Who to Test for Hepatitis C Virus in the Middle East and North Africa?: Pooled Analyses of 2,500 Prevalence Measures, Including 49 Million Tests.

Expanding hepatitis C virus (HCV) treatment coverage is challenged by limited testing and diagnosis. This study assessed the risk of exposure, for the Middle East and North Africa, by population, yields of testing, and program efficiency of testing strategies. A standardized and systematically assembled database of 2,542 HCV antibody prevalence studies on 49 million individuals was analyzed. Random effects meta-analyses were conducted to estimate pooled measures for risk of exposure, risk ratio (RR) of exposure, and yields of testing. Program expansion path curves were calculated to assess program efficiency. Countries clustered into two patterns: generalized versus concentrated epidemics. In generalized epidemics (Egypt and Pakistan) relative to general populations, RR of exposure was 6.8 for people who inject drugs (PWID), 6.7 for populations with liver conditions, and 5.0 for populations with high-risk health care exposures. In concentrated epidemics (remaining countries), corresponding RRs were 97.2, 45.1, and 22.2, respectively. In generalized epidemics, the number of tests needed to identify a chronic infection was 2.5 for PWID, 2.4 for populations with liver conditions, 2.7 for populations with high-risk health care exposures, and 14.2 for general populations. In concentrated epidemics, corresponding numbers were 2.8, 8.6, 5.1, and 222.2, respectively. Program expansion path curves demonstrated major gains in program efficiency by targeting specific populations. Risk of exposure varies immensely by population and shows a distinctive hierarchy, particularly in concentrated epidemics. Testing strategies can be much more efficient through population prioritization by risk of exposure. General population testing is not programmatically efficient in concentrated epidemics

Model-guided therapy for hepatocellular carcinoma: A role for information technology in predictive, preventive and personalized medicine

Predictive, preventive and personalized medicine (PPPM) may have the potential to eventually improve the nature of health care delivery. However, the tools required for a practical and comprehensive form of PPPM that is capable of handling the vast amounts of medical information that is currently available are currently lacking. This article reviews a rationale and method for combining and integrating diagnostic and therapeutic management with information technology (IT), in a manner that supports patients through their continuum of care. It is imperative that any program devised to explore and develop personalized health care delivery must be firmly rooted in clinically confirmed and accepted principles and technologies. Therefore, a use case, relating to hepatocellular carcinoma (HCC), was developed. The approach to the management of medical information we have taken is based on model theory and seeks to implement a form of model-guided therapy (MGT) that can be used as a decision support system in the treatment of patients with HCC. The IT structures to be utilized in MGT include a therapy imaging and model management system (TIMMS) and a digital patient model (DPM). The system that we propose will utilize patient modeling techniques to generate valid DPMs (which factor in age, physiologic condition, disease and co-morbidities, genetics, biomarkers and responses to previous treatments). We may, then, be able to develop a statistically valid methodology, on an individual basis, to predict certain diseases or conditions, to predict certain treatment outcomes, to prevent certain diseases or complications and to develop treatment regimens that are personalized for that particular patient. An IT system for predictive, preventive and personalized medicine (ITS-PM) for HCC is presented to provide a comprehensive system to provide unified access to general medical and patient-specific information for medical researchers and health care providers from different disciplines including hepatologists, gastroenterologists, medical and surgical oncologists, liver transplant teams, interventional radiologists and radiation oncologists. The article concludes with a review providing an outlook and recommendations for the application of MGT to enhance the medical management of HCC through PPPM

Biomarkers of Nutrition for Development (BOND)—Iron Review

This is the fifth in the series of reviews developed as part of the Biomarkers of Nutrition for Development (BOND) program. The BOND Iron Expert Panel (I-EP) reviewed the extant knowledge regarding iron biology, public health implications, and the relative usefulness of currently available biomarkers of iron status from deficiency to overload. Approaches to assessing intake, including bioavailability, are also covered. The report also covers technical and laboratory considerations for the use of available biomarkers of iron status, and concludes with a description of research priorities along with a brief discussion of new biomarkers with potential for use across the spectrum of activities related to the study of iron in human health. The I-EP concluded that current iron biomarkers are reliable for accurately assessing many aspects of iron nutrition. However, a clear distinction is made between the relative strengths of biomarkers to assess hematological consequences of iron deficiency versus other putative functional outcomes, particularly the relationship between maternal and fetal iron status during pregnancy, birth outcomes, and infant cognitive, motor and emotional development. The I-EP also highlighted the importance of considering the confounding effects of inflammation and infection on the interpretation of iron biomarker results, as well as the impact of life stage. Finally, alternative approaches to the evaluation of the risk for nutritional iron overload at the population level are presented, because the currently designated upper limits for the biomarker generally employed (serum ferritin) may not differentiate between true iron overload and the effects of subclinical inflammation

Diseases of the liver and biliary tract : standardization of nomenclature, diagnostic criteria, and diagnostic methodology /

Includes index.Bibliography: p. 181-205.Mode of access: Internet

Activation of interferon and NF-kB pathways in early human alcoholic liver disease development

Background and aims : Animal data suggest a role for TLR4 with subsequent activation of NFkB in alcohol liver injury. Here, we assessed cytokines, TLR and TLR-dependent pathways expressions in human ALD. Methods : Liver biopsies from 41 actively drinking ALD patients were compared with normal liver tissue (n=6) and with liver biopsies from ALD patients after 2 weeks of abstinence (n=27). Quantitative PCR and Western blotting were used for mRNA and protein analysis, respectively, immunohistochemistry for cellular localization of inflammatory processes. Our local ethics committee has approved the study. Results : Compared with normal livers, already early ALD (fibrosis < F2) showed significant activation of NFkB with increased total and phosphorylated p65 protein expression and up-regulation of NFkB responsive genes mRNA levels TNFalphaand IL-1. Interestingly, TLR4 mRNA expression remained unchanged whereas CD14 and TNF receptor 1 mRNA were down-regulated in active ALD. Only IL-1 returned to control levels after abstinence. The interferon pathway was strongly activated in early ALD with significant increase in total and phosphorylated interferon regulatory factor-3, up-regulation of interferon-beta and interferon responsive genes ISG6-16 and OAS-1 mRNA levels. Interferon-beta levels significantly correlated with up-regulation of TLR3 and 7 mRNA. Activation of the interferon pathway was not reversed after abstinence. CD68 mRNA was significantly increased and CD68 immunohistochemistry revealed enlarged, aggregated Kupffer cells and small inflammatory cells in early ALD compared to scattered Kupffer cells in normal liver. Conclusions: Besides NFkB, early activation of the interferon pathway could play an important role in human ALD pathogenesis

Expression of pro-inflammatory and hepatoprotective factors at early stages of alcoholic liver disease in humans and the impact of short term abstinence.

Background and Aims: Animal models imperfectly mimic the spectrum of alcoholic liver disease (ALD) seen in humans. Some studies have investigated late stages and severe forms of human ALD, but little is known about the pathophysiological mechanisms occurring in the human liver at early stages of the disease. Here,we investigated inflammatory mechanisms in alcohol dependent patients undergoing a standardized inpatient alcohol withdrawal program. Methods: Patients with suspicion of significant ALD (ALT, AST increase, fibroscan >7.8 kPa) were randomly assigned to undergo liver biopsy either in the active drinking phase or after 2 weeks of abstinence. Patients without significant fibrosis on histology were included in the study (n = 40). Liver tissue (n = 6) from size-reduced liver grafts was used as normal controls. Expression and cellular localization of various factors was assessed by Western-blotting, qPCR and immunohistochemistry and immunofluorescence. Results: the active drinking phase, a strong activation of the Kupffer cell (KC) compartment was found with KCs forming clusters adjacent to ballooned, steatotic hepatocytes. KC showed a pro-inflammatory M1 phenotype with activation of NFkB and increased expression of TNF, IL-1 and iNOS. After 2 weeks of abstinence, the staining pattern of KC returned to normal and NFkB, IL-1 and iNOS levels but not TNF decreased to almost control levels. In addition, abstinence induced a partial shift to a M2 phenotype with increased production of the anti-inflammatory cytokine IL-10. Interestingly,we did not find activation of TLR4 since TLR4, CD14, and LBP levels remained at control values in active drinkers. By contrast, we found a strong and persistent upregulation of the intracellular TLR3 and TLR7 which correlated with high production of interferon beta and gamma principally located to hepatocytes and bile ducts. Moreover, the hepatoprotective factors IL-6, IL-22, MCP-1 and Stat3 DNA-binding were strongly down-regulated in active drinkers and did not recover after short term abstinence. Hepatocyte Ki67 proliferation index was low in active drinkers and increased modestly but significantly after 2 weeks of abstinence. Conclusions: At early stages of ALD, a strong pro-inflammatory, KC-dependent response is observed which rapidly reversed upon abstinence. By contrast, down-regulation of hepatoprotective factors is more long lasting and might significantly impair liver repair mechanisms in sustained drinkers

Results of Liver Transplantation in Adult Polycystic Liver Disease: Report of a Single Center Experience

Introduction: Polycystic liver disease (PCLD) occurs either in an isolated form (Autosomal Dominant Polycystic Liver Disease [ADPLD]) or in association with Autosomal Dominant Polycystic Kidney Disease (ADPKD). It remains an uncommon and controversial indication for liver transplantation (LT). Objectives: 1. to assess the results of LT in patients with massive PCLD; 2. to determine whether previous hepatic surgery is associated with a higher rate of complications following LT; 3. to examine the evolution of renal function after LT in order to determine whether pre-emptive renal transplantation is justified in case of ADPKD without (pre-)terminal renal failure. Methods: We retrospectively reviewed the medical charts of 19 patients (15 females) who underwent LT for PCLD between 1999 and 2008. Fifteen patients had ADPKD (12 females). Three received a combined liver and kidney transplantation (LKT) for associated terminal (n = 1) or pre-terminal renal failure. Two patients had previous kidney transplantation (KT) and 7 had undergone hepatic surgery. Results: Median duration of follow-up is 30 months [5-112]. All patients are alive and relieved of their symptoms. Their median Karnofsky score is 90% [80-100]. Intervention tended to be longer (10:30h vs. 7:20h, p=0.098) in the group who had previous surgery. There was no significant difference in intra-operative blood transfusion, severity of postoperative complications, length of ICU or hospital stay. Median pre-LT GFR of ADPLD and ADPKD patients (excluding those who underwent LKT or previous KT) is 89.5ml/min/1.73m2 [69-114] and 69ml/min/1.73m2 [33-120] respectively (p=0.129). Median GFR 1 year post-LT is 68ml/min/1.73m2 [57-95] and 51ml/min/1.73m2 [29-85] respectively (p=0.089). Median decrease in GFR at one year post-LT is 17.5 ml/min/1.73m2 and 18 ml/min/1.73m2 respectively (p=0.694). Conclusions: LT is an effective treatment for selected patients with massive PCLD. Prior conservative surgery tends to increase the length of the transplant operation. Renal function decreases at an identical rate after LT in ADPLD and ADPKD patients with pre-LT GFR >30 ml/min/1.73m2. Thus, pre-emptive renal transplantation would not have been justified in the latter