Liver transplantation for alcoholic hepatitis in the United States: Excellent outcomes with profound temporal and geographic variation in frequency.

Medical-refractory severe alcoholic hepatitis (AH) has a high mortality. The national frequency, longer term outcomes and regional practices of AH liver transplantation (LT) in the United States are not well described, despite the increasing mortality from alcohol-associated liver disease. We analyzed the trends in frequency and outcomes of UNOS data on 39 455 adult patients who underwent LT from 2014 to 2019, including AH LT recipients. LTs for AH increased 5-fold, from 28 in 2014 to 138 in 2019, varying 8-fold between UNOS regions. Three transplant centers accounted for 50%-90% of AH LTs within each region. The number of transplant centers performing AH LTs increased from 14 in 2014 to 47 in 2019. AH patients were younger (mean = 39.4 years), had higher MELD scores (mean = 36.8), and were more often on dialysis (46.0%) and in ICU (38.4%), compared to other indications (all P < .05). One- and 5-year graft survivals for AH LT recipients were 91.7% and 81.9%, respectively. The frequency of AH LT is increasing rapidly, with excellent medium-term outcomes. An impact of AH recurrence on patient or graft survival is not apparent in this national analysis. There are marked geographic variations in practices, highlighting the lack of selection criteria standardization.

Is 70 the new 50? Complications and outcomes of transjugular intrahepatic portosystemic shunt in older versus younger patients.

BACKGROUND: An increased risk of complications of TIPS in patients older than 65 years of age has been described, but data is limited. The objective of this study was to determine if the rate of complications post-TIPS differs in patients 65 or younger, compared to those older than 65 years of age. METHODS: A retrospective chart review was performed for all patients who underwent TIPS procedure at Banner-University Medical Center Phoenix, from 2010 to 2018, specifically focusing on complications and outcomes post-TIPS. In total, 402 patients were included in this analysis. Complications included portosystemic encephalopathy, post-TIPS infection, acute kidney injury requiring hemodialysis, hemorrhage, respiratory complications, need for transplant, or death. RESULTS: A total of 402 patients were included and divided into two groups: 300 (74.6%) were 65 years or younger (ages 53 ± 9), and 102 were older than 65 years (70 ± 5 (p < 0.001)). There were no statistically significant differences between age groups when comparing portosystemic encephalopathy, post-TIPS infection, acute kidney injury, respiratory complications, need for transplant, or death. CONCLUSION: In this large, single-center cohort, there was no statistically significant difference in the rate of complications of TIPS between the two age groups. Based on our results, TIPS procedure is an equally safe option for properly selected patients with complications of portal hypertension, regardless of age.

Immunosuppression in liver transplant.

The increasing potency of immunosuppression (IS) agents resulted in significantly decreased rates of steroid resistant rejection and rejection related graft loss in liver transplantation (LT). Currently, more than two thirds of late mortality after LT is unrelated to graft function. However, the increased benefit of more potent IS drugs, coupled with the prolonged survival of transplant recipients led to longer patients exposure to these drugs and their unwanted adverse effects, creating a double-edged sword. In this article the authors describe the mechanism of action and the adverse effects of the most commonly used immunosuppressed drugs, and the most commonly used IS regimens for both induction and maintenance regimens. The balance between the ideal IS regimen to prevent rejection and the need to minimize the dose of IS drugs in order to prevent the adverse effects related to its use requires the knowledge of the science and the experience with the art of medicine. The different protocols aimed at protecting renal function and preventing the development of de novo cancer and metabolic syndrome are discussed here. The main causes of mortality late after liver transplant are associated with prolonged use of IS medications, and clear evidence exists about over-immunosuppression of recipients of liver transplant. The current status of strategies of IS minimization and withdrawal are reviewed in this article, with evaluation of its benefits and pitfalls.

Improved Graft Survival After Liver Transplantation for Recipients With Hepatitis C Virus in the Direct-Acting Antiviral Era.

Highly effective direct-acting antiviral (DAA) therapy has transformed outcomes of liver transplantation in hepatitis C virus (HCV) patients. We examined longer-term outcomes in HCV-positive recipients in the DAA era and analyzed the Scientific Registry of Transplant Recipients for primary adult, single-organ, nonfulminant liver transplant recipients in the United States from January 1, 2008 to June 30, 2018. Graft loss was compared among HCV-positive liver transplant recipients who received either an HCV-negative or HCV-positive donor (donor [D]-/recipient [R]+; D+/R+) and HCV-negative liver transplant recipients who received a HCV-negative donor (D-/R-). The groups were further divided between the pre-DAA and DAA eras. There were 52,526 patients included: 31,193 were D-/R- patients; 18,746 were D-/R+ patients; and 2587 were D+/R+ patients. The number of D-/R+ transplants decreased from 2010 in 2008 to 1334 in 2017, with this decline particularly noticeable since 2015. D-/R+ patients in the DAA era (n = 7107) were older, had higher rates of hepatocellular carcinoma, and lower Model for End-Stage Liver Disease scores than those in the pre-DAA era. Graft survival improved for all recipients in the DAA era but improved most dramatically in HCV-positive recipients: D-/R+ 1-year survival was 92.4% versus 88.7% and 3-year survival was 83.7% versus 77.7% (DAA versus pre-DAA era, respectively) compared with D-/R- 1-year survival of 92.7% versus 91.0% and 3-year survival of 85.7% versus 84.0% (DAA versus pre-DAA era, respectively). The magnitude of improvement in 3-year graft survival was almost 4-fold greater for D-/R+ patients. The 3-year survival for D+/R+ patients was similar to HCV-negative patients. In conclusion, the number of liver transplants for HCV has decreased by more than one-third over the past decade. Graft survival among HCV-positive recipients has increased disproportionately in the DAA era with HCV-positive recipients now achieving similar outcomes to non-HCV recipients.

Increasing Utilization and Excellent Initial Outcomes Following Liver Transplant of Hepatitis C Virus (HCV)-Viremic Donors Into HCV-Negative Recipients: Outcomes Following Liver Transplant of HCV-Viremic Donors.

Direct-acting antiviral (DAA) therapy has altered the frequency and outcome of liver transplantation (LT) for hepatitis C virus (HCV). The high efficacy and tolerability of DAA therapy has also created a rationale for utilizing HCV-viremic (HCV-RNA-positive) donors, including into HCV-negative recipients. We examined trends in frequency of organ utilization and graft survival in recipients of HCV-viremic donors (HCV-RNA positive as measured by nucleic acid testing [NAT]). Data were collected from the Scientific Registry of Transplant Recipients (SRTR) on adult patients who underwent a primary, single-organ, deceased donor LT from January 1, 2008 to January 31, 2018. Outcomes of HCV-negative transplant recipients (R- ) who received an allograft from donors who were HCV-RNA positive (DNAT+ ) were compared to outcomes for R- patients who received organs from donors who were HCV-RNA negative (DNAT- ). There were 11,270 DNAT- /R- ; 4,748 DNAT- /R+ ; 87 DNAT+ /R- ; and 753 DNAT+ /R+ patients, with 2-year graft survival similar across all groups: DNAT- /R- 88%; DNAT- /R+ 88%; DNAT+ /R- 86%; and DNAT+ /R+ 90%. Additionally, there were 2,635 LTs using HCV antibody-positive donors (DAb+ ): 2,378 DAb+ /R+ and 257 DAb+ /R- . The annual number of DAb+ /R- transplants increased from seven in 2008 to 107 in 2017. In the post-DAA era, graft survival improved for all recipients, with 3-year survival of DAb+ /R- patients and DAb+ /R+ patients increasing to 88% from 79% and to 85% from 78%, respectively. Conclusion: The post-DAA era has seen increased utilization of HCV-viremic donor livers, including HCV-viremic livers into HCV-negative recipients. Early graft outcomes are similar to those of HCV-negative recipients. These results support utilization of HCV-viremic organs in selected recipients both with and without HCV infection.

Stretching the boundaries for liver transplant in the 21st century.

Given the high waiting list mortality, there is a clear need to identify strategies to increase the number of livers for transplantation. Some strategies require policy changes, whereas others depend on a better understanding of available opportunities. We divided the strategies to increase the number of livers for transplantation into two categories-those aiming to increase the use of organs considered to be of suboptimal quality, and those aiming to increase the use of organs considered to be of suboptimal size. Enough evidence suggests that, if considered in the context of other donor and recipient variables, grafts from elderly donors are a safe option. The severity of steatosis, and not simply its presence, is an important factor in contemplating the utility of steatotic grafts. Use of organs that have steatosis together with other factors that define extended-criteria organs should be avoided, particularly prolonged cold ischaemia time. Donation after circulatory death has an important role in increasing the donor pool, given the wide availability of organs from donors with this cause of death. This type of donation is hampered by a higher risk of ischaemia-reperfusion injury than other types of donation, which can result in graft complications and potential graft loss. Different types of machine perfusion have the potential to overcome these issues, and further research is needed to establish the best techniques and most cost-effective models. Despite the scarcity of data, the availability of safe and highly effective antiviral therapies means that the use of donors infected with hepatitis C virus (HCV) in recipients who are HCV negative can be considered as a strategy to increase the donor pool. Although data on transplantations using livers from living donors in patients with a Model for End-Stage Liver Disease (MELD) score higher than 20-24 are scarce, outcomes are similar to those achieved in patients with lower MELD scores, at least in reference centres. Increased use of split livers is an option if donors and recipients are carefully selected.

Isolated hepatic hemangiomatosis in 2 septuagenarians.

We report 2 cases of isolated hepatic hemangiomatosis: a 76-year-old woman who is, to our knowledge, the oldest person with this diagnosis, and a 74-year-old woman. Magnetic resonance imaging of the abdomen showed T2 hyper intense lesions throughout the liver, peripheral nodular arterial enhancement, and filling of contrast on the portal venous and delayed phases. Computed tomography showed liver lesions with peripheral nodular enhancement in the early phase and a centripetal pattern or "filling in" during the late phase; the lesions opacified after a delay of 3 or more minutes and remained isodense or hyperdense on delayed scans. Both images were consistent with hepatic hemangiomatosis. These cases help increase awareness about benign and unusual liver lesions with radiologic characteristics similar to those of malignant liver tumors. The authors also present a review of 15 other cases of isolated hepatic hemangiomatosis reported in English literature from 1970 to present.

International Liver Transplantation Society Consensus Statement on Immunosuppression in Liver Transplant Recipients.

Effective immunosupression management is central to achieving optimal outcomes in liver transplant recipients. Current immunosuppression regimens and agents are highly effective in minimizing graft loss due to acute and chronic rejection but can also produce a substantial array of toxicities. The utilization of immunosuppression varies widely, contributing to the wide disparities in posttransplant outcomes reported between transplant centers. The International Liver Transplantation Society (ILTS) convened a consensus conference, comprised of a global panel of expert hepatologists, transplant surgeons, nephrologists, and pharmacologists to review the literature and experience pertaining to immunosuppression management to develop guidelines on key aspects of immunosuppression. The consensus findings and recommendations of the ILTS Consensus guidelines on immunosuppression in liver transplant recipients are presented in this article.

The New Era of Hepatitis C: Therapy in Liver Transplant Recipients.

Hepatitis C virus (HCV) is the leading cause of end-stage liver disease in both Europe and the United States and is the most common reason for liver transplant. In the absence of antiviral therapy, recurrent infection is the norm with subsequent graft hepatitis and impaired survival. Whether it may be better to postpone therapy in patients in whom higher risk of failure and toxicity is coupled with lower chance of liver function improvement likely depends on several factors, including waiting time, center allocation policy, presence of hepatocellular carcinoma and local prevalence of anti-HCV-positive donors.

Current Concepts in Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis.

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are chronic, cholestatic diseases of the liver with common clinical manifestations. Early diagnosis and treatment of PBC slows progression and decreases the need for transplant. However, one-third of patients will progress regardless of treatment. Bilirubin <1.0 and alkaline phosphatase <2.0 x the upper limit of normal at 1 year after treatment appear to predict 10-year survival. Ursodeoxycholic acid (UDCA) is the recommended treatment for PBC, and recent studies with obeticholic acid showed promising results for UDCA non-responders. Unlike PBC, no therapy has been shown to alter the natural history of PSC. The recommended initial diagnostic test for PSC is magnetic resonance cholangiopancreatography, typically showing bile duct wall thickening, focal bile duct dilatation, and saccular dilatation of the intra- and/or extrahepatic bile ducts. Immunoglobulin 4-associated cholangitis must be excluded when considering the diagnosis of PSC, to allow for proper treatment, and monitoring of disease progression. In addition to the lack of therapy, PSC is a pre-malignant condition and close surveillance is indicated.

Coated transjugular intrahepatic portosystemic shunt does not improve thrombocytopenia in patients with liver cirrhosis.

BACKGROUND/AIM: Thrombocytopenia is a common complication of chronic liver disease. The theory of portal decompression to improve thrombocytopenia due to hypersplenism has led to the study of transjugular intrahepatic portosystemic shunt (TIPS) as a potential therapy. However, there is a paucity of data and results have been conflicting. The aim of this study was to determine whether platelet counts improved in cirrhotic patients after placement of the new polytetrafluoroethylene (PTFE)-coated TIPS, developed in 2004. METHODS: This is a retrospective cohort study of 68 patients with chronic liver disease who underwent a TIPS procedure. One-hundred twenty controls who did not undergo a TIPS procedure were matched on average for age, sex, race, model for end-stage liver disease (MELD) score, and etiology of liver disease. Platelet and hemoglobin counts were recorded during the month prior to the TIPS procedure (baseline) and over the following 12-14 months or until transplanted or death. RESULTS: While platelet counts improved during the first 3 months after TIPS with a mean increase of 11.25 × 103/µL (p = 0.064), they returned to baseline (pre-TIPS) with mean platelets of 91.31 × 103 µL by 12-14 months in comparison with a mild decrease of 10.2 × 103 µL in platelet counts in the control group from 100.4 × 103 µL to 90.2 × 103 (p = 0.119). There was also no significant correlation between platelet counts and etiology of liver disease, age, race, gender, or MELD score. Hemoglobin counts were found to have a small increase of 0.657 g/dL over the 12-14 month course in the TIPS group, which was statistically significant (p = 0.003). CONCLUSION: There does not appear to be a significant improvement in thrombocytopenia in cirrhotic patients after TIPS placement, despite advances in TIPS stents. However, there may be a mild improvement in anemia after TIPS implantation.

Results of a protocol for the management of patients with fulminant liver failure.

OBJECTIVE: To assess the safety and efficacy of a protocol to support management of intracerebral pressure in patients with fulminant liver failure (FLF). DESIGN AND SETTING: A prospective series was conducted between May 2004 and September 2006 at Banner Good Samaritan Medical Center, a 650-bed teaching hospital in Phoenix, Arizona. PATIENTS: We recruited consecutive patients with FLF and stage 3 or 4 encephalopathy. INTERVENTIONS: We placed an intracranial pressure monitor in each patient and employed a protocol to support decisions regarding hemostatic management and prevention and treatment of intracranial hypertension (IHTN). Treatment modalities included hypothermia, hypocarbia, intravenous pentobarbital, intravenous mannitol and vasopressor titration for maintenance of cerebral perfusion pressure. The main outcome measure was survival in transplant candidates. MEASUREMENTS AND MAIN RESULTS: Twenty-two patients entered the study and 21 (95%) had at least one episode of IHTN. Eighty-two discrete episodes of IHTN occurred, and 78 of these (95%) resolved with treatment. Overall survival was 55%. Eleven of 18 (61%) of transplant candidates survived with good neurologic outcome. No patient died from isolated cerebral edema. Three patients had intracranial hemorrhages related to the intracranial pressure monitor. CONCLUSIONS: Protocol-driven management of intracranial pressure in FLF can result in good clinical outcomes in most transplant candidates, even if IHTN occurs.