with reference sequences available from GenBank (n = 290). The sequences were aligned using Clustal X and edited in the SE‐AL software. Bayesian phylogenetic analyses were conducted by Markov Chain Monte Carlo simulations (MCMC) for 10 million generations in order to obtain the substitution tree using BEAST. The sequences were also analyzed for the presence of primary drug resistance mutations using CodonCode Aligner Software. The phylogenetic analyses indicated that all sequences were found to be the HBV subgenotype F1b, clustered into four different groups, suggesting that diverse lineages of this subgenotype may be circulating within this population of Chilean patients. J. Med. Virol. 83:1530–1536, 2011.

Prevalence of hepatitis B virus genotypes in chronic carriers in Santiago, Chile

The eight genotypes (designated A–H) of hepatitis B virus (HBV) display distinctive geographical distribution worldwide, with genotypes A, D and F frequently detected in South America. To determine the prevalence of HBV genotypes in Santiago, Chile, 131 samples from chronic carriers were used for PCR amplification, and genotyping was performed by RFLP. The results indicated that genotype F was the most prevalent among HBV carries (84% of the cases), whereas genotypes A, B, C and D were found at a prevalence of 3.8, 3.8, 6.1, and 2.3%, respectively. We discuss these data in the complex scenario of HBV epidemiology.

Hepatitis crónica por virus C y enfermedad celíaca: una asociación infrecuente

Celiac sprue (CS) has been described in association with hepatitis C virus (HCV) as another immunologic manifestation of this infectious disease. We report 2 patients, a 42-year-old woman and a 59-year-old man, with chronic HCV hepatitis. Upper digestive endoscopy and duodenal biopsy were performed to investigate diverse symptoms. The results of histological analysis and serological study were compatible with CS. The association between both diseases, including immunological aspects and the implications of anti-HCV treatment, is discussed.

Estudio de enfermedad celíaca en pacientes con enfermedad por hígado graso no alcohólico y con hepatopatías autoinmunes

Resumen La enfermedad celiaca (EC) se ha asociado con higado graso no alcoholico (HGNA) y hepatopatias cronicas, como cirrosis biliar primaria (CBP), hepatitis autoinmune (HAI) y colangitis esclerosante primaria (CEP). Objetivo Estudiar la frecuencia de marcadores serologicos de EC en pacientes con las hepatopatias mencionadas y su correlacion con la biopsia duodenal. Pacientes y metodos En pacientes con HGNA, CBP, HAI y CEP, se estudiaron los anticuerpos IgA antiendomisio (AE) por inmunofluorescencia indirecta, IgA-IgG antigliadina (AG) y anticuerpos antitransglutaminasa tisular humano (h-ATG) mediante ELISA. En los casos positivos para al menos un marcador, se realizo una biopsia duodenal. Resultados Nueve de 101 pacientes tuvieron marcadores positivos de EC (8,9%): 7 de ellos solo h-ATG, uno con AE y AG, y uno con los tres marcadores. Los casos positivos fueron 3/38 (7,9%) en HGNA, 3/44 (6,8%) en CBP, 2/16 (12,5%) en HAI y 1/3 en CEP. Cuatro casos con h-ATG positivos tuvieron titulos bajos (20-30 U; valores normales 30 U). Se realizo una endoscopia con biopsia duodenal en 8 de ellos, que fue normal en 7 y compatible con EC en etapa I de Marsh en un paciente con HGNA, AG y AE positivos. El caso del unico paciente con los tres marcadores positivos no se estudio por fallecer contemporaneamente. Ninguno de ellos tenia clinica sugerente de EC. Conclusiones La frecuencia del marcador serologico h-ATG de EC es significativa en las hepatopatias descritas. Sin embargo, debe confirmarse con biopsia duodenal, dada las elevadas tasas de histologia normal en nuestro estudio.

Full-Genome Sequence of a Hepatitis B Virus Genotype F1b Clone from a Chronically Infected Chilean Patient

ABSTRACT The hepatitis B virus (HBV) is a DNA virus belonging to the Hepadnaviridae family. Viral isolates have been classified into 10 genotypes, named from A to J, and several subtypes. We report the full-genome sequence from a single molecular clone of HBV genotype F1b, amplified from a chronically infected Chilean patient.

Hemobilia traumática: caso clínico y revisión de la literatura médica

Traumatic hemobilia consists of hemorrhage into the biliary tract as a result of abdominal trauma. The classical triad of biliary colic, jaundice and upper gastrointestinal bleeding is not a constant finding, and clinically silent hemobilia has been reported. The treatment of choice is selective embolization, but spontaneous cessation of bleeding can occur, especially in mild forms. We report a case of occult traumatic hemobilia in which the diagnosis was suggested by transitory changes in ultrasonography and hepatic biochemistry.

Fallo hepático fulminante por un linfoma no hodgkiniano de estirpe T asociado al virus de la hepatitis C. Caso clínico

Hematological malignancies can affect the liver, without producing severe hepatic involvement. We report the case of a 57-year-old man with hepatitis C virus infection and mild chronic hepatitis without antiviral treatment, who developed an aggressive T-cell non-Hodgkins lymphoma confirmed by histological studies including liver, lymph nodes and bone marrow. The patient developed massive hepatic infiltration and acute liver failure. Rescue chemotherapy was administered but the patient died soon after with severe lactic acidosis. The immunopathological features of this association and the few reports of cases presenting with acute liver failure are reviewed.

[Hepatitis E virus seroprevalence: a reappraisal].

Reported seroprevalence of hepatitis E virus (HEV) in developed countries is between 0.3-53%. Published data relies on the assays used and its technical performance. Sensitivity on new available tests has improved, which has changed HEV seroprevalence around the world. We re-evaluated retrospectively, 178 serum samples of patients with previous anti HEV IgG determination between 2009 and 2012. Initial analysis was performed with ELISA kit Genelabs (Singapore), with 7.3% positivity. The reevaluation was done with ELISA kit AccuDiag TM HEV-IgG (Diagnostic Automation, United States), with reported sensitivity and specificity over 99.8%. With the new assay, 32.6% positive samples were found, significantly greater to the previous result (p<0.001) (4.5 times more). There were no differences in gender but a significant association between age and HEV IgG seropositivity was found (p<0.001). This suggests that previous testing might have underestimated HEV seroprevalence in Chile, which should be reevaluated using the new available test.