No inflammation? No cancer! Clear HBV early and live happily

COMMENTARY ON:Clearance of Hepatitis B Surface Antigen and Risk of Hepatocellular Carcinoma in a cohort Chronically Infected with Hepatitis B Virus. Simonetti J, Bulkow L, McMahon BJ, Homan C, Snowball M, Negus S, Williams J, Livingston SE. Hepatology. 2009 Nov 30. [Epub ahead of print]. Copyright 2009. Reprinted with permission of John Wiley and Sons, Inc.Abstract: Some individuals who are chronically infected with hepatitis B virus (HBV) eventually lose hepatitis B surface antigen (HBsAg). Hepatocellular carcinoma (HCC) has been demonstrated to occur in a few patients after loss of HBsAg. Neither factors associated with loss of HBsAg nor the incidence of HCC thereafter have been clearly elucidated. We performed a prospective population-based cohort study in 1271 Alaska native persons with chronic HBV infection followed for an average of 19.6years to determine factors associated with loss of HBsAg and risk of developing HCC thereafter. HBsAg loss occurred in 158 persons for a rate of HBsAg clearance of 0.7%/year. Older age, but not sex, was associated with clearance of HBsAg, and loss of HBsAg was not associated with any particular HBV genotypes (A–D, and F) found in this population. Participants were followed for an average of 108.9months after HBsAg loss. Six patients, two with cirrhosis and four without, developed HCC a mean of 7.3years after HBsAg clearance (range, 2.0–15.5years). The incidence of HCC after clearance of HBsAg was 36.8 per 100,000 per year (95% CI 13.5–80.0) which was significantly lower than the rate in those who remained HBsAg-positive (195.7 cases per 100,000 person-years of follow-up [95% CI 141.1–264.5; P<0.001). After loss of HBsAg, HBV DNA was detected in the sera of 28 (18%) of those who cleared a median of 3.6years after clearance. Conclusion: HCC can occur in persons with chronic hepatitis B who have lost HBsAg, even in the absence of cirrhosis. These persons should still be followed with periodic liver ultrasound to detect HCC early

Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome after Liver Transplant

Liver transplant is the unique curative therapy for patients with acute liver failure or end-stage liver disease, with or without hepatocellular carcinoma. Increase of body weight, onset of insulin resistance and drug-induced alterations of metabolism are reported in liver transplant recipients. In this context, post-transplant diabetes mellitus, hyperlipidemia, and arterial hypertension can be often diagnosed. Multifactorial illnesses occurring in the post-transplant period represent significant causes of morbidity and mortality. This is especially true for metabolic syndrome. Non-alcoholic steatosis and steatohepatitis are hepatic manifestations of metabolic syndrome and after liver transplant both recurrent and de novo steatosis can be found. Usually, post-transplant steatosis shows an indolent outcome with few cases of fibrosis progression. However, in the post-transplant setting, both metabolic syndrome and steatosis might play a key role in the stratification of morbidity and mortality risk, being commonly associated with cardiovascular disease. The single components of metabolic syndrome can be treated with targeted drugs while lifestyle intervention is the only reasonable therapeutic approach for transplant patients with non-alcoholic steatosis or steatohepatitis

Anticoagulation in cirrhosis: a new paradigm?

The liver plays a crucial role in coagulation cascade. Global hemostatic process is profoundly influenced by the presence of liver disease and its complications. Patients with cirrhosis have impaired synthesis of most of the factors involved in coagulation and fibrinolysis process due to a reduced liver function and altered platelet count secondary to portal hypertension. Altered routine tests and thrombocytopenia were considered in the past as associated with increased risk of bleeding. These concepts explain both the routine use of plasma and/or platelets transfusion in patients with liver cirrhosis, especially before invasive procedures, and why these patients were considered "auto-anticoagulated". New recent evidences show that patients with liver cirrhosis have a more complex hemostatic alteration. Despite the presence of altered levels of factors involved in primary hemostasis, coagulation and fibrinolysis, patients with stable cirrhosis have a rebalanced hemostatic, which however can easily be altered by decompensation or infection, both in hemorrhagic or thrombotic direction. Patients with cirrhosis have an increased risk of venous thrombotic events (namely portal vein thrombosis) while bleeding seems to be related to the grade of portal hypertension rather than to a hemostatic imbalance. The use of anticoagulants both as treatment or prophylaxis is safe, reduces the rate of portal vein thrombosis and decompensation, and improves survival. Standard laboratory coagulation tests are unable to predict bleeding and are inadequate for the assessment of hemostatic status in these patients, hence more comprehensive tests are required to guide the management of thrombotic and bleeding complications

Treatment of nonalcoholic steatohepatitis in adults: present and future

Nonalcoholic steatohepatitis has become one of the most common liver-related health problems. This condition has been linked to an unhealthy diet and weight gain, but it can also be observed in nonobese people. The standard of care is represented by the lifestyle intervention. However, because this approach has several limitations, such as a lack of compliance, the use of many drugs has been proposed. The first-line pharmacological choices are vitamin E and pioglitazone, both showing a positive effect on transaminases, fat accumulation, and inflammation. Nevertheless, vitamin E has no proven effect on fibrosis and on long-term morbidity and mortality and pioglitazone has a negative impact on weight. Other drugs have been studied such as metformin, ursodeoxycholic acid, statins, pentoxiphylline, and orlistat with only partially positive results. Among the emerging treatments, telmisartan is particularly interesting as it seems to have an impact on insulin resistance, liver steatosis, inflammation, and fibrosis. However, the pathogenesis of steatohepatitis is highly complex and is determined by different parallel hits; indeed, the association of different drugs that act on various levels has been suggested. In conclusion, lifestyle intervention should be optimised and the associations of different drugs should be tested in large studies with long-term outcomes

Study of the Serum Metabolomic Profile in Nonalcoholic Fatty Liver Disease: Research and Clinical Perspectives

In recent years, metabolomics has attracted great scientific attention. The metabolomics methodology might permit a view into transitional phases between healthy liver and nonalcoholic steatohepatitis. Metabolomics can help to analyze the metabolic alterations that play a main role in the progression of nonalcoholic steatohepatitis. Lipid, glucose, amino acid, and bile acid metabolism should be widely studied to understand the complex pathogenesis of nonalcoholic steatohepatitis. The discovery of new biomarkers would be important for diagnosis and staging of liver disease as well as for the assessment of efficacy of new drugs. Here, we review the metabolomics data regarding nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. We analyzed the main studies regarding the application of metabolomics methodology in the complex context of nonalcoholic steatohepatitis, trying to create a bridge from the basic to the clinical aspects

ÍNDICES DE INTEGRIDADE BIÓTICA USANDO PEIXES DE ÁGUA DOCE: USO NAS REGIÕES TROPICAL E SUBTROPICAL

The Index of Biotic Integrity (IBI) using freshwater fish assemblages is an effective biomonitoring tool that is widely used in temperate countries. Despite the fact that the IBI is being adjusted to be applied to studies in tropical and subtropical countries for almost 15 years, it still is rarely used with these regions. The present review visits 15 publications of IBI adaptations for tropical regions. Most studies were performed in subtropical regions and mainly on streams, while some were done in large rivers, and one in lakes. There is evident need for a clear definition of the reference condition and for standardized and non-selective methodologies (e.g., electrofishing), even in large river systems. Metrics were created or adapted using families or functional groups that proved sensitive in the studied regions. However, the metrics must be selected through rigorous statistical methods. Although IBI fi sh models were shown to be effective in detecting environmental changes in all studies analyzed, it is evident that the applicability and effectiveness of these models in tropical and subtropical countries (chiefly developing countries with high diversity and ecological complexity) depend on filling in the informationgaps in diversity and ecological processes. We highlight the importance of government taking part in the coordination of biomonitoring programs within these regions, noting that all the initiatives developed up to now were carried out by research groups.O Índice de Integridade Biótica (IIB), utilizando assembléias de peixes de água doce, tem sido uma ferramenta efetiva de biomonitoramento amplamente utilizada em paises de regiões temperadas. Em países tropicais e subtropicais, no entanto, seu uso é ainda reduzido, apesar da adaptação nestas regiões ter se iniciado há quase 15 anos. Esta revisão inclui 15 adaptações do IIB publicadas para essas regiões. Verificamos que a maioria delas foi realizada em zonas subtropicais, principalmente em riachos; algumas em rios de maior porte e apenas uma em lagos. Tornou-se evidente a necessidade de uma definição clara do local de referencia e implementação de metodologias padronizadas e não seletivas (e.g. pesca elétrica), inclusive para rios de grande porte. As métricas foram criadas ou adaptadas usando as famílias ou grupos funcionais que se mostraram sensíveis na região estudada. No entanto, e fundamental que a seleção seja respaldada por métodos estatísticos rigorosos. Apesar do modelo do IIB ter se mostrado efetivo na detecção de alterações ambientais em todos os trabalhos analisados, é evidente que a aplicabilidade e eficácia nos países tropicais e subtropicais (em geral em desenvolvimento, com grande diversidade e complexidade ecológica) depende do preenchimento das lacunas de informação, tanto sobre diversidade como sobre processos ecológicos. Ressalta-se a importância da participação e coordenação governamental na implantação do biomonitoramento nessas regiões, uma vez que as iniciativas, até o momento, partiram exclusivamente de grupos de pesquisa.

Complete resolution of non-necrotizing lung granuloma and pyoderma gangrenosum after restorative proctocolectomy in a woman with severe ulcerative colitis and cytomegalovirus infection

Here, we report the unusual case of an ulcerative colitis female patient presenting together with cytomegalovirus infection, pyoderma gangrenosum and a noncaseating lung granuloma, both resistant to immunomodulatory drugs which dramatically obtained a clinical stable remission after restorative proctocolectomy

Measuring freshwater aquatic ecosystems: The need for a hyperspectral global mapping satellite mission

AbstractFreshwater ecosystems underpin global water and food security, yet are some of the most endangered ecosystems in the world because they are particularly vulnerable to land management change and climate variability. The US National Research Council's guidance to NASA regarding missions for the coming decade includes a polar orbiting, global mapping hyperspectral satellite remote sensing mission, the Hyperspectral Infrared Imager (HyspIRI), to make quantitative measurements of ecosystem change. Traditionally, freshwater ecosystems have been challenging to measure with satellite remote sensing because they are small and spatially complex, require high fidelity spectroradiometry, and are best described with biophysical variables derived from high spectral resolution data. In this study, we evaluate the contribution of a hyperspectral global mapping satellite mission to measuring freshwater ecosystems. We demonstrate the need for such a mission, and evaluate the suitability and gaps, through an examination of the measurement resolution issues impacting freshwater ecosystem measurements (spatial, temporal, spectral and radiometric). These are exemplified through three case studies that use remote sensing to characterize a component of freshwater ecosystems that drive primary productivity. The high radiometric quality proposed for the HyspIRI mission makes it uniquely well designed for measuring freshwater ecosystems accurately at moderate to high spatial resolutions. The spatial and spectral resolutions of the HyspIRI mission are well suited for the retrieval of multiple biophysical variables, such as phycocyanin and chlorophyll-a. The effective temporal resolution is suitable for characterizing growing season wetland phenology in temperate regions, but may not be appropriate for tracking algal bloom dynamics, or ecosystem responses to extreme events in monsoonal regions. Global mapping missions provide the systematic, repeated measurements necessary to measure the drivers of freshwater biodiversity change. Archival global mapping missions with open access and free data policies increase end user uptake globally. Overall, an archival, hyperspectral global mapping mission uniquely meets the measurement requirements of multiple end users for freshwater ecosystem science and management

Methylprednisolone-induced toxic hepatitis after intravenous pulsed therapy for multiple sclerosis relapses

High-dose, intravenous methylprednisolone (MP) is the only recommended first-line treatment for multiple sclerosis relapses. However, there are increasing reports on liver toxicity induced by this treatment regimen. We report of 4 multiple sclerosis patients with no history of viral/metabolic liver disorders or alcohol/hepatotoxic drug intake, who developed hypertransaminasaemia following intravenous MP. In 2 of the patients, liver biopsy showed periportal fibrosis, piecemeal necrosis, and inflammatory cell infiltrates. A rechallenge test confirmed a causal association in 1 case. MP-induced liver toxicity may be more frequent than commonly thought and it is important to report this adverse reaction, which is potentially lethal, and to raise awareness on the potential hepatotoxicity of corticosteroid pulses