George Therapondos

INTRODUCTION: Surveillance for hepatocellular carcinoma (HCC) in patients with cirrhosis is associated with improved patient outcomes. We aim to evaluate real-world utilization of HCC surveillance among safety-net populations with cirrhosis. METHODS: We performed a retrospective cohort study of adults with cirrhosis across 4 safety-net health systems from March 1, 2017, to February 28, 2022. Receipt of abdominal imaging with ultrasound, computed tomography, or magnetic resonance imaging and the corresponding ICD-9-CM/ICD-10-CM diagnosis codes at 6 months and 12 months were used to assess HCC surveillance. RESULTS: Among 14,556 patients with cirrhosis (61.8% male, 73.0% non-White ethnic minorities, 54.4% with Medicaid or indigent care/uninsured), 70.9% and 78.1% received abdominal imaging agnostic to indication within 6 months and 12 months, respectively. When evaluating the receipt of abdominal imaging with a specific indication for HCC surveillance, 29.1% and 34.0% of patients received surveillance within 6 months and 12 months, respectively. On adjusted multivariable regression, greater odds of HCC surveillance were observed in older patients, ethnic minorities, and those with commercial insurance. Lower odds of HCC surveillance were observed in patients with indigent care (vs Medicare: odds ratio [OR] 0.85, 95% confidence interval [CI] 0.72–1.00), drug use (OR 0.63, 95% CI 0.55–0.71), and concurrent mental health/psychiatric diagnoses (OR 0.88, 95% CI 0.80–0.97). DISCUSSION: Among a multicenter safety-net cohort of patients with cirrhosis, fewer than 30% received HCC surveillance within 6 months. While greater proportions received abdominal imaging agnostic to indication, the clinical benefit of these examinations for HCC surveillance may be limited because of concerns with abbreviated protocols, quality, and interpretation.

INTRODUCTION: Early (i.e., without mandated period of abstinence) liver transplant (LT) for alcohol-associated hepatitis is the fastest-growing indication for LT in the United States and Europe. Harmful alcohol use after LT is associated with poor outcomes, but the distinction of establishing abstinence after return to drinking (i.e., reabstinence) is understudied. This study aims to characterize the survival outcomes of achieving reabstinence after post-LT harmful alcohol use. METHODS: We analyzed early LT recipients from 12 US LT centers between 2006 and 2021. Post-LT alcohol use was characterized as harmful using criteria of “binge” (≥5 [men] or ≥4 [women] drinks in < 24 hours) or “frequent” (≥4 days in one week) by interview or phosphatidylethanol >20 ng/mL. Reabstinence was defined as ≥12 consecutive months without harmful alcohol use after harmful alcohol use. RESULTS: Among 347 LT recipients (64% male, median age 43, median Model for End-Stage Liver Disease-Sodium score 38) with median post-LT follow-up of 2.2 years (interquartile interval 1.1–3.6), 276 (80%) recipients had no evidence of harmful alcohol use, 35 (10%) recipients had reabstinence, and 36 (10%) recipients had continued harmful alcohol use without reabstinence. Five-year predicted survival, adjusted for age, sex, and Model for End-Stage Liver Disease-Sodium score, was lowest among LT recipients with continued harmful alcohol use (77%), but similar among those with no harmful use (93%) and reabstinence (94%). DISCUSSION: Achieving reabstinence after post-LT harmful alcohol use is associated with similar 5-year post-LT survival compared with those without evidence of post-LT harmful alcohol use. Our findings highlight the importance of early detection and treatment of post-LT alcohol use.

Key Points: Raising the mean arterial pressure (MAP) during management of hepatorenal syndrome type 1 (HRS-1) is associated with improvement in kidney function, independently of baseline MAP or model for end-stage liver disease. Raising the MAP by 15 mm Hg or greater leads to greater reduction in serum creatinine in HRS-1. Norepinephrine use confers greater probability of improvement in kidney function in HRS-1 compared with midodrine/octreotide. Background: Raising mean arterial pressure (MAP) during treatment of hepatorenal syndrome type 1 (HRS-1) with vasoconstrictors (VCs) is associated with renal recovery. However, the optimal MAP target and factors associated with response to VCs remain unclear. Methods: Records from hospitalized patients with HRS-1 treated with VCs without shock were reviewed searching for those who achieved ≥5 mm Hg rise in MAP within 48 hours. We examined the relationship between the mean MAP achieved during the first 48–72 hours of VC therapy and the change in serum creatinine (sCr) up to day 14. Endpoints were >30% reduction in sCr without need for dialysis or death by day 14 (primary) or by day 30 (secondary). Results: Seventy-seven patients with HRS-1 treated for 2–10 days with either norepinephrine (n=49) or midodrine/octreotide (n=28) were included. The median age was 52 years (interquartile range [IQR], 46–60), 40% were female, and 48% had alcoholic cirrhosis. At VC initiation, median MAP was 70 mm Hg (IQR, 66–73), and median sCr was 3.8 mg/dl (IQR, 2.6–4.9). When analyzed by tertiles of mean MAP increment (5–9, 10–14, ≥15 mm Hg), there was greater reduction in sCr with greater rise in MAP (ANOVA for trend, P < 0.0001). By multivariate logistic regression analysis, mean MAP rise during the first 48–72 hours (odds ratio [OR], 1.15 [1.02 to 1.299], P=0.025), norepinephrine as VC (OR, 5.46 [1.36 to 21.86], P=0.017), and baseline sCr [OR, 0.63 [0.41 to 0.97], P=0.034) were associated with the primary endpoint, whereas mean MAP rise during the first 48–72 hours (OR, 1.17 [1.04 to 1.33], P=0.012) and baseline sCr (OR, 0.63 [0.39 to 0.98], P=0.043) were associated with the secondary endpoint. Conclusions: Greater magnitude of rise in MAP with VC therapy in HRS-1, lower baseline sCr, and use of norepinephrine over midodrine/octreotide are associated with kidney recovery. Targeting an increment of MAP ≥15 mm Hg may lead to favorable renal outcomes.

Hepatorenal index (HRI) has been shown to be an effective, noninvasive ultrasound tool to screen patients for those with or without >5% hepatic steatosis. Objective: The aim of this study was to further refine this HRI tool in order to stratify patients according to their degree of liver steatosis and give direction as to which patients should undergo random liver biopsy. Methods: We conducted a retrospective review of 267 consecutive patients from 2015 to 2017 who had abdominal ultrasounds and a subsequent random liver biopsy within one month. The HRI was calculated and compared with the percent steatosis as assessed by histology. Results: An HRI of ≤1.17 corresponds with >95% positive predictive value of ≤5% steatosis. Between HRI values 1.18 and 1.39, performance of steatosis prediction is mixed. However, for values 1.37. An HRI of ≥1.4 corresponds with >95% positive predictive value of ≥10% steatosis. Conclusion: HRI is an accurate noninvasive tool to quantify degree of steatosis and guide who should undergo random liver biopsy, potentially significantly reducing the total number of necessary liver biopsies.

Gastrointestinal (GI) symptoms impact quality of life and increase health care utilization after liver transplantation (LTx). Esophagogastroduodenoscopy (EGD) is commonly used to investigate these symptoms. The aim of this study was to investigate the diagnostic yield and utilization of EGD after LTx for common GI symptoms. This single-center retrospective cohort study was conducted at a large liver transplant center and included all adults who underwent EGD within the first year after receiving LTx between January 1, 2015, and December 31, 2016. Biliary procedures were excluded. Of 437 patients who underwent LTx during the study period, 64 (15%) underwent EGD for the evaluation of GI symptoms within the first year of transplantation. After applying exclusion criteria, 57 (13%) cases were analyzed. GI hemorrhage (hematemesis/melena) was the most common reason (4%; n=18) for evaluation with EGD followed by nausea/anorexia (3%; n=12). Symptoms were investigated with EGD, including epigastric/abdominal pain (2%; n=9), dysphagia/odynophagia (2%; n=8), anemia (1%; n=5), diarrhea (1%; n=4), and heartburn (0.2%; n=1). The diagnostic yield of EGD was highest with GI hemorrhage (83%) followed by dysphagia/odynophagia (75%). EGD diagnostic yield was lower for the other symptoms, ranging from 0% to 25%. EGD was commonly utilized within the first year of LTx, with the highest diagnostic yields for GI hemorrhage and dysphagia/odynophagia. Because of the low diagnostic yield of EGD for other symptoms, we recommend a careful selection of patients for EGD following LTx.

Liver transplantation (LT) using allografts from hepatitis C virus (HCV)‐viremic/nucleic acid testing–positive donors’ (DNAT+) organs into HCV‐aviremic recipients (rHCV−) has been limited owing to nearly universal HCV transmission and concerns regarding availability, safety, and efficacy post‐LT with direct‐acting antiviral (DAA) therapy. We report our experience of LT using DNAT+ organs into rHCV− as a routine standard of care. Following verification of DAA access, absence of critical drug‐drug interactions (DDIs) with DAAs, and informed consent, allocated DNAT+ organs were offered to patients on the waiting list for LT irrespective of recipient HCV status. Between June 2018 and December 2019, 292/339 rHCV− received an LT. Forty‐seven patients were excluded from analysis because of recipient HCV viremia, refusal to receive DNAT+ organs, or inability to receive DAA therapy post‐LT. Of these 292 patients, 61 rHCV− received DNAT+ livers (study group), and 231 rHCV− received DNAT− (aviremic donors [nuclear acid test‐negative donors]) livers (control group). Recipient and donor characteristics as well as 1‐year post‐LT patient and graft survival were similar between groups. In the study group, 4 patients died, and 1 patient required retransplantation within the first year post‐LT (all unrelated to HCV); 56 patients received DAA therapy, with a median time from LT to the start of DAA treatment of 66.9 days (interquartile range [IQR], 36‐68.5), and 51 patients completed DAA treatment, all achieving sustained virologic response for 12 or more weeks (SVR‐12) (1 patient required retreatment owing to relapse following initial DAA therapy). No patients had evidence of fibrosing cholestatic hepatitis or extrahepatic manifestations of HCV. This report indicates that transplantation of DNAT+ livers into rHCV− and subsequent DAA therapy is associated with clinical outcomes comparable to those achieved with DNAT− allografts.