Hepatocellular carcinoma after direct-acting antivirals for hepatitis C is associated with KIR-HLA types predicting weak NK cell-mediated immunity.

BACKGROUND AND AIMS: Second-generation direct-acting antivirals (2G DAA) to cure HCV have led to dramatic clinical improvements. HCV-associated hepatocellular carcinoma (HCC), however, remains common. Impaired immune tumor surveillance may play a role in HCC development. Our cohort evaluated the effects of innate immune types and clinical variables on outcomes including HCC. METHODS: Participants underwent full HLA class I/KIR typing and long-term HCV follow-up. RESULTS: A total of 353 HCV+ participants were followed for a mean of 7 years. Cirrhosis: 25% at baseline, developed in 12% during follow-up. 158 participants received 2G DAA therapy. HCC developed without HCV therapy in 20 subjects, 24 HCC after HCV therapy, and 10 of these after 2G DAA. Two predictors of HCC among 2G DAA-treated patients: cirrhosis (OR, 10.0, p = 0.002) and HLA/KIR profiles predicting weak natural killer (NK) cell-mediated immunity (NK cell complementation groups 6, 9, 11, 12, OR of 5.1, p = 0.02). Without 2G DAA therapy: cirrhosis was the main clinical predictor of HCC (OR, 30.8, p < 0.0001), and weak NK-cell-mediated immunity did not predict HCC. CONCLUSION: Cirrhosis is the main risk state predisposing to HCC, but weak NK-cell-mediated immunity may predispose to post-2G DAA HCC more than intermediate or strong NK-cell-mediated immunity.

Problematic alcohol use and its impact on liver disease quality of life in a multicenter study of patients with cirrhosis.

BACKGROUND: Management of cirrhosis is challenging and has been complicated by the COVID-19 pandemic due to decreased access to care, increased psychological distress, and alcohol misuse. Recently, The National Institute on Alcohol Abuse and Alcoholism has broadened the definition of recovery from alcohol use disorder to include quality of life (QoL) as an indicator of recovery. This study examined the associations of alcohol-associated cirrhosis etiology and problematic drinking with liver disease QoL (LDQoL). METHODS: Patients with cirrhosis (N=329) were recruited from 3 sites (63% from 2 Veterans Affairs Health Care Systems and 37% from 1 safety net hospital) serving populations that are economically or socially marginalized. Cirrhosis etiology was ascertained by chart review of medical records. Problematic drinking was defined by ≥8 on the Alcohol Use Disorders Identification Test. Multivariable general linear modeling adjusting for age, sex, race/ethnicity, site, pandemic-related stress, and history of anxiety/depressive disorder were conducted. Sensitivity analyses further adjusted for indicators of liver disease severity. RESULTS: Participants were on average 64.6 years old, 17% female, 58% non-White, 44% with alcohol-associated cirrhosis, and 17% with problematic drinking. Problematic drinking was significantly associated with worse LDQoL scores in the overall scale and in the memory/concentration and health distress subscales. These associations remained significant after adjusting for indicators of liver disease severity, including Model for End-Stage Liver Disease-Sodium score and decompensated cirrhosis status. CONCLUSIONS: Among patients with cirrhosis, problematic drinking was associated with worse LDQoL, especially in the domains of memory/concentration and health distress. Assessment and awareness of cognitive deficits and negative emotionality within the context of cirrhosis and problematic drinking may help clinicians provide better integrated care for this population.

Telehepatology Satisfaction Is Associated with Ethnicity: The Real-World Experience of a Vulnerable Population with Fatty Liver Disease.

BACKGROUND: Since the coronavirus disease 2019 (COVID-19) pandemic began, telemedicine use has transformed healthcare delivery. Yet there is concern that telemedicine may widen care disparities for vulnerable populations, and patient experience data are limited. AIMS: We aimed to assess patient satisfaction with hepatology-related telemedicine (telehepatology) for delivery of fatty liver disease (FLD) care in a safety-net healthcare system. METHODS: Adult patients with FLD were surveyed regarding satisfaction with telehepatology. Clinical, demographic, resources, and social determinants of health (SDoH) data were collected to identify factors associated with satisfaction through multivariable modeling. RESULTS: From June 2020 to March 2022, 220 participants were enrolled: the median age was 52 years, 37% were men, and 68% were Hispanic. One hundred nineteen (54%) had prior telehepatology experience. Overall, satisfaction was high; 70% reported being somewhat or very satisfied. On univariate analysis, Hispanic ethnicity (versus non-Hispanic, OR 0.34, 95% CI 0.1-0.9, p = 0.03) and limited access to personal cellphone/internet (OR 0.16, 95% CI 0.04-0.6, p = 0.01) were associated with lower satisfaction. On multivariable logistic regression modeling adjusted for pandemic duration, age, sex, severity of liver disease, and coexisting liver disease, Hispanic ethnicity and lack of personal cellphone/internet remained independently associated with lower telehepatology satisfaction (OR 0.24, 95% CI 0.07-0.9, p = 0.03 and OR 0.2, 95% CI 0.04-0.9, p = 0.04, respectively). The association remained statistically significant after inclusion of various SDoH in the multivariable model. CONCLUSIONS: Satisfaction with telehepatology among FLD patients in a safety-net clinical setting was high overall. However, Hispanic ethnicity and lack of personal cellphone/internet were independently associated with lower telehepatology satisfaction. A better understanding of patients' experience with telehepatology is needed to identify reasons for dissatisfaction, and in-person visits should remain an option for patients to ensure equitable care.

Hepatocellular Carcinoma Diagnosis and Management in 2021: A National Veterans Affairs Quality Improvement Project.

BACKGROUND & AIMS: The coronavirus disease-2019 pandemic profoundly disrupted preventative health care services including cancer screening. As the largest provider of cirrhosis care in the United States, the Department of Veterans Affairs (VA) National Gastroenterology and Hepatology Program aimed to assess factors associated with hepatocellular carcinoma (HCC) stage at diagnosis, treatment, and survival. METHODS: Veterans with a new diagnosis of HCC in 2021 were identified from electronic health records (N = 2306). Structured medical record extraction was performed by expert reviewers in a 10% random subsample of Veterans with new HCC diagnoses. Factors associated with stage at diagnosis, receipt of treatment, and survival were assessed using multivariable models. RESULTS: Among 199 patients with confirmed HCC, the average age was 71 years and most (72%) had underlying cirrhosis. More than half (54%) were at an early stage (T1 or T2) at diagnosis. Less-advanced liver disease, number of imaging tests adequate for HCC screening, HCC diagnosis in the VA, and receipt of VA primary care were associated significantly with early stage diagnosis. HCC-directed treatments were administered to 145 (73%) patients after a median of 37 days (interquartile range, 19-54 d) from diagnosis, including 70 (35%) patients who received potentially curative treatments. Factors associated with potentially curative (vs no) treatments included HCC screening, early stage at diagnosis, and better performance status. Having fewer comorbidities and better performance status were associated significantly with noncurative (vs no) treatment. Early stage diagnosis, diagnosis in the VA system, and receipt of curative treatment were associated significantly with survival. CONCLUSIONS: These results highlight the importance of HCC screening and engagement in care for HCC diagnosis, treatment, and survival while demonstrating the feasibility of developing a national quality improvement agenda for HCC screening, diagnosis, and treatment.

Alcohol Use Patterns During and After the COVID-19 Pandemic Among Veterans in the United States.

BACKGROUND: Veterans may be especially susceptible to increased alcohol consumption following the COVID-19 pandemic. We aim to evaluate trends in alcohol use among US Veterans prior to, during, and following the onset of the COVID-19 pandemic. METHODS: All US Veterans utilizing Veterans Affairs health care facilities in the United States from March 1, 2018 to February 28, 2023 with ≥1 AUDIT-C score were categorized into 1) No alcohol use (AUDIT-C = 0), 2) Low-risk alcohol use (AUDIT-C 1-2 for women, 1-3 for men), and 3) High-risk alcohol use (AUDIT-C ≥ 3 for women, ≥ 4 for men). Trends in the proportion of Veterans reporting high-risk alcohol use, stratified by sex, age, race/ethnicity, and urbanicity were evaluated. RESULTS: Among a cohort of 2.15 to 2.60 million Veterans, 15.5% reported high-risk alcohol use during March 2018-February 2019, which decreased to 14.6% during the first year of the pandemic, increased to 15.2% in the second year, and then decreased to 14.9% from March 2022-February 2023. Among non-Hispanic whites, African Americans, Asians, and Hispanics, the proportion of women reporting high-risk alcohol use surpassed that of men during the onset of the pandemic and beyond. The greatest proportion of high-risk alcohol use was observed among young Veterans ages 18-39 years (17%-27%), which was consistent across all race/ethnic groups. CONCLUSIONS: High-risk alcohol use among US Veterans has increased since the COVID-19 pandemic onset, and in the third year following pandemic onset, 15% of Veterans overall and over 20% of young Veterans ages 18-39 years reported high-risk alcohol use.

Portal Vein Thrombosis After Transarterial Embolization for Hepatocellular Carcinoma.

This cross-sectional study assesses the association between venous thrombosis and embolization in patients with hepatocellular carcinoma.

Clinical Characteristics and Outcomes Among People Living With HIV Undergoing Percutaneous Coronary Intervention: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program.

Background Clinical characteristics and outcomes in people living with HIV (PLWH) undergoing percutaneous coronary intervention (PCI) remain poorly described. We sought to compare real-world treatment of coronary artery disease, as well as patient and procedural factors and outcomes after PCI between PLWH and uninfected controls. Methods and Results We utilized procedural registry data from the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program between January 1, 2009 and December 31, 2019 to analyze patients with obstructive coronary artery disease on angiography. In the PCI subgroup, we used inverse probability of treatment weighting and applied Cox proportional hazards to evaluate the association of HIV serostatus with outcomes, including all-cause mortality at 5 years. Among 184 310 patients with obstructive coronary artery disease, treatment strategy was similar between PLWH and controls-35.7% versus 34.2% PCI, 13.6% versus 15% coronary artery bypass grafting, and 50.7% versus 50.8% medical therapy. The PCI cohort consisted of 546 (0.9%) PLWH and 56 811 (99.1%) controls. PLWH undergoing PCI had well-controlled HIV disease, and compared with controls, were younger, more likely to be Black, had fewer traditional risk factors, more acute coronary syndrome, less extensive coronary artery disease, and similar types of stents and P2Y12 therapy. However, PLWH experienced worse survival as early as 6 months post-PCI, which persisted over time and amounted to a 21% increased mortality risk by 5 years (hazard ratio, 1.21 [95% CI, 1.03-1.42; P=0.02]). Conclusions Despite well-controlled HIV disease, a more favorable overall cardiovascular risk profile, and similar PCI procedural metrics, PLWH still have significantly worse long-term survival following PCI than controls.

SACRED: Effect of simvastatin on hepatic decompensation and death in subjects with high-risk compensated cirrhosis: Statins and Cirrhosis: Reducing Events of Decompensation.

BACKGROUND/AIMS: The development of decompensation in cirrhosis demarcates a marked change in the natural history of chronic liver disease. HMG-CoA reductase inhibitors (statins) exert pleiotropic effects that reduce inflammation and fibrosis as well as improve vascular reactivity. Retrospective studies uniformly have associated statin utilization with improved outcomes for patients with cirrhosis. Prospective human studies have shown that statins reduce portal hypertension and reduce death in patients with decompensated cirrhosis after variceal hemorrhage when added to standard therapy with an acceptable safety profile. This proposal aims to extend these findings to demonstrate that simvastatin reduces incident hepatic decompensation events among cirrhotic patients at high risk for hepatic decompensation. METHODS: We will perform the SACRED Trial (NCT03654053), a phase III, prospective, multi-center, double-blind, randomized clinical trial at 11 VA Medical Centers. Patients with compensated cirrhosis with clinically significant portal hypertension will be stratified based upon the concomitant use of nonselective beta-blockers and randomized to simvastatin 40 mg/day versus placebo for up to 24 months. Patients will be observed for the development of hepatic decompensation (variceal hemorrhage, ascites, encephalopathy), hepatocellular carcinoma, liver-related death, death from any cause, and/or complications of statin therapy. Ancillary studies will evaluate patient-reported outcomes and pharmacogenetic corollaries of safety and/or efficacy. CONCLUSION: Statins have a long track-record of safety and tolerability. This class of medications is generic and inexpensive, and thus, if the hypothesis is proven, there will be few barriers to widespread acceptance of the role of statins to prevent decompensation in patients with compensated cirrhosis. ClinicalTrials.gov Identifier: NCT03654053.

Hepatitis C Virus Cure in Human Immunodeficiency Virus Coinfection Dampens Inflammation and Improves Cognition Through Multiple Mechanisms.

BACKGROUND: Chronic inflammation in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection increases cognitive impairment. With newer, direct-acting antiviral therapies for HCV, our objective was to determine whether chronic inflammation would be decreased and cognition improved with HCV sustained viral response (SVR) in coinfection. METHODS: We studied 4 groups longitudinally: 7 HCV-monoinfected and 12 HIV/HCV-coinfected persons before and after treatment for HCV, 12 HIV-monoinfected persons, and 9 healthy controls. We measured monocyte activation and gene expression, monocyte-derived exosome micro-ribonucleic acid (miRNA) expression, plasma inflammation, and cognitive impairment before and after therapy. RESULTS: Plasma soluble CD163 and neopterin were decreased in HCV mono- and coinfected persons. Blood CD16+ monocytes were decreased in coinfection after HCV treatment. Global deficit score improved 25% in coinfection with the visual learning/memory domain the most improved. Hepatitis C virus SVR decreased monocyte interferon genes MX1, IFI27, and CD169 in coinfection and MX1, LGALS3BP, and TNFAIP6 in HCV monoinfection. Monocyte exosomes from coinfected persons increased in microRNA (miR)-19a, miR-221, and miR-223, all of which were associated with decreasing inflammation and nuclear factor-κB activation. CONCLUSIONS: Hepatitis C virus cure in coinfection brings monocyte activation to levels of HIV alone. Cognitive impairment is significantly improved with cure but not better than HIV infection alone, which strong suggests that cognitive impairment was driven by both HIV and HCV.SummaryHCV cure in HIV coinfection improves monocyte and plasma activation markers and increases cognitive function in the visual learning/memory domain.

Ombitasvir/paritaprevir/ritonavir and dasabuvir±ribavirin for chronic HCV infection in US veterans with psychiatric disorders.

Hepatitis C virus (HCV) infections are more common among US veterans receiving care through Veterans Affairs (VA) Medical Centers than among the general population. Historically, HCV therapies had lower efficacy rates in VA patients, possibly due to common comorbidities such as psychiatric disorders and substance abuse. The direct-acting antivirals ombitasvir/paritaprevir/ritonavir and dasabuvir (OBV/PTV/r+DSV)±ribavirin (RBV) are approved in the US for HCV genotype 1 (GT1)-infected adults with or without cirrhosis. This study prospectively evaluated the safety and efficacy of OBV/PTV/r+DSV±RBV in VA patients with HCV GT1 infection. TOPAZ-VA was a phase 3b, open-label trial. Adult US veterans with HCV GT1 infection, without cirrhosis or with compensated cirrhosis, were eligible for enrollment. Patients with GT1a infection received OBV/PTV/r +DSV+RBV for 12 weeks or 24 weeks (for those with cirrhosis); GT1b-infected patients without cirrhosis received OBV/PTV/r +DSV for 12 weeks; those with cirrhosis received OBV/PTV/r +DSV with RBV. The primary endpoint was sustained virologic response at posttreatment week 12 (SVR12); safety was also assessed. Ninety-nine patients were enrolled at 10 sites from May through November 2015. The majority were male (96%), white (60%), and with GT1a infection (68%); 49% reported ongoing psychiatric disorders. Overall, 94% (93/99) achieved SVR12; three patients had a virologic failure. The most common AEs were fatigue (28%), headache (20%), and nausea (15%); six patients discontinued treatment due to AEs. In US veterans with HCV GT1 infection, OBV/PTV/r +DSV±RBV yielded a 94% overall SVR12 rate and was well tolerated. The presence of psychiatric disorders and/or injection drug use did not impact efficacy.

Preoperative Treatment of Hepatitis C Is Associated With Lower Prosthetic Joint Infection Rates in US Veterans.

BACKGROUND: Hepatitis C virus (HCV) is associated with poorer outcomes in total joint arthroplasty (TJA). Recently, oral direct-acting antivirals (DAAs) have become available for HCV curative treatment. The goal of this study is to determine if HCV may be a modifiable risk factor in TJA by comparing postoperative complications among patients with and without preoperative treatment for HCV. METHODS: US Department of Veterans Affairs dataset of all consecutive primary TJAs performed between 2014 and 2018, when DAAs were available, was retrospectively reviewed. HCV-infected patients were identified using International Classification of Diseases, Ninth and Tenth Revision codes and laboratory values. HCV-infected patients treated prior to TJA with DAA were included in the "treated" group. HCV-infected patients untreated preoperatively were assigned to the "untreated" group. Medical and surgical complications up to 1 year postoperatively were identified using International Classification of Diseases, Ninth and Tenth Revision inpatient and outpatient codes. RESULTS: In total, 42,268 patients underwent TJA at Veterans Affairs Hospitals between 2014 and 2018. About 6.0% (n = 2557) of TJA patients had HCV, 17.3% of whom received HCV treatment preoperatively. When evaluating inpatient and outpatient codes, implant infection rates were statistically lower at 90 days and 1 year postoperatively among HCV-treated patients than among those untreated. Odds ratios (ORs) favor lower infection rates in HCV-treated patients (90-day OR: 3.30, P = .045; 1-year OR: 2.16, P = .07). CONCLUSION: Preoperative HCV treatment was associated with lower periprosthetic infection rates among US veterans undergoing TJA. Further investigation is necessary for definitive conclusions.

Evaluation of an abbreviated screening MRI protocol for patients at risk for hepatocellular carcinoma.

PURPOSE: In this study, we compare an abbreviated screening MRI protocol (aMRI), utilizing only dynamic contrast-enhanced images, to a conventional liver MRI (cMRI) for the characterization of observations in at-risk patients. MATERIALS AND METHODS: 164 consecutive HCC screening MRIs were retrospectively analyzed. Two sets of de-identified image sets were created: one with all acquired sequences including T2- and diffusion-weighted sequences (cMRI), and one with only T1-weighted precontrast and dynamic post-contrast images utilizing an extracellular gadolinium contrast agent (aMRI). Three readers assigned a LI-RADS score based on the lesion with the highest LI-RADS category using the aMRI and cMRI datasets during separate reads. RESULTS: There was no change between the aMRI and cMRI LI-RADS categorization in 93%, 96%, and 96% of cases for readers 1, 2, and 3, respectively. In the majority of the discrepant cases, the score increased from LI-RADS 3 to LI-RADS 4 due to the presence of ancillary features on T2 and DWI. Kappa values for interobserver variability demonstrated fair-to-moderate LI-RADS agreement among the 3 readers. CONCLUSION: There was strong agreement between the abbreviated T1-only MRI protocol and a full liver MRI, with only 5% of cases changing LI-RADS categorization due to the inclusion of T2 and DWI. The estimated time to run this abbreviated MRI is approximately 7-10 min, possibly allowing for a more cost-effective screening MRI than our cMRIs.

Memory T Cell Proliferation before Hepatitis C Virus Therapy Predicts Antiviral Immune Responses and Treatment Success.

The contribution of the host immune system to the efficacy of new anti-hepatitis C virus (HCV) drugs is unclear. We undertook a longitudinal prospective study of 33 individuals with chronic HCV treated with combination pegylated IFN-α, ribavirin, and telaprevir/boceprevir. We characterized innate and adaptive immune cells to determine whether kinetics of the host response could predict sustained virologic response (SVR). We show that characteristics of the host immune system present before treatment were correlated with successful therapy. Augmentation of adaptive immune responses during therapy was more impressive among those achieving SVR. Most importantly, active memory T cell proliferation before therapy predicted SVR and was associated with the magnitude of the HCV-specific responses at week 12 after treatment start. After therapy initiation, the most important correlate of success was minimal monocyte activation, as predicted by previous in vitro work. In addition, subjects achieving SVR had increasing expression of the transcription factor T-bet, a driver of Th1 differentiation and cytotoxic effector cell maturation. These results show that host immune features present before treatment initiation predict SVR and eventual development of a higher frequency of functional virus-specific cells in blood. Such host characteristics may also be required for successful vaccine-mediated protection.

Efficacy of Sofosbuvir Plus Ribavirin in Veterans With Hepatitis C Virus Genotype 2 Infection, Compensated Cirrhosis, and Multiple Comorbidities.

BACKGROUND & AIMS: We conducted a phase 4, open-label study with limited exclusion criteria to evaluate the safety and efficacy of sofosbuvir and ribavirin in veterans with hepatitis C virus genotype 2 infection, and compensated cirrhosis. This population is often excluded from clinical studies. METHODS: We performed a prospective study of treatment-naive (n = 47) and treatment-experienced (n = 19) patients with chronic hepatitis C virus genotype 2 infection and compensated cirrhosis at 15 Department of Veterans Affairs sites. All subjects were given sofosbuvir (400 mg, once daily) plus ribavirin (1000-1200 mg/day) in divided doses for 12 weeks. Patients with major psychiatric diseases or alcohol or substance use disorders were not excluded. The primary endpoint was sustained virologic response 12 weeks after therapy. RESULTS: Fifty-two patients achieved a sustained virologic response 12 weeks after therapy (79%; 95% confidence interval, 67%-88%); 16 of these patients were treatment experienced (84%; 95% confidence interval, 60%-97%) and 36 were treatment naive (77%; 95% confidence interval, 62%-88%). All patients had at least 1 comorbidity. Thirty-five percent had depression, 24% had posttraumatic stress disorder, and 30% had anxiety disorder. In addition, 29% had current substance use. Of the 7 patients (11%) who discontinued the study treatment prematurely, 3 did so because of adverse events. The most common adverse events were fatigue, anemia, nausea, and headache. Serious adverse events occurred in 8 patients. Only 2 of the serious adverse events (anemia and nausea) were considered to be related to study treatment. CONCLUSIONS: In a phase 4 study, 12 weeks treatment with sofosbuvir and ribavirin led to a sustained virologic response 12 weeks after therapy in almost 80% of veterans with hepatitis C virus genotype 2 infection, compensated cirrhosis, and multiple comorbidities, regardless of their treatment history. ClinicalTrials.gov, Number: NCT02128542.

Multiple arterial phase MRI of arterial hypervascular hepatic lesions: improved arterial phase capture and lesion enhancement.

PURPOSE: To establish if triple-phase arterial imaging improves the detection of arterial phase hyperintense lesions based on arterial phase capture, motion artifact degradation, and lesion enhancement when compared to single-phase imaging. MATERIALS AND METHODS: Patients at risk for hepatocellular carcinoma were imaged at 3.0T. Seventy-three consecutive patients with a standard single-phase MRI and eighty-five consecutive patients were imaged using extracellular contrast with triple arterial phase MRI using three sequential accelerated acquisitions of 8 s. Arterial phase capture and image quality were qualitatively categorized. Forty single-phase and forty-four triple-phase studies contained arterially enhancing lesions > 1 cm with washout appearance. The contrast-to-noise ratio (CNR) of the lesions was calculated. We compared the differences in means with Student t-tests and those in arterial phase capture with a Chi squared test with Yates correction. RESULTS: The triple-phase acquisitions captured the early or late arterial phases more frequently than did the single-phase acquisition (99% vs 86%; P value = 0.006). Triple-phase also provided greater number of patients with early or late arterial phase imaging without motion artifact (92% vs 79%, P-value = 0.05). The lesion analysis revealed increased maximum CNR in the triple-phase imaging (704.4) vs. single-phase imaging (517.2), P-value < 0.001. CONCLUSION: Triple-phase acquisition provides more robust arterial phase imaging for hepatic lesions, with increased lesion CNR, compared to standard single-phase arterial phase imaging.

Genetic Variation in the IL-6 and HLA-DQB1 Genes Is Associated with Spontaneous Clearance of Hepatitis C Virus Infection.

Background. Millions of people are infected with hepatitis C virus (HCV) worldwide and 30% spontaneously clear the infection. Reasons for HCV clearance without antiviral treatment are not well understood. Methods. Blood was collected for DNA analysis from patients with chronic HCV infection or evidence of spontaneous clearance. To overcome anticipated limitations of small sample size, primary analyses consisted of a candidate gene analysis of 12 preselected genes based on known association with host immunologic response to HCV infection. To further reduce the impact of multiple testing on power, a single likelihood ratio test was conducted for each gene using all associated SNPs assayed on the Illumina Quad 610/660W chip. Step-down permutation methods were used to adjust for multiple testing in all analyses. Results. Ninety-five and 62 patients with HCV chronic infection or spontaneous clearance, respectively, were included for analysis. HLA-DQB1 (p = 1.76⁎10(-5)) and IL-6 (p = 0.0007) genes were significantly associated with spontaneous HCV clearance. IL-28B was not significantly associated with spontaneous clearance (p = 0.17). Conclusion. Our whole-gene analytic strategy identified a previously unreported association of IL-6 with spontaneous clearance of HCV infection. We also confirmed the finding that HLA-DQB1 is associated with spontaneous resolution of HCV infection.

Improved Survival Among all Interferon-α-Treated Patients in HCV-002, a Veterans Affairs Hepatitis C Cohort of 2211 Patients, Despite Increased Cirrhosis Among Nonresponders.

BACKGROUND: As the era of interferon-alpha (IFN)-based therapy for hepatitis C ends, long-term treatment outcomes are now being evaluated. AIM: To more fully understand the natural history of hepatitis C infection by following a multisite cohort of patients. METHODS: Patients with chronic HCV were prospectively enrolled in 1999-2000 from 11 VA medical centers and followed through retrospective medical record review. RESULTS: A total of 2211 patients were followed for an average of 8.5 years after enrollment. Thirty-one percent of patients received HCV antiviral therapy, 15 % with standard IFN/ribavirin only, 16 % with pegylated IFN/ribavirin, and 26.7 % of treated patients achieved sustained virologic response (SVR). Cirrhosis developed in 25.8 % of patients. Treatment nonresponders had a greater than twofold increase in the hazard of cirrhosis and hepatocellular carcinoma, compared to untreated patients, whereas SVR patients were only marginally protected from cirrhosis. Nearly 6 % developed hepatocellular carcinoma, and 27.1 % died during the follow-up period. Treated patients, regardless of response, had a significant survival benefit compared to untreated patients (HR 0.58, CI 0.46-0.72). Improved survival was also associated with college education, younger age, lower levels of alcohol consumption, and longer duration of medical service follow-up-factors typically associated with treatment eligibility. CONCLUSIONS: As more hepatitis C patients are now being assessed for all-oral combination therapy, these results highlight that patient compliance and limiting harmful behaviors contribute a significant proportion of the survival benefit in treated patients and that the long-term clinical benefits of SVR may be less profound than previously reported.

Examining Hepatitis C Virus Treatment Preference Heterogeneity Using Segmentation Analysis: Treat Now or Defer?

OBJECTIVE: To improve our understanding of patients' treatment preferences for chronic hepatitis C (HCV). METHODS: Subjects with HCV were recruited from 2 VA medical centers. Preferences were ascertained using conjoint analysis. We used segmentation analysis to examine whether there were groups of respondents with similar preferences that were systematically different from the preferences of others. We then measured the associations between treatment preference with subjects' characteristics and their gist principles related to living with HCV and the burden of therapy. RESULTS: A total of 199 subjects participated in this study. The segmentation analysis demonstrated that subjects could be classified into 2 distinct groups. The larger group [group 1, n=118 (59%)] opted for current treatment and the other [group 2, n=81 (41%)] preferred to defer. Patients with cirrhosis were less likely to belong to group 2 (prefer to defer) compared with those without cirrhosis (40.5% vs. 21.3%), whereas subjects self-identifying as African American were more likely to belong to group 2 than white subjects (51.3% vs. 30.5%). Members of group 1 had a more positive overall gist principles related to HCV compared with members of group 2 [mean (SD) score=28.63 (3.06) vs. 26.46 (2.79), P<0.0001]. These gist principles mediated the relationship between race and treatment preference (Sobel test statistic=-2.68, 2-tailed P=0.007). CONCLUSIONS: Our findings indicate that there are groups of HCV patients with similar preferences that are distinct from other groups' preferences. Patients' gist principles related to the significance of having a chronic viral infection and the burdens of therapy are strongly related to their current treatment decisions. These findings help inform how best to initiate and deliver treatment for patients with HCV.

Variation in Treatment Priorities for Chronic Hepatitis C: A Latent Class Analysis.

BACKGROUND: Data describing patients' priorities, or main concerns, are essential to inform important decisions in healthcare, including treatment planning, diagnostic testing, and the development of programs to improve access and delivery of care. To date, the majority of studies performed does not account for variability in patients' priorities, and as a consequence may not effectively inform end users. The objective of this study was to examine the value of segmentation analysis as a method to illustrate variability in priorities for treatment of chronic hepatitis C (HCV). METHODS: We elicited patients' main concerns when considering antiviral therapy for HCV using a Best-Worst Scaling experiment (Case 1) with ten objects. Latent class analysis was used to estimate part-worth utilities and the probability that each respondent belongs to each segment. RESULTS: In the aggregate, subjects (N = 162) had three main concerns: (1) not being cured; (2) experiencing a lot of side effects; and (3) developing viral resistance to therapy. Segmentation into two groups demonstrated that both groups prioritized the likelihood of cure and coping with side effects, but that only one group (n = 78) was concerned about developing viral resistance to therapy, while subjects in the second group (n = 84) prioritized being able to keep up with their responsibilities. Further segmentation revealed distinct clusters of patients with unique priorities. CONCLUSIONS: Patients' priorities vary significantly. Preference studies should consider including methods to determine whether distinct clusters of priorities and/or concerns exist in order to accurately inform end users' decision making.