Background and aim

The American Association for the Study of Liver Disease (AASLD) recommends screening for esophageal varices (EV) by esophagoduodenoscopy (EGD) in patients with cirrhosis to guide decisions regarding primary prophylaxis for EV hemorrhage. We aimed to identify patient and facility factors associated with EV screening in veterans with hepatitis C (HCV)-associated cirrhosis.

Methods

This was a population-based cohort study. Veterans with HCV and newly diagnosed cirrhosis between 1/1/2004 and 12/31/2005 and followed until 12/31/2011 were included. The primary outcome was receipt of EGD within 1 year of cirrhosis diagnosis. Patient- and facility-level factors associated with EV screening were determined.

Results

A total of 4230 patients with HCV cirrhosis were identified. During median follow-up of 6.1 years (IQR: 4.0-8.0), 21.5 % developed a decompensating event, and 38.3 % died. Fifty-four percent received an EGD, and 33.8 % had an EGD within guidelines. Median time from cirrhosis diagnosis to EGD was 72 days (IQR: 12-176). Factors independently associated with receipt of EV screening were a decompensation event (OR 1.16, CI 1.01-1.32) and gastroenterology/hepatology clinic access (OR 2.1, CI 1.73-2.46), whereas cardiovascular (OR 0.81, CI 0.69-0.95), mental health (OR 0.79, CI 0.68-0.91), and respiratory (OR 0.85, CI 0.72-0.99) comorbidities were associated with reduced likelihood of EV screening.

Conclusion

EV screening per AASLD guidelines occurs in only one-third of patients. This missed opportunity was strongly associated with access to gastroenterology/hepatology specialty care. Additionally, providers may be relying on clinical cues (i.e., decompensation) to prompt referral for endoscopy suggesting education to improve compliance with guidelines is needed.

Direct-acting antiviral (DAA) therapy, recently approved for patients with decompensated cirrhosis (DC) secondary to hepatitis C virus (HCV), is associated with improved hepatic function. We analyzed trends in liver transplant (LT) wait-listing (WL) to explore potential impact of effective medical therapy on WL registration. This is a cohort study using the Scientific Registry of Transplant Recipients database from 2003 to 2015. A total of 47,591 adults wait-listed for LT from HCV, hepatitis B virus (HBV), and nonalcoholic steatohepatitis (NASH) were identified. LT indication was defined as DC if the Model for End-Stage Liver Disease (MELD) at WL was ≥15 or hepatocellular carcinoma (HCC). Era of listing was divided into interferon (IFN; 2003-2010), protease inhibitor (PI; 2011-2013), and direct-acting antiviral (DAA; 2014-2015). Annual standardized incidence rates of WL were analyzed using Poisson regression. Adjusted incidences of LT WL for DC in HCV patients decreased by 5% in the PI era (P = 0.004) and 32% in the DAA era (P < 0.001) compared to the IFN era. Listing for DC in HBV also decreased in the PI (-17%; P = 0.002) and DAA eras (-24%; P < 0.001). Conversely, WL for DC in NASH increased by 41% in the PI era (P < 0.001) and 81% in the DAA era (P < 0.001). WL for HCC in both the HCV and NASH populations increased in both the PI and DAA eras (P < 0.001 for all) whereas HCC WL in HBV remained stable (P > 0.05 for all).

Conclusion

The rate of LT WL for HCV complicated by DC has decreased by over 30% in the era of DAA therapy. Further reductions in WL are anticipated with increased testing, linkage to care, and access to DAA therapy. (Hepatology 2017;65:804-812).

Older donor age is associated with lower graft and patient survival among all recipients of liver transplantation (LT). Among patients with hepatitis C virus (HCV), donor age is one of the strongest predictors of fibrosis severity and graft loss. We evaluated the implementation of a donor age restriction policy for LT patients with HCV at a single center and the effects that this policy had on wait-list (WL) and post-LT outcomes for HCV and non-HCV patients. This was a cohort study of 2388 WL patients and 1015 LT recipients between March 2002 and January 2013 and reflected 3 different eras of donor age policies. With the donor age restriction, the median donor age was reduced in LT recipients with HCV versus LT recipients without HCV (30 versus 48 years, P < 0.001) without differences in the WL time (10.6 versus 8.0 months, P = 0.23). According to a competing risks regression, those with HCV and those without HCV had lower subhazard ratios (SHRs) of dropout or death on the WL during the donor age restriction era versus the era without donor age restriction [SHR = 0.68 (P < 0.01) and SHR = 0.64 (P = 0.01), respectively]. No differences were seen in early post-LT survival for patients with or without HCV between eras (P = 0.7 and P = 0.88, respectively). In conclusion, we show that donor age restriction for HCV results in a lower donor age for HCV recipients without obvious adverse WL consequences. Although additional studies are needed, our results demonstrate the feasibility of donor age restriction for LT recipients with HCV, and such information may be relevant to programs with limited access to new antiviral therapies for which modifying the risk of severe disease remains of paramount importance.

Introduction

Cirrhosis incidence in pregnancies from outside the United States (US) is rising, although contemporary data including maternal and perinatal outcomes within the United States are lacking.

Methods

Using discharge data from the racially diverse US National Inpatient Sample, temporal trends of cirrhosis in pregnancies were compared with noncirrhotic chronic liver disease (CLD) or no CLD. Outcomes included preterm birth, postpartum hemorrhage, hypertensive complications (preeclampsia, eclampsia, and/or hemolysis, elevated liver enzymes, and low platelets syndrome), and maternal or fetal death. Logistic regression was adjusted for age, race, multiple gestation, insurance status, and prepregnancy metabolic comorbidities.

Results

Among 18,573,000 deliveries from 2012 to 2016, 895 had cirrhosis, 119,875 had noncirrhotic CLD, and 18,452,230 had no CLD. Pregnancies with cirrhosis increased from 2.5/100,000 in 2007 to 6.5/100,000 in 2016 (P = 0.01). On adjusted analysis, cirrhosis was associated with hypertensive complications (vs no CLD, OR 4.9, 95% confidence intervals [CI] 3.3-7.4; vs noncirrhotic CLD, OR 4.4, 95% CI 3.0-6.7), postpartum hemorrhage (vs no CLD, OR 2.8, 95% CI 1.6-4.8; vs noncirrhotic CLD, OR 2.0, 95% CI 1.2-3.5), and preterm birth (vs no CLD, OR 3.1, 95% CI 1.9-4.9; vs noncirrhotic CLD, OR 2.0, 95% CI 1.3-3.3, P ≤ 0.01). Cirrhosis was statistically associated with maternal mortality, although rarely occurred (≤ 1%).

Discussion

In this racially diverse, US population-based study, pregnancies with cirrhosis more than doubled over the past decade. Cirrhosis conferred an increased risk of several adverse events, although maternal and perinatal mortality was uncommon. These data underscore the need for reproductive counseling and multidisciplinary pregnancy management in young women with cirrhosis.

Background

All patients with cirrhosis are at risk of developing hepatocellular carcinoma (HCC). This risk is not uniform because other patient-related factors influence the risk of HCC. The objective of the current study was to develop an HCC risk prediction model to estimate the 1-year probability of HCC to assist with patient counseling.

Methods

Between 2002 and 2011, a cohort of 34,932 patients with cirrhosis was identified from a national liver transplantation waitlist database from the United States. Cox proportional hazards regression methods were used to develop and validate a risk prediction model for incident HCC. In the validation cohort, discrimination and calibration of the model was examined. External validation was conducted using patients with cirrhosis who were enrolled in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) study.

Results

HCC developed in 1960 patients (5.6%) during a median follow-up of 1.3 years (interquartile range, 0.47 years-2.83 years). Six baseline clinical variables, including age, diabetes, race, etiology of cirrhosis, sex, and severity (ADRESS) of liver dysfunction were independently associated with HCC and were used to develop the ADRESS-HCC risk model. C-indices in the derivation and internal validation cohorts were 0.704 and 0.691, respectively. In the validation cohort, the predicted cumulative incidence of HCC by the ADRESS-HCC model closely matched the observed data. In patients with cirrhosis in the HALT-C cohort, the model stratified patients correctly according to the risk of developing HCC within 5 years.

Conclusions

The ADRESS-HCC risk model is a useful tool for predicting the 1-year risk of HCC among patients with cirrhosis.

Unlabelled

We report on the long-term intention-to-treat (ITT) outcome of 118 patients with hepatocellular carcinoma (HCC) undergoing downstaging to within Milan/United Network for Organ Sharing T2 criteria before liver transplantation (LT) since 2002 and compare the results with 488 patients listed for LT with HCC meeting T2 criteria at listing in the same period. The downstaging subgroups include 1 lesion >5 and ≤8 cm (n = 43), 2 or 3 lesions at least one >3 and ≤5 cm with total tumor diameter ≤8 cm (n = 61), or 4-5 lesions each ≤3 cm with total tumor diameter ≤8 cm (n = 14). In the downstaging group, 64 patients (54.2%) had received LT and 5 (7.5%) developed HCC recurrence. Two of the five patients with HCC recurrence had 4-5 tumors at presentation. The 1- and 2-year cumulative probabilities for dropout (competing risk) were 24.1% and 34.2% in the downstaging group versus 20.3% and 25.6% in the T2 group (P = 0.04). Kaplan-Meier's 5-year post-transplant survival and recurrence-free probabilities were 77.8% and 90.8%, respectively, in the downstaging group versus 81% and 88%, respectively, in the T2 group (P = 0.69 and P = 0.66, respectively). The 5-year ITT survival was 56.1% in the downstaging group versus 63.3% in the T2 group (P = 0.29). Factors predicting dropout in the downstaging group included pretreatment alpha-fetoprotein ≥1,000 ng/mL (multivariate hazard ratio [HR]: 2.42; P = 0.02) and Child's B versus Child's A cirrhosis (multivariate HR: 2.19; P = 0.04).

Conclusion

Successful downstaging of HCC to within T2 criteria was associated with a low rate of HCC recurrence and excellent post-transplant survival, comparable to those meeting T2 criteria without downstaging. Owing to the small number of patients with 4-5 tumors, further investigations are needed to confirm the efficacy of downstaging in this subgroup.