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.

Diagnostic yield of bidirectional endoscopy for iron deficiency anemia in young patients.

BACKGROUND: While bidirectional endoscopy is recognized as the standard approach for investigating iron deficiency anemia (IDA) in men older than 45 and postmenopausal women, evidence supporting the application of this approach in younger men and premenopausal women is scarce in the absence of symptoms. Our primary aim is to identify the diagnostic yield of bidirectional endoscopy in men younger than 45 and premenopausal women, and describe the clinical characteristics of those with significant endoscopic and pathology-proven findings. METHODS: We performed a retrospective chart review including patients younger than age 45 with IDA who underwent esophagogastroduodenoscopy (EGD) and/or colonoscopy at the Brooklyn VA Hospital between 2009 and 2023. Demographic, clinical, and endoscopic patient data was all collected, stratified, analyzed, and interpreted. RESULTS: In 143 patients younger than age 45 with IDA, 28.6% were found to have positive upper gastrointestinal (GI) findings, of which 70.3% were pathology-proven H. pylori cases. 57.9% of patients reported upper GI symptoms, while 42.9% of patients were asymptomatic. In total, 18.2% of symptomatic patients were found to have clinically significant findings on EGD as compared with 42.9% of asymptomatic patients. Additionally, 9.1% of symptomatic patients were found to have biopsy proven H. pylori-associated gastritis or duodenitis as compared with 33.9% of asymptomatic patients. Of the patients who underwent colonoscopy, 8.3% were found to have lower GI lesions. CONCLUSIONS: We found the diagnostic yield of EGD to be significantly higher than that of colonoscopy in younger IDA patients. Our findings suggest current guidelines are clinically relevant to the young patient cohort. Our study also found asymptomatic IDA patients below age 45 to have a significantly higher diagnostic yield of EGD as compared to symptomatic IDA patients within the same age cohort. The differences in diagnostic yields may be a result of symptomatic patients being more likely to have been prescribed proton pump inhibitors or histamine receptor antagonists prior to endoscopy.

Chronic Liver Disease in the Older Patient-Evaluation and Management.

PURPOSE OF REVIEW: As our population ages, the number of elderly patients with advanced chronic liver disease (ACLD) will increase. In this review we explore risk factors for liver injury, noninvasive assessment of liver disease, complications of cirrhosis, and management of frailty and sarcopenia in the older patient with ACLD. RECENT FINDINGS: Multiple guidelines regarding ACLD have been updated over the past few years. New cutoffs for FIB-4 and NAFLD (MASLD - Metabolic Dysfunction Associated Steatotic Liver Disease) fibrosis scores for elderly patients are being validated. Older patients with MASLD benefit from caloric restriction, exercise programs, and GLP-1 agonists. Patients with ACLD need to be screened for alcohol use disorder with modified scoring systems, and if positive, benefit from referral to chemical dependency programs. Carvedilol and diuretics may safely be used in the elderly for portal hypertension and ascites, respectively, with careful monitoring. Malnutrition, frailty, sarcopenia, and bone mineral disease are common in older patients with ACLD, and early intervention may improve outcomes. Early identification of ACLD in elderly patients allows us to manage risk factors for liver injury, screen for complications, and implement lifestyle and pharmacological therapy to reduce decompensation and death. Future studies may clarify the role of noninvasive imaging in assessing liver fibrosis in the elderly and optimal interventions for nutrition, frailty, sarcopenia, bone health in addition to reevaluation of antibiotic prophylaxis for liver conditions with rising antibiotic resistance.

Effects of Metformin Exposure on Survival in a Large National Cohort of Patients With Diabetes and Cirrhosis.

BACKGROUND & AIMS: Type II diabetes mellitus worsens the prognosis of cirrhosis. Multiple medications including metformin and statins often are co-administered to manage patients with diabetes. The aim of this study was to assess the impact of metformin exposure on mortality, hepatic decompensation, and hepatocellular carcinoma in individuals with diabetes and cirrhosis, controlling for multiple concomitant exposures. METHODS: We performed a retrospective cohort study of patients with cirrhosis diagnosed between January 1, 2008, through June 30, 2016, in the Veterans Health administration. Marginal structural models and propensity-matching approaches were implemented to quantify the treatment effect of metformin in patients with pre-existing diabetes with or without prior metformin exposure. RESULTS: Among 74,984 patients with cirrhosis, diabetes mellitus was present before the diagnosis of cirrhosis in 53.8%, and was diagnosed during follow-up evaluation in 4.8%. Before the diagnosis of cirrhosis, 11,114 patients had active utilization of metformin. In these patients, metformin, statin, and angiotensinogen-converting enzyme inhibitor/angiotensin-2-receptor blocker exposure were associated independently with reduced mortality (metformin hazard ratio, 0.68; 95% CI, 0.61-0.75); metformin was not associated with reduced hepatocellular carcinoma or hepatic decompensation after adjustment for concomitant statin exposure. For patients with diabetes before a diagnosis of cirrhosis but no prior metformin exposure, metformin similarly was associated with reduced mortality (hazard ratio, 0.72; 95% CI, 0.35-0.97), but not with reduced hepatocellular carcinoma or hepatic decompensation. CONCLUSIONS: Metformin use in patients with cirrhosis and diabetes appears safe and is associated independently with reduced overall, but not liver-related, mortality, hepatocellular carcinoma, or decompensation after adjusting for concomitant statin and angiotensinogen-converting enzyme inhibitor/angiotensin-2-receptor blocker exposure.

Continuing Medical Education Questions: September 2021.

Article Title: Initial Evaluation, Long-Term Monitoring, and Hepatocellular Carcinoma Surveillance of Chronic Hepatitis B in Routine Practice: A Nationwide US Study.

Effects of Hypercholesterolemia and Statin Exposure on Survival in a Large National Cohort of Patients With Cirrhosis.

BACKGROUND & AIMS: Concerns related to hepatotoxicity frequently lead to discontinuation or non-initiation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase therapy in patients with cirrhosis despite data supporting statin use. We investigated the independent effects of hyperlipidemia and statin exposure on mortality, hepatic decompensation, and hepatocellular carcinoma development in a large national cohort of patients with cirrhosis. METHODS: We performed a retrospective cohort study of patients with newly diagnosed cirrhosis from January 1, 2008 through June 30, 2016 in the Veterans Health Administration. Subjects were divided into 2 cohorts: 21,921 patients with prior statin exposure (existing users) and 51,023 statin-naïve individuals, of whom 8794 subsequently initiated statin therapy (new initiators) and 44,269 did not (non-initiators). Multivariable Cox proportional hazard models with inverse probability weighting were constructed to assess the effects of time-updating lipid profiles and cumulative exposure to statins on survival and hepatic decompensation. Statin-naïve new initiators were propensity matched with non-initiators to simulate a randomized controlled trial of statin use in cirrhosis. RESULTS: In statin-naïve subjects, every 10-mg/dL increase in baseline total cholesterol was associated with a 3.6% decrease in mortality. In existing users, each year of continued statin exposure was associated with a hazard ratio of 0.920 (95% confidence interval 0.0.897-0.943) for mortality. After risk-set matching, each year of statin exposure among new initiators was associated with a hazard ratio of 0.913 (95% confidence interval 0.890-0.937) for mortality. CONCLUSIONS: In a retrospective cohort study of veterans with a new diagnosis of cirrhosis, we associated hypercholesterolemia with well-preserved hepatic function and decreased mortality. Nonetheless, each cumulative year of statin exposure was associated with an independent 8.0%-8.7% decrease of mortality of patients with cirrhosis of Child-Turcotte-Pugh classes A and B.

Association of Provider Specialty and Multidisciplinary Care With Hepatocellular Carcinoma Treatment and Mortality.

BACKGROUND & AIMS: Little is known about provider and health system factors that affect receipt of active therapy and outcomes of patients with hepatocellular carcinoma (HCC). We investigated patient, provider, and health system factors associated with receipt of active HCC therapy and overall survival. METHODS: We performed a national, retrospective cohort study of all patients diagnosed with HCC from January 1, 2008 through December 31, 2010 (n = 3988) and followed through December 31 2014 who received care through the Veterans Administration (128 centers). Outcomes were receipt of active HCC therapy (liver transplantation, resection, local ablation, transarterial therapy, or sorafenib) and overall survival. RESULTS: In adjusted analyses, receiving care at an academically affiliated Veterans Administration hospital (odds ratio [OR], 1.97; 95% confidence interval [CI], 1.60-2.41) or a multi-specialist evaluation (OR, 1.60; 95% CI, 1.15-2.21), but not review by a multidisciplinary tumor board (OR, 1.19; 95% CI, 0.98-1.46), was associated with a higher likelihood of receiving active HCC therapy. In time-varying Cox proportional hazards models, liver transplantation (hazard ratio [HR], 0.22; 95% CI, 0.16-0.31), liver resection (HR, 0.38; 95% CI, 0.28-0.52), ablative therapy (HR, 0.63; 95% CI, 0.52-0.76), and transarterial therapy (HR, 0.83; 95% CI, 0.74-0.92) were associated with reduced mortality. Subspecialist care by hepatologists (HR, 0.70; 95% CI, 0.63-0.78), medical oncologists (HR, 0.82; 95% CI, 0.74-0.91), or surgeons (HR, 0.79; 95% CI, 0.71-0.89) within 30 days of HCC diagnosis, and review by a multidisciplinary tumor board (HR, 0.83; 95% CI, 0.77-0.90), were associated with reduced mortality. CONCLUSIONS: In a retrospective cohort study of almost 4000 patients with HCC cared for at VA centers, geographic, provider, and system differences in receipt of active HCC therapy are associated with patient survival. Multidisciplinary methods of care delivery for HCC should be prospectively evaluated and standardized to improve access to HCC therapy and optimize outcomes.

Healthcare Costs Related to Treatment of Hepatocellular Carcinoma Among Veterans With Cirrhosis in the United States.

BACKGROUND & AIMS: It is important to quantify medical costs associated with hepatocellular carcinoma (HCC), the incidence of which is rapidly increasing in the United States, for development of rational healthcare policies related to liver cancer surveillance and treatment of chronic liver disease. We aimed to comprehensively quantify healthcare costs for HCC among patients with cirrhosis in an integrated health system and develop a model for predicting costs that is based on clinically relevant variables. METHODS: Three years subsequent to liver cancer diagnosis, costs accrued by patients included in the Veteran's Outcome and Cost Associated with Liver disease cohort were compiled by using the Department of Veterans Affairs Corporate Data Warehouse. The cohort includes all patients with HCC diagnosed in 2008-2010 within the VA with 100% chart confirmation as well as chart abstraction of tumor and clinical characteristics. Cancer cases were matched 1:4 with non-cancer cirrhosis controls on the basis of severity of liver disease, age, and comorbidities to estimate background cirrhosis-related costs. Univariable and multivariable generalized linear models were developed and used to predict cancer-related overall cost. RESULTS: Our analysis included 3188 cases of HCC and 12,722 controls. The mean 3-year total cost of care in HCC patients was $154,688 (standard error, $150,953-$158,422) compared with $69,010 (standard error, $67,344-$70,675) in matched cirrhotic controls, yielding an incremental cost of $85,679; 64.9% of this value reflected increased inpatient costs. In univariable analyses, receipt of transplantation, Barcelona Clinic Liver Cancer (BCLC) stage, liver disease etiology, hospital academic affiliation, use of multidisciplinary tumor board, and identification through surveillance were associated with cancer-related costs. Multivariable generalized linear models incorporating transplantation status, BCLC stage, and multidisciplinary tumor board presentation accurately predicted liver cancer-related costs (Hosmer-Lemeshow goodness of fit; P value ≅ 1.0). CONCLUSIONS: In a model developed to comprehensively quantify healthcare costs for HCC among patients with cirrhosis in an integrated health system, we associated receipt of liver transplantation, BCLC stage, and multidisciplinary tumor board with higher costs. Models that predict total costs on the basis of receipt of liver transplantation were constructed and can be used to model cost-effectiveness of therapies focused on HCC prevention.

Identifying barriers to hepatocellular carcinoma surveillance in a national sample of patients with cirrhosis.

Hepatocellular carcinoma (HCC) is a leading cause of morbidity and mortality in cirrhosis patients. This provides an opportunity to target the highest-risk population, yet surveillance rates in the United States and Europe range from 10% to 40%. The goal of this study was to identify barriers to HCC surveillance, using data from the Veterans Health Administration, the largest provider of liver-related health care in the United States. We included all patients 75 years of age or younger who were diagnosed with cirrhosis from January 1, 2008, until December 31, 2010. The primary outcome was a continuous measure of the percentage of time up-to-date with HCC surveillance (PTUDS) based on abdominal ultrasound (secondary outcomes included computed tomography and magnetic resonance imaging). Among 26,577 patients with cirrhosis (median follow-up = 4.7 years), the mean PTUDS was 17.8 ± 21.5% (ultrasounds) and 23.3 ± 24.1% when any liver imaging modality was included. The strongest predictor of increased PTUDS was the number of visits to a specialist (gastroenterologist/hepatologist and/or infectious diseases) in the first year after cirrhosis diagnosis; the association between visits to a primary care physician and increasing surveillance was very small. Increasing distance to the closest Veterans Administration center was associated with decreased PTUDS. There was an inverse association between ultrasound lead time (difference between the date an ultrasound was ordered and requested exam date) and the odds of it being performed: odds ratio = 0.77, 95% confidence interval 0.72-0.82 when ordered > 180 days ahead of time; odds ratio = 0.90, 95% confidence interval 0.85-0.94 if lead time 91-180 days. CONCLUSIONS: The responsibility for suboptimal surveillance rests with patients, providers, and the overall health care system; several measures can be implemented to potentially increase HCC surveillance, including increasing patient-specialist visits and minimizing appointment lead time. (Hepatology 2017;65:864-874).

Recalibrating the Child-Turcotte-Pugh Score to Improve Prediction of Transplant-Free Survival in Patients with Cirrhosis.

BACKGROUND: The Child-Turcotte-Pugh (CTP) score is a widely used and validated predictor of long-term survival in cirrhosis. However, the cutpoints for stratifying laboratory variables in CTP have never been validated. OBJECTIVE: The objective of this study was to identify evidence-based cutpoints for the CTP laboratory subscores to improve its predictive capacity for transplant-free survival. DESIGN: Retrospective observational study. DATA SOURCE: Using a cohort of 30,897 cirrhotic US Veteran patients with at least 5 years of follow-up, we performed Cox proportional hazard survival model iterations varying the upper and lower cutpoints for INR, total bilirubin and albumin CTP subscores. Cutpoints yielding the highest Harrell's C-statistics for concordance with transplant-free survival were incorporated into a modified CTP (mCTP) score. Validation of the mCTP was performed at multiple time frames within the follow-up period of the cohort and within subsets defined by disease etiology. RESULTS: Modification of CTP cutpoints increased the Harrell's C-statistic for age- and gender-adjusted Cox proportional hazard models from 0.701 ± 0.002 to 0.709 ± 0.002 and the risk ratio per unit change from 1.49 (1.48-1.50) to 1.53 (1.52-1.54). The modified cutpoints showed superiority in predicting 5-year transplant-free survival in various disease etiology subgroups. A mCTP substituting serum creatinine for INR performed superiorly for predicting 5-year transplant-free survival. CONCLUSION: We propose an evidence-based recalibration of CTP score cutpoints that optimizes this model's capacity to predict transplant-free survival in patients with cirrhosis. The CTP score remains the best predictor of 5-year overall and transplant-free survival in patients with cirrhosis.

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.

Development and Performance of an Algorithm to Estimate the Child-Turcotte-Pugh Score From a National Electronic Healthcare Database.

BACKGROUND & METHODS: The Child-Turcotte-Pugh (CTP) score is a widely used and validated predictor of long-term survival in cirrhosis. The CTP score is a composite of 5 subscores, 3 based on objective clinical laboratory values and 2 subjective variables quantifying the severity of ascites and hepatic encephalopathy. To date, no system to quantify CTP score from administrative databases has been validated. The Veterans Outcomes and Costs Associated with Liver Disease study is a multicenter collaborative study to evaluate the outcomes and costs of hepatocellular carcinoma in the U.S. Veterans Health Administration. We developed and validated an algorithm to calculate electronic CTP (eCTP) scores by using data from the Veterans Health Administration Corporate Data Warehouse. METHODS: Multiple algorithms for determining each CTP subscore from International Classification of Diseases version 9, Common Procedural Terminology, pharmacy, and laboratory data were devised and tested in 2 patient cohorts. For each cohort, 6 site investigators (Boston, Bronx, Brooklyn, Philadelphia, Minneapolis, and West Haven VA Medical Centers) were provided cases from which to determine validity of diagnosis, laboratory data, and clinical assessment of ascites and encephalopathy. The optimal algorithm (designated eCTP) was then applied to 30,840 cirrhotic patients alive in the first quarter of 2008 for whom 5-year overall and transplant-free survival data were available. The ability of the eCTP score and other disease severity scores (Charlson-Deyo index, Veterans Aging Cohort Study index, Model for End-Stage Liver Disease score, and Cirrhosis Comorbidity) to predict survival was then assessed by Cox proportional hazards regression. RESULTS: Spearman correlations for administrative and investigator validated laboratory data in the HCC and cirrhotic cohorts, respectively, were 0.85 and 0.92 for bilirubin, 0.92 and 0.87 for albumin, and 0.84 and 0.86 for international normalized ratio. In the HCC cohort, the overall eCTP score matched 96% of patients to within 1 point of the chart-validated CTP score (Spearman correlation, 0.81). In the cirrhosis cohort, 98% were matched to within 1 point of their actual CTP score (Spearman, 0.85). When applied to a cohort of 30,840 patients with cirrhosis, each unit change in eCTP was associated with 39% increase in the relative risk of death or transplantation. The Harrell C statistic for the eCTP (0.678) was numerically higher than those for other disease severity indices for predicting 5-year transplant-free survival. Adding other predictive models to the eCTP resulted in minimal differences in its predictive performance. CONCLUSION: We developed and validated an algorithm to extrapolate an eCTP score from data in a large administrative database with excellent correlation to actual CTP score on chart review. When applied to an administrative database, this algorithm is a highly useful predictor of survival when compared with multiple other published liver disease severity indices.

Distinct features in natural history and outcomes of acute hepatitis C.

BACKGROUND: Acute hepatitis C (AHCV) provides a diagnostic challenge with diverse clinical presentations. GOALS: This study was aimed to examine the clinical and demographic features as well as outcomes in AHCV patients identified from inpatient and outpatient hospital settings. STUDY: Patients with suspected AHCV were recruited from Philadelphia VA Medical Center, Hospital of University of Pennsylvania and Brooklyn VA Medical Center between 2000 and 2010. AHCV was diagnosed by acute serum alanine aminotransferase elevation with anti-hepatitis C virus (HCV) seroconversion, HCV-RNA fluctuations above 1 log, and/or recent high-risk exposure without prior HCV infection, excluding those with human immunodeficiency virus infection. Clinical and therapeutic outcomes were monitored for at least 6 months. RESULTS: A total of 40 AHCV patients were enrolled with a median follow-up of 129 weeks. They were mostly men (68%) and whites (73%) with median age of 43 years, diverse risk factors (33% injection drugs, 20% health care-associated, 3% sexual, and 45% unknown), and wide variations in peak alanine aminotransferase (143 to 3435 U/L) and total bilirubin levels (0.4 to 19.3 mg/dL). Viremia resolved spontaneously in 23% and persisted without therapy in 27%, whereas 50% received interferon α-based therapy with 90% cure (18/20). Distinct clinical scenarios included: (1) wide viremic fluctuations >1 log (65%) and intermittent HCV-RNA negativity; (2) autoantibodies (25% antinuclear antibodies, 69% antismooth muscle antibodies) or autoimmune features; (3) delayed spontaneous viral clearance in 2 patients; (4) rapid cirrhosis progression in 2 patients. CONCLUSIONS: AHCV is a heterogenous disease that requires careful monitoring. The lack of apparent risk factor in high proportion of patients and its diverse presentations warrant diagnostic vigilance.

Association of tattooing and hepatitis C virus infection: a multicenter case-control study.

UNLABELLED: Although injection drug use (IDU) and blood transfusions prior to 1992 are well-accepted risk factors for hepatitis C virus (HCV) infection, many studies that evaluated tattooing as a risk factor for HCV infection did not control for a history of IDU or transfusion prior to 1992. In this large, multicenter, case-control study, we analyzed demographic and HCV risk factor exposure history data from 3,871 patients, including 1,930 with chronic HCV infection (HCV RNA-positive) and 1,941 HCV-negative (HCV antibody-negative) controls. Crude and fully adjusted odds ratios (ORs) of tattoo exposure by multivariate logistic regression in HCV-infected versus controls were determined. As expected, IDU (65.9% versus 17.8%; P < 0.001), blood transfusion prior to 1992 (22.3% versus 11.1%; P < 0.001), and history of having one or more tattoos (OR, 3.81; 95% CI, 3.23-4.49; P < 0.001) were more common in HCV-infected patients than in control subjects. After excluding all patients with a history of ever injecting drugs and those who had a blood transfusion prior to 1992, a total of 1,886 subjects remained for analysis (465 HCV-positive patients and 1,421 controls). Among these individuals without traditional risk factors, HCV-positive patients remained significantly more likely to have a history of one or more tattoos after adjustment for age, sex, and race/ethnicity (OR, 5.17; 95% CI, 3.75-7.11; P < 0.001). CONCLUSION: Tattooing is associated with HCV infection, even among those without traditional HCV risk factors such as IDU and blood transfusion prior to 1992.

Simultaneous portal vein thrombosis and splenic vein thrombosis in a COVID-19 patient: A case report and review of literature.

BACKGROUND: It is well-described that the coronavirus disease 2019 (COVID-19) infection is associated with an increased risk of thrombotic complications. While there have been many cases of pulmonary emboli and deep vein thrombosis in these patients, reports of COVID-19 associated portal vein thrombosis (PVT) have been uncommon. We present a unique case of concomitant PVT and splenic artery thrombosis in a COVID-19 patient. CASE SUMMARY: A 77-year-old-male with no history of liver disease presented with three days of left-sided abdominal pain. One week earlier, the patient was diagnosed with mildly symptomatic COVID-19 and was treated with nirmatrelvir/ritonavir. Physical exam revealed mild right and left lower quadrant tenderness, but was otherwise unremarkable. Significant laboratory findings included white blood cell count 12.5 K/µL, total bilirubin 1.6 mg/dL, aminoaspartate transferase 40 U/L, and alanine aminotransferase 61 U/L. Computed tomography of the abdomen and pelvis revealed acute PVT with thrombus extending from the distal portion of the main portal vein into the right and left branches. Also noted was a thrombus within the distal portion of the splenic artery with resulting splenic infarct. Hypercoagulable workup including prothrombin gene analysis, factor V Leiden, cardiolipin antibody, and JAK2 mutation were all negative. Anticoagulation with enoxaparin was initiated, and the patient's pain improved. He was discharged on apixaban. CONCLUSION: It is quite uncommon for PVT to present simultaneously with an arterial thrombotic occlusion, as in the case of our patient. Unusual thrombotic manifestations are classically linked to hypercoagulable states including malignancy and hereditary and autoimmune disorders. Viral infections such as Epstein-Barr virus, cytomegalovirus, viral hepatitis, and COVID-19 have all been found to increase the risk of splanchnic venous occlusions, including PVT. In our patient, prompt abdominal imaging led to early detection of thrombus, early treatment, and an excellent outcome. This case is unique in that it is the second known case within the literature of simultaneous PVT and splenic artery thrombosis in a COVID-19 patient.

Development and Implementation of Multidisciplinary Liver Tumor Boards in the Veterans Affairs Health Care System: A 10-Year Experience.

In this perspective piece, we summarize the development and implementation of multidisciplinary liver tumor boards across the Veterans Affairs health care system dating back to 2010. Referral to multidisciplinary tumor boards (MDLTB) has been demonstrated to decrease the number of unnecessary invasive procedures, reduce health care costs and maximize patient outcomes. Although the VA is the largest single care provider in the US, there is significant heterogeneity in healthcare delivery. We have shown that receiving care at VA centers with MDLTB is associated with higher odds of receiving active therapy and a 13% reduction in mortality. Access to expert hepatology care appears to be one of the critical benefits of MDLTB resulting in 30% reduction in mortality. Integrated health care systems such as the VA have the unique capability of implementing virtual tumor boards that can easily overcome geographic barriers and standardize care across multiple facilities regardless of their access to hepatology or other disciplines. Significant barriers remain requiring implementation plans. This document serves as a roadmap to establish multidisciplinary tumor boards, including standardization of imaging reports, identifying stake holders who need to be present at tumor board, institution buy-in, and specifics for local, regional and integrated service network tumor boards.

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.

Management of posttransplant hepatitis C infection.

PURPOSE OF REVIEW: Chronic hepatitis C virus (HCV) infection is the leading cause of liver transplantation. Outcome of HCV-associated liver transplantation has been worse than transplantation from other causes. This is mostly related to universal recurrence of HCV in the allograft leading to graft and patient loss or retransplantation. Current antiviral therapies (AVTs) are inadequate and ineffective in the vast majority of the patients with intolerable side effects in most. However, a sustained virologic response (SVR) is associated with improved graft and patient survival. New specifically targeted AVTs for HCV (STAT-C) agents in development will significantly improve the success of AVT. This review focuses on recent data in peritransplant management of HCV with special emphasis on predictors of outcome, diagnosis, prevention and control of reinfection with newer treatments on the horizon. RECENT FINDINGS: In the immediate pretransplant setting, AVT should be considered in select patients to eradicate the virus. Careful donor selection, immunosuppression (IMS) modulation with steroid and calcineurin inhibitor (CNI) minimization, avoidance of T-cell-depleting treatments and acute rejection episodes, and control of metabolic syndrome can improve allograft outcomes and improve the response to AVT. AVT prior to significant damage to the allograft is strongly recommended. SUMMARY: With modified novel IMS protocols, careful donor selection, and AVT prior to significant damage to the allograft we can improve the outcome of posttransplant hepatitis C infection. Albeit there are no available data on new antiviral agents, STAT-Cs will have a significant impact in this setting in the near future.

Hepatitis C virus screening at a Veterans Administration Hospital in New York City.

BACKGROUND: Asymptomatic hepatitis C virus (HCV) infection has the highest prevalence in "baby boomers" born in 1945 through 1965. New York State mandates that all persons born during this period be screened at least once for hepatitis C. LOCAL PROBLEM: Military veteran HCV screening is often missed during primary care visits. METHODS: After baseline screening, provider education with and without an HCV education dashboard of information in the Electronic Medical Record system was used to determine if screening proportions could be improved. The Chi-square and Z-test for independent proportions compared after with before education screening. The odds ratio compared after versus before screening odds. INTERVENTIONS: Two interventions were tested. One was provider education with a 30-minute lecture. The second was the lecture with addition of an HCV education computer dashboard. RESULTS: The Chi-square test and Z-test comparing the month immediately after provider education was significant for increased screening (p < .01) compared with baseline. There was a 2.04-fold (95% confidence interval, 1.31-3.20) greater odds of screening in the month after education. If two or more months went by after education, the effect of education no longer improved screening proportions. Provider education plus the use of HCV education dashboard did not improve screening from baseline to the month immediately after screening (p = .95). CONCLUSION: Provider education significantly improved HCV screening the month immediately after education, then regressed toward baseline. Adding an HCV education dashboard to education did not improve screening. To maintain elevated screening proportions, provider screening education must be reinforced on a frequent basis for sustained effect.