In a systematic review and meta-analysis, Giovanni Musso and colleagues examine the association between non-alcoholic fatty liver disease and chronic kidney disease. Please see later in the article for the Editors' Summary

The CD4 (T4) antigen is a cell-surface glycoprotein that is expressed predominantly on the surface ofhelper T cells and has been implicated in the regulation of T-cell activation and in the associative recognition of class II antigens of the major histocompatibility complex. In addition, the CD4 antigen appears to serve as a receptor for the human immunodeficiency virus (HIV). An important question has been whether the CD4 receptor is linked to an intracellular mediator that could regulate the activation of the CD4+ subset. In this paper, we provide preliminary evidence that the CD4 receptor is complexed in detergent lysates to a protein-tyrosine kinase (PTK) of 55-60 kDa, which is expressed specifically in T cells.The PTK is the human analogue of the murine pp56ISTRA (ppS6Ick) and has significant homology with c-src, c-yes, and other members of the src family. The identification of the PTK associated with CD4 receptor was made by use of an antiserum to a synthetic peptide that was deduced from the DNA sequence of PTK. Two-dimensional nonequilibrium pH gradient gel electrophoresis/NaDodSO4/PAGE revealed the kinase to focus as a heterogeneous collection of spots in the pH range of 4.0-5.0. Furthermore, in vitro phosphorylation revealed the phosphorylation of two additional polypeptides at 40 and 80 kDa, in addition to the autophosphorylation of the PIK at 55-60 kDa.The potential importance of the association between the CD4 receptor and the PTK of T cells is discussed in relation to T-cell activation and HIV infectivity.The CD4 (T4) antigen is a polypeptide of 55 kDa that is expressed predominately on the surface of helper T cells and has been implicated in association with the T3 (CD3)-Ti complex in the recognition of class II antigens of the major histocompatibility complex (1, 2). The CD4 antigen also appears to serve as a receptor for the human immunodeficiency virus (HIV) [the acquired immunodeficiency syndrome (AIDS) virus] (3-5). Structurally, the CD4 antigen is a member of the immunoglobulin superfamily (6) and, as such, appears capable of regulating the proliferation of the CD4 subset of T cells (7)(8)(9)(10)(11). Monoclonal antibodies to the CD4 antigen were initially reported to inhibit specific T-cell function by reducing the strength of interaction of the T cell with its target (1, 2, 7). However, it also appears that monoclonal antibodies to the CD4 receptor can inhibit or potentiate the activation of T lymphocytes in a manner independent of the recognition of HLA-D region antigens (8)(9)(10)(11). The inhibitory effect of antibodies to CD4 appears to preferentially influence the T4+2H4+ subset within the CD4 population, a subset defined by the differential expression of the L-C/T200 (CD45) antigens (12,13 Tyrosine phosphorylation is thought to be a relatively rare modification to proteins; however, the past few years have seen a rapidly expanding number of retroviral oncogenes and cellular receptors within the src family. These include the retroviral oncogenes such as v-abl, v-erb, v-fes/...

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Bile acids (BAs) are a group of important physiological agents for cholesterol metabolism, intestinal nutrient absorption, and biliary secretion of lipids, toxic metabolites, and xenobiotics. Extensive research in the last two decades has unveiled new functions of BAs as signaling molecules and metabolic regulators that modulate hepatic lipid, glucose, and energy homeostasis through the activation of nuclear receptors and G-protein-coupled receptor signaling in gut-liver metabolic axis involving host-gut microbial co-metabolism. Therefore, investigation of serum BA profiles, in healthy human male and female subjects with a wide range of age and body mass index (BMI), will provide important baseline information on the BA physiology as well as metabolic homeostasis among human subjects that are regulated by two sets of genome, host genome, and symbiotic microbiome. Previous reports on age- or gender-related changes on BA profiles in animals and human showed inconsistent results, and the information acquired from various studies was highly fragmentary. Here we profiled the serum BAs in a large population of healthy participants (n = 502) and examined the impact of age, gender, and BMI on serum BA concentrations and compositions using a targeted metabonomics approach with ultraperformance liquid chromatography triple-quadrupole mass spectrometry. We found that the BA profiles were dependent on gender, age, and BMI among study subjects. The total BAs were significantly higher in males than in females (p < 0.05) and higher in obese females than in lean females (p < 0.05). The difference in BA profiles between male and female subjects was decreased at age of 50-70 years, while the difference in BA profiles between lean and obese increased for subjects aged 50-70 years. The study provides a comprehensive understanding of the BA profiles in healthy subjects and highlights the need to take into account age, gender, and BMI differences when investigating pathophysiological changes of BAs resulting from gastrointestinal diseases.

Percutaneous needle biopsies are frequently used to evaluate focal lesions of the liver. Needle-tract implantation of hepatocellular cancer has been described in case reports, but the true risk for this problem has not been clearly defined. We retrospectively reviewed 91 cases of hepatocellular cancer during a 4-year period from 1994 to 1997. Data on diagnostic studies, therapy, and outcome were noted. Of 91 patients with hepatocellular cancer, 59 patients underwent percutaneous needle biopsy as part of their diagnostic workup for a liver mass. Three patients (5.1%) were identified with needle-tract implantation of tumor. Two patients required en bloc chest wall resections for implantation of hepatocellular cancer in the soft tissues and rib area. The third patient, who also received percutaneous ethanol injection of his tumor, required a thoracotomy and lung resection for implanted hepatocellular cancer. Percutaneous needle biopsy of suspicious hepatic lesions should not be performed indiscriminately because there is a significant risk for needle-tract implantation. These biopsies should be reserved for those lesions in which no definitive surgical intervention is planned and pathological confirmation is necessary for a nonsurgical therapy. Copyright 2000 by the American Association for the Study of Liver DiseasesF ocal lesions of the liver often present challenging diagnostic and management problems. Incidental detection of hepatic lesions by the increasing use of modern imaging techniques further complicates the problem. The diagnostic armamentarium used to evaluate these lesions has been enhanced with the advent of computed tomographic (CT) scan and ultrasound-guided needle biopsy.Although percutaneous needle biopsy of the liver has been shown to be a generally safe procedure, serious complications have been reported. Complications include hemorrhage, biliary leak, pneumothorax, intrahepatic hematomas, diagnostic error, and needletract seeding. 1 Needle-tract seeding has been reported previously with a low incidence of 0.005% (3 of 63,108 cases). This study included, however, a large series of biopsies of many different organs (liver, pancreas, lymph nodes, kidney, spleen, and adrenal gland) performed for a variety of reasons, both neoplastic and nonneoplastic. 2 Several cases showing seeding of hepatocellular carcinoma during percutaneous procedures have been documented at our institution and have prompted closer scrutiny of this problem. MethodsAll patients referred to our group of surgeons with hepatocellular carcinoma over the 5-year period between January 1993 and December 1997 were the subjects of this study. Records were retrospectively reviewed for diagnostic studies, procedures performed, pathological examination, and outcome. Ninety-one patients with hepatocellular carcinoma were identified, and patterns of recurrence were noted. Three documented cases of needle-tract seeding were found and form the basis of this report. ResultsDuring the 5-year study period between January 1993 and December 1997, ...

Aim: Worldwide, hepatocellular cancer (HCC) is the fourth leading cause of cancer death and occurs 3 times more commonly in males than females. Current surveillance practices do not fully address gender differences in HCC. Methods: Clinical characteristics and survival were compared between males and females using a prospectively collected database of HCC patients. Results: In a cohort of 1206 patients, 307 (25%) were female who presented with older age, more non-alcoholic fatty liver disease/steatohepatitis (NAFLD/NASH), family history of HCC, and hypertension. Males (75%) were more likely to use alcohol and cigarettes. Females were more likely to undergo HCC surveillance, have smaller tumor size at diagnosis, and less vascular involvement. Males who met Milan criteria were more likely to undergo liver transplant than women who met the criteria. Median/mean survival was similar between the genders. Multivariate analysis showed that NAFLD/NASH was predictive of mortality for both males and females, age and smoking were predictive of mortality for males, and transplant was predictive of survival for males. Conclusion: Gender differences in HCC appear related to both behavioral risk factors and biologic factors. Older females with HCC have more NAFLD/NASH and may be overlooked by current surveillance guidelines. These gender disparities may lend support to future studies of gender-based HCC screening.