Predictors of long-term clinical outcomes after TIPS: An ALTA group study.

BACKGROUND AND AIMS: While transjugular intrahepatic portosystemic shunt (TIPS) is traditionally considered a bridge to liver transplant (LT), some patients achieve long-term transplant-free survival (TFS) with TIPS alone. Prognosis and need for LT should not only be assessed at time of procedure, but also re-evaluated in patients with favorable early outcomes. APPROACH AND RESULTS: Adult TIPS recipients in the multicenter Advancing Liver Therapeutic Approaches retrospective cohort study were included (N=1,127 patients; 2,040 person-years follow-up). Adjusted competing risk regressions were used to assess factors associated with long-term post-TIPS clinical outcomes at time of procedure and at 6 months post-TIPS. MELD-Na at TIPS was significantly associated with post-TIPS mortality (sHR of death 1.1 [p=0.42], 1.3 [p=0.04], and 1.7 [p<0.01] for MELD-Na 15-19, 20-24, and ≥25 relative to MELD-Na <15, respectively). MELD 3.0 was also associated with post-TIPS outcomes. Among the 694 (62%) patients who achieved early (6 mo) post-TIPS TFS, rates of long-term TFS were 88% at 1-year and 57% at 3-years post-TIPS. Additionally, a within-individual increase in MELD-Na score of >3 points from TIPS to 6 months post-TIPS was significantly associated with long-term mortality, regardless of initial MELD-Na score (sHR of death 1.8, p<0.01). For patients with long-term post-TIPS TFS, rates of complications of the TIPS or portal hypertension were low. CONCLUSIONS: Among patients with early post-TIPS TFS, prognosis and need for LT should be reassessed, informed by post-procedure changes in MELD-Na and clinical status. For selected patients, "destination TIPS" without LT may offer long-term survival with freedom from portal hypertensive complications.

The impact of right atrial pressure on outcomes in patients undergoing TIPS, an ALTA group study.

BACKGROUND AND AIMS: Single-center studies in patients undergoing TIPS suggest that elevated right atrial pressure (RAP) may influence survival. We assessed the impact of pre-TIPS RAP on outcomes using the Advancing Liver Therapeutic Approaches (ALTA) database. APPROACH AND RESULTS: Total 883 patients in ALTA multicenter TIPS database from 2010 to 2015 from 9 centers with measured pre-TIPS RAP were included. Primary outcome was mortality. Secondary outcomes were 48-hour post-TIPS complications, post-TIPS portal hypertension complications, and post-TIPS inpatient admission for heart failure. Adjusted Cox Proportional hazards and competing risk model with liver transplant as a competing risk were used to assess RAP association with mortality. Restricted cubic splines were used to model nonlinear relationship. Logistic regression was used to assess RAP association with secondary outcomes.Pre-TIPS RAP was independently associated with overall mortality (subdistribution HR: 1.04 per mm Hg, 95% CI, 1.01, 1.08, p =0.009) and composite 48-hour complications. RAP was a predictor of TIPS dysfunction with increased odds of post-90-day paracentesis in outpatient TIPS, hospital admissions for renal dysfunction, and heart failure. Pre-TIPS RAP was positively associated with model for end-stage liver disease, body mass index, Native American and Black race, and lower platelets. CONCLUSIONS: Pre-TIPS RAP is an independent risk factor for overall mortality after TIPS insertion. Higher pre-TIPS RAP increased the odds of early complications and overall portal hypertensive complications as potential mechanisms for the mortality impact.

Dietary macro and micronutrients associated with MASLD: Analysis of a national US cohort database.

INTRODUCTION AND OBJECTIVES: Our objective was to measure and compare the intake of macro and micronutrients in a cohort of individuals with Metabolic Syndrome Associated Steatotic Liver Disease (MASLD) compared with matched controls to identify areas of further research in this area; we identified nutrition-associated associations with MASLD in the United States general population. MATERIALS AND METHODS: We used the 2017 - 2018 NHANES dataset. Elastography Controlled Attenuation Parameter (CAP score>280) in the absence of other liver disease was defined as MASLD in adults (>18). Advanced fibrosis was defined by transient elastography >10 kPa. Controls were adults without liver disease. RESULTS: 1648 MASLD cases (11.4 % advanced fibrosis) and 2527 controls were identified. MASLD cases were older (P<0.001), more likely males (P = 0.01), less likely to have a college education (P = 0.04) and more likely married (P = 0.002). MASLD cases were more likely to be of Mexican American or Hispanic ethnicity (P = 0.002), have higher BMI, and have higher prevalence of diabetes, hyperlipidemia and hypertension (P<0.001 for all). MASLD cases had higher hs-CRP (P = 0.02) and ferritin (P = 0.02). MASLD cases had lower total (P = 0.004) and added vitamin E in their diet (P = 0.002), lower vitamin K intake (P = 0.005), and higher selenium intake (P = 0.03). Caloric intake (P = 0.04), carbohydrate intake (P = 0.02), cholesterol intake (P = 0.03) and saturated fatty acid intake (P = 0.05) were higher in MASLD. Individuals with MASLD were more likely to be on a diet (P<0.001), sedentary (P = 0.008) and less likely to participate in moderate or vigorous recreational activities (P<0.001). CONCLUSIONS: The deficiencies of micronutrients and excess of macronutrients point to oxidative stress, pro-inflammatory state, and lipotoxicity as pathways linking the US diet to MASLD. MASLD patients are more often on special diets, which may reflect prior provider counseling on diet changes to improve health.

Change in Platelet Count after Transjugular Intrahepatic Portosystemic Shunt Creation: An Advancing Liver Therapeutic Approaches (ALTA) Group Study.

PURPOSE: To evaluate recovery of platelet count after transjugular intrahepatic portosystemic shunt (TIPS) creation and patient factors predicting platelet recovery after TIPS creation. MATERIALS AND METHODS: Adults with cirrhosis who underwent TIPS creation at 9 U.S. hospitals from 2010 to 2015 were included in this retrospective analysis. Change in platelets from before TIPS to 4 months after TIPS creation was characterized. Logistic regression was used to assess factors associated with top quartile percentage platelet increase after TIPS. Subgroup analyses were performed among patients with a pre-TIPS platelet count of ≤50 ×109/L. RESULTS: A total of 601 patients were included. The median absolute change in platelets was 1 × 109/L (-26 × 109/L to 25 × 109/L). Patients with top quartile percent platelet increase experienced ≥32% platelet increase. In multivariable analysis, pre-TIPS platelet counts (odds ratio [OR], 0.97 per 109/L; 95% CI, 0.97-0.98), age (OR, 1.24 per 5 years; 95% CI, 1.10-1.39), and pre-TIPS model for end-stage liver disease (MELD) scores (OR, 1.06 per point; 95% CI, 1.02-1.09) were associated with top quartile (≥32%) platelet increase. Ninety-four (16%) patients had a platelet count of ≤50 × 109/L before TIPS. The median absolute platelet change was 14 × 109/L (2 × 109/L to 34 × 109/L). Fifty-four percent of patients in this subgroup were in the top quartile for platelet increase. In multivariable logistic regression, age (OR, 1.50 per 5 years; 95% CI, 1.11-2.02) was the only factor associated with top quartile platelet increase in this subgroup. CONCLUSIONS: TIPS creation did not result in significant platelet increase, except among patients with a platelet count of ≤50 × 109/L before TIPS. Lower pre-TIPS platelet counts, older age, and higher pre-TIPS MELD scores were associated with top quartile (≥32%) platelet increase in the entire cohort, whereas only older age was associated with this outcome in the patient subset with a pre-TIPS platelet count of ≤50 × 109/L.

Microwave Ablation as Bridging to Liver Transplant for Patients with Hepatocellular Carcinoma: A Single-Center Retrospective Analysis.

PURPOSE: To evaluate the efficacy and safety of microwave (MW) ablation as first-line locoregional therapy (LRT) for bridging patients with hepatocellular carcinoma (HCC) to liver transplant. MATERIALS AND METHODS: This retrospective study evaluated 88 patients who received percutaneous MW ablation for 141 tumors as first-line LRT for HCC and who were listed for liver transplantation at a single medical center between 2011 and 2019. The overall survival (OS) rate statuses after liver transplant, waitlist retention, and disease progression were evaluated using the Kaplan-Meier techniques. RESULTS: Among the 88 patients (72 men and 16 women; mean age, 60 years; Model for End-Stage Liver Disease score, 11.2) who were listed for transplant, the median waitlist time was 9.4 months (interquartile range, 5.5-18.9). Seventy-one (80.7%) patients received transplant after a median waitlist time of 8.5 months. Seventeen (19.3%) patients were removed from the waitlist; of these, 4 (4.5%) were removed because of tumors outside of the Milan criteria (HCC-specific dropout). No difference in tumor size or alpha-fetoprotein was observed in the transplanted versus nontransplanted patients at the time of ablation (2.1 vs 2.1 cm and 34.4 vs 34.7 ng/mL for transplanted vs nontransplanted, respectively; P > .05). Five (5.1%) of the 88 patients experienced adverse events after ablation; however, they all recovered. There were no cases of tract seeding. The local tumor progression (LTP) rate was 7.2%. The OS status after liver transplant at 5 years was 76.7%, and the disease-specific survival after LTP was 89.6%, with a median follow-up of 61 months for all patients. CONCLUSIONS: MW ablation appears to be safe and effective for bridging patients with HCC to liver transplant without waitlist removal from seeding, adverse events, or LTP.

Outcomes After TIPS for Ascites and Variceal Bleeding in a Contemporary Era-An ALTA Group Study.

INTRODUCTION: Advances in transjugular intrahepatic portosystemic shunt (TIPS) technology have led to expanded use. We sought to characterize contemporary outcomes of TIPS by common indications. METHODS: This was a multicenter, retrospective cohort study using data from the Advancing Liver Therapeutic Approaches study group among adults with cirrhosis who underwent TIPS for ascites/hepatic hydrothorax (ascites/HH) or variceal bleeding (2010-2015). Adjusted competing risk analysis was used to assess post-TIPS mortality or liver transplantation (LT). RESULTS: Among 1,129 TIPS recipients, 58% received TIPS for ascites/HH and 42% for variceal bleeding. In patients who underwent TIPS for ascites/HH, the subdistribution hazard ratio (sHR) for death was similar across all Model for End-Stage Liver Disease Sodium (MELD-Na) categories with an increasing sHR with rising MELD-Na. In patients with TIPS for variceal bleeding, MELD-Na ≥20 was associated with increased hazard for death, whereas MELD-Na ≥22 was associated with LT. In a multivariate analysis, serum creatinine was most significantly associated with death (sHR 1.2 per mg/dL, 95% confidence interval [CI] 1.04-1.4 and 1.37, 95% CI 1.08-1.73 in ascites/HH and variceal bleeding, respectively). Bilirubin and international normalized ratio were most associated with LT in ascites/HH (sHR 1.23, 95% CI 1.15-1.3; sHR 2.99, 95% CI 1.76-5.1, respectively) compared with only bilirubin in variceal bleeding (sHR 1.06, 95% CI 1.00-1.13). DISCUSSION: MELD-Na has differing relationships with patient outcomes dependent on TIPS indication. These data provide new insights into contemporary predictors of outcomes after TIPS.

Nonalcoholic Fatty Liver Disease and Diabetes Mellitus Are Associated With Post-Transjugular Intrahepatic Portosystemic Shunt Renal Dysfunction: An Advancing Liver Therapeutic Approaches Group Study.

Transjugular intrahepatic portosystemic shunt (TIPS) is an effective intervention for portal hypertensive complications, but its effect on renal function is not well characterized. Here we describe renal function and characteristics associated with renal dysfunction at 30 days post-TIPS. Adults with cirrhosis who underwent TIPS at 9 hospitals in the United States from 2010 to 2015 were included. We defined "post-TIPS renal dysfunction" as a change in estimated glomerular filtration rate (ΔeGFR) ≤-15 and eGFR ≤ 60 mL/min/1.73 m2 or new renal replacement therapy (RRT) at day 30. We identified the characteristics associated with post-TIPS renal dysfunction by logistic regression and evaluated survival using adjusted competing risk regressions. Of the 673 patients, the median age was 57 years, 38% of the patients were female, 26% had diabetes mellitus, and the median MELD-Na was 17. After 30 days post-TIPS, 66 (10%) had renal dysfunction, of which 23 (35%) required new RRT. Patients with post-TIPS renal dysfunction, compared with those with stable renal function, were more likely to have nonalcoholic fatty liver disease (NAFLD; 33% versus 17%; P = 0.01) and comorbid diabetes mellitus (42% versus 24%; P = 0.001). Multivariate logistic regressions showed NAFLD (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.00-4.17; P = 0.05), serum sodium (Na; OR, 1.06 per mEq/L; 95% CI, 1.01-1.12; P = 0.03), and diabetes mellitus (OR, 2.04; 95% CI, 1.16-3.61; P = 0.01) were associated with post-TIPS renal dysfunction. Competing risk regressions showed that those with post-TIPS renal dysfunction were at a higher subhazard of death (subhazard ratio, 1.74; 95% CI, 1.18-2.56; P = 0.01). In this large, multicenter cohort, we found NAFLD, diabetes mellitus, and baseline Na associated with post-TIPS renal dysfunction. This study suggests that patients with NAFLD and diabetes mellitus undergoing TIPS evaluation may require additional attention to cardiac and renal comorbidities before proceeding with the procedure.

Utility of Multiparametric CT for Identification of High-Risk NAFLD.

OBJECTIVE. The purpose of this study was to evaluate the utility of laboratory and CT metrics in identifying patients with high-risk nonalcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS. Patients with biopsy-proven NAFLD who underwent CT within 1 year of biopsy were included. Histopathologic review was performed by an experienced gastrointestinal pathologist to determine steatosis, inflammation, and fibrosis. The presence of any lobular inflammation and hepatocyte ballooning was categorized as nonalcoholic steatohepatitis (NASH). Patients with NAFLD and advanced fibrosis (stage F3 or higher) were categorized as having high-risk NAFLD. Aspartate transaminase to platelet ratio index and Fibrosis-4 (FIB-4) laboratory scores were calculated. CT metrics included hepatic attenuation, liver segmental volume ratio (LSVR), splenic volume, liver surface nodularity score, and selected texture features. In addition, two readers subjectively assessed the presence of NASH (present or not present) and fibrosis (stages F0-F4). RESULTS. A total of 186 patients with NAFLD (mean age, 49 years; 74 men and 112 women) were included. Of these, 87 (47%) had NASH and 112 (60%) had moderate to severe steatosis. A total of 51 patients were classified as fibrosis stage F0, 42 as F1, 23 as F2, 37 as F3, and 33 as F4. Additionally, 70 (38%) had advanced fibrosis (stage F3 or F4) and were considered to have high-risk NAFLD. FIB-4 score correlated with fibrosis (ROC AUC of 0.75 for identifying high-risk NAFLD). Of the individual CT parameters, LSVR and splenic volume performed best (AUC of 0.69 for both for detecting high-risk NAFLD). Subjective reader assessment performed best among all parameters (AUCs of 0.78 for reader 1 and 0.79 for reader 2 for detecting high-risk NAFLD). FIB-4 and subjective scores were complementary (combined AUC of 0.82 for detecting high-risk NAFLD). For NASH assessment, FIB-4 performed best (AUC of 0.68), whereas the AUCs were less than 0.60 for all individual CT features and subjective assessments. CONCLUSION. FIB-4 and multiple CT findings can identify patients with high-risk NAFLD (advanced fibrosis or cirrhosis). However, the presence of NASH is elusive on CT.

Utilization of hepatitis C viremic donors for liver transplant recipients without hepatitis C. A veterans transplant center report.

BACKGROUND: We report our experience utilizing liver donors with HCV Viremia (RNA+) for HCV-negative recipients (HCV D+R-) at a Veterans Affairs (VA) transplant center. METHODS: In 2018, we introduced an informed consent process for HCV D+R- liver transplants. RESULTS: Eight HCV D+R- liver transplants (LT) were performed. Median time from listing to LT was 189 days (range 41-511). Median MELD at LT was 23.5 (median MELD at LT of 31 for center). All recipients developed HCV viremia after transplant. Median time to DAA initiation was 10 days after viremia (range 3-25). After transplant, the DAAs used were Mavyret in five recipients and Epclusa in three, all for 12 weeks. All eight patients completed DAA therapy and achieved negative HCV RNA by end of therapy (ETR) and seven reached sustained virologic response (SVR) by 12 weeks after end of therapy. One patient died from chronic ischemic encephalopathy after ETR, before SVR. CONCLUSIONS: HCV D+R- is a practical strategy to expand the pool of donor organs. It shortened waiting time, allowing patients to receive transplants at lower MELD scores. VA liver transplant programs have provided universal and timely access to post-transplant HCV DAA therapy after donor-derived infection.

Direct-Acting Antiviral Therapy for Hepatitis C Virus Infection Is Associated With Increased Survival in Patients With a History of Hepatocellular Carcinoma.

BACKGROUND & AIMS: There is controversy regarding the benefits of direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection for patients with a history of hepatocellular carcinoma (HCC). We performed a multicenter cohort study to compare overall survival between patients with HCV infection treated with DAAs and patients who did not receive DAA treatment for their HCV infection after complete response to prior HCC therapy. METHODS: We conducted a retrospective cohort study of patients with HCV-related HCC who achieved a complete response to resection, local ablation, transarterial chemo- or radioembolization, or radiation therapy, from January 2013 through December 2017 at 31 health care systems throughout the United States and Canada. We used Cox proportional hazards regression to determine the association between receipt of DAA therapy, modeled as a time-varying covariate, and all-cause mortality, accounting for informative censoring and confounding using inverse probability weighting. RESULTS: Of 797 patients with HCV-related HCC, 383 (48.1%) received DAA therapy and 414 (51.9%) did not receive treatment for their HCV infection after complete response to prior HCC therapy. Among DAA-treated patients, 43 deaths occurred during 941 person-years of follow-up, compared with 103 deaths during 526.6 person-years of follow-up among patients who did not receive DAA therapy (crude rate ratio, 0.23; 95% confidence interval [CI], 0.16-0.33). In inverse probability-weighted analyses, DAA therapy was associated with a significant reduction in risk of death (hazard ratio, 0.54; 95% CI, 0.33-0.90). This association differed by sustained virologic response to DAA therapy; risk of death was reduced in patients with sustained virologic response to DAA therapy (hazard ratio, 0.29; 95% CI, 0.18-0.47), but not in patients without a sustained virologic response (hazard ratio, 1.13; 95% CI, 0.55-2.33). CONCLUSIONS: In an analysis of nearly 800 patients with complete response to HCC treatment, DAA therapy was associated with a significant reduction in risk of death.

Direct-Acting Antiviral Therapy Not Associated With Recurrence of Hepatocellular Carcinoma in a Multicenter North American Cohort Study.

BACKGROUND & AIMS: There is controversy over the effects of direct-acting antiviral (DAA) therapies for hepatitis C virus (HCV) infection on hepatocellular carcinoma (HCC) recurrence and tumor aggressiveness. We compared HCC recurrence patterns between DAA-treated and untreated HCV-infected patients who had achieved a complete response to HCC treatment in a North American cohort. METHODS: We conducted a retrospective cohort study of patients with HCV-related HCC with a complete response to resection, local ablation, transarterial chemo- or radioembolization, or radiation therapy from January 2013 through December 2017 at 31 health systems throughout the United States and Canada. Cox regression was used to examine the association between DAA therapy and time to recurrence after a complete response, with DAA therapy analyzed as a time-varying exposure. We also estimated the association between DAA therapy and risk of early HCC recurrence (defined as 365 days after complete response). RESULTS: Of 793 patients with HCV-associated HCC, 304 (38.3%) received DAA therapy and 489 (61.7%) were untreated. HCC recurred in 128 DAA-treated patients (42.1%; early recurrence in 52 patients) and 288 untreated patients (58.9%; early recurrence in 227 patients). DAA therapy was not associated with HCC recurrence (hazard ratio 0.90, 95% confidence interval 0.70-1.16) or early HCC recurrence (hazard ratio 0.96, 95% confidence interval 0.70-1.34) after we adjusted for study site, age, sex, Child-Pugh score, α-fetoprotein level, tumor burden, and HCC treatment modality. In DAA-treated and untreated patients, most recurrences were within the Milan criteria (74.2% vs 78.8%; P = .23). A larger proportion of DAA-treated than untreated patients received potentially curative HCC therapy for recurrent HCC (32.0% vs 24.6%) and achieved a complete or partial response (45.3% vs 41.0%) but this did not achieve statistical significance. CONCLUSION: In a large cohort of North American patients with complete response to HCC treatment, DAA therapy was not associated with increased overall or early HCC recurrence. HCC recurrence patterns, including treatment response, were similar in DAA-treated and untreated patients.

Provider Attitudes and Practice Patterns for Direct-Acting Antiviral Therapy for Patients With Hepatocellular Carcinoma.

BACKGROUND & AIMS: Direct-acting antivirals (DAAs) are effective against hepatitis C virus and sustained virologic response is associated with reduced incidence of hepatocellular carcinoma (HCC). However, there is controversy over the use of DAAs in patients with active or treated HCC and uncertainty about optimal management of these patients. We aimed to characterize attitudes and practice patterns of hepatology practitioners in the United States regarding the use of DAAs in patients with HCC. METHODS: We conducted a survey of hepatology providers at 47 tertiary care centers in 25 states. Surveys were sent to 476 providers and we received 279 responses (58.6%). RESULTS: Provider beliefs about risk of HCC recurrence after DAA therapy varied: 48% responded that DAAs reduce risk, 36% responded that DAAs do not change risk, and 16% responded that DAAs increase risk of HCC recurrence. However, most providers believed DAAs to be beneficial to and reduce mortality of patients with complete response to HCC treatment. Accordingly, nearly all providers (94.9%) reported recommending DAA therapy to patients with early-stage HCC who received curative treatment. However, fewer providers recommended DAA therapy for patients with intermediate (72.9%) or advanced (57.5%) HCC undergoing palliative therapies. Timing of DAA initiation varied among providers based on HCC treatment modality: 49.1% of providers reported they would initiate DAA therapy within 3 months of surgical resection whereas 45.9% and 5.0% would delay DAA initiation for 3-12 months and >1 year post-surgery, respectively. For patients undergoing transarterial chemoembolization (TACE), 42.0% of providers would provide DAAs within 3 months of the procedure, 46.7% would delay DAAs until 3-12 months afterward, and 11.3% would delay DAAs more than 1 year after TACE. CONCLUSIONS: Based on a survey sent to hepatology providers, there is variation in provider attitudes and practice patterns regarding use and timing of DAAs for patients with HCC. Further studies are needed to characterize the risks and benefits of DAA therapy in this patient population.

Statin Use is Protective Against Hepatocellular Carcinoma in Patients With Nonalcoholic Fatty Liver Disease: A Case-control Study.

BACKGROUND AND GOAL: The incidence of nonalcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC) is rising. We aimed to characterize risk factors for NAFLD-HCC development. METHODS: We performed a retrospective case-control study of HCC cases from a cohort of NAFLD patients who underwent at least 2 computed tomography scans. NAFLD-HCC cases confirmed on contrast imaging and/or biopsy were included. Controls were NAFLD patients without HCC matched by sex and age. Clinical variables were assessed. Visceral adipose tissue and subcutaneous adipose tissue were measured by computed tomography at 2 timepoints: before HCC diagnosis and at diagnosis. RESULTS: We identified 102 subjects [34 HCC cases, 68 controls, 65% (n=66) males, mean age: 69 y] from 2002 to 2016. Cirrhosis was present in 91%. In multivariate analysis, statin use was protective against HCC [odds ratio (OR)=0.20, 95% confidence interval (CI): 0.07-0.60, P=0.004], while hypertension was a risk factor for HCC (OR=5.80, 95% CI: 2.01-16.75, P=0.001). In multivariate analysis, visceral adipose tissue in males was higher before HCC diagnosis and declined by HCC diagnosis in 86%, which was a significant difference compared with controls (OR=2.78, 95% CI: 1.10-7.44, P=0.04). CONCLUSIONS: In a cohort of NAFLD-HCC patients, statin use was protective against HCC, while hypertension conferred an increased risk. Visceral adiposity at baseline was not a risk factor, but was higher in male patients before HCC development, declining in the majority by HCC diagnosis.

Four-dimensional Flow MRI as a Marker for Risk Stratification of Gastroesophageal Varices in Patients with Liver Cirrhosis.

Purpose To assess the feasibility of four-dimensional (4D) flow MRI as a noninvasive imaging marker for stratifying the risk of variceal bleeding in patients with liver cirrhosis. Materials and Methods This study recruited participants scheduled for both liver MRI and gastroesophageal endoscopy. Risk of variceal bleeding was assessed at endoscopy by using a three-point scale: no varices, low risk, and high risk requiring treatment. Four-dimensional flow MRI was used to create angiograms for evaluating visibility of varices and to measure flow volumes in main portal vein (PV), superior mesenteric vein, splenic vein (SV), and azygos vein. Fractional flow changes in PV and SV were calculated to quantify shunting (outflow) from PV and SV into varices. Logistic analysis was used to identify the independent indicator of high-risk varices. Results There were 23 participants (mean age, 52.3 years; age range, 25-75 years), including 14 men (mean age, 51.7 years; age range, 25-75 years) and nine women (mean age, 53.2 years; age range, 31-72 years) with no varices (n = 8), low-risk varices (n = 8), and high-risk varices (n = 7) determined at endoscopy. Four-dimensional flow MRI-based angiography helped radiologists to view varices in four of 15 participants with varices. Independent indicators of high-risk varices were flow volume in the azygos vein greater than 0.1 L/min (P = .034; 100% sensitivity [seven of seven] and 62% specificity [10 of 16]) and fractional flow change in PV of less than 0 (P < .001; 100% sensitivity [seven of seven] and 94% specificity [15 of 16]). Conclusion Azygos flow greater than 0.1 L/min and portal venous flow less than the sum of splenic and superior mesenteric vein flow are useful markers to stratify the risk of gastroesophageal varices bleeding in patients with liver cirrhosis. © RSNA, 2018 Online supplemental material is available for this article.

Deficiencies in reproductive health counseling in liver transplant recipients.

BACKGROUND: In liver transplant (LT) recipients of childbearing age, there is often rapid return of fertility post-transplant. Our aim was to determine whether healthcare providers are documenting reproductive health counseling in LT recipients. METHODS: We performed a review of 365 LT recipients (164 female, 201 male) of childbearing age transplanted between 1994 and 2015 at a single center. We evaluated documentation of reproductive health counseling, content of the counseling and its provider. RESULTS: Reproductive health counseling was documented in 7% of LT recipients (14% of females, 0.5% of males). The transplant team provided the counseling in 56%, obstetrics/gynecology in 35%, and primary care in 9%. Twenty-four post-LT pregnancies occurred; these were unplanned in 13%. Miscarriage/stillbirth occurred in 7/24 pregnancies (29%). Mycophenolic acid was used by 20% of female recipients at conception. Only age at transplant (P = 0.001) and post-LT pregnancy was associated with documentation of reproductive health counseling in female recipients (P = 0.0001). CONCLUSION: Despite rapid return of fertility in reproductive-aged LT recipients, documentation of reproductive health counseling in this population is rare in men and women. This increases the potential for adverse maternal and fetal outcomes in this high-risk population.

Multiparametric CT for Noninvasive Staging of Hepatitis C Virus-Related Liver Fibrosis: Correlation With the Histopathologic Fibrosis Score.

OBJECTIVE: The objective was to develop a multiparametric CT algorithm to stage liver fibrosis in patients with chronic hepatitis C virus (HCV) infection. MATERIALS AND METHODS: Abdominal CT and laboratory measures in 469 patients with HCV (340 men and 129 women; mean age, 50.1 years) were compared against the histopathologic Metavir fibrosis reference standard (F0, n = 49 patients; F1, n = 69 patients; F2, n = 102 patients; F3, n = 76 patients; F4, n = 173 patients). From the initial candidate pool, nine CT and two laboratory measures were included in the final assessment (CT-based features: hepatosplenic volumetrics, texture features, liver surface nodularity [LSN] score, and linear CT measurements; laboratory-based measures: Fibrosis-4 [FIB-4] score and aspartate transaminase-to-platelets ratio index [APRI]). Univariate logistic regression and multivariate logistic regression were performed with ROC analysis, proportional odds modeling, and probabilities. RESULTS: ROC AUC values for the model combining all 11 parameters for discriminating significant fibrosis (≥ F2), advanced fibrosis (≥ F3), and cirrhosis (F4) were 0.928, 0.956, and 0.972, respectively. For all nine CT-based parameters, these values were 0.905, 0.936, and 0.972, respectively. Using more simplified panels of two, three, or four parameters yielded good diagnostic performance; for example, a two-parameter model combining only LSN score with FIB-4 score had ROC AUC values of 0.886, 0.915, and 0.932, for significant fibrosis, advanced fibrosis, and cirrhosis. The LSN score performed best in the univariate analysis. CONCLUSION: Multiparametric CT assessment of HCV-related liver fibrosis further improves performance over the performance of individual parameters. An abbreviated panel of LSN score and FIB-4 score approached the diagnostic performance of more exhaustive panels. Results of the abbreviated panel compare favorably with elastography, but this approach has the advantage of retrospective assessment using preexisting data without planning.

Considerations When Treating Hepatitis C in a Cirrhotic Transplant Candidate.

PURPOSE OF REVIEW: This review examines the issues in determining the decision to treat a HCV-positive patient who is a liver transplant (LT) candidate with highly effective and well-tolerated direct-acting antiviral (DAA) therapies. RECENT FINDINGS: Cure of HCV with DAA can improve liver function and allow delisting in some patients. Beyond a threshold of hepatic impairment (likely MELD score > 16 to 20), patients may experience a decline in MELD score with HCV cure without improvement in liver-related complications resulting in decreased opportunity to receive a LT. Eradicating HCV from patients who need LT regardless also deprives them of the option of receiving HCV-positive donor organs. Patients with MELD > 16 or Child-Pugh B/C may also have reduced cure rates of HCV, increased risk of hepatic decompensation, and adverse events with DAA pre-LT compared to post-LT DAA therapy. Preliminary data demonstrates increase risk of hepatocellular carcinoma (HCC) recurrence after treatment with DAA with subsequent studies raising doubts about this association. Patients with HCV cirrhosis on the LT waiting list with MELD score > 16, CTP-B/C, and HCC are best treated after LT with better response, tolerability, and the ability to receive organs from a larger donor pool that includes HCV-positive donors. Larger, prospective studies are needed to assess whether increased HCC recurrence after DAA is a true effect.

Added value of gadoxetic acid-enhanced T1-weighted magnetic resonance cholangiography for the diagnosis of post-transplant biliary complications.

OBJECTIVES: Biliary complications after liver transplantation (LT) are common. This study aimed to ascertain the value of gadoxetic acid-enhanced T1-weighted (T1w) magnetic resonance cholangiography (MRC) to evaluate anastomotic strictures (AS), non-anastomotic strictures (NAS) and biliary casts (BC). METHODS: Sixty liver-transplanted patients with suspicion of biliary complications and T2w-MRCP and T1w-MRC followed by endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC) were analysed. Two readers reviewed the MRCs and rated image quality (IQ) and likelihood for AS/NAS/BC on Likert scales. Sensitivity, specificity and predictive values were calculated, ROC curve analysis performed, and inter-reader variability assessed. The subjective added value of T1w-MRC was rated. RESULTS: IQ was high for all sequences without significant differences (2.83-2.88). In 39 patients ERCP/PTC detected a complication. Sensitivity and specificity for AS were 64-96 using T2w-MRCP, increasing to 79-100 using all sequences. Use of all sequences increased the sensitivity of detecting NAS/BC from 72-92% to 88-100% and 67-89% to 72-94%, respectively. Kappa values were substantial (0.45-0.62). T1w-MRC was found to be helpful in 75-83.3%. CONCLUSIONS: Combining T1w-MRC and T2w-MRCP increased sensitivity and specificity and diagnostic confidence in patients after LT with suspected biliary complications. T1w-MRC is a valuable tool for evaluating post-transplant biliary complications. KEY POINTS: • T1w-MRC is a valuable tool for evaluating post-transplant biliary complications. • Adding T1w-MRC to T2w-MRC increases diagnostic confidence for detection of biliary complications. • A combination of T1w-MRC and T2w-MRCP leads to the best results.

Opioid and opioid substitution therapy in liver transplant candidates: A survey of center policies and practices.

This national survey sought to determine the practices and policies pertaining to opioid and opioid substitution therapy (OST) use in the selection of liver transplant (LT) candidates. Of 114 centers, 61 (53.5%) responded to the survey, representing 49.2% of the LT volume in 2016. Only two programs considered chronic opioid (1 [1.6%]) or OST use (1 [1.6%]) absolute contraindications to transplant, while 63.9% and 37.7% considered either one a relative contraindication, respectively. The majority of programs did not have a written policy regarding chronic opioid use (73.8%) or OST use (78.7%) in LT candidates. Nearly half (45.9%) of centers agreed that there should be a national consensus policy addressing opioid and OST use. The majority of responding LT centers did not consider opioid or OST use in LT candidates to be absolute contraindications to LT, but there was significant variability in center practices. These surveys also demonstrated a lack of written policies in the assessment of the candidacy of such patients. The results of our survey identify an opportunity to develop a national consensus statement regarding opioid and OST use in LT candidates to bring greater uniformity and equity into the selection of LT candidates.