Access to technology to support telehealth in areas without specialty care for liver disease.

BACKGROUND AND AIMS: Telehealth may be a successful strategy to increase access to specialty care for liver disease, but whether the areas with low access to care and a high burden of liver-related mortality have the necessary technology access to support a video-based telehealth strategy to expand access to care is unknown. APPROACH AND RESULTS: Access to liver disease specialty care was defined at the county level as <160.9 km (100 miles) from a liver transplant (LT) center or presence of local gastroenterology (GI). Liver-related mortality rates were compared by access to care, and access to technology was compared by degree of access to care and burden of liver-related mortality. Counties with low access to liver disease specialty care had higher rates of mortality from liver disease, and this was highest in areas both >160.9 km from an LT center and without local GI. These counties were more rural, had higher poverty, and had decreased access to devices and internet at broadband speeds. Technology access was lowest in areas with low access to care and the highest burden of liver-related mortality. CONCLUSIONS: Areas with poor access to liver disease specialty care have a greater burden of liver-related mortality, and many of their residents lack access to technology. Therefore, a telehealth strategy based solely on patient device ownership and internet access will exclude a large proportion of individuals in the areas of highest need. Further work should be done at the local and state levels to design optimal strategies to reach their populations of need.

Inadequate Dietary Education and Poor Adherence to a High Protein, Low Sodium Diet in Cirrhosis: Mixed Methods Approach.

BACKGROUND: Malnutrition in cirrhosis is associated with poor outcomes, leading to guidelines for a high protein, low sodium diet; however, there is no guidance regarding the implementation of diet education in clinical practice. METHODS: A mixed methods study enrolled 21 patients with cirrhosis and their caregivers. Semi-structured interviews on barriers and facilitators of dietary education and adherence were conducted. Demographic and clinical data were obtained, along with quantitative measures of dietary adherence, including 24-h food recall and spot urine sodium. Combined deductive and inductive coding was used to identify qualitative themes, along with a quantitative assessment of interviews. Quantitative data was reported using descriptive statistics with frequencies, mean and confidence intervals. RESULTS: Participants were mostly male (16/21) with a mean age 57.8 years (SE 2.8) and MELD-Na 9 (SE 1.2). 4 themes emerged: 1. More than 50% of participants and caregivers endorsed no or inadequate diet education 2. They reported mostly negative experiences with dietary adherence with largest impact on social life 3. Facilitators of adherence included the presence of household support and fear of complications of cirrhosis 4. Overwhelmingly desired non-generic handouts and information. Dietary adherence was poor with only one participant meeting protein and sodium requirements based on food recall. Four participants who adhered to < 2000 mg sodium had inadequate daily caloric intake. CONCLUSIONS: Dietary education is inadequate, and adherence to dietary recommendations is poor in patients with cirrhosis. Future studies should use these barriers and facilitators for intervention development.

Safety and Sustained Efficacy of the Farnesoid X Receptor (FXR) Agonist Cilofexor Over a 96-Week Open-label Extension in Patients With PSC.

BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is a major unmet medical need in clinical hepatology. Cilofexor is a nonsteroidal farnesoid X receptor agonist being evaluated for the treatment of PSC. Here, we describe the safety and preliminary efficacy of cilofexor in a 96-week, open-label extension (OLE) of a phase II trial. METHODS: Noncirrhotic subjects with large-duct PSC who completed the 12-week, blinded phase of a phase II study (NCT02943460) were eligible, after a 4-week washout period, for a 96-week OLE with cilofexor 100 mg daily. Safety, liver biochemistry, and serum markers of fibrosis, cellular injury, and pharmacodynamic effects of cilofexor (fibroblast growth factor 19, C4, and bile acids [BAs]) were evaluated. RESULTS: Among 52 subjects enrolled in the phase II study, 47 (90%) continued in the OLE phase (median age, 44 years; 60% male patients, 60% with inflammatory bowel disease, and 45% on ursodeoxycholic acid [UDCA]). At OLE baseline (BL), the median serum alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) were 368 U/L (interquartile range [IQR], 277-468 U/L) and 417 U/L (IQR, 196-801 U/L), respectively. Of the 47 subjects enrolled, 15 (32%) discontinued treatment prematurely (pruritus [n = 5], other adverse events [n = 5], subject decision/investigator discretion [n = 5]). At week 96, reductions in liver biochemistry parameters occurred, including serum ALP (median, -8.3% [IQR, -25.9% to 11.0%]; P = .066), GGT (-29.8% [IQR, -42.3% to -13.9%]; P < .001), alanine aminotransaminase (ALT) (-29.8% [IQR, -43.7% to -6.6%]; P = .002), and aspartate aminotransaminase (AST) (-16.7% [IQR, -35.3% to 1.0%]; P = .010), and rebounded after 4 weeks of untreated follow-up. ALP response (≥20% reduction from BL to week 96) was similar in the presence or absence of UDCA therapy (29% vs 39%; P = .71). At week 96, cilofexor treatment was associated with a significant reduction in serum 7α-hydroxy-4-cholesten-3-one (C4) (-29.8% [IQR, -64.3% to -8.5%]; P = .001). In subjects with detectable serum BAs at BL (n = 40), BAs decreased -23.9% (IQR, -44.4% to -0.6%; P = .006) at week 48 (n = 28) and -25.7% (IQR, -35.9% to 53.7%; P = .91) at week 96 (n = 26). Serum cytokeratin 18 (CK18) M30 and M65 were reduced throughout the OLE; significant reductions were observed at week 72 (CK18 M30, -17.3% [IQR, -39.3% to 8.8%]; P = .018; CK18 M65, -43.5% [IQR, -54.9% to 15.3%]; P = .096). At week 96, a small, but statistically significant absolute increase of 0.15 units in Enhanced Liver Fibrosis score was observed compared with BL (median, 9.34 vs 9.53; P = .028). CONCLUSIONS: In this 96-week OLE of a phase II study of PSC, cilofexor was safe and improved liver biochemistry and biomarkers of cholestasis and cellular injury. CLINICALTRIALS: gov identifier: NCT02943460.

Characterization of social determinants of health of a liver transplant referral population.

Disparities exist in referral and access to the liver transplant (LT) waitlist, and social determinants of health (SDOH) are increasingly recognized as important factors driving health inequities, including in LT. The SDOH of potential transplant candidates is therefore important to characterize when designing targeted interventions to promote equity in access to LT. Yet, it is uncertain how a transplant center should approach this issue, characterize SDOH, identify disparities, and use these data to inform interventions. We performed a retrospective study of referrals for first-time, single-organ LT to our center from 2016 to 2020. Addresses were geoprocessed and mapped to the corresponding county, census tract, and census block group to assess their geospatial distribution, identify potential disparities in referrals, and characterize their communities across multiple domains of SDOH to identify potential barriers to evaluation and selection. We identified variability in referral patterns and areas with disproportionately low referrals, including counties in the highest quartile of liver disease mortality (9%) and neighborhoods in the highest quintile of socioeconomic deprivation (17%) and quartile of poverty (21%). Black individuals were also under-represented compared with expected state demographics (12% vs. 18%). Among the referral population, several potential barriers to evaluation and selection for LT were identified, including poverty, educational attainment, access to healthy food, and access to technology. This approach to the characterization of a transplant center's referral population by geographic location and associated SDOH demonstrates a model for identifying disparities in a referral population and potential barriers to evaluation that can be used to inform targeted interventions for disparities in LT access.

Cirrhosis regression is associated with improved clinical outcomes in patients with nonalcoholic steatohepatitis.

BACKGROUND AND AIMS: Surrogate endpoints that predict complications are necessary for assessment and approval of NASH therapies. We assessed associations between histologic and noninvasive tests (NITs) of fibrosis with liver-related complications in patients with NASH cirrhosis. APPROACH AND RESULTS: Patients with compensated cirrhosis due to NASH were enrolled in two placebo-controlled trials of simtuzumab and selonsertib. Liver fibrosis at baseline and week 48 (W48) was staged by NASH Clinical Research Network (CRN) and Ishak classifications and a machine learning (ML) approach, hepatic collagen and alpha-smooth muscle actin (α-SMA) expression were quantified by morphometry, liver stiffness (LS) was measured by transient elastography, and serum NITs (enhanced liver fibrosis [ELF], NAFLD fibrosis score [NFS], and Fibrosis-4 index [FIB-4]) were calculated. Cox regression determined associations between these parameters at baseline and their changes over time with adjudicated liver-related clinical events. Among 1,135 patients, 709 (62%) had Ishak stage 6 fibrosis, and median ELF and LS were 10.66 and 21.1 kPa, respectively. During a median follow-up of 16.6 months, 71 (6.3%) had a liver-related event; associated baseline factors included Ishak stage 6 fibrosis, and higher hepatic collagen, α-SMA expression, ML-based fibrosis parameters, LS, ELF, NFS, and FIB-4. Cirrhosis regression observed in 16% (176/1,135) between BL and W48 was associated with a lower risk of events versus nonregression (1.1% [2/176] vs. 7.2% [69/957]; HR, 0.16; 95% CI, 0.04, 0.65 [p = 0.0104]). Conversely, after adjustment for baseline values, increases in hepatic collagen, α-SMA, ML-based fibrosis parameters, NFS, and LS were associated with an increased risk of events. CONCLUSIONS: In patients with compensated cirrhosis due to NASH, regression of fibrosis is associated with a reduction in liver-related complications. These data support the utility of histologic fibrosis regression and NITs as clinical trial endpoints for NASH cirrhosis.

Performance of the Pooled Cohort Equations in non-alcoholic fatty liver disease: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is associated with a high risk of cardiovascular disease. Whether risk scores developed in the general population accurately assess cardiovascular risk in the NAFLD population is unknown. This study aimed to evaluate the performance of the Pooled Cohort Equations (PCE) in NAFLD. METHODS: Individuals in the Multi-Ethnic Study of Atherosclerosis with baseline non-contrast cardiac computed tomography scans with sufficient data to determine the presence of hepatic steatosis were identified and assessed for the development of incident 10-year atherosclerotic cardiovascular disease. The discrimination and calibration of the PCE were evaluated, and the observed and expected events by risk category (<5%, 5-<7.5%, 7.5-<20%, ≥20%) were determined. Risk reclassification with the addition of NAFLD to the PCE was assessed. RESULTS: Of 4014 participants included, 698 (17.4%) with NAFLD were identified, including 247 (35.3%) with moderate-to-severe steatosis. Discrimination of the PCE was suboptimal in NAFLD (c-statistic 0.69), particularly moderate-to-severe steatosis (0.65), and calibration was overall poor. While risk was overestimated in non-NAFLD, it was underestimated in NAFLD in lower/intermediate risk categories, predominantly in women (5-<7.5% observed/expected ratio = 1.67). The addition of NAFLD to the PCE improved risk classification in women. CONCLUSIONS: The PCE overall performed suboptimally in cardiovascular risk assessment in NAFLD, particularly in women and individuals with moderate-to-severe steatosis in clinically relevant risk categories. Primary prevention may need to be considered at a lower risk threshold in these groups, and further work is needed to improve risk stratification in this growing high-risk population.

A Fibrosis-Independent Hepatic Transcriptomic Signature Identifies Drivers of Disease Progression in Primary Sclerosing Cholangitis.

BACKGROUND AND AIMS: Primary sclerosing cholangitis (PSC) is a heterogeneous cholangiopathy characterized by progressive biliary fibrosis. RNA sequencing of liver tissue from patients with PSC (n = 74) enrolled in a 96-week clinical trial was performed to identify associations between biological pathways that were independent of fibrosis and clinical events. APPROACH AND RESULTS: The effect of fibrosis was subtracted from gene expression using a computational approach. The fibrosis-adjusted gene expression patterns were associated with time to first PSC-related clinical event (e.g., cholangitis, hepatic decompensation), and differential expression based on risk groups and Ingenuity Pathway Analysis were performed. Baseline demographic data were representative of PSC: median age 48 years, 71% male, 49% with inflammatory bowel disease, and 44% with bridging fibrosis or cirrhosis. The first principle component (PC1) of RNA-sequencing data accounted for 18% of variance and correlated with fibrosis stage (ρ = -0.80; P < 0.001). After removing the effect of fibrosis-related genes, the first principle component was not associated with fibrosis (ρ = -0.19; P = 0.11), and a semisupervised clustering approach identified two distinct patient clusters with differential risk of time to first PSC-related event (P < 0.0001). The two groups had similar fibrosis stage, hepatic collagen content, and α-smooth muscle actin expression by morphometry, Enhanced Liver Fibrosis score, and serum liver biochemistry, bile acids, and IL-8 (all P > 0.05). The top pathways identified by Ingenuity Pathway Analysis were eukaryotic translation inhibition factor 2 (eIF2) signaling and regulation of eIF4/p70S6K signaling. Genes involved in the unfolded protein response, activating transcription factor 6 (ATF6) and eIF2, were differentially expressed between the PSC clusters (down-regulated in the high-risk group by log-fold changes of -0.18 [P = 0.02] and -0.16 [P = 0.02], respectively). Clinical events were enriched in the high-risk versus low-risk group (38% [12/32] vs. 2.4% [1/42], P < 0.0001). CONCLUSIONS: Removing the contribution of fibrosis-related pathways uncovered alterations in the unfolded protein response, which were associated with liver-related complications in PSC.

A Pragmatic, Randomized Controlled Trial of Oral Antivirals for the Treatment of Chronic Hepatitis C: The PRIORITIZE Study.

BACKGROUND AND AIMS: Multiple direct-acting antiviral (DAA) regimens are available to treat HCV genotype 1 infection. However, comparative effectiveness from randomized controlled trials of DAA regimens is unavailable. APPROACH AND RESULTS: We conducted a pragmatic randomized controlled trial (NCT02786537) to compare the effectiveness of DAAs for HCV genotype 1a or 1b on viral response, safety, tolerability, and medication nonadherence. Adults with compensated liver disease, HCV genotype 1, not pregnant or breastfeeding, and with health insurance likely to cover ledipasvir/sofosbuvir (LDV/SOF) were recruited from 34 US viral hepatitis clinics. Participants were randomized (± ribavirin) to LDV/SOF, elbasvir/grazoprevir (EBR/GZR), and paritaprevir/ritonavir/ombitasvir+dasabuvir (PrOD; treatment arm stopped early). Primary outcomes included sustained viral response at 12 weeks (SVR12), clinician-recorded adverse events, patient-reported symptoms, and medication nonadherence. Between June 2016 and March 2018, 1,609 participants were randomized. Among 1,128 participants who received ≥1 dose of EBR/GZR or LDV/SOF (± ribavirin), SVR12 was 95.2% (95% CI, 92.8%-97.6%) and 97.4% (95% CI, 95.5%-99.2%), respectively, with a difference estimate of 2.2% (-0.5% to 4.7%), falling within the "equivalence" interval (-5% to 5%). While most (56%) participants experienced adverse events, few were serious (4.2%) or severe (1.8%). In the absence of ribavirin, discontinuations due to adverse events were rare. Patient-reported symptoms and medication nonadherence were similar. Study limitations were dropout due to insurance denial and loss to follow-up after treatment, limiting the ability to measure SVR12. CONCLUSIONS: This pragmatic trial demonstrated high SVR12 for participants treated with EBR/GZR and LDV/SOF with few adverse effects. Overall, the two regimens were equivalent in effectiveness. The results support current HCV guidelines that do not distinguish between ribavirin-free EBR/GZR and LDV/SOF.

MELD-Na Accurately Predicts 6-Month Mortality in Patients With Decompensated Cirrhosis: Potential Trigger for Hospice Referral.

GOAL: The goal of this study was to determine the accuracy of Model of End-stage Liver Disease-Sodium (MELD-Na) in predicting 6-month mortality for patients listed for liver transplantation on the United Network of Organ Sharing (UNOS) waitlist. BACKGROUND: End-stage liver disease patients underutilize hospice services despite significant morbidity and mortality associated with advanced liver disease. A well-known barrier to hospice referral is clinician uncertainty in identifying patients with an expected survival of <6 months, a requirement for a referral. METHODS: Retrospective cross-sectional analysis was performed from UNOS data spanning February 27, 2002, to September 30, 2019. Inclusion criteria of patients aged 18 years and above, diagnosis of cirrhosis, liver transplant eligible, and listed in the UNOS database. Exclusion criteria included fulminant hepatic failure, prior history of liver transplantation, diagnosis of hepatocellular carcinoma, receipt of liver transplant in <180 days, or removal from waiting list <180 days for a reason other than death. MEASUREMENT: Mortality by 180 days. RESULTS: Of the 93,157 patients that met inclusion criteria, MELD-Na was calculated for all patients with sodium, total bilirubin, international normalized ratio, and creatinine available (N=79,611). The c -statistic with 95% confidence interval for MELD-Na for the predicted 6-month mortality was 0.83 (0.827-0.835). Mean MELD-Na of 28.2 was associated with ≤50% 6-month survival. CONCLUSION: MELD-Na is an objective, quick measure that can aid providers in identifying patients with increased 6-month mortality in time-constrained settings, and a score of 28 can trigger the discussion for hospice as a means of improving value-based health care.

Patient-Predicted Outcomes Are Associated with Quality of Life in Patients with Primary Sclerosing Cholangitis.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic, progressive liver disease, and many patients ultimately require liver transplantation (LT). PSC also confers an increased risk of malignancies, including cholangiocarcinoma (CCA) and colorectal cancer. AIMS: This study aimed to evaluate patient-perceived outcomes and the extent to which these impact health-related quality of life (HRQoL). METHODS: Patients with PSC completed a risk perception questionnaire, the Short Form-36 (SF-36), and the Chronic Liver Disease Questionnaire. Multivariable models were used to determine factors associated with patient-perceived risks of malignancy, LT, and life expectancy, as well as their relationship with HRQoL scores. RESULTS: A total of 95 patients completed the risk perception questionnaire, and 73 returned the remaining instruments. The estimated risks varied widely. Half overestimated their one-year or lifetime CCA risk, while some predicted zero chance. Predicted LT risk was the only outcome concordant with disease severity. Pruritus was associated with higher predicted one-year risks and lower life expectancy. Lifetime CCA and LT risks were associated with the SF-36 physical component score, while perceived life expectancy was strongly associated with mental health domains, including the SF-36 mental component score. CONCLUSIONS: Predicted prognosis varies widely among patients with PSC and is influenced more by symptoms than objective disease severity. The psychological burden of shorter perceived life expectancy impacts mental HRQoL more than the risks of malignancy or LT. These findings highlight an opportunity for improved patient communication regarding these outcomes, as well as the importance of discussing them, as they may impact HRQoL.

Racial and Socioeconomic Disparities in Utilization of Telehealth in Patients with Liver Disease During COVID-19.

BACKGROUND AND AIMS: The coronavirus disease 2019 (COVID-19) pandemic resulted in a rapid expansion of telehealth services in hepatology. However, known racial and socioeconomic disparities in internet access potentially translate into barriers for the use of telehealth, particularly video technology. The specific aim of this study was to determine if disparities in race or socioeconomic status exist among patients utilizing telehealth visits during COVID-19. METHODS: We performed a retrospective cohort study of all adult patients evaluated in hepatology clinics at Duke University Health System. Visit attempts from a pre-COVID baseline period (January 1, 2020 through February 29, 2020; n = 3328) were compared to COVID period (April 1, 2020 through May 30, 2020; n = 3771). RESULTS: On multinomial regression modeling, increasing age was associated with higher odds of a phone or incomplete visit (canceled, no-show, or rescheduled after May 30,2020), and non-Hispanic Black race was associated with nearly twice the odds of completing a phone visit instead of video visit, compared to non-Hispanic White patients. Compared to private insurance, Medicaid and Medicare were associated with increased odds of completing a telephone visit, and Medicaid was associated with increased odds of incomplete visits. Being single or previously married (separated, divorced, widowed) was associated with increased odds of completing a phone compared to video visit compared to being married. CONCLUSIONS: Though liver telehealth has expanded during the COVID-19 pandemic, disparities in overall use and suboptimal use (phone versus video) remain for vulnerable populations including those that are older, non-Hispanic Black, or have Medicare/Medicaid health insurance.

Inter- and Intra-individual Variation, and Limited Prognostic Utility, of Serum Alkaline Phosphatase in a Trial of Patients With Primary Sclerosing Cholangitis.

BACKGROUND & AIMS: Serum alkaline phosphatase (ALP) and the enhanced liver fibrosis (ELF) score are used as endpoints in trials of patients with primary sclerosing cholangitis (PSC). We aimed to quantify inter- and intra-individual variation in levels of ALP and the ELF score over time, and evaluated their association with fibrosis progression. METHODS: We analyzed data from 234 patients with large-duct PSC enrolled in a 2-year, phase 2b placebo-controlled trial of simtuzumab. Participants were assessed by laboratory tests every 4 weeks, and liver biopsies collected at time of screening, week 48, and week 96. RESULTS: Serum levels of ALP and ELF scores did not differ significantly between simtuzumab and placebo groups, so the data were pooled. Median per-patient variations in ALP between clinic visits were approximately 12% over 12 weeks, 20% over 48 weeks, and 20% over 96 weeks. Reductions, unrelated to study intervention, of more than 40% in ALP were observed in 10.9% of patients with baseline activity greater than 2-fold the upper limit of normal (ULN) and 12.5% of patients with more than 3-fold the ULN at 1 year. At 2 years, reductions of more than 40% in ALP were observed in 15.8% of patients with baseline activity greater than 2-fold the ULN and 17.9% of patients with more than 3-fold the ULN. Among the 209 patients with Ishak fibrosis stage 0-4 at baseline, serum ALP activity did not associate with development of cirrhosis or with a 2-point increase in fibrosis stage at 2 years. In contrast, the median per-patient variation in ELF scores between clinic visits was approximately 3% over 12 weeks, 4% over 48 weeks, and 4% over 96 weeks. Elevated ELF scores at baseline and at weeks 12, 24 and 48, each associated with development of cirrhosis at 2 years (odds ratio >2.75; P < .01 for all timepoints). ELF scores at baseline and weeks 12, 24 and 48, also associated with a 2-point increase in fibrosis stage at 2 years (odds ratios all greater than 2; P < .01 for all timepoints). CONCLUSIONS: In an analysis of data from patients with large-duct PSC enrolled in a prospective trial, we found large interindividual and intraindividual variations in serum ALP activity. Serum ALP activity did not associate with disease progression over a 2-year period. Variations in ELF score were smaller, and scores determined at multiple timepoints associated with fibrosis progression and development of cirrhosis.

Why do patients with chronic hepatitis C drink alcohol? An examination of pain, depression and drinking motives.

Alcohol consumption in the setting of chronic HCV is associated with accelerated progression towards cirrhosis, increased risk of hepatocellular carcinoma and higher mortality. This analysis contextualizes how sociodemographic factors, chronic pain and depression relate to the motivations of individuals with chronic HCV to consume alcohol. We conducted a secondary analysis of baseline data from the Hep ART trial of behavioural interventions on alcohol use among patients with HCV. Alcohol consumption was measured using the Drinking Motives Questionnaire and a novel 6-item measure of pain-related drinking motives. Statistical analyses performed included ANOVA for bivariate analyses and multivariable ordinary least-squares linear regression. At study baseline, 181 participants had an average age of 55 years; the majority (66.7%) reported beyond-minor pain; and a third (37%) met criteria for depression; drinking motives were higher for individuals with beyond-minor pain (means 9.9 vs. 4.6, p < .001) and who met criteria for depression (means 10.9 vs. 6.4, p < .001) when using the pain-related drinking motives items. Average pain(coef = 1.0410067141 < .001) was significantly associated with increased motives to drink to relieve pain in the full baseline model specification controlling for all covariates using ordinary at least squares; depression (coef = 7.06; 95% CI 1.32, 12.81; p = .016) was significantly associated with increased non-pain-related motives to drink. From baseline to 3-month follow-up, compared to participants who had mean average pain scores among the sample, motives to drink to relieve pain decreased in participants who had higher average pain scores (coef = -0.30; 95% CI -0.59, -0.01; p = .40). Physical pain and depression are associated with increased motives to consume alcohol. Patients with chronic liver disease should be screened for chronic pain and depression and, if present, referred to pain specialists or co-managed in partnership with pain specialists in hepatology clinics.

A Randomized Controlled Trial of an Integrated Alcohol Reduction Intervention in Patients With Hepatitis C Infection.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) and alcohol use are patient risk factors for accelerated fibrosis progression, yet few randomized controlled trials have tested clinic-based alcohol interventions. APPROACH AND RESULTS: A total of 181 patients with HCV and qualifying alcohol screener scores at three liver center settings were randomly assigned to the following: (1) medical provider-delivered Screening, Brief Intervention, and Referral to Treatment (SBIRT), including motivational interviewing counseling and referral out for alcohol treatment (SBIRT-only), or (2) SBIRT plus 6 months of integrated colocated alcohol therapy (SBIRT + Alcohol Treatment). The timeline followback method was used to assess alcohol use at baseline and 3, 6, and 12 months. Coprimary outcomes were alcohol abstinence at 6 months and heavy drinking days between 6 and 12 months. Secondary outcomes included grams of alcohol consumed per week at 6 months. Mean therapy hours across 6 months were 8.8 for SBIRT-only and 10.1 for SBIRT + Alcohol Treatment participants. The proportion of participants exhibiting full alcohol abstinence increased from baseline to 3, 6, and 12 months in both treatment arms, but no significant differences were found between arms (baseline to 6 months, 7.1% to 20.5% for SBIRT-only; 4.2% to 23.3% for SBIRT + Alcohol Treatment; P = 0.70). Proportions of participants with any heavy drinking days decreased in both groups at 6 months but did not significantly differ between the SBIRT-only (87.5% to 26.7%) and SBIRT + Alcohol Treatment (85.7% to 42.1%) arms (P = 0.30). Although both arms reduced average grams of alcohol consumed per week from baseline to 6 and 12 months, between-treatment effects were not significant. CONCLUSIONS: Patients with current or prior HCV infection will engage in alcohol treatment when encouraged by liver medical providers. Liver clinics should consider implementing provider-delivered SBIRT and tailored alcohol treatment referrals as part of the standard of care.

Diagnosis of LI-RADS M lesions on gadoxetate-enhanced MRI: identifying cholangiocarcinoma-containing tumor with serum markers and imaging features.

OBJECTIVES: The LI-RADS M (LR-M) category describes hepatic lesions probably or definitely malignant, but not specific for hepatocellular carcinoma in at-risk patients. Differentiation among LR-M entities, particularly detecting cholangiocarcinoma-containing tumors (M-CCs), is essential for treatment and prognosis. Thus, we aimed to develop diagnostic models on gadoxetate disodium-enhanced MRI comprising serum tumor markers and LI-RADS imaging features for M-CC. METHODS: Consecutive at-risk patients with LR-M lesions exclusively (no co-existing LR-4 and/or LR-5 lesions) were retrieved retrospectively from a prospectively collected database spanning 3 years. Intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular-cholangiocarcinoma (c-HCC-CCA) were classified together as M-CC. LI-RADS features determined by three independent radiologists and clinically relevant serum tumor markers were used to generate M-CC diagnostic models through logistic regression analysis against histology. Per-patient performance was evaluated using area under the receiver operating curve (AUC), sensitivity, and specificity. RESULTS: Forty-five patients were included, 42.2% (19/45) with hepatocellular carcinoma, 33.3% (15/45) with ICC, 13.3% (6/45) with c-HCC-CCA, and 11.1% (5/45) with other hepatic lesions. Carbohydrate antigen (CA)19-9 > 38 U/mL, α-fetoprotein (AFP) > 4.8 ng/mL, and absence of the LI-RADS feature "blood products in mass" were significant predictors of M-CC. Combining three predictors demonstrated AUC of 0.862, sensitivity of 76%, and specificity of 88%. The risk of M-CC with all three criteria fulfilled was 98% (AUC, 0.690; sensitivity, 38%; specificity, 100%). CONCLUSIONS: In at-risk patients with LR-M lesions, integrating CA19-9, AFP, and the LI-RADS feature "blood products in mass" achieved high diagnostic performance for M-CC. When all three criteria were fulfilled, the specificity for M-CC was 100%. KEY POINTS: • In at-risk patients who had LR-M lesions exclusively (no concomitant LR-4/5 lesions), a model with carbohydrate antigen > 38 U/mL, α-fetoprotein > 4.8 ng/mL, and absence of the LI-RADS feature "blood products in mass" achieved high accuracy for diagnosing cholangiocarcinoma-containing tumors. • In patients of whom all three criteria were fulfilled, the specificity for M-CC was 100%, which might reduce or eliminate the need for biopsy confirmation.

Socioeconomic Status Is Associated with the Risk of Hepatic Encephalopathy after Transjugular Intrahepatic Portosystemic Shunt Creation.

PURPOSE: To determine whether socioeconomic status (SES) is associated with hepatic encephalopathy (HE) risk after transjugular intrahepatic portosystemic shunt (TIPS) creation. MATERIALS AND METHODS: This single-institution retrospective study included 368 patients (mean age = 56.7 years; n = 229 males) from 5 states who underwent TIPS creation. SES was estimated using the Agency for Healthcare Research and Quality SES index, a metric based on neighborhood housing, education, and income statistics. Episodes of new or worsening HE after TIPS creation, defined as hospitalization for HE or escalation in outpatient medical therapy, were identified from medical records. Multivariable ordinal regression, negative binomial regression, and competing risks survival analysis were used to identify factors associated with SES quartile, the number of episodes of new or worsening HE per unit time after TIPS creation, and mortality after TIPS creation, respectively. RESULTS: There were 83, 113, 99, and 73 patients in the lowest, second, third, and highest SES quartiles, respectively. In multivariable regression, only older age (ß = 0.04, confidence interval [CI] = 0.02-0.05; P < .001) and white, non-Hispanic ethnicity (ß = 0.64, CI = 0.07-1.21; P = .03) were associated with higher SES quartile. In multivariable regression, lower SES quartile (incidence rate ratio [IRR] = 0.80, CI = 0.68-0.94; P = .004), along with older age, male sex, higher model for end-stage liver disease score, nonalcoholic steatohepatitis, and proton pump inhibitor use were associated with higher rates of HE after TIPS creation. Ethnicity was not associated with the rate of HE after TIPS creation (IRR = 0.77, CI = 0.46-1.29; P = .28). In multivariable survival analysis, neither SES quartile nor ethnicity predicted mortality after creation of a TIPS. CONCLUSION: Lower SES is associated with higher rates of new or worsening HE after TIPS creation.

Reduced Alcohol Use Is Sustained in Patients Provided Alcohol-Related Counseling During Direct-Acting Antiviral Therapy for Hepatitis C.

BACKGROUND: Patients with chronic hepatitis C and risky/harmful alcohol use experience poor outcomes. Granular data evaluating whether alcohol counseling during hepatitis C treatment impacts longitudinal alcohol consumption are lacking. AIMS: To evaluate whether provider-delivered counseling in the context of direct-acting antiviral hepatitis C treatment associates with decreased longitudinal alcohol consumption. METHODS: We performed secondary data analysis from the Hep ART study including adults with hepatitis C who underwent provider-delivered counseling during direct-acting antiviral treatment between October 2014 and September 2017. Demographics and disease characteristics were summarized. Alcohol consumption, abstinence, and heavy drinking were evaluated in periods before, during, and after direct-acting antiviral treatment. Multivariate regression analyses were performed to evaluate the association of alcohol consumption with each 12-week time period for all patients and a subsample with cirrhosis. RESULTS: One hundred twenty-three patients were included; 41 had cirrhosis. Most patients were male (74.0%) and Black (58.5%). Alcohol consumption improved during direct-acting antiviral treatment and was notably sustained (< 12 weeks before treatment 32.5 g/day; during treatment 20.0 g/day; and 12-24 weeks after treatment 23.7 g/day). Multivariable analyses showed significantly improved alcohol consumption metrics during and after antiviral treatment compared to < 12 weeks before treatment (during treatment 13.04 g/day less, p = 0.0001; > 24 weeks after treatment 15.29 g/day less, p = 0.0001). The subsample with cirrhosis showed similar results (during treatment 13.21 g/day less, p = 0.0001; > 24 weeks after treatment 7.69 g/day less, p = 0.0001). CONCLUSIONS: Patients with chronic HCV and risky/harmful alcohol use given provider-delivered alcohol-related counseling during HCV treatment sustain decreased alcohol consumption patterns during and after treatment.

Complications and outcomes of swine that underwent cesarean section for resolution of dystocia: 110 cases (2013-2018).

OBJECTIVE: To report the surgical survival of dams and piglets and follow-up survival and future breeding potential of swine that underwent cesarean section for correction of dystocia. STUDY DESIGN: Retrospective study. ANIMALS: One hundred ten client-owned, female swine. All swine included in this study were breeding stock for market pigs to be used for exhibition purposes. METHODS: Medical records of swine that underwent cesarean section at The Ohio State University Hospital for Farm Animals for resolution of dystocia between January of 2013 and July of 2018 were reviewed. Signalment, history, number of piglets per litter, treatments, and surgical procedure were recorded. Follow-up information (survival, complications, and additional pregnancies) was obtained via telephone interview. RESULTS: A fetus was not palpable in 77 of 110 (70%) cases at presentation. The median litter size was eight piglets (range, 1-14), with medians of five (range, 0-13) live and one dead (range, 0-11) piglets per litter. Follow-up was available for 52 dams, of which 39 (75%) survived. Complications were recorded in 20 of 52 (38.46%) cases and included incisional seroma formation, lethargy, and anorexia. Twenty-three dams became pregnant and farrowed after the cesarean section, with no reported complication in 13 of these. CONCLUSION: Cesarean section in swine is associated with a good prognosis for recovery from the procedure and a fair to guarded prognosis for future breeding. CLINICAL SIGNIFICANCE: Cesarean section may be considered for resolution of dystocia in swine. However, owners should be advised that nearly half of sows require assistance in subsequent deliveries.

Direct-Acting Antivirals and Organ Transplantation: Is There Anything We Can't Do?

The opioid epidemic has resulted in an increase in organ donors with hepatitis C virus (HCV) infection in the United States. With the development of direct-acting antiviral regimens that offer high sustained virologic response rates even in the setting of immunosuppression after transplantation, these HCV-viremic organs are now being offered to transplant candidates with or without preexisting HCV infection. Strategies for HCV treatment with HCV-viremic organs have included delayed and preemptive approaches. This review will discuss key studies in the different solid organ transplants, recent reports of adverse events, and ethical and regulatory considerations. The efficacy of current HCV therapies has created this important opportunity to improve survival for patients with end-organ failure through greater access to organ transplantation and decreased waitlist mortality rate.

Not Achieving Sustained Viral Eradication of Hepatitis C Virus After Treatment Leads to Worsening Patient-reported Outcomes.

BACKGROUND: The causative relationship between the clearance of infections and long-term, health-related quality-of-life (HRQL) improvements in patients with hepatitis C virus (HCV) has been generally accepted. The aim of this study was to assess long-term HRQL trends in HCV patients who did not achieve sustained virologic responses (SVRs) after treatment with direct-acting antivirals. METHODS: HCV patients who completed treatment in clinical trials and did not achieve SVRs were enrolled in a long-term registry (#NCT01457768). HRQL scores were prospectively collected using the short form-36 instrument (8 HRQL domains and 2 summary scores). RESULTS: There were 242 patients included: they had a median age of 54 years (standard deviation ± 8 years), 85% were male, and 38% had cirrhosis. Before treatment, patients' HRQL scores were similar to the general population norms (all 1-sided P > 0.05), but were followed by significant decreases by the end of treatment (-3.4 to -6.2 points; P < .05 for 5/8 HRQL domains and mental summary). By the time subjects entered the registry, all but 1 of the mean HRQL scores had returned to their pretreatment levels (P > .05). During subsequent periods in the registry, patients experienced further HRQL decrements: up to -9.2 points (P < .05 for all HRQL domains) at Week 24 and up to -8.3 points (P < .05 for 5/8 HRQL domains) at Week 48. Although these HRQL decrements were observed regardless of cirrhosis status, they were more pronounced in patients with cirrhosis (P < .05 for 3/8 HRQL domains). CONCLUSIONS: Patients who did not achieve an SVR after treatment experienced worsening HRQL scores in long-term follow-ups. Retreatment of these patients will be important not only to improve their clinical outcomes, but also their quality of life.