Eric R. Yoo

Clinical epidemiology and disease burden of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, excessive alcohol consumption, and other conditions that may lead to hepatic steatosis. NAFLD encompasses a broad clinical spectrum ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis, and finally hepatocellular carcinoma (HCC). NAFLD is the most common liver disease in the world and NASH may soon become the most common indication for liver transplantation. Ongoing persistence of obesity with increasing rate of diabetes will increase the prevalence of NAFLD, and as this population ages, many will develop cirrhosis and end-stage liver disease. There has been a general increase in the prevalence of NAFLD, with Asia leading the rise, yet the United States is following closely behind with a rising prevalence from 15% in 2005 to 25% within 5 years. NAFLD is commonly associated with metabolic comorbidities, including obesity, type II diabetes, dyslipidemia, and metabolic syndrome. Our understanding of the pathophysiology of NAFLD is constantly evolving. Based on NAFLD subtypes, it has the potential to progress into advanced fibrosis, end-stage liver disease and HCC. The increasing prevalence of NAFLD with advanced fibrosis, is concerning because patients appear to experience higher liver-related and non-liver-related mortality than the general population. The increased morbidity and mortality, healthcare costs and declining health related quality of life associated with NAFLD makes it a formidable disease, and one that requires more in-depth analysis.

Improved Outcomes in HCV Patients Following Liver Transplantation During the Era of Direct-Acting Antiviral Agents

*Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California; Division of Gastroenterology and Hepatology, University of Tennessee Health Science Center, Memphis, Tennessee; Department of Medicine, University of Illinois College of Medicine, Chicago, Illinois; kSimmons Transplant Institute, Baylor All Saints Medical Center, Fort Worth, Texas; Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia

Nutritional Needs and Support for Children with Chronic Liver Disease

Malnutrition has become a dangerously common problem in children with chronic liver disease, negatively impacting neurocognitive development and growth. Furthermore, many children with chronic liver disease will eventually require liver transplantation. Thus, this association between malnourishment and chronic liver disease in children becomes increasingly alarming as malnutrition is a predictor of poorer outcomes in liver transplantation and is often associated with increased morbidity and mortality. Malnutrition requires aggressive and appropriate management to correct nutritional deficiencies. A comprehensive review of the literature has found that infants with chronic liver disease (CLD) are particularly susceptible to malnutrition given their low reserves. Children with CLD would benefit from early intervention by a multi-disciplinary team, to try to achieve nutritional rehabilitation as well as to optimize outcomes for liver transplant. This review explains the multifactorial nature of malnutrition in children with chronic liver disease, defines the nutritional needs of these children, and discusses ways to optimize their nutritional.

Timing of Hepatitis C Virus Treatment in Liver Transplant Candidates in the Era of Direct-acting Antiviral Agents

Abstract Chronic hepatitis C virus (HCV) infection remains the leading indication for liver transplantation (LT) in the United States. While most patients with chronic HCV infection remain asymptomatic, up to one-third develop progressive liver disease resulting in cirrhosis. LT is often the only curative treatment once significant hepatic decompensation develops. However, antiviral therapy for HCV infection has advanced markedly in the past 5 years with the discovery and approval of direct-acting antiviral agents. These new regimens are well tolerated, of short duration and highly effective, unlike the traditional treatment with pegylated-interferon and ribavirin. As achieving sustained virological response becomes increasingly attainable for a majority of HCV-infected patients, concerns have been raised regarding the optimal timing of treatment for HCV infection in the setting of end-stage liver disease and during the peri-transplant period. On one hand, HCV treatment may improve hepatic function and negate the need for LT in some, which is crucial given the scarcity of donor organs and mortality on the waiting list in certain regions. On the other hand, HCV treatment may result in lowering the priority for LT without improving quality of life, thereby delaying potentially curative LT surgery. This review evaluates the evidence supporting the use of direct-acting antiviral agents in the period before and following LT.

Rising Rates of Hepatocellular Carcinoma Leading to Liver Transplantation in Baby Boomer Generation with Chronic Hepatitis C, Alcohol Liver Disease, and Nonalcoholic Steatohepatitis-Related Liver Disease

We aim to study the impact of the baby boomer (BB) generation, a birth-specific cohort (born 1945–1965) on hepatocellular carcinoma (HCC)-related liver transplantation (LT) in patients with chronic hepatitis C virus (HCV), alcoholic liver disease (ALD), and non-alcoholic steatohepatitis (NASH). We performed a retrospective analysis using the United Network for Organ Sharing (UNOS)/Organ Procurement Transplant Network (OPTN) database from 2003 to 2014 to compare HCC-related liver transplant surgery trends between two cohorts—the BB and non-BB—with a secondary diagnosis of HCV, ALD, or NASH. From 2003–2014, there were a total of 8313 liver transplant recipients for the indication of HCC secondary to HCV, ALD, or NASH. Of the total, 6658 (80.1%) HCC-related liver transplant recipients were BB. The number of liver transplant surgeries for the indication of HCC increased significantly in NASH (+1327%), HCV (+382%), and ALD (+286%) during the study period. The proportion of BB who underwent LT for HCC was the highest in HCV (84.7%), followed by NASH (70.3%) and ALD (64.7%). The recommendations for birth-cohort specific HCV screening stemmed from a greater understanding of the high prevalence of chronic HCV and HCV-related HCC within BB. The rising number of HCC-related LT among BB with ALD and NASH suggests the need for increased awareness and improved preventative screening/surveillance measures within NASH and ALD cohorts as well.

Underutilization of Living Donor Liver Transplantation in the United States: Bias against MELD 20 and Higher.

Abstract Background and Aims: Utilization of living donor liver transplantation (LDLT) and its relationship with recipient Model for End-Stage Liver Disease (MELD) needs further evaluation in the United States (U.S.). We evaluated the association between recipient MELD score at the time of surgery and survival following LDLT. Methods: All U.S. adult LDLT recipients with MELD < 25 were evaluated using the 1995–2012 United Network for Organ Sharing registry. Survival following LDLT was stratified into three MELD categories (MELD < 15 vs. MELD 15–19 vs. MELD 20–24) and evaluated using Kaplan-Meier methods and multivariate Cox proportional hazards models. Results: Overall, 2,258 patients underwent LDLT. Compared to patients with MELD < 15, overall 5-year survival following LDLT was similar among patients with MELD 15–19 (80.9% vs. 80.3%, p = 0.77) and MELD 20–24 (81.2% vs. 80.3%, p = 0.73). When compared to patients with MELD < 15, there was no significant difference in long-term post-LDLT survival among those with MELD 15–19 (HR: 1.11, 95% CI: 0.85−1.45, p = 0.45) and a non-significant trend towards lower survival in patients with MELD 20–24 (HR: 1.28, 95% CI: 0.91−1.81, p = 0.16). Only 14% of LDLTs were performed in patients with MELD 20–24 and the remaining 86% in patients with MELD < 20. Conclusion: LDLT is underutilized in patients with MELD 20 and higher.

Use of direct-acting antiviral agents in hepatitis C virus-infected liver transplant candidates

Since the advent of direct acting antiviral (DAA) agents, chronic hepatitis C virus (HCV) treatment has evolved at a rapid pace. In contrast to prior regimen involving ribavirin and pegylated interferon, these newer agents are highly effective, well-tolerated, have shorter course of therapy and safer essentially in all HCV patients including those with advanced liver disease and following liver transplantation. Clinicians caring for HCV-infected patients on the liver transplant (LT) waitlist are often faced with a dilemma whether to treat HCV infection before or after liver transplantation. Sustained virological response (SVR) rates following HCV treatment may improve hepatic function sufficiently enough to negate the need for LT in certain patients. On the other hand, the decrease in MELD without improvement in quality of life in certain patients may lead to delay or dropout from potentially curative LT surgery list. In this context, our review focuses on the approach to and optimal timing of DAA-based treatment of HCV infection in LT candidates in the peri-transplant period.

Direct-acting Antiviral Therapy and Improvement in Graft Survival of Hepatitis C Liver Transplant Recipients

FIGURE 1. Annual rate for AGF in HCV compared to non-HCV LT recipients in the United States from 2011 to 2016. L iver transplantation of patients with untreated hepatitis C virus (HCV) infection leads to universal reinfection of the graft. Up to 10% of liver transplant (LT) recipients with recurrent HCV infection can develop fibrosing cholestatic hepatitis (FCH) followed by acute graft failure (AGF). LT recipients with severe and rapid recurrence of HCV infection, including FCH and cirrhosis-related hepatic decompensation with a life expectancy of 1 year or less were offered treatment under the sofosbuvir compassionate use program in 2013 (prior to regulatory approval of sofosbuvir). Due to the lack of direct corroborating evidence, it has been presumed that direct-acting antiviral (DAA) agents, such as sofosbuvir, may have impacted and potentially improved the short-term graft survival in HCV LT recipients. Using the United Network for Organ Sharing (UNOS) registry, annual rates for AGF were analyzed among HCVand non-HCV LT recipients. AGF was defined as graft failure diagnosed within 1-year of LT surgery and documented in the UNOS registry. From 2011 to 2016, there was a significant decline in the annual rate of AGF in HCV compared with non-HCV LT recipients (Figure 1). Notably, AGF rate in HCV group declined sharply in 2013 to 2014 by 26.3%. From 2014 to 2016 (DAA era), annual rates for AGF in HCV and non-HCV LT recipients were comparable and statistically insignificant (HCV 3.6% vs non-HCV 3.5; P = 0.85). For the first time in 2016, AGF rate in HCV LT recipients was observed to be lower

An Overview of Dietary Interventions and Strategies to Optimize the Management of Non-Alcoholic Fatty Liver Disease

Aim: To investigate the efficacy of lifestyle adjustment strategies as a preventive measure and/or treatment of obesity-related non-alcoholic fatty liver disease in adults. Method: A systematic review of literature through 1 July 2017 on the PubMed Database was performed. A comprehensive search was conducted using key terms, such as non-alcoholic fatty liver disease (NAFLD), combined with lifestyle intervention, diet, and exercise. All of the articles and studies obtained from the search were reviewed. Redundant literature was excluded. Results: Several types of dietary compositions and exercise techniques were identified. Most studies concluded and recommended reduction in the intake of saturated and trans fatty acids, carbohydrates, and animal-based protein, and increased intake of polyunsaturated fatty acids (PUFAs), monounsaturated fatty acids (MUFAs), plant-based proteins, antioxidants, and other nutrients was recommended. The Mediterranean and Paleo diet both seem to be promising schemes for NAFLD patients to follow. Exercise was also encouraged, but the type of exercise did not affect its efficacy as a NAFLD treatment when the duration is consistent. Conclusions: Although these different dietary strategies and exercise regimens can be adopted to treat NAFLD, current literature on the topic is limited in scope. Further research should be conducted to truly elucidate which lifestyle adjustments individually, and in combination, may facilitate patients with obesity-related NAFLD.

Task-shifting – A practical strategy to improve the global access to treatment for chronic hepatitis C

Recently, the extended role of nurses have been evaluated and reported in the International Journal of Nursing Studies through a number of research studies and reviews, including but not limited to a recent survey of advanced nursing practice roles in Australia (Gardner et al., 2016), a recent systematic review of the effectiveness of roles of advanced practice nursing in older people (Morilla-Herrera et al., 2016), a survey of clinical nurse practice roles in Canada (Kilpatrick et al., 2013), and a survey of the perceived safety of a nurse prescribing of ionising radiation (Hyde et al., 2016). In this editorial, we draw upon our clinical experience to propose an extended role for licensed vocational nurses as the primary treatment provider for patients suffering from Chronic hepatitis C. Chronic hepatitis C infection is a major contributor to the global burden of infectious diseases, with approximately 180 million patients with chronic hepatitis C worldwide, representing about 2%–3% of the population (Stanaway et al., 2016). The actual number of those infected with hepatitis C is likely underestimated given the asymptomatic nature of the disease. There has been increasing interest in initiatives to provide advanced precision healthcare to hepatitis C-infected patients with a focus on tangible benefits within two to five years and the secondary positive economic impact of the proposed intervention or platform, when implemented into clinical practice. We propose our experience with a licensed vocational nurse as the primary treatment provider for chronic hepatitis C infections, as an option to optimize the management of chronic hepatitis C globally (Jayasekera et al., 2015). A licensed vocational nurse is an entry level nursing staff who has earned a state license with a oneor two-year training program. Registered nurses and licensed vocational nurses, also known as licensed practical nurses in many states in the United States, have similar duties in caring for patients. There are, however, differences related to critical thinking skills, care planning, nursing scope of practice, education, and overall responsibilities. Registered nurses are independent in many areas, while licensed vocational nurses must work under the supervision of a registered nurses or physician. In under-resourced regions of the world where there is a shortage of specialist physicians, a nurse treatment provider model is an ideal approach to improving global access to the highly favorable safety, tolerance, and efficacy profile