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Ascites in patients with end-stage liver disease and resultant portal hypertension worsens prognosis and accelerates mortality of up to 40% within one year and 50% within two years. In case of refractory ascites, median survival often does not exceed six months due to the development of complications including spontaneous bacterial peritonitis, hyponatremia and renal failure. Additionally, ascites hinders quality of life (QOL) and its management poses a challenge. Sodium restriction and diuresis are the first line treatment which may be limited by renal failure and/ or hypotension. Diuretic-resistant ascites may necessitate periodic large volume paracentesis which is invasive and provides only temporary relief. Alternatively, refractory ascites can be curtailed with creation of a trans-jugular intrahepatic portosystemic shunt in very selective patients due to the shunt's propensity to exacerbate hepatic encephalopathy and heart failure. The alfapump system, a novel innovation, is an investigational therapy for ascites management. It is a remotely-rechargeable, battery-operated, subcutaneously implantable device that is designed to continuously divert intraperitoneal ascites into the bladder without external components. This invention is aimed to significantly improve the QOL for patients with ascites., (Copyright© South Dakota State Medical Association.)

Background: At present, there are no definitive optimal treatment options for patients with hepatocellular carcinoma (HCC) following first-line treatment failure. To maximize the survival benefit of patients, we compared the combination therapy of regorafenib and programmed death-1 (PD-1) inhibitors with regorafenib monotherapy as a second-line treatment for patients with advanced HCC., Methods: Our multicenter retrospective study evaluated consecutive patients with advanced HCC who received regorafenib plus PD-1 inhibitors or regorafenib alone as a later-line therapy from May 2019 to January 2022. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Efficacy was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria, and safety was assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0., Results: A total of 133 patients were included in the study (regardless of first-line treatment), including 94 who received regorafenib plus PD-1 inhibitors and 39 who received regorafenib. The regorafenib plus PD-1 inhibitors group had a significantly higher ORR (25.53% vs. 10.26%, P=0.015), higher DCR (87.23% vs. 66.67%, P=0.006), and longer PFS (median 9.0 vs. 4.0 months, P<0.0001) than the regorafenib group. Meanwhile, the median OS (mOS) did not differ between the regorafenib plus PD-1 and regorafenib monotherapy groups {mOS, 14.0 months [95% confidence interval (CI), 14.0-16.0 months] vs. 12.0 months (95% CI, 10.0-22.0 months)}. There was no notable difference in the total incidence of treatment-related adverse effects (TRAEs) (71.79% vs. 78.72%, P=0.39) and the incidence of grade 3/4 serious adverse effects (5.13% vs. 18.09%, P=0.19) between the regorafenib monotherapy group and PD-1 inhibitors combination group., Conclusions: Compared with regorafenib alone, regorafenib combined with PD-1 inhibitors therapy increased PFS, ORR but did not improve OS, and can be used an option in second-line HCC therapy, regardless of first-line treatments. Regorafenib combined with PD-1 inhibitors is recommended as early as a second-line therapy to benefit patients. The combination regimen was as safe as regorafenib monotherapy for treatment of HCC in patients with compensated liver disease [Child-Turcotte-Pugh (CTP) A/B]., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-6614/coif). TBC received honoraria from BMS and Bayer for advisory boards and lectures. The other authors have no conflicts of interest to declare., (2023 Annals of Translational Medicine. All rights reserved.)

Background: Circular RNAs (circRNAs) are important for the process of cancer initiation and progression. However, the role of circRNAs in hepatocellular carcinoma (HCC) remains incompletely understood. Therefore, we further explored the expression network of circRNAs in HCC., Methods: Whole-transcriptome microarrays of HCC and paired normal liver tissues were obtained from the Gene Expression Omnibus (GEO) database. The structures of tumor-associated circRNAs were acquired by the Cancer-Specific CircRNA Database (CSCD). StarBase, circBank, and R packages (miRNAtap and multiMiR) were used to predict miRNA targets of circRNAs and downstream molecules of miRNAs. Expression relationships between RNA-RNA interactions were evaluated by data from The Cancer Genome Atlas (TCGA) and GEO databases. ClusterProfiler and DOSE R packages were used for pathway enrichment to explore the biological functions of potential target genes. Finally, a possible circRNA-miRNA-mRNA regulatory network was established based on the competing endogenous RNA (ceRNA) hypothesis., Results: The differentially expressed circRNAs (DECs) were matched with cancer-specific circRNAs in the CSCD database and a screening analysis was performed to obtain 5 cancer-specific circRNAs. A total of 329 possible target miRNAs for 5 cancer-specific circRNAs were predicted by the circBank database, and intersection analysis with differentially expressed miRNAs (DEmiRNAs) revealed that miR-6746-3p and miR-96-5p were the two most suitable miRNAs targets for our selected circRNAs. Further expression verification and prediction of base complementary paired binding sites demonstrated the hsa&#95;circ&#95;0039466/miR-96-5p axis as a crucial pathway in HCC. Next, we found that FOXO1 and LEPR were two potential downstream molecules of the hsa&#95;circ&#95;0039466/miR-96-5p axis through target gene prediction analysis, differential expression analysis, and intersection analysis. The pathway enrichment results suggested that the hsa&#95;circ&#95;0039466/miR-96-5p axis affects the progression and outcome of HCC through the insulin resistance pathway. Finally, through multi-data crossover analysis and data analysis of HCC samples further confirmed the existence of the hsa&#95;circ&#95;0039466/miR-96-5p/FOXO1 ceRNA regulatory network and that the axis was closely related to clinical stage., Conclusions: hsa&#95;circ&#95;0039466 facilitates the expression of FOXO1 by sponging miR-96-5p, and ultimately inhibits tumor progression. These results provide a theoretical basis for further understanding of the gene expression network of HCC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-3147/coif). DR reports consulting fees from Medtronic’s liver ablation division from speaker’s bureau and medical device development unit. The other authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Background: Cancer-associated metabolic reprogramming promotes cancer cell differentiation, growth, and influences the tumor immune microenvironment (TIME) to promote hepatocellular carcinoma (HCC) progression. However, the clinical significance of metabolism-related lncRNA remains largely unexplored., Methods: Based on The Cancer Genome Atlas (TCGA) Liver hepatocellular carcinoma (LIHC) dataset, we identified characteristic prognostic long non-coding RNAs (lncRNAs) and construct metabolism-related lncRNA prognostic signature for HCC. Gender, age, grade, stage and TP53 status were used as covariates were used to assess the prognostic capacity of the characteristic lncRNA signature. Subsequently, the molecular and immune characteristics and drug sensitivity in metabolism-related lncRNA signature defined subgroups were analyzed., Results: We identified 34 metabolism-related lncRNAs significantly associated with the prognosis of HCC (P<0.05). Subsequently, we constructed a multigene signature based on 9 characteristics prognostic lncRNAs and classified HCC patients into high- and low-risk groups based on cutoff values. We found the lncRNA signature [hazard ratio (HR) =3.55 (2.44-5.15), P<0.001] to be significantly associated with survival. The receiver operating characteristic curve (ROC) curves area under the curve (AUC) values for 1-, 3-, and 5-year survival were 0.811, 0.773, and 0.753, respectively. In univariate and multivariate Cox regression analyses, prognostic characteristic lncRNAs were the most crucial prognostic factor besides the stage. The prognostic signature was subsequently validated in the test set. In addition, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) analyses revealed potential biological features and signaling pathways associated with the prognostic signature. We constructed a nomogram including risk groups and clinical parameters (age, gender, grade, and stage). Calibration plots and decision curve analysis (DCA) showed that our nomogram had a good predictive performance. Finally, we found reduced expression of immune-activated cells in the high-risk group., Conclusions: The metabolism-related lncRNA signature is a promising biomarker to distinguish the prognosis and an immune characteristic in HCC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-2194/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Background: The preoperative selection of patients with intermediate-stage hepatocellular carcinoma (HCC) who are likely to have an objective response to first transarterial chemoembolization (TACE) remains challenging., Objective: To develop and validate a clinical-radiomic model (CR model) for preoperatively predicting treatment response to first TACE in patients with intermediate-stage HCC., Methods: A total of 595 patients with intermediate-stage HCC were included in this retrospective study. A tumoral and peritumoral (10 mm) radiomic signature (TPR-signature) was constructed based on 3,404 radiomic features from 4 regions of interest. A predictive CR model based on TPR-signature and clinical factors was developed using multivariate logistic regression. Calibration curves and area under the receiver operating characteristic curves (AUCs) were used to evaluate the model's performance., Results: The final CR model consisted of 5 independent predictors, including TPR-signature ( p < 0.001), AFP ( p = 0.004), Barcelona Clinic Liver Cancer System Stage B (BCLC B) subclassification ( p = 0.01), tumor location ( p = 0.039), and arterial hyperenhancement ( p = 0.050). The internal and external validation results demonstrated the high-performance level of this model, with internal and external AUCs of 0.94 and 0.90, respectively. In addition, the predicted objective response via the CR model was associated with improved survival in the external validation cohort (hazard ratio: 2.43; 95% confidence interval: 1.60-3.69; p < 0.001). The predicted treatment response also allowed for significant discrimination between the Kaplan-Meier curves of each BCLC B subclassification., Conclusions: The CR model had an excellent performance in predicting the first TACE response in patients with intermediate-stage HCC and could provide a robust predictive tool to assist with the selection of patients for TACE., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 by S. Karger AG, Basel.)

Hepatocellular cancer (HCC) is a cancer with an overall poor prognosis and an alarming globally rising incidence. While viral etiology of chronic liver disease and HCC is down-trending, alcohol and excess calorie intake have emerged as major culprits. Alcohol related liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) share similar pathogenetic mechanism of hepatic injury and in promoting development of HCC; yet some genetic and epigenetic features are distinct and may promise clinical utility. Population based intervention are urgently needed to reduce alcohol use and improve metabolic factors such as obesity and diabetes. The goal is to identify at-risk patients, to link these patients to care and to provide effective management of chronic liver disease and HCC. This review focuses on the epidemiology, pathophysiology including genetic and epigenetic altercation as well as clinical aspects of ALD and NAFLD associated HCC., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2019 Translational Gastroenterology and Hepatology. All rights reserved.)

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., (Copyright © 2018. Published by Elsevier Inc.)

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)., (© 2016 by the American Association for the Study of Liver Diseases.)

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., Competing Interests: None of the authors have any conflicts of interest to disclose.

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., Competing Interests: All authors declare that they have no conflict of interest related to the data or interpretation of this study.

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., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Hepatocellular carcinoma (HCC) is a cancer with globally rising incidence. Growing evidence supports associations between metabolic syndrome and diabetes as well as obesity and HCC arising in patients with nonalcoholic fatty liver disease (NAFLD). This constitutes a problem of alarming magnitude given the rising epidemic of these conditions. The role of diabetes seems to be particularly important when associated with obesity or cirrhosis. Excess hepatic iron may be another potential risk factor for the development of NAFLD-associated HCC. In the context of NAFLD, HCC frequently develops in a not-yet cirrhotic liver. As there are no surveillance programs for these patients, diagnosis often occurs at a tumor stage beyond curative options. Clinical, tumor, and patient characteristics in NAFLD-associated HCC differ from other etiologies. Older age and cardiovascular comorbidities may limit treatment options further. The outcome in patients with NAFLD-associated early HCC is excellent and therefore aggressive treatment should be pursued in appropriate patients. Population-based prevention to reduce the culprit-NAFLD-early recognition through targeted surveillance programs in risk-stratified patients and effective treatment of HCC associated with NAFLD are urgently needed. In this review, the authors summarize the epidemiology, risk factors, features, and prevention of NAFLD-associated HCC., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Aims: To determine the efficacy of motivational enhancement therapy (MET) on alcohol use in patients with the hepatitis C virus (HCV) and an alcohol use disorder (AUD)., Design: Randomized, single-blind, controlled trial comparing MET to a control education condition with 6-month follow-up., Setting: Patients were recruited from hepatitis clinics at the Minneapolis, Minnesota and Portland, Oregon Veterans Affairs Health Care Systems, USA., Participants and Intervention: Patients with HCV, an AUD and continued alcohol use (n = 139) were randomized to receive either MET (n = 70) or a control education condition (n = 69) over 3 months., Measurements: Data were self-reported percentage of days abstinent from alcohol and number of standard alcohol drinks per week 6 months after randomization., Findings: At baseline, subjects in MET had 34.98% days abstinent, which increased to 73.15% at 6 months compared to 34.63 and 59.49% for the control condition. Multi-level models examined changes in alcohol consumption between MET and control groups. Results showed a significant increase in percentage of days abstinent overall (F(1120.4)  = 28.04, P < 0.001) and a significant group × time effect (F(1119.9)  = 5.23, P = 0.024) with the MET group showing a greater increase in percentage of days abstinent at 6 months compared with the education control condition. There were no significant differences between groups for drinks per week. The effect size of the MET intervention was moderate (0.45) for percentage of days abstinent., Conclusion: Motivational enhancement therapy (MET) appears to increase the percentage of days abstinent in patients with chronic hepatitis C, alcohol use disorders and ongoing alcohol use., (Published 2014. This article is a U.S. Government work and is in the public domain in the USA.)

Background and Aims: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for patients with chronic hepatitis C virus (HCV) infection. Research suggests that serotonin promotes the development and growth of hepatocellular carcinoma (HCC). We tested the hypothesis whether exposure to SSRIs is associated with an increased risk of HCC in HCV patients., Method: Patients who entered the United States Veterans Affairs (VA) Hepatitis C Clinical Case Registry in 2000 to 2009 were analyzed. During the 8 years of follow-up, 36,192 patients filled at least 1 SSRI prescription. Cases of HCC were identified by diagnosis codes (ICD-9 155.0). Multivariable Cox regression analyses estimated adjusted HCC hazard ratios (HRs) for SSRI-exposed versus SSRI-unexposed subjects and categories of average SSRI doses., Results: The annual incidence of HCC in the VA registry cohort of 109,736 patients was 0.5% and significantly greater in the 8% with cirrhosis at baseline (HR = 5.2; 95% CI, 4.7-5.7). There was no evidence for significant interactions between the effect of SSRI-exposure and cirrhosis. Baseline characteristics of the exposed (n = 36,192) and unexposed (n = 73,544) subjects were similar. The median (interquartile range [IQR]) follow-up period after SSRI-exposure began was 44 (20-74) months with 18 (3-49) months between the first and last prescription. The median average SSRI dose during follow-up expressed as a fraction of initial recommended doses for depression was 0.94 (IQR, 0.5 to 1.3). The risk of HCC was not significantly increased after SSRI exposure (HR = 0.96; 95% CI, 0.87-1.05) or with increasing SSRI doses., Conclusions: Analysis of a large cohort of HCV patients did not support the hypothesis that SSRIs increase the risk of developing HCC., (© Copyright 2014 Physicians Postgraduate Press, Inc.)

Background: Antiviral therapy for the hepatitis C virus (HCV) reduces all-cause and liver-related morbidity and mortality. Few studies are available from populations with multiple medical and psychiatric comorbidities where the impact of successful antiviral therapy might be limited., Aim: The purpose of this study was to determine the effect of sustained virologic response (SVR) on all-cause and liver-related mortality in a cohort of HCV patients treated in an integrated hepatitis/mental health clinic., Methods: This was a retrospective review of all patients who initiated antiviral treatment for chronic HCV between January 1, 1997 and December 31, 2009. Cox regression analysis was used to determine factors involved in all-cause mortality, liver-related events and hepatocellular carcinoma., Results: A total of 536 patients were included in the analysis. Median follow-up was 7.5 years. Liver and non-liver-related mortality occurred in 2.7 and 5.0 % of patients with SVR and in 17.8 and 6.4 % of patients without SVR. In a multivariate analysis, SVR was the only factor associated with reduced all-cause mortality (HR 0.47; 95 % CI 0.26-0.85; p = 0.012) and reduced liver-related events (HR 0.23; 95 % CI 0.08-0.66, p = 0.007). Having stage 4 liver fibrosis increased all-cause mortality (HR 2.50; 95 % CI 1.23-5.08; p = 0.011). Thrombocytopenia at baseline (HR 2.66; 95 % CI 1.22-5.79; p = 0.014) and stage 4 liver fibrosis (HR 4.87; 95 % CI 1.62-14.53; p = 0.005) increased liver-related events., Conclusions: Despite significant medical and psychiatric comorbidities, SVR markedly reduced liver-related outcomes without a significant change in non-liver-related mortality after a median follow-up of 7.5 years.

Objective: The objective was to determine the impact of stimulant use on antiviral treatment for chronic hepatitis C patients in an integrated hepatitis clinic., Methods: A retrospective chart review of 449 consecutive patients seen in an integrated hepatitis clinic that included co-located mental health clinicians was performed. Psychiatric measures included drug use questionnaire, Beck Depression Inventory (BDI), Alcohol Use Disorders Identification Test-Consumption questions (AUDIT-C), urine drug screen and antiviral treatment outcomes. Patients with stimulant use were compared to patients with no drug use, other drug users and an unknown drug use group using χ(2) and analysis of variance tests., Results: Over 15% of hepatitis C patients presenting to the clinic were using stimulants. Stimulant users had higher BDI and AUDIT-C scores. They were more likely to be followed by a co-located mental health clinician than other groups and were just as likely to initiate and finish antiviral therapy., Conclusions: Recent stimulant use is common in hepatitis C patients presenting to a hepatitis clinic. Stimulant users were more depressed and used alcohol to a greater degree than nonusers but were as likely to start antiviral therapy. An integrated mental health/medical care approach appears to be effective in addressing this difficult-to-treat population., (Published by Elsevier Inc.)

Chronic hepatitis C virus (HCV) infection affects approximately 1.3 % of the United States population and 4 % of veterans who use Department of Veterans Affairs medical services. Chronic HCV is the primary cause of cirrhosis, hepatocellular carcinoma (HCC), and end-stage liver disease requiring liver transplantation in the United States. Management of chronic HCV is aimed at halting disease progression, preventing cirrhosis decompensation, reducing the risk of HCC, and treating extrahepatic complications of the infection. As part of a comprehensive HCV management strategy, peginterferon alfa and ribavirin, along with the addition of a hepatitis C protease inhibitor therapy for many genotype 1-infected patients, are the current standard of care. Antiviral therapy should be provided to those individuals who are clinically stable, have moderate liver disease or compensated cirrhosis, and are motivated to pursue therapy. Many patients have comorbid medical and psychiatric conditions, which may affect their adherence to antiviral therapy or worsen while on antiviral therapy. To optimally manage hepatitis C and associated comorbidities, patients benefit from multidisciplinary teams that can provide HCV-specific care and treatment. Sustained virologic response is associated with "cure" of chronic HCV, and results in improved liver disease outcomes and prolonged survival.

In 2005, a professional society issued a level I recommendation to use ultrasonography to screen the 3 million Americans with cirrhosis for hepatocellular carcinoma (HCC) every 6 months. This designation was based on a large randomized trial from China that reported a reduction in HCC deaths from screening in carriers of hepatitis B surface antigen. However, besides the difference in population, this trial did not report all deaths, excluded patients after randomization, and would almost certainly have found no significant difference if the cluster randomization had been accounted for in the analysis. Misplaced confidence in the Chinese trial has led many writers to accept the effectiveness of HCC screening as proven, making it more difficult to conduct the high-quality randomized trials that are needed to ensure optimal patient care.

Six Sigma and Lean Thinking are quality initiatives initially deployed in industry to improve operational efficiency leading to better quality and subsequent cost savings. The financial rationale for embarking on this quality journey is clear; applying it to today's health care remains challenging. The cost of medical care is increasing at an alarming rate; most of these cost increases are attributed to an aging population and technological advances; therefore, largely beyond control. Furthermore, health care cost increases are caused by unnecessary operational inefficiency associated with the direct medical service delivery process. This article describes the challenging journey of implementing Six Sigma methodology at a tertiary care medical center. Many lessons were learned; however, of utmost importance were team approach, "buy in" of the stakeholders, and the willingness of team members to change daily practice and to adapt new and innovative ways how health care can be delivered. Six Sigma incorporated as part of the "company's or hospital's culture" would be most desirable but the learning curve will be steep.

Intrahepatic portal-systemic venous shunt is defined as a communication between the portal and the systemic-venous circulation, measuring more than 1 mm in diameter and at least partially located inside the liver. This is a rare condition, and the etiopathogenesis is unclear. Of the various types, Type I, with patent paraumbilical veins, located in the liver, is commonly encountered in portal hypertension. Other types are much less common. Only 47 cases have been reported in the entire French and English literature. Shunts may be congenital or acquired. This report describes a case of portal-systemic encephalopathy due to a spontaneous large-caliber portal-hepatic venous shunt in the right lobe of the liver confirmed by percutaneous transhepatic portography and hepatic venous angiogram. The treatment with coil embolization was successful, and hepatic encephalopathy resolved postoperatively with normalization of ammonia level. The etiology of the shunt was unclear. Given the age of the patient, the shunt was thought to have developed spontaneously.