Andrew A. Li

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

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

Optimizing the Nutritional Support of Adult Patients in the Setting of Cirrhosis

Aim: The aim of this work is to develop a pragmatic approach in the assessment and management strategies of patients with cirrhosis in order to optimize the outcomes in this patient population. Method: A systematic review of literature was conducted through 8 July 2017 on the PubMed Database looking for key terms, such as malnutrition, nutrition, assessment, treatment, and cirrhosis. Articles and studies looking at associations between nutrition and cirrhosis were reviewed. Results: An assessment of malnutrition should be conducted in two stages: the first, to identify patients at risk for malnutrition based on the severity of liver disease, and the second, to perform a complete multidisciplinary nutritional evaluation of these patients. Optimal management of malnutrition should focus on meeting recommended daily goals for caloric intake and inclusion of various nutrients in the diet. The nutritional goals should be pursued by encouraging and increasing oral intake or using other measures, such as oral supplementation, enteral nutrition, or parenteral nutrition. Conclusions: Although these strategies to improve nutritional support have been well established, current literature on the topic is limited in scope. Further research should be implemented to test if this enhanced approach is effective.

The Role of Cannabinoids in the Setting of Cirrhosis

Although the mortality rates of cirrhosis are underestimated, its socioeconomic burden has demonstrated a significant global impact. Cirrhosis is defined by the disruption of normal liver architecture after years of chronic insult by different etiologies. Treatment modalities are recommended primarily in decompensated cirrhosis and specifically tailored to the different manifestations of hepatic decompensation. Antifibrogenic therapies are within an active area of investigation. The endocannabinoid system has been shown to play a role in liver disease, and cirrhosis specifically, with intriguing possible therapeutic benefits. The endocannabinoid system comprises cannabinoid receptors 1 (CB1) and cannabinoid receptor 2 (CB2) and their ligands, endocannabinoids and exocannabinoids. CB1 activation enhances fibrogenesis, whereas CB2 activation counteracts progression to fibrosis. Conversely, deletion of CB1 is associated with an improvement of hepatic fibrosis and steatosis, and deletion of CB2 results in increased collagen deposition, steatosis, and enhanced inflammation. CB1 antagonism has also demonstrated vascular effects in patients with cirrhosis, causing an increase in arterial pressure and vascular resistance as well as a decrease in mesenteric blood flow and portal pressure, thereby preventing ascites. In mice with hepatic encephalopathy, CB1 blockade and activation of CB2 demonstrated improved neurologic score and cognitive function. Endocannabinoids, themselves also have mechanistic roles in cirrhosis. Arachidonoyl ethanolamide (AEA) exhibits antifibrogenic properties by inhibition of HSC proliferation and induction of necrotic death. AEA induces mesenteric vasodilation and hypotension via CB1 induction. 2-arachidonoyl glycerol (2-AG) is a fibrogenic mediator independent of CB receptors, but in higher doses induces apoptosis of HSCs, which may actually show antifibrotic properties. 2-AG has also demonstrated growth-inhibitory and cytotoxic effects. The exocannabinoid, THC, suppresses proliferation of hepatic myofibroblasts and stellate cells and induces apoptosis, which may reveal antifibrotic and hepatoprotective mechanisms. Thus, several components of the endocannabinoid system have therapeutic potential in cirrhosis.

Leucocyte telomere shortening is associated with nonalcoholic fatty liver disease‐related advanced fibrosis

Telomere length and telomerase have been linked with cirrhosis and hepatocellular carcinoma. However, the impact of telomere length on nonalcoholic fatty liver disease and advanced fibrosis in a large national population sample is not well understood.

Impact of Drug Overdose Deaths on Solid Organ Transplantation in the United States

In 2015, prescription opioids and heroin overdoses resulted in more than 30,000 fatalities in the United States (US). The preventable deaths in these young and relatively healthy victims have contributed to the expansion of a scarce donor organ pool for critically ill patients waitlisted for solid organ transplantation due to single/multi-organ failure refractory to medical treatment options. The aim of this study was to evaluate the contribution and outcomes associated with the utilization of drug overdose (DO) donors on solid organ transplantation in the US.

Hepatitis C in Pregnancy

The prevalence of hepatitis C in pregnancy is as high as 3.6% in large cohorts. The prevalence of hepatitis C acquired by vertical transmission is 0.2% to 0.4% in the United States and Europe. Although screening is not recommended in the absence of certain risk factors, the importance of understanding hepatitis C in pregnancy lies in its association with adverse maternal and neonatal outcomes. There is potential for those infants infected by vertical transmission to develop chronic hepatitis C, cirrhosis or hepatocellular carcinoma. The risk of vertical transmission is increased when mothers are co-infected with Human Immunodeficiency Virus (HIV) or possess a high viral load. There is no clear data supporting that mode of delivery increases or reduces risk. Breastfeeding is not associated with increased risk of transmission. Premature rupture of membranes, invasive procedures (such as amniocentesis), intrapartum events, or fetal scalp monitoring may increase risk of transmission. In pregnant patients, hepatitis C is diagnosed with a positive ELISA-3 and detectable Hepatitis C Virus (HCV) RNA viral load. Infants born to HCV-infected mothers should be tested for either HCV RNA on at least two separate occasions. Although prevention is not possible, there may be a role for newer direct acting anti-viral medications in the future.

Potential Therapeutic Benefits of Herbs and Supplements in Patients with NAFLD

Our aim is to review the efficacy of various herbs and supplements as a possible therapeutic option in the treatment and/or prevention of nonalcoholic fatty liver disease (NAFLD). We performed a systematic review of medical literature using the PubMed Database by searching the chemical names of many common herbs and supplements with “AND (NAFLD or NASH)”. Studies and medical literature that discussed the roles and usage of herbs and supplements in NAFLD and nonalcoholic steatohepatitis (NASH) from inception until 20 June 2018 were reviewed. Many studies have claimed that the use of various herbs and supplements may improve disease endpoints and outcomes related to NAFLD and/or NASH. Improvement in liver function tests were noted. Amelioration or reduction of lobular inflammation, hepatic steatosis, and fibrosis were also noted. However, well-designed studies demonstrating improved clinical outcomes are lacking. Furthermore, experts remain concerned about the lack of regulation of herbs/supplements and the need for further research on potential adverse effects and herb–drug interactions. In conclusion, preliminary data on several herbs have demonstrated promising antioxidant, anti-inflammatory, anti-apoptotic, and anti-adipogenic properties that may help curtail the progression of NAFLD/NASH. Clinical trials testing the safety and efficacy must be completed before widespread use can be recommended.

Increased Waitlist Mortality and Lower Rate for Liver Transplantation in Hispanic Patients with Primary Biliary Cholangitis

BACKGROUND & AIMS: Data on the differences in ethnicity and race among patients with primary biliary cholangitis (PBC) awaiting liver transplantation (LT) are limited. We evaluated liver transplant waitlist trends and outcomes based on ethnicity and race in patients with PBC in the United States. METHODS: Using the United Network for Organ Sharing (UNOS) registry, we collected data on patients with PBC on the liver transplant waitlist, and performed analysis with a focus on ethnicity and race‐based variations clinical manifestations, waitlist mortality and LT rates from 2000 to 2014. Outcomes were adjusted for demographics, complications of portal hypertension, and Model for End‐stage Liver Disease score at time of waitlist registration. RESULTS: Although the number of white PBC waitlist registrants and additions decreased from 2000 to 2014, there were no significant changes in the number of Hispanic PBC waitlist registrants and additions each year. The proportion of Hispanic patients with PBC on the liver transplant waitlist increased from 10.7% in 2000 to 19.3% in 2014. Hispanics had the highest percentage of waitlist deaths (20.8%) of any ethnicity or race evaluated. After adjusting for demographic and clinical characteristics, Hispanic patients with PBC had the lowest overall rate for undergoing LT (adjusted hazard ratio, 0.71; 95% CI, 0. 60–0.83; P < .001) and a significantly higher risk of death while on the waitlist, compared to whites (adjusted hazard ratio, 1.41; 95% CI, 1.15–1.74; P < .001). Furthermore, Hispanic patients with PBC had the highest proportion of waitlist removals due to clinical deterioration. CONCLUSIONS: In an analysis of data from UNOS registry focusing on outcomes, we observed differences in rates of LT and liver transplant waitlist mortality of Hispanic patients compared with white patients with PBC. Further studies are needed to improve our understanding of ethnicity and race‐based differences in progression of PBC.

An Unexpected Colonic Mass

A 74-year-old man was admitted to the intensive care unit for progressive muscle weakness leading to hypercarbic respiratory failure requiring intubation, elevated creatine kinase, diplopia, and bilateral ptosis. Due to concern for severe, progressive inflammatory myositis, he was started on pulse dose methylprednisolone 1 g daily for 3 days followed by 1 mg/kg daily and intravenous immunoglobulin (IVIG) infusions. After 1 week of glucocorticoid treatment, he developed dark, bloody stools with clots and abdominal discomfort. On further history, he had been having rare, intermittent bloody diarrhea over the past year. He was born in Mexico and no known family history of colon cancer. With concern for a possible paraneoplastic syndrome underlying his myopathy, a CT scan of the chest, abdomen, and pelvis obtained the day of his bloody stools identified eccentric cecal wall thickening concerning for malignancy. He subsequently underwent a colonoscopy, and a circumferential area of an ulcerated, friable fungating mass in the ascending colon extending into the cecum was seen (Fig. 1a). Additionally, other multiple foci of ulcerated masses were identified in the cecum and transverse colon. Biopsies were taken. Although atypical, the overall clinical picture was felt to be most concerning for colon cancer. Surprisingly, histologic sections showed a dense acute inflammatory infiltrate with ulceration and necrosis, as well as numerous amebic organisms with foamy cytoplasm and occasionally containing erythrocytes, consistent with Entamoeba histolytica amebic colitis and ameboma (Fig. 1b). E. histolytica immunoglobin levels later resulted as positive. Separately, a muscle biopsy was consistent with polymyositis, and his presenting symptoms responded to treatment with corticosteroids and IVIG. Although rare cases have described muscle abscesses, myositis is not a known complication associated with E. histolytica infection. It was thus felt that immunosuppression with high dose steroids for treatment of polymyositis led to the progression of a chronic infection in light of his 1-year history of intermittent bloody stools. His amebic colitis was treated with 3 weeks of metronidazole followed by a 1 week of oral paromomycin given his immunosuppression and an episode of recurrent bleeding. E. histolytica is an important enteric pathogen in developing countries, causing amebic colitis and extra-intestinal manifestations including hepatic abscesses. Patients typically have a history of diarrhea with or without blood. Considered a rare complication, amebomas are a mass of granulation tissue surrounding a dense inflammatory core secondary to chronic amebic infection. They occur most commonly in the cecum and ascending colon in the and can mimic colon cancer, both radiographically and endoscopically [1]. They are usually associated with concurrent hepatic abscesses [2] which were interestingly not seen in this patient. Serological testing is a helpful adjunct in the diagnosis of intestinal amebiasis [3]. Corticosteroids are associated with an increased risk of fulminant amebic colitis [4]. Finally, treatment with metronidazole followed by paromomycin is highly effective. This case report of a patient who immigrated from an endemic region on immunosuppressive therapy with the surprising finding of ameboma illustrates the need to consider it in the differential diagnosis of colonic masses in the appropriate clinical context.