Leise, Michael D.

ABSTRACT Background The accuracy of current criteria for ruling out large oesophageal varices (LEV) and other endoscopic lesions of portal hypertension (PH) may be compromised by obesity and MASLD/MASH. Aims In the US multicentre SHUNT‐V study, we evaluated the disease severity index (DSI) for detecting LEV and other lesions of PH at endoscopy. Methods Subjects were adults with compensated cirrhosis scheduled for endoscopy to screen for varices. DSI was calculated from clearances of labelled cholates after oral and intravenous administration. DSI ≤ 18.3 was evaluated as a cut‐off for ruling out LEV with acceptance criteria of negative likelihood ratio < 0.52 and sensitivity > 85%. Results SHUNT‐V enrolled 306 subjects; 275 had both DSI and endoscopy, and 238 had Child–Pugh A cirrhosis (52.1% MASLD/MASH, 25.2% chronic hepatitis C and 15.6% alcoholic liver disease; 87% were overweight, 64% were obese and 54% had diabetes). AUROCs for DSI ranged from 0.81 to 0.82 for LEV and 0.79 to 0.80 for all significant PH lesions. DSI 18.3 had sensitivity 96.3%–100% for LEV and 97.3%–100% for all significant PH lesions. If DSI ≤ 18.3 were used as the sole determinant to defer EGD, 27%–35% of EGDs could have been avoided with 0%–3.7% of LEV and 0%–2.7% of all significant PH lesions missed. Conclusions HepQuant DSI predicts the likelihood of LEV and significant PH lesions across a spectrum of patient characteristics and disease aetiologies. DSI, based on liver function and portal‐systemic shunting, can aid in the decision to defer endoscopy for varices in patients with Child–Pugh A cirrhosis. Trial Registration: The SHUNT‐V study was registered at ClinicalTrials.gov (NCT03583996)

AbstractBackground: Liver transplant (LT) recipients with untreated hepatitis C (HCV) are at risk for cirrhosis graft failure. The advent of direct acting antiviral agents (DAA) has improved outcomes in HCV.Aims: We aim to examine liver transplant outcomes and allograft fibrosis development/progression after sustained virologic response (SVR).Methods: We performed a retrospective cohort study of 226 consecutive liver transplant recipients with HCV from 2007 to 2018. The cohort was split into transplants pre (Group A) and post (Group B) 2014 to reflect the introduction of DAAs. Fibrosis was monitored with liver biopsy and non‐invasive imaging.Results: Group B had significantly improved HCV treatment rates and earlier SVR compared to Group A, with a cumulative incidence rate of SVR at 2 years of 86.7% versus 15.4% (HR = .11, p < .001). Prior to achieving SVR, Group A demonstrated worsening of fibrosis stage per year (+.21, p < .001) whereas Group B showed minimal change on protocol annual biopsy (−.02, p = .80). After SVR, most patients were followed non‐invasively and demonstrated stable or improved fibrosis stage over time. Patients undergoing transient elastography showed regression in fibrosis stage per year (−.19, p < .001).Conclusion: HCV patients undergoing LT after 2014 had higher rates of SVR and improved clinically relevant transplant outcomes, namely less graft loss and death relating to HCV. Fibrosis progression halted or improved after SVR in both cohorts, suggesting that LT recipients with SVR do not require fibrosis monitoring even with established fibrosis prior to SVR.

Abstract Background: Starting in November 2017, 3 liver transplant centers in a single health care system tested and implemented a new protocol to begin accepting livers from hepatitis C virus–seropositive donors for seronegative liver transplant recipients. Although reports show an increase in donors after protocol implementation, there are no details regarding protocol uptake at each transplant center. Literature is limited on protocol implementation that is developed and disseminated by the same protocol producers. The purpose of this study was to evaluate the implementation of a new liver transplant protocol adopted at 3 transplant centers in the same health care system. Methods: A multimethod implementation study using interview, survey, and transplant data was conducted to develop a conceptual model of protocol implementation, identify facilitators of and barriers to implementation, and detect differences in implementation between 3 centers. Results: The conceptual model included 4 domains: rationale, development, implementation, and sustainability. Facilitators included clear, science-based rationale, input from multiple hepatologists, leadership support, and funded pilot data. Barriers included insurance coverage of posttransplant medication and donor field availability. A total of 94 physicians and staff at the 3 transplant centers completed the survey. Implementation factors were all rated moderately high to high at all 3 centers. One-way analysis of variance showed significant differences in mean implementation scores between the centers (F(2, 84)=11.65; P<.001) and between physicians at the 3 centers (F(2, 23)=4.65; P=.02); post hoc comparisons indicated that the scores for physicians differed only between the leading center and 1 participating center. Transplant numbers increased across all 3 centers from 2017 to 2021. Conclusions: Protocol implementation was successful across all 3 centers, especially at the leading transplant center where the protocol was developed. Future efforts should examine the appropriateness of the protocol for other organs (eg, heart, kidney) and additional medical outcome data (eg, mortality, morbidity, quality of life). Trial Registration: Not applicable

Combination anti-retroviral therapy has drastically improved solid organ transplantation outcomes in persons living with HIV. DAA therapy has led to the successful eradication of HCV. While recent data have suggested improvement in outcomes in HIV/HCV-coinfected liver transplant recipients, temporal trends in patient survival within pre- and post-DAA eras are yet to be elucidated. The UNOS database was utilized to identify deceased donor liver transplant recipients between 1 January 2000 and 30 September 2020 and stratify them by HIV and HCV infection status. A total of 85,730 patients met the inclusion criteria. One-year and five-year patient survival improved (93% and 80%, respectively) for all transplants performed post-2015. For HIV/HCV-coinfected recipients, survival improved significantly from 78% (pre-2015) to 92% (post-2015). Multivariate regression analyses identified advanced recipient age, Black race, diabetes mellitus and decompensated cirrhosis as risk factors associated with higher one-year mortality. Liver transplant outcomes in HIV/HCV-coinfected liver transplant recipients have significantly improved over the last quinquennium in the setting of the highly effective combination of ART and DAA therapy. The presence of HIV, HCV, HIV/HCV-coinfection and active HCV viremia at the time of transplant do not cause higher mortality risk in liver transplant recipients in the current era.

Background: Direct-acting antivirals (DAA) are highly effective for the treatment of hepatitis C (HCV), although there are limited data on the safety and efficacy of DAA therapy in hepatitis C-positive individuals awaiting liver transplantation for hepatocellular carcinoma (HCC). Methods: We conducted a retrospective cohort study of HCV-positive patients who underwent liver transplantation for HCC at 3 liver transplant centers across the United States from 2014 to 2017 with follow-up to July 2018. Transplant recipients who received DAA before transplant were compared with those who did not (DAA naive) for posttransplant HCC recurrence rate, sustained virological response (SVR), allograft failure, and death using Kaplan-Meier analysis and Cox proportional hazard models. Results: A total of 171 HCV-HCC transplant recipients (99 pretransplant DAA; 72 DAA naive controls) were included, with a median follow-up of 24 months. The overall posttransplant HCC recurrence rate was 9% (15/171). Pretransplant DAA was not associated with HCC recurrence (5% versus 14%; P = 0.07), graft failure (7% versus 3%; P = 0.21), or death (12% versus 19%; P = 0.19) as compared with DAA naive patients. SVR rates were significantly lower (P < 0.01) with pretransplant DAA (75%, 39/52) than posttransplant DAA (97%, 59/61) therapies. Those who received pretransplant DAA and those who did not were not statistically different in age, gender, alpha fetal protein levels, model for end-stage liver disease scores, or transplant wait time. Conclusions: Pretransplant DAA for HCV was not associated with an increased risk of posttransplant HCC recurrence, though pretransplant DAA had lower efficacy than posttransplant DAA in HCV-HCC transplant recipients.

Background. The role of MZ phenotype of α 1 antitrypsin (α1AT) deficiency as a potential cofactor in advanced liver disease arising from other primary causes is not widely understood. In the general population, MZ phenotype accounts for 2%–4% in Europe and 2%–7.1% in North America. The aim of this study was to determine the prevalence of the MZ phenotype among various causes of cirrhosis in the United States in the modern era and its impact on pulmonary function before and after liver transplantation. Methods. This retrospective study included adult patients with cirrhosis who underwent liver transplantation at Mayo Clinic. Participants’ data including pathogenesis of cirrhosis, model for end-stage liver disease-Na score, α1AT phenotype, liver decompensation events, and pulmonary outcomes was determined by retrospective review of the liver transplantation database. Results. One hundred thirty of 1341 adult patients with cirrhosis (9.7%) were α1AT MZ carriers. When comparing the distribution of protease inhibitor (PI) MZ among different pathogenesis, the prevalence of MZ was significantly increased in nonalcoholic steatohepatitis (NASH), alcoholic liver disease (ALD), and cryptogenic cirrhosis compared with other causes. Thirty-seven of 171 with NASH (22%), 37 of 187 with ALD (20%), and 9 of 39 with cryptogenic cirrhosis (23.1%) were identified as PI MZ, while in other subgroups; we detected 18 of 320 with viral hepatitis, and 11 of 339 with primary biliary cholangitis/primary sclerosing cholangitis. Also, MZ patients were more likely to develop preoperative chronic obstructive lung disease, and postoperative pulmonary hypertension and pulmonary embolism than MM patients. Conclusions. The rates of preoperative and postoperative pulmonary complications were found to be higher in PI MZ patients than in PI MM patients. The MZ phenotype was significantly enriched in NASH, ALD, and cryptogenic cirrhosis.

Background and Aims Compared to other chronic diseases, patients with chronic liver disease (CLD) have significantly higher inpatient mortality; accurate models to predict inpatient mortality are lacking. Serum lactate (LA) may be elevated in patients with CLD due to both tissue hypoperfusion as well as decreased LA clearance. We hypothesized that a parsimonious model consisting of Model for End‐Stage Liver Disease (MELD) and LA at admission may predict inpatient mortality in patients with CLD. Approach and Results We examined all patients with CLD in two large and diverse health care systems in Texas (North Texas [NTX] and Central Texas [CTX]) between 2010 and 2015. We developed (n = 3,588) and validated (n = 1,804) a model containing MELD and LA measured at the time of hospitalization. We further validated the model in a second cohort of 14 tertiary care hepatology centers that prospectively enrolled nonelective hospitalized patients with cirrhosis (n = 726). MELD‐LA was an excellent predictor of inpatient mortality in development (concordance statistic [C‐statistic] = 0.81, 95% confidence interval [CI] 0.79‐0.82) and both validation cohorts (CTX cohort, C‐statistic = 0.85, 95% CI 0.78‐0.87; multicenter cohort C‐statistic = 0.82, 95% CI 0.74‐0.88). MELD‐LA performed especially well in patients with specific cirrhosis diagnoses (C‐statistic = 0.84, 95% CI 0.81‐0.86) or sepsis (C‐statistic = 0.80, 95% CI 0.78‐0.82). For MELD score 25, inpatient mortality rates were 11.2% (LA = 1 mmol/L), 19.4% (LA = 3 mmol/L), 34.3% (LA = 5 mmol/L), and >50% (LA > 8 mmol/L). A linear increase (P < 0.01) was seen in MELD‐LA and increasing number of organ failures. Overall, use of MELD‐LA improved the risk prediction in 23.5% of patients compared to MELD alone. Conclusions MELD‐LA (bswh.md/meldla) is an early and objective predictor of inpatient mortality and may serve as a model for risk assessment and guide therapeutic options.