Host genetics predict clinical deterioration in HCV-related cirrhosis

Single nucleotide polymorphisms (SNPs) in the epidermal growth factor (EGF, rs4444903), patatin-like phospholipase domain-containing protein 3 (PNPLA3, rs738409) genes, and near the interleukin-28B (IL28B, rs12979860) gene are linked to treatment response, fibrosis, and hepatocellular carcinoma (HCC) in chronic hepatitis C. Whether these SNPs independently or in combination predict clinical deterioration in hepatitis C virus (HCV)-related cirrhosis is unknown. We genotyped SNPs in EGF, PNPLA3, and IL28B from liver tissue from 169 patients with biopsy-proven HCV cirrhosis. We estimated risk of clinical deterioration, defined as development of ascites, encephalopathy, variceal hemorrhage, HCC, or liver-related death using Cox proportional hazards modeling. During a median follow-up of 6.6 years, 66 of 169 patients experienced clinical deterioration. EGF non-AA, PNPLA3 non-CC, and IL28B non-CC genotypes were each associated with increased risk of clinical deterioration in age, sex, and race-adjusted analysis. Only EGF non-AA genotype was independently associated with increased risk of clinical deterioration (hazard ratio [HR] 2.87; 95% confidence interval [CI] 1.31-6.25) after additionally adjusting for bilirubin, albumin, and platelets. Compared to subjects who had 0-1 unfavorable genotypes, the HR for clinical deterioration was 1.79 (95%CI 0.96-3.35) for 2 unfavorable genotypes and 4.03 (95%CI 2.13-7.62) for unfavorable genotypes for all three loci (Ptrend<0.0001). In conclusion, among HCV cirrhotics, EGF non-AA genotype is independently associated with increased risk for clinical deterioration. Specific PNPLA3 and IL28B genotypes also appear to be associated with clinical deterioration. These SNPs have potential to identify patients with HCV-related cirrhosis who require more intensive monitoring for decompensation or future therapies preventing disease progression

A neo-institutional perspective on ethical decision-making

Drawing on neo-institutional theory, this study aims to discern the poorly understood ethical challenges confronted by senior executives in Indian multinational corporations and identify the strategies that they utilize to overcome them. We conducted in-depth interviews with 40 senior executives in Indian multinational corporations to illustrate these challenges and strategies. By embedding our research in contextually relevant characteristics that embody the Indian environment, we identify several institutional- and managerial-level challenges faced by executives. The institutional-level challenges are interpreted as regulative, normative and cognitive shortcomings. We recommend a concerted effort at the institutional and managerial levels by identifying relevant strategies for ethical decision-making. Moreover, we proffer a multi-level model of ethical decision-making and discuss our theoretical contributions and practical implications

Corruption and its effects on FDI:Analysing the interaction between the corruption levels of the home and host countries and its effects at the decision-making level

This study furthers our understanding of how corruption affects the decision-making process of allocating foreign direct investment. Drawing on the responses of 28 managers in charge of establishing operations in a highly corrupt host country, we argue that those firms based in home countries with low levels of corruption are more proactive in preparing to face corruption abroad than those based in countries with high corruption levels. This means that firms from less corrupt home countries have strategies in place to deal with high corruption abroad. This finding is based on the fact that these firms have stronger pressures to not engage in corruption from their home stakeholders. Also, these firms might not have the experience of dealing with corruption at home, which hinders their potential to deal with corruption abroad. On the other hand, those firms based in highly corrupt home countries do not have clear strategies to deal with corruption abroad. This assertion is based on the fact that these firms might have familiarity in dealing with corruption and thus, might not see it as an obstacle to operating abroad

Integrating Palliative Care in the Management of Patients With Advanced Liver Disease

http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-4-reading-patel a video presentation of this article

Liver Transplant Survivorship

For both children and adults with end-stage liver disease, liver transplantation represents a life-long treatment, not a cure. The physical and psychological process of undergoing transplantation begins well before the surgery itself. Concerns regarding suffering and death from end-stage liver disease are replaced by a life-long need for multiple medications, ongoing monitoring of graft function, and heightened vigilance for complications related not only to the transplant itself but to long-term immunosuppression. The psychological toll from the entire transplant experience on the patient and caregivers, as well as the strain that such a major treatment places on these human interactions can leave emotional scars that persist longer than the surgical healing process itself. The concept of “survivorship”, originally applied to patients with cancer, acknowledges the ongoing spectrum of care and support that patients and their caregivers require to optimize long-term outcomes after serious medical treatment. Transplant survivorship would expand the focus of care of a patient with end-stage liver disease beyond disease-specific issues and survival alone. This viewpoint explores the need for such a construct in the field of liver transplantation to promote a more holistic approach that encompasses the overall physical, psychological, social and spiritual well-being of the liver transplant patient

The 5Ms of Geriatrics in Gastroenterology: The Path to Creating Age-Friendly Care for Older Adults With Inflammatory Bowel Diseases and Cirrhosis.

The number of Americans 65 years or older in 2060 will be more than double what it was in 2014. Approximately 40% of patients seen in gastroenterology (GI) and hepatology practices in the United States are 60 years or older. Adapting care delivery models, curating data on shifting risk-benefit decisions with geriatric syndromes, understanding appropriate assessments, and focusing on tailored implementation strategies are challenges that are actively confronting us as we provide care for a burgeoning population of older adults. Limited availability of geriatric specialists results in an onus of specialists caring for older adults, such as gastroenterologists, to innovate and develop tailored, comprehensive, and evidence-based care for adults in later life stages. In this article, we present the 5M framework from geriatrics to achieve age-friendly healthcare. The 5Ms are medications, mind, mobility, multicomplexity, and what matters most. We apply the 5M framework to 2 chronic conditions commonly encountered in clinical GI practice: inflammatory bowel diseases and cirrhosis. We highlight knowledge gaps and outline future directions to expand evidence-based care and advance the creation of age-friendly GI care

Review article: current and emerging therapies for the management of cirrhosis and its complications

BackgroundCirrhosis is increasingly common and morbid. Optimal utilisation of therapeutic strategies to prevent and control the complications of cirrhosis are central to improving clinical and patient-reported outcomes.MethodsWe conducted a narrative review of the literature focusing on the most recent advances.ResultsWe review the aetiology-focused therapies that can prevent cirrhosis and its complications. These include anti-viral therapies, psychopharmacological therapy for alcohol-use disorder, and the current landscape of clinical trials for non-alcoholic steatohepatitis. We review the current standard of care and latest developments in the management of hepatic encephalopathy (HE), ascites and hepatorenal syndrome. We evaluate the promise and drawbacks of chemopreventative therapies that have been examined in trials and observational studies which may reduce the risk of hepatocellular carcinoma and cirrhosis complications. Finally, we examine the therapies which address the non-pain symptoms of cirrhosis including pruritis, muscle cramps, sexual dysfunction and fatigue.ConclusionThe improvement of clinical and patient-reported outcomes for patients with cirrhosis is possible by applying evidence-based pharmacotherapeutic approaches to the prevention and treatment of cirrhosis complications