Feasibility and acceptability of patient- and clinician-level antithrombotic stewardship interventions to reduce gastrointestinal bleeding risk in patients using warfarin (Anticoagulation with Enhanced Gastrointestinal Safety): a factorial randomized controlled pilot trial.

Background: Overuse of antiplatelet therapy and underuse of gastroprotection contribute to preventable bleeding in patients taking anticoagulants. Objectives: (1) Determine the feasibility of a factorial trial testing patient activation and clinician outreach to reduce gastrointestinal (GI) bleeding risk in patients prescribed warfarin-antiplatelet therapy without proton pump inhibitor gastroprotection and (2) assess intervention acceptability. Methods: Pragmatic 2 × 2 factorial cluster-randomized controlled pilot comparing (1) a patient activation booklet vs usual care and (2) clinician notification vs clinician notification plus nurse facilitation was performed. The primary feasibility outcome was percentage of patients completing a structured telephone assessment after 5 weeks. Exploratory outcomes, including effectiveness, were evaluated using chart review, surveys, and semistructured interviews. Results: Among 47 eligible patients, 35/47 (74.5%; 95% CI, 58.6%-85.7%) met the feasibility outcome. In the subset confirmed to be high risk for upper GI bleeding, 11/29 (37.9%; 95% CI, 16.9%-64.7%) made a medication change, without differences between intervention arms. In interviews, few patients reported reviewing the activation booklet; barriers included underestimating GI bleeding risk, misunderstanding the booklet's purpose, and receiving excessive health communication materials. Clinicians responded to notification messages for 24/47 patients (51.1%; 95% CI, 26.4%-75.4%), which was lower for surgeons than nonsurgeons (22.7% vs 76.0%). Medical specialists but not surgeons viewed clinician notification as acceptable. Conclusion: The proposed trial design and outcome ascertainment strategy were feasible, but the patient activation intervention is unlikely to be effective as designed. While clinician notification appears promising, it may not be acceptable to surgeons, findings which support further refinement and testing of a clinician notification intervention.

Assessment of Population-Based Approach to Direct Oral Anticoagulant Management.

Background: As preferences for oral anticoagulation shift from warfarin to direct oral anticoagulants (DOACs), a new care management model is needed. A population approach leveraging a DOAC Dashboard was implemented to track all patients on a DOAC followed by a physician at an academic medical center. The DOAC Dashboard is a real-time report within the electronic health record (EHR) that identifies patients who require evaluation for DOAC dose/therapy adjustment due to changing renal function, age, weight, indication, and/or significant drug-drug interaction (DDI). Objective: This study aims to describe the initial phase of DOAC Dashboard implementation, to evaluate the effectiveness of interventions, and to assess a multidisciplinary approach to management. Method: Retrospective descriptive study of the DOAC Dashboard from August 22, 2019, to January 20, 2022. Primary outcomes include total number of alerts addressed and interventions needed. Secondary outcome is the proportion of interventions implemented by the prescribing clinician. Result: A total of 10 912 patients were identified by the DOAC Dashboard at baseline. A total of 5038 alerts were identified, with 668 critical alerts, 3337 possible critical alerts, and 1033 other alerts. Pharmacists addressed 1796 alerts during the study period (762 critical alerts and 1034 possible critical). Critical alerts included 62 significant DDI, 379 inappropriate dosing, and 321 others. Of the critical alerts, intervention was needed in 291 cases (38%), with 255 (88%) of proposed interventions implemented. Critical alerts and possible critical alerts not requiring intervention were resolved by data entry. Conclusion: The DOAC Dashboard provides an efficient method of identifying patients on DOACs that require dose adjustments or therapeutic modifications.

Choice and Duration of Anticoagulation for Venous Thromboembolism.

Venous thromboembolism (VTE) is a prevalent medical condition with high morbidity, mortality, and associated costs. Anticoagulation remains the main treatment for VTE, though the decision on when, how, and for how long to administer anticoagulants is increasingly complex. This review highlights the different phases of VTE management, with special circumstances for consideration such as antiphospholipid syndrome, coronary artery disease, cancer-associated thrombus, COVID-19, and future anticoagulation options. Anticoagulation management will continue to be a complex decision, applying evidence-based medicine to individual patients with the hope of maximizing effectiveness while minimizing risks.

Proportion of Patients on Warfarin Therapy Who Are Eligible for Conversion to a Direct Oral Anticoagulant in the Setting of COVID-19.

BACKGROUND: Warfarin, a commonly prescribed anticoagulant, requires frequent lab monitoring. Lab monitoring puts patients at risk of COVID-19 exposure and diverts medical resources away from health care systems. Direct oral anticoagulants (DOACs) do not require routine therapeutic monitoring and are indicated first line for nonvalvular atrial fibrillation (NVAF) stroke prevention and venous thromboembolism (VTE) prevention/treatment. OBJECTIVE: The purpose of the study was to determine the proportion of patients who qualify for DOACs and assess for predictors of qualification. METHODS: This cross-sectional study investigated patients on warfarin managed by Michigan Medicine Anticoagulation Service. Direct oral anticoagulant eligibility criteria were established using apixaban, dabigatran, and rivaroxaban package inserts. Patient eligibility was determined through chart review. The primary outcome was the proportion of patients who qualify for DOACs based on clinical factors. Predictors of DOAC qualification were assessed. RESULTS: This study included 3205 patients and found 51.8% (n = 1661) of patients qualified for DOACs. Qualifying patients were older (71.9 vs 59.4 years, P < 0.0001) with a higher CHA2DS2 VASc (3.7 vs 3.4, P < 0.0007). The primary disqualifying factor was extreme weight, high and low. Accounting for a patient's sex and referral source, age > 65 (odds ratio [OR] = 1.9, P < 0.0001) and NVAF indication (OR = 5.6, P < 0.0001) were significant predictors for DOAC qualification. CONCLUSION AND RELEVANCE: Approximately 52% of patients on warfarin were eligible for DOACs. This presents an opportunity to reduce patient exposure to health care settings and health care utilization in the setting of COVID-19. Increased costs of DOACs need to be assessed.

Development of a multicomponent implementation strategy to reduce upper gastrointestinal bleeding risk in patients using warfarin and antiplatelet therapy, and protocol for a pragmatic multilevel randomized factorial pilot implementation trial.

BACKGROUND: The concomitant use of anticoagulant and antiplatelet medications increases the risk of upper gastrointestinal (GI) bleeding. Two underused evidence-based practices (EBPs) can reduce the risk: de-prescribe unnecessary antiplatelet therapy or initiate a proton pump inhibitor. We describe the development of a multicomponent intervention to increase use of these EBPs in patients treated with warfarin and followed by an anticoagulation monitoring service (AMS), and the design of a pilot pragmatic implementation trial. METHODS: A participatory planning group iteratively used Implementation Mapping and the Multiphase Optimization Strategy to develop implementation strategies and plan the trial. Informed by qualitative interviews with patients and clinicians, we drew on several implementation science theories, as well as self-determination theory, to design interventions. For patients, we developed an activation guide to help patients discuss the EBPs with their clinicians. For clinicians, we developed two electronic health record (EHR)-based interventions: (1) clinician notification (CN) consists of a templated message that identifies a patient as high risk, summarizes the EBPs, and links to a guidance statement on appropriate use of antiplatelet therapy. (2) Clinician notification with nurse facilitation (CN+NF) consists of a similar notification message but includes additional measures by nursing staff to support appropriate and timely decision-making: the nurse performs a chart review to identify any history of vascular disease, embeds indication-specific guidance on antiplatelet therapy in the message, and offers to assist with medication order entry and patient education. We will conduct a pilot factorial cluster- and individual-level randomized controlled trial with a primary objective of evaluating feasibility. Twelve clinicians will be randomized to receive either CN or CN+NF for all their patients managed by the AMS while 50 patients will be individually randomized to receive either the activation guide or usual care. We will explore implementation outcomes using patient and clinician interviews along with EHR review. DISCUSSION: This pilot study will prepare us to conduct a larger optimization study to identify the most potent and resource conscious multicomponent implementation strategy to help AMSs increase the use of best practices for upper GI bleeding risk reduction. TRIAL REGISTRATION: ClinicalTrials.gov NCT05085405 . Registered on October 19, 2021-retrospectively registered.

Management of anticoagulation in patients with human immunodeficiency virus/acquired immunodeficiency virus.

PURPOSE: Limited guidance is available to assist practitioners in managing complex human immunodeficiency virus (HIV) related pharmacotherapy. Management recommendations of oral anticoagulation (warfarin and direct oral anticoagulants [DOACs]) and highly active antiretroviral therapy (HAART) based on drug-drug interactions (DDI) studies and pharmacokinetic (PK) data are provided. METHODS: Search of PubMed, EMBASE, and Google Scholar (01/1985 to 12/2018) using the terms "HIV," "DDI," and names of HAART. PK information and DDI screening were obtained from medication package inserts and drug information resources: Micromedex, Lexicomp, HIV-DDI Checker- University of Liverpool. All English literature on DDI or PK interactions was considered for inclusion. In the absence of data, PK principles were used to predict the likelihood of interactions. RESULTS: No clinically significant DDI are expected to occur between DOACs and nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs), maraviroc, enfuvirtide, or integrase strand inhibitors (INSTIs) that do not include a pharmacologic booster. Potent cytochrome P (CYP) 450 enzyme inhibition by protease inhibitors (PIs) or pharmacologic boosters may lead to higher concentrations of the DOAC and potentially increase the risk of bleeding. CYP450 enzyme induction by non-nucleoside reverse transcriptase inhibitors (NNRTIs) may lower concentrations of DOACs, which may lead to treatment failure. Warfarin DDIs are variable, therefore close monitoring of the INR is recommended. CONCLUSIONS: The potential for DDIs between HAART and oral anticoagulation exists based on PK profiles. Management of these interactions should involve careful selection based on patient characteristics and HAART and anticoagulants with a low potential for DDI should be selected.

Clinical Safety Outcomes in Patients With Nonvalvular Atrial Fibrillation on Rivaroxaban and Diltiazem.

BACKGROUND: It is unknown whether diltiazem, a moderate cytochrome P450 enzyme (CYP3A4) and P-glycoprotein (P-gp) inhibitor, increases the incidence of bleeding events in combination with rivaroxaban, a CYP3A4 and P-gp substrate. OBJECTIVE: To assess major and clinically relevant nonmajor (CRNM) bleeding outcomes in patients with nonvalvular atrial fibrillation (NVAF) on rivaroxaban with concomitant diltiazem in a real-world setting. METHODS: This retrospective case-cohort study included adult patients with NVAF prescribed both rivaroxaban and diltiazem for at least 30 days. Patients were matched 1:1 by age and baseline creatinine clearance (CrCl) to control patients taking rivaroxaban alone. The primary outcome was the composite of major and CRNM bleeding. Additional outcomes included bleeding events resulting in discontinuation of rivaroxaban, time to first bleeding event, and type of first bleed. RESULTS: A total of 143 cases and 143 controls were included. The mean age was 69 years and median baseline CrCl was 87 mL/min. Median follow-up time was 12.4 months for cases and 16.5 months for controls. There was no significant difference in proportion of patients experiencing a major and/or CRNM bleeding event between cases and controls: 23.1% versus 28.0%, respectively; 9 cases and 8 controls permanently discontinued rivaroxaban because of bleeding. Gastrointestinal/rectal bleeding and hematuria were the most frequently reported bleeding events in both groups. Conclusion and Relevance: This is the first study to assess major and CRNM bleeding outcomes in patients with NVAF on rivaroxaban and diltiazem. Diltiazem use was not associated with an increased rate of bleeding events.

Impact of a Guideline for the Management of Antimicrobial/Warfarin Interactions in the Inpatient Setting and Across Transition of Care.

BACKGROUND: Drug-drug interactions (DDIs) with warfarin and antimicrobial agents are a common cause of international normalized ratio (INR) instability, which can affect the risk for bleeding and thrombotic events. OBJECTIVE: The purpose of this study was to assess the impact of a comprehensive guideline for the management of warfarin-antimicrobial DDIs across transitions of care. The guideline emphasizes improving identification of significant antimicrobial-warfarin DDIs during hospitalization, empirical warfarin dose modification based on DDI and baseline INR, patient education, documentation of the DDI, communication with outpatient providers regarding the DDI and anticipated antimicrobial stop date, and warfarin dose adjustment on discontinuation of antimicrobial. METHODS: This retrospective, single-center, quasiexperimental, pre-post study compared end points 3 months before and after guideline implementation. The primary outcome was time within therapeutic range (TTR). RESULTS: The study included 78 preguideline and 31 postguideline patients; baseline characteristics were similar between groups. Implementation of the guideline resulted in greater in-hospital TTR (72% vs 50%, P = 0.04) and improved TTR across transition of care (70% vs 46%, P = 0.01). Documentation of DDI in the pharmacy anticoagulation discharge summary significantly improved in the postguideline group (40% vs 14%, P = 0.02) and numerically improved within the daily pharmacy progress notes (94% vs 82%, P = 0.13). The implementation of the guideline was associated with a nonsignificant, numerical reduction in bleeding events compared with the preguideline group (0 vs 4 events, P = 0.11). CONCLUSION: This single-center approach to optimize the comprehensive management of significant antimicrobial-warfarin DDIs resulted in improved communication with outpatient providers and improved INR TTR.

Anticoagulation in Patients With Cirrhosis: Caught Between a Rock-Liver and a Hard Place.

OBJECTIVE: To review current literature for anticoagulation in patients with cirrhosis and provide a summary of the effects of cirrhosis on the coagulation cascade, therapeutic monitoring through interpretation of antifactor Xa (anti-Xa), activated partial thromboplastin time (aPTT), and international normalized ratio (INR) as well as current prophylaxis and treatment recommendations in cirrhotic patients. METHODS: A systematic electronic literature search was conducted in PubMed using the key termsanticoagulation, warfarin, low-molecular-weight heparin(LMWH),unfractionated heparin(UFH),target-specific oral anticoagulants, deep-vein thrombosis(DVT),pulmonary embolism(PE),portal vein thrombosis(PVT),venous thromboembolism, anti-Xa, activated partial thromboplastin time, anticoagulation therapeutic monitoring, coagulopathy, coagulation cascade, chronic liver disease, cirrhosis, anddecompensated liver disease STUDY SELECTION: Studies written in the English language from January 2000 to December 2015 were considered for this review article. All search results were reviewed, and the relevance of each article was determined by authors independently. CONCLUSIONS: Patients with cirrhosis are at higher risk for both bleeding and thrombosis-related complications. Cirrhosis affects production of both procoagulant and anticoagulant factors, thus resulting in increased INR and aPTT levels and decreased anti-Xa levels. LMWH is the treatment of choice for the prevention and treatment of DVT/PE/PVT in patients with cirrhosis, and monitoring with anti-Xa levels for dose adjustment is not recommended. UFH is an alternative in cirrhotic patients for shorter-term use and in cases of severe renal dysfunction and/or hemodynamic instability. Cirrhotic patients on anticoagulation therapy should be monitored closely for signs and symptoms of bleeding and thrombosis.

Renal Function in Chronic Hepatitis B Patients Treated With Tenofovir Disoproxil Fumarate or Entecavir Monotherapy: A Matched Case-Cohort Study.

BACKGROUND AND AIMS: Tenofovir (TDF)-associated renal dysfunction has been described in various studies of human immunodeficiency virus-infected patients. Our goal is to examine the incidence and magnitude of decrease in renal function in chronic hepatitis B patients treated with TDF. METHODS: We performed a case-cohort study of 103 patients on TDF 300 mg and 103 patients unexposed to TDF (Entecavir) at 4 centers, who were matched for age±10 years, sex, and baseline estimated glomerular filtration rate (eGFR) group. Calculation and evaluation of eGFR were performed with both the Cockcroft-Gault formula and the Modification of Diet in Renal Disease formula. RESULTS: The exposed and unexposed populations were well matched with a similar mean age (44±10 y), proportion of male patients (63.1%), and baseline eGFR groups (86.4% unimpaired). There was no significant difference in the proportion of patients reclassified to a more severe renal classification (RMSRC) or in the proportion of patients with decrease in eGFR of ≥20% in those exposed to TDF versus control. The incidence density for RMSRC was 7.4 cases per 100 patient-years in the exposed group compared with 11.5 cases per 100 patient-years in the unexposed group (95% CI, 0.31-1.34). The relative risk of exposed to unexposed was 0.64 (95% CI, 0.31-1.34). On Cox proportional hazard analysis following adjustment for sex, age, baseline diagnosis hypertension, diabetes, impaired baseline renal function, and cirrhosis, TDF was not a predictor for RMSRC or decrease in eGFR≥20%. CONCLUSIONS: TDF treatment was not an independent predictor for significant deterioration of renal function. Renal function of chronic hepatitis B patients on antiviral therapy should be monitored, especially in those who are older and/or with mildly impaired renal function.

Similar response to entecavir 0.5 and 1.0 mg in treatment-naïve chronic hepatitis B patients: a case-control study.

BACKGROUND AND AIMS: The dose recommendation for entecavir (ETV) is 0.5 mg daily for treatment-naïve chronic hepatitis B (CHB) patients and 1.0 mg daily for lamivudine-refractory patients; however, few data are available for the efficacy of a 1.0-mg daily dose in treatment-naïve CHB patients. Our goal is to examine the treatment outcome of treatment-naïve patients placed on ETV 0.5 mg or ETV 1.0 mg daily through week 48. METHODS: Cases were 40 consecutive hepatitis B e antigen (HBeAg)-positive CHB patients treated with ETV 1.0 mg daily between January 2005 and September 2010, and controls were 40 consecutive CHB patients treated with ETV 0.5 mg daily between January 2005 and September 2010 at three US gastroenterology/liver clinics. Controls were matched for age (±5 years), sex, HBeAg, and baseline hepatitis B virus (HBV) DNA (±0.5 log10 IU/ml). Complete viral suppression was defined as undetectable HBV DNA by polymerase chain reaction (<100 IU/ml). RESULTS: Both groups had similar distributions of age (38 ± 11 years), male patients (55 %), and mean HBV DNA (7.7 ± 1.1 log10 IU/ml). The complete viral suppression rate was similar in both cases and controls through week 24 (15 vs. 15 %, p = 1.00) and week 48 (22 vs. 36 %, p = 0.17). Non-adherence was reported in three patients in the ETV 1.0 mg daily cohort at week 48. CONCLUSIONS: There were no significant differences in the proportion of patients with complete viral suppression in patients treated with ETV 0.5 mg daily or the higher daily dose of 1.0 mg.

Chronic hepatitis B management based on standard guidelines in community primary care and specialty clinics.

BACKGROUND AND AIMS: Prior studies have underlined the need for increased screening and awareness of chronic hepatitis B (CHB), especially in certain high-risk populations. However, few studies have examined the patterns of evaluation and management of CHB between primary care physicians (PCP) and specialists according to commonly-used professional guidelines. Our goal was to examine whether necessary laboratory parameters used to determine disease status and eligibility for antiviral therapy were performed by PCPs and specialists. METHODS: We conducted a retrospective study of 253 treatment-naïve CHB patients who were evaluated by PCP only (n=63) or by specialists (n=190) for CHB at a community multispecialty medical center between March 2007 and June 2009. Criteria for CHB management and treatment eligibility were based on the American Association for the Study of Liver Diseases 2007 guideline and the US Panel 2006 algorithm. Required parameters for optimal evaluation for CHB included hepatitis B e antigen (HBeAg), HBV DNA, and alanine aminotransferase (ALT). Preferred antiviral agents for CHB included pegylated interferon, adefovir, and entecavir. RESULTS: The majority of patients were Asians (90%) and (54%) with a mean age of 43±11.6 years. Compared to PCPs, specialists were more likely to order laboratory testing for ALT (94 vs. 86%, P=0.05), HBeAg (67 vs. 41%, P<0.0001) and HBV DNA (83 vs. 52%, P<0.0001). The proportion of patients having all three laboratory parameters was significantly higher among those evaluated by specialists compared to PCP (62 vs. 33%, P<0.0001). A total of 55 patients were initiated on antiviral treatment (n=47 by specialists and n=6 by PCPs). Lamivudine was prescribed more often by PCPs than specialists (33 vs. 2%, P=0.05). Preferred agents were used 96% of the time by specialists compared to 67% of those treated by PCPs (P=0.05). CONCLUSION: Patients evaluated by specialists for CHB are more likely to undergo more complete laboratory evaluation and, if eligible, are also more likely to be treated with preferred longer-term agents for CHB compared to those evaluated by PCPs only. A collaborative model of care involving both PCP and specialists may further optimize management of patients with CHB.

Prevalence, risk factors, and disease knowledge of chronic hepatitis B infection in Vietnamese Americans in California.

Our goal is to examine the prevalence, risk factors, and disease knowledge of chronic hepatitis B (CHB) among Vietnamese Americans in California. We also examined treatment eligibility and linkage to care among patients who tested positive for CHB. We enrolled 717 subjects from ten different hepatitis B virus (HBV) screening events in five locations from January 2009 to June 2010 in California. HBV status was determined by hepatitis B surface antigen (HBsAg) and antibody. Data were collected by a 36-question survey. A total of 99 patients (13.8 %) had positive HBsAg, especially those aged 31-40 years (23.6 %), and 177 (24.7 %) were still susceptible to HBV infection. A significant proportion of those who were HBsAg positive or still susceptible reported a history of HBV vaccination (10 and 20 %, respectively). Following adjustments for age and sex, significant predictors for HBsAg positivity were lack of healthcare coverage (OR=2.4, p=0.004), having a family history of CHB (OR=2.1, p=0.009), and prior occupational exposure (OR=3.0, p=0.007). Of those who tested positive, 13.3 % met criteria for antiviral therapy, but none had been initiated on treatment. HBV prevalence in Vietnamese Americans in California was high (13.8 %), especially in those between 31 and 40 years of age. Patient disease and treatment knowledge was poor, as were follow-up and management of those found to have CHB and/or have indication for antiviral therapy.

Response to higher dose of entecavir 1.0 mg daily in patients with partial response to entecavir 0.5 mg daily.

BACKGROUND: Despite its high potency against hepatitis B virus (HBV), entecavir (ETV) 0.5 mg daily may not be sufficient to induce complete viral suppression in some patients with very high pretreatment viremia. It is not clear whether ETV 1.0 mg daily would have additive effect in such patients. GOALS: Our goal was to examine virologic outcome of ETV 1.0 mg daily in patients with partial response to ETV 0.5 mg daily. METHODS: We retrospectively studied 31 consecutive treatment-naive patients who were switched to ETV 1.0 mg daily after partial response [reduction of HBV DNA ≥2 log10 IU/mL but with detectable HBV DNA levels (>100 IU/mL) after 24 weeks of therapy or longer] with ETV 0.5 mg daily from January 2005 to January 2010 at 2 clinics. RESULTS: All patients were Asians and 90% had positive hepatitis B e antigen. Mean HBV DNA was 8.04±0.65 log10 IU/mL before therapy and 3.64±0.91 log10 IU/mL at the time of switch. Overall rate of complete viral suppression were 29% (n=9/31) after 24 weeks of ETV 1.0 mg daily and 22% (n=5/23) after 48 weeks. Complete viral suppression after 24 weeks with ETV 1.0 mg daily was significantly higher in patients with lower HBV DNA (<3 log10 IU/mL) at time of switch: 75% versus 5%, P<0.0001. CONCLUSIONS: The majority of patients with partial response to ETV 0.5 mg daily did not achieve complete viral suppression with the higher dose of ETV 1.0 mg daily except those with minimal residual viremia (HBV DNA <3 log10 IU/mL).

Risk factors for hepatocellular carcinoma in patients with chronic liver disease: a case-control study.

The majority of data on risk factors (RFs) for hepatocellular carcinoma (HCC) comes from studies involving populations without underlying liver disease. It is important to evaluate RFs for HCC in patients with chronic liver disease since HCC rarely occurs in those without underlying liver disease. We conducted a hospital-based case-control study of 259 incident HCC cases and 781 controls by convenience sampling between 02/2001 and 12/2009 from the liver clinic at Stanford University Medical Center. The study population was 41% White, 14% Hispanic, 3% African American, 40% Asian American, and 2% other race/ethnicity. RFs were examined through medical records and an in-person questionnaire. Alcohol and tobacco use was calculated by cumulative grams of alcohol or cumulative pack(s) of cigarette consumed over one's lifetime. Diabetes mellitus (DM) was defined by random glucose level of ≥200 mg/dL. RFs were evaluated using multivariate logistic regression. Independent predictors of HCC risk, after mutual adjustment and additional control for alcohol use, etiology of liver diseases, and DM, included age >40 (OR = 8.5 [2.6-28.3]), male gender (OR = 3.5 [2.2-5.8]), presence of cirrhosis (OR = 2.8 [1.6-4.9]), Asian ethnicity (OR = 2.8 [1.8-4.6]), AFP > 50 (OR = 4.2 [2.6-6.8]), and cumulative lifetime tobacco use of >11,000 packs (OR = 1.7 [1.0-2.9]). Heavy prolonged cigarette smoking, but not alcohol use, was a significant independent predictor for HCC in patients with underlying liver disease. Besides older age, male gender, presence of cirrhosis, and elevated AFP, Asian ethnicity and heavy cumulative tobacco use are strong independent predictors of HCC.

Medication nonadherence with long-term management of patients with hepatitis B e antigen-negative chronic hepatitis B.

BACKGROUND AND AIMS: Antiviral treatment responses for patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) are well-defined by data from registration trials but may differ from patients seen in community settings where medical adherence is usually not as strictly monitored. The goal of this study was to examine the long-term outcomes of HBeAg-negative patients in a community clinical setting. METHODS: We performed a cohort study of 189 consecutive treatment-naïve patients with CHB who were treated with either entecavir (ETV) 0.5 mg daily (n=107) or adefovir dipivoxil (ADV) 10 mg daily (n=82) from 2002 to 2009 at two community clinics. RESULTS: All patients were Asians. Both ETV and ADV cohorts had similar median baseline ALT and HBV DNA levels. By year 4, a similar proportion of ETV and ADV patients who remained on monotherapy achieved complete viral suppression (91-96%); however, more patients in the ADV cohort required alternative therapy (27 vs. 5%). No patients in the ETV cohort developed resistance while 18% of the ADV cohort did. Cumulative nonadherence rates were 10 and 12% in ADV and ETV cohorts, respectively. CONCLUSIONS: Failure to monotherapy in a community clinical setting is due to both antiviral resistance and patient nonadherence. Medication nonadherence is likely to be a more important contributor to treatment failure than antiviral resistance, especially with new anti-HBV agents such as ETV and tenofovir.

Adherence to screening for hepatocellular carcinoma among patients with cirrhosis or chronic hepatitis B in a community setting.

BACKGROUND: Screening for hepatocellular carcinoma (HCC) has been shown to improve survival via earlier cancer detection. Although HCC screening is considered standard of care in the USA, little is known of the adherence to this practice, especially in a community setting. AIMS: Our primary goal was to evaluate adherence to HCC screening and to find predictors of screening adherence in a community setting. Our secondary objective was to determine the impact of screening on survival. METHODS: We studied a cohort of 557 consecutive patients at high risk for HCC: patients with cirrhosis and older chronic hepatitis B (CHB) patients without cirrhosis (≥45 years old). Patients initiated screening 1/2001-1/2005 and were monitored ≥12 months to 12/2008 in two community gastroenterology clinics in Northern California. HCC screening was categorized into four groups based on combined frequency of serum alpha-fetoprotein and imaging: optimal, suboptimal, poor, and no screening. RESULTS: About 40.6% of our cohort received poor or no screening. Noncirrhotic CHB patients had worse screening than cirrhotic patients. Multivariate analysis revealed that patients with a greater number of clinical visits per year were 3.4 times more likely to have regular screening than patients with fewer clinical visits per year (P<0.001). There was a trend for association between HCC screening and greater access to curative treatment. CONCLUSION: Since more frequent clinic visits is a strong independent predictor of improved screening adherence, regular routine clinic visits may help improve adherence to HCC screening, which may also lead to improved clinical outcomes.

Prevalence of hepatitis B virus genotype B in Vietnamese patients with chronic hepatitis B.

PURPOSE: Hepatitis B virus (HBV) genotypes can affect treatment response to interferon-based therapy and disease outcomes in patients with chronic hepatitis B (CHB). Little data exist to characterize HBV genotypes in Vietnamese, one of the largest minority groups in the United States and also one with one of the highest CHB and liver cancer disease burdens. The goal of this study was to compare the distribution of HBV genotypes in Vietnamese and Chinese patients. METHODS: We performed a cross-sectional study of 567 consecutive patients of Vietnamese (n = 478) or Chinese (n = 89) descent, with HBV genotype mutation analysis performed between 7/2,005 and 6/2,008 at a community gastroenterology clinic and a university-affiliated liver clinic in the United States. RESULTS: There were no significant differences between the Vietnamese and Chinese groups in mean age (45 and 44 years), gender (58% and 61% male), HBeAg status (64% and 65% negative), median alanine aminotransferase (33 and 41 U/L), and log(10) HBV DNA (4.9 and 5.0 log(10) IU/ml), or the prevalence of precore/basic core promoter mutations (72% and 71%), respectively. Vietnamese patients had a much higher prevalence of HBV genotype B and a lower prevalence of genotype C than Chinese patients: 74% and 25% vs. 55% and 43% (P = 0.001). CONCLUSIONS: Chinese patients with CHB often carry either B or C genotype. Vietnamese patients with CHB mostly have HBV genotype B. Additional studies are needed to further characterize the clinical significance of HBV genotype in the natural history and treatment outcomes of CHB in Vietnamese patients.

Renal dysfunction in chronic hepatitis B patients treated with adefovir dipivoxil.

UNLABELLED: Renal dysfunction has been reported in patients treated with adefovir dipivoxil (ADV); however, its incidence and clinical importance may be underappreciated given the lack of long-term follow-up and data outside of a clinical trial setting. Our goal was to examine the severity and incidence of renal dysfunction in a real-life setting for patients treated with ADV and whose baseline estimated glomerular filtration rate (eGFR) was >50 mL/minute. We performed a cohort study of 290 chronic hepatitis B patients: 145 patients treated with 10 mg ADV and 145 patients unexposed to ADV at two community clinics, who were matched for age (+/-10 years), sex, and baseline eGFR. The exposed and unexposed populations were well-matched with a similar mean age (46-47 years), proportion of male patients (76.5%), baseline serum creatinine (0.97-0.99 mg/dL), and baseline creatinine clearance (85.0-85.4 mL/minute). The incidence density for renal dysfunction defined by treatment termination and/or development of eGFR < or =50 mL/minute was five cases per 100 patient-years in the exposed group compared with 1.36 cases per 100 patient-years in the unexposed group (P = 0.02). The relative risk of exposed to unexposed was 3.68 (95% confidence interval 1.1-19.3). On Cox proportional hazard analysis also inclusive of sex, ADV was a significant predictor of significant renal dysfunction (hazard ratio [HR] 3.94, P = 0.03). There were also significant trends for age >50 years (HR 3.49, P = 0.087), mild renal impairment at baseline (HR 4.49, P = 0.073), and hypertension and/or diabetes mellitus (HR 2.36, P = 0.074). CONCLUSION: ADV is an independent predictor for significant deterioration of renal function. Patients on ADV should be monitored, especially patients who are older, have baseline renal insufficiency, or have hypertension and/or diabetes mellitus.