COVID-19 in liver transplant patients: Impact and considerations.

The coronavirus disease 2019 pandemic has significantly impacted liver tran splantation worldwide, leading to major effects on the transplant process, including the pretransplant, perioperative, and post-transplant periods. It is believed that patients with chronic liver disease, especially those with cirrhosis, have a higher risk of complications from coronavirus disease 2019 infection compared to the general population. However, evaluation of coronavirus disease 2019 effects on liver transplant patients has not uniformly demonstrated worse outcomes. Nonetheless, the pandemic created significant challenges and restrictions on transplant policies and organ allocation.

Liver transplantation amidst the COVID-19 era: Our center's experience.

Coronavirus disease 2019 significantly impacted the liver transplant process worldwide. Consequently, it brought significant challenges and limitations to transplant policies and organ allocation forcing liver transplant centers to adjust their protocols to ensure maximum benefit and avoid harm to their patients. Our center, like many others, was obliged to adapt to the challenges. This paper provided an overview of the effects of coronavirus disease 2019 on liver transplantations and detailed our center's experience and efforts during this unprecedented pandemic to serve as a guide for future public health crises.

Consensus recommendations for use of maintenance immunosuppression in solid organ transplantation: Endorsed by the American College of Clinical Pharmacy, American Society of Transplantation, and the International Society for Heart and Lung Transplantation.

Advances in maintenance immunosuppression over the past three decades have improved solid organ transplantation outcomes dramatically. Uninterrupted access to immunosuppression is paramount to minimize rejection and maintain allograft and patient survival. There is no standardized approach to maintenance immunosuppression management. Agents used vary based on transplanted organ, center-specific protocol, provider expertise, insurance formularies, ability to cover co-pays, recipient characteristics and tolerability. Published data reflects this heterogeneity. Despite this limitation, maintenance immunosuppression usage cross pollinates between organ groups with standard of care agents often being used off-label, making medication access a challenge for many transplant recipients. A multidisciplinary panel of American transplant clinicians was formed to review published literature on maintenance immunosuppression with the goal to formulate consensus recommendations for their use in specific organ groups. These consensus recommendations are intended to provide transplant clinicians with a summary of literature on maintenance immunosuppression in the modern era and to support transplant team members working to secure medication access for patients.

Consensus recommendations for use of maintenance immunosuppression in solid organ transplantation: Endorsed by the American College of Clinical Pharmacy, American Society of Transplantation, and International Society for Heart and Lung Transplantation: An executive summary.

Advances in maintenance immunosuppression over the past three decades have improved solid organ transplantation outcomes dramatically. Uninterrupted access to immunosuppression is paramount to minimize rejection and maintain allograft and patient survival. Agents used vary based on transplanted organ, center-specific protocol, provider expertise, insurance formularies, ability to cover co-pays, recipient characteristics and tolerability. Published data reflects this heterogeneity. Despite these obstacles, the information about maintenance immunosuppression use cross pollinates between organ groups with standard of care agents often being used off-label, making medication access a challenge for many transplant recipients. A multidisciplinary panel of American transplant clinicians was formed to review published literature on maintenance immunosuppression with the goal to formulate consensus recommendations for their use in specific organ groups. These consensus recommendations are intended to provide transplant clinicians with a summary of literature on maintenance immunosuppression in the modern era, and to support transplant team members working to secure medication access for patients.

Safety of anti-TNF agents in patients with compensated cirrhosis: a case-control study.

BACKGROUND: There is limited data on the use of anti-TNF agents in patients with concomitant cirrhosis. The aim of this study is to assess the safety of anti-TNF agents in patients with compensated cirrhosis who used these medications for the treatment of an underlying rheumatologic condition or IBD. METHODS: Multicenter, retrospective, matched, case-control study. A one to three case-control match was performed. Adults who received anti-TNF therapy were matched to three adults with cirrhosis who did not receive anti-TNF therapy. Patients were matched for etiology of cirrhosis, MELD-Na and age. Primary outcome was the development of hepatic decompensation. Secondary outcomes included development of infectious complications, hepatocellular carcinoma (HCC), extra-hepatic malignancy, and mortality. RESULTS: Eighty patients with cirrhosis who received anti-TNF agents were matched with 240 controls. Median age was 57.2 years. Median MELD-Na for the anti-TNF cohort was seven and median MELD-Na for the controls was eight. The most common etiology of cirrhosis was NAFLD. Anti-TNF therapy did not increase risk of decompensation (HR: 0.91, 95% CI: 0.64-1.30, p = 0.61) nor influence the time to development of a decompensating event. Anti-TNF therapy did not increase the risk of hepatic mortality or need for liver transplantation (HR: 1.18, 95% CI: 0.55-2.53, p = 0.67). Anti-TNF therapy was not associated with an increased risk of serious infection (HR: 1.21, 95% CI: 0.68-2.17, p = 0.52), HCC (OR: 0.45, 95% CI: 0.13-1.57, p = 0.21), or extra-hepatic malignancy (OR: 0.82, 95% CI: 0.29-2.30, p = 0.71). CONCLUSIONS: Anti-TNF agents in patients with compensated cirrhosis does not influence the risk of decompensation, serious infections, transplant free survival, or malignancy.

An Evaluation of the Fecal Microbiome in Lynch Syndrome.

PURPOSE: There is limited data regarding the fecal microbiome findings in patients with Lynch syndrome. We aimed to study the fecal micobiome of patients with Lynch syndrome with and without cancer. METHODS: We performed an observational study comparing the fecal microbiome of patients with Lynch syndrome (LS) with cancer with those without cancer. We included subjects older than 18 years with LS and excluded those with a history of colectomy or inflammatory bowel disease. We analyzed their fecal microbiome by 16S ribosomal subunit PCR amplification and performed comparative analyses. RESULTS: Eight patients were included: 3 of these with LS and cancer (LS-C) and 5 patients with LS and no cancer (LS-NC). We found non-significant differences at the phyla and genera level between the LS-C and LS-NC groups. At the phyla level, LS-C patients had a higher percentage of Bacteroidetes (42.2% vs. 28.5%; P = 0.068) and Verrucomicrobia (0.644% vs 0.0007%; P = 0.10), and a lower percentage of Firmicutes (48.3% vs. 65.4%; P = 0.078). At the genus level, LS-C patients had a higher rate of Akkermania (0.766% vs. 0.001%; P = 0.11). LS-C patients with endometrial cancer had a higher rate of Bacteroides (37.4% vs 17.3%; P = 0.10). LS-C patients had a lower rate of Pseudobutyrvibrio (0.74% vs. 2.71%; P = 0.10). CONCLUSIONS: The fecal microbiome of LS patients with extraintestinal cancer differs that of LS patients without cancer. Further studies are needed to explore microbiome changes in these high risk patients.

Managing liver transplantation during the COVID-19 pandemic: A survey among transplant centers in the Southeast United States.

BACKGROUND: The coronavirus disease-2019 (COVID-19) pandemic has had a profound worldwide impact. Indeed, it has led to a vast decrease in organ transplantation, including liver transplants (LT). There is little data regarding adjustments made by LT centers as a response to the COVID-19 pandemic. AIM: To assess the experience of LT centers in the United States during the pandemic. METHODS: We performed an observational survey study from May 11, 2020 to June 5, 2020. We sent out a 13 question survey to 15 LT centers across the southeastern United States. RESULTS: Eleven LT centers responded to the survey. We found that (11/11) 100% of transplant centers made adjustments because of the COVID-19 pandemic. At least 50% of transplant centers had at least one transplant recipient infected with COVID-19. To adjust, greater than 50% of centers performed fewer LT, 100% of patients were tested for COVID-19, and most centers implemented a virtual platform. CONCLUSION: The COVID-19 pandemic greatly affected liver transplantation in the southeastern United States. It was evident that a concerted effort was made by LT centers to protect their patients and employees from COVID-19 but also to continue the life-saving procedure of LT in this sick patient population. Further studies are needed to assess how LT centers around the world managed the pandemic in order to learn strategies to continue life-saving procedures in this patient population.

High-risk third trimester pregnancy with decompensated cirrhosis safely delivered following emergent preoperative interventional radiology for mitigation of variceal bleeding.

Coagulopathy coupled with severe portal hypertension in the setting of cirrhosis increases the risk of mortality from variceal bleeding in pregnant women. Studies suggest transjugular intrahepatic portosystemic shunt (TIPS) creation to be a safe procedure during pregnancy in preventing variceal bleeding complications; however, it is not typically employed in severely decompensated cirrhosis. This case report of a pregnant woman presenting at 34.7 weeks' gestation demonstrates successful variceal mapping, emergent TIPS creation and variceal embolization to allow safe cesarean delivery despite severe hypofibrinogenemia and decompensated alcoholic cirrhosis. With careful medical optimization, angiographic imaging and vascular interventional radiology may be employed outside of usual indications to achieve safe pregnancy delivery and postpartum recovery.

A Big Step Forward in Hepatitis C Screening.

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

Hepatitis C Virus NAT-Positive Solid Organ Allografts Transplanted Into Hepatitis C Virus-Negative Recipients: A Real-World Experience.

BACKGROUND AND AIMS: Hepatitis C virus (HCV)-viremic organs are underutilized, and there is limited real-world experience on the transplantation of HCV-viremic solid organs into recipients who are HCV negative. APPROACH AND RESULTS: Patients listed or being evaluated for solid organ transplant after January 26, 2018, were educated and consented by protocol on the transplantation of HCV-viremic organs. All recipients were HCV nucleic acid test and anti-HCV antibody negative at the time of transplant and received an HCV-viremic organ. The primary outcome was sustained virological response (SVR) at 12 weeks after completion of direct-acting antiviral (DAA) therapy (SVR12 ). Seventy-seven patients who were HCV negative underwent solid organ transplantation from a donor who was HCV viremic. No patients had evidence of advanced hepatic fibrosis. Treatment regimen and duration were at the discretion of the hepatologist. Sixty-four patients underwent kidney transplant (KT), and 58 KT recipients had either started or completed DAA therapy. Forty-one achieved SVR12 , 10 had undetectable viral loads but are not eligible for SVR12 , and 7 remain on treatment. One KT recipient was a nonresponder because of nonstructural protein 5A resistance. Four patients underwent liver transplant and 2 underwent liver-kidney transplant. Three patients achieved SVR12 , 1 has completed DAA therapy, and 2 remain on treatment. Six patients underwent heart transplant and 1 underwent heart-kidney transplant. Six patients achieved SVR12 and 1 patient remains on treatment. CONCLUSIONS: Limited data exist on the transplantation of HCV-viremic organs into recipients who are HCV negative. Our study is the largest to describe a real-world experience of the transplantation of HCV-viremic organs into recipients who are aviremic. In carefully selected patients, the use of HCV-viremic grafts in the DAA era appears to be efficacious and well tolerated.

Fibrosing cholestatic hepatitis after kidney transplantation from HCV-viremic donors to HCV-negative recipients: A unique complication in the DAA era.

Fibrosing cholestatic hepatitis (FCH) posttransplantation can lead to graft failure and death. In the era of direct acting antiviral therapy (DAA), several studies have demonstrated the efficacy and safety of transplanting hepatitis C virus (HCV)-positive allografts into HCV-negative recipients. In this case series, we present two cases of HCV-negative recipients who underwent kidney transplantation from viremic donors and developed FCH. Both patients presented after transplant with abnormal liver function tests and HCV viral loads of greater than 100 000 000 IU/mL. FCH was diagnosed by histology and/or clinical data. Both patients were started on DAA therapy within 24 hours of admission with improvement in LFTs. One patient has undetectable HCV 12 weeks after completing treatment and the other patient has undetectable HCV after completing DAA treatment. The introduction of DAAs has changed the landscape of solid organ transplantation with the potential to expand the donor pool and increase access to organs. While HCV viremic organs have tremendous potential to increase access to a scarce resource, FCH is a potentially fatal complication and therefore clinicians must maintain a high index of suspicion for this unique complication.

Transplantation of HCV Viremic Livers into HCV Viremic Recipients Followed by Direct-acting Antiviral Therapy.

Background and Aims: Hepatitis C virus (HCV)-infected organs are underutilized. We aimed to assess the safety and efficacy of direct-acting antiviral agents (DAAs) therapy in HCV viremic patients who are transplanted with a liver from a HCV viremic donor. Methods: We conducted a retrospective study, including patients seen from July 2015 to April 2017. HCV viremic patients transplanted with a liver from a HCV viremic donor and subsequently treated with DAAs were included. Outcomes assessed included undetectable viral load at 12 weeks after completing DAA therapy (sustained virologic response, SVR12), adverse events, and interactions with immunosuppression. Results: Twenty-four HCV viremic recipients received livers from HCV viremic donors. Median age was 63 years, and the majority (79.2%) were genotype 1a. Donors and recipients were viremic at the time of transplant. Median modified model for end-stage liver disease score was 19, and median time on the waitlist was 81 days. Median time from transplant to initiation of DAA therapy was 123 days. Several DAA regimens were used and 15 (62.5%) patients did not receive ribavirin. Treatment duration ranged from 12 to 24 weeks. Twenty-three (95.8%) patients achieved SVR12. Five (20.8%) patients developed adverse events; however, none required DAA discontinuation. Conclusions: DAA therapy was efficacious and well tolerated in HCV viremic recipients who underwent liver transplantation from a HCV viremic donor.

Open Access Colonoscopy for Colorectal Cancer Prevention: An Evaluation of Appropriateness and Quality.

BACKGROUND: Open access colonoscopy (OAC) has gained widespread acceptance and has the potential to increase colorectal cancer (CRC) screening. However, there is little data evaluating its appropriateness for CRC prevention. AIMS: The aim of this study is to evaluate the appropriateness of OAC in CRC screening and polyp surveillance by comparing to procedures ordered by gastroenterologists (NOAC). As secondary outcomes, we compared the quality of bowel preparation and adenoma detection rate (ADR) between OAC and NOAC. METHODS: It is retrospective single-center study. Inclusion criteria included patients > 50 years of age undergoing a colonoscopy for CRC screening and surveillance. Appropriateness was defined as those colonoscopies performed within 12 months of the recommended 2012 consensus guidelines. Secondary outcomes included the quality of bowel preparation and ADR. RESULTS: 5211 colonoscopies met inclusion criteria, and 64.9% were OAC. Screening OAC was appropriately 91.6% and NOAC 92.9% of the time (p = 0.179). Surveillance NOAC were inappropriate in 26.4% of cases, and surveillance OAC was 32.6% (p = 0.008). Multivariate analysis demonstrated that OAC did not influence ADR (OR for NOAC 0.97; 95% CI 0.86-1.1; p = 0.644) or an adequate bowel preparation (OR for NOAC 1.11; 95% CI 0.91-1.36; p = 0.306). CONCLUSION: OAC performed similarly to NOAC for screening indications, quality of bowel preparation, and ADR. However, more surveillance procedures were inappropriate in the OAC group although both groups had a high number of inappropriate indications. Although OAC can be efficiently performed for screening indications, measures to decrease inappropriate surveillance colonoscopies are needed.

The Use of Vedolizumab in Patients with Concomitant Cirrhosis and Crohn's Disease.

Vedolizumab is a humanized monoclonal α4ß7 integrin antibody used in patients with Crohn's disease (CD) and ulcerative colitis (UC). Limited data are available on the use of vedolizumab in patients with concurrent cirrhosis and inflammatory bowel disease (IBD). Patients with cirrhosis are unique, as they have a predilection for developing opportunistic infections and malignancies. Additionally, it is not known if vedolizumab alters the natural course of cirrhosis. We report our experience in three patients with concomitant CD and cirrhosis, who were treated with vedolizumab. In our limited cohort, all the three patients tolerated vedolizumab well. None of them experienced significant infectious complications, nor did any have decompensated cirrhosis. Our limited series suggest that vedolizumab is well tolerated in patients with compensated cirrhosis.