Management of overt hepatic encephalopathy

Hepatic encephalopathy (HE) is a potentially reversible state of impaired cognitive function or altered consciousness in patients with liver disease or portosystemic shunting. Overt HE is a particularly pressing problem. Given the many targets of treatment and lack of a clear singular cause of overt HE, there is no consensus on a single best treatment. Over the past several years, high-quality studies have been conducted on the various pharmacologic therapies for HE and, as more data emerge, hopefully HE will become a much more easily treated complication of decompensated liver disease.     

Treating hepatitis C: current standard of care and emerging direct-acting antiviral agents

Summary. During the late 1990s and early 2000s, major advances were made in the treatment of patients with chronic hepatitis C virus (HCV) infection. Interferon, combination interferon plus ribavirin (RBV) and pegylated interferon plus RBV increased sustained virologic response (SVR) rates from ~5% to ~40-80%, depending on the genotype of HCV infection. Advances in molecular biology have allowed investigators to begin to understand the mechanisms of HCV infection and replication. Advances in understanding of viral kinetics have provided tools to identify patients who are most likely to attain SVR. With the advances in the science of HCV infection, the first part of the 21st century has seen the development and early introduction of a number of direct-acting antiviral (DAA) drugs. These novel medications interfere with critical steps in HCV replication and have the potential to significantly increase SVR rates. This article will review the key elements of HCV replication and evaluate the various classes of new and investigational DAA that have the potential to create a revolution in the management of patients with chronic hepatitis C.     

Interferon Free Hepatitis C Treatment Regimens: The Beginning of Another Era

Hepatitis C is a virus affecting millions worldwide and is a major health risk. With the potentially severe adverse event profile of the current backbone of therapy, interferon, there is an impetus to discover interferon free treatment regimens. With the development of new oral direct acting antivirals, interferon free regimens may be available in the next few years. This article discusses some of the preliminary data from interferon free studies.     

Eleven novel mutations in the factor VIII gene from Brazilian hemophilia A patients

The molecular characterization of the mutations in hemophilia A patients is hampered by the large size of the factor VIII gene and the great heterogeneity of mutations. In this study, we have performed a protocol involving multiplex polymerase chain reaction in which 19 exons were amplified in four different combinations followed by nonradioactive single-strand conformational polymorphism (SSCP) to screen for mutations. Southern blotting was used to detect inversion of the factor VIII gene resulting from recombination between copies of the gene A (F8A) located in intron 22 of the factor VIII gene and two copies close telomeric region of X chromosome. Forty-two hemophilia A patients (21 with severe and 21 with mild-to-moderate disease) were studied. The inversion of factor VIII occurred in 13 of 21 patients affected by severe hemophilia A. One patient showed a large extra band in addition to the three bands observed after Southern blotting with the F8A probe. An abnormal electrophoretic pattern of SSCP was detected in 85% and 50% of the patients affected by mild-to-moderate and severe disease, respectively. Sixteen different mutations were identified. Eleven mutations were novel and comprised 9 point mutations and 2 small deletions. This study shows that the methodology used is safe and rapid and has potential for detecting almost all of the genetic defects of the studied hemophilia A patients.     

Detection of the hemoglobin E mutation using the color complementation assay: application to complex genotyping

The color complementation assay (CCA) is a method of allele-specific DNA amplification by which competitive priming and extension of fluorescently labeled oligonucleotide primers determine the color of DNA amplification product. This diagnostic method precludes the need for radioisotopes, electrophoresis, and multiple high-stringency reaction conditions. The multiplicity of mutant globin genes present in Southeast Asians complicates clinical diagnosis and underscores the importance of DNA-based diagnostic methods. We have applied CCA to distinguish beta A and beta E alleles. Competing 15mer primers were a fluorescein-labeled complement to beta A and a rhodamine-labeled complement to beta E, identical except for their central nucleotides. A common unlabeled primer was used to amplify DNA product, the color of which was determined by the perfectly complementary primer. Color photography and spectrofluorometry, as well as a method of black-white photography that we developed to distinguish fluorescein- and rhodamine- labeled DNA, were used to record results. We applied CCA to define the complex genotype of a Thai woman with thalassemia intermedia, 96% HbE, and 4% HbF whose possible genotypes included several permutations of alpha-thalassemia, beta-thalassemia, and beta E genes. zeta-Globin gene mapping of DNA doubly digested with Bg/II and Asp 718 showed the -alpha 3.7/--SEA genotype, and CCA confirmed homozygous beta E/beta E. The CCA is useful for diagnosing the compound hemoglobin genotypes of Southeast Asians and could be applied also to prenatal diagnosis in this population.     

Early hepatic nodular hyperplasia and submicroscopic fibrosis associated with 6-thioguanine therapy in inflammatory bowel disease

BACKGROUND: 6-Thioguanine (6-TG) has been used as an alternative thiopurine for inflammatory bowel disease (IBD) patients not responsive to or intolerant of azathioprine (AZA) and 6-mercaptopurine (6-MP). 6-TG-related hepatotoxicity, including liver biochemistry value elevations, sinusoidal collagen deposition on electron microscopy, and veno-occlusive disease, have been described related to its use as therapy for neoplastic disease. METHODS: We studied 38 liver biopsies from patients treated with 6-TG, almost all of whom (n = 125) received 6-TG for 1 to 3 years at the Inflammatory Bowel Disease Center at Cedars-Sinai Medical Center. All biopsies were fixed in 4% buffered formalin and prepared in the usual manner. Hematoxylin and eosin, Masson's trichrome (trichrome), and reticulin silver impregnation (reticulin) stained slides were studied. In 23 cases, tissue was also prospectively fixed in glutaraldehyde and processed for electron microscopy. RESULTS: In 20 of the 37 patients studied (53%), nodular regeneration of varying degree was seen with reticulin. In only 4 of these 20 instances (11% of the total) were the changes seen with hematoxylin and eosin and in 3 of the 4, only in retrospect after studying the reticulin preparation. Minimal fibrosis was seen with trichrome in only 13 biopsies (34%), but sinusoidal collagen deposition was observed in 14 of the 23 cases studied with electron microscopy (60%). The biopsy from the 1 patient with nodular hyperplasia obvious with hematoxylin and eosin also demonstrated changes of venous outflow obstruction. CONCLUSIONS: 6-TG-treated IBD patients are at significant risk for nodular hyperplasia, early fibrosis and, less often, venous outflow disease (Budd-Chiari). The natural history of these changes is unknown and follow-up biopsies are needed to determine histologic and clinical sequela. Patients not demonstrating nodular hyperplasia or fibrosis who continue with 6-TG because there are no better therapeutic choices should be periodically rebiopsied.     

垂全催乳素瘤的诊断和治疗指南

3.男性:高催乳素血症通常导致阳痿、不孕和性功能低下.男性患者通常为大腺瘤,有神经系统症状.其原因可能是对症状认识的延误或者肿瘤生物学行为的差异.