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BACKGROUND AND AIMS: To examine neighborhood-level disparities in waitlist mortality for adult liver transplantation (LT), we developed novel area-based social determinants of health (SDOH) index using a national transplant database. METHODS: ZIP Codes of individuals listed for or received LT in the Scientific Registry of Transplant Recipients database between June 18, 2013, and May 18, 2019, were linked to 36 American Community Survey (ACS) variables across 5 SDOH domains for index development. A step-wise principal component analysis was used to construct the Liver Outcomes and Equity (LOEq) index. We then examined the association between LOEq quintiles (Q1 = worst and Q5 = best neighborhood SDOH) and waitlist mortality with competing risk regression among listed adults in the study period and acuity circle (AC) era. RESULTS: The final LOEq index consisted of 13 ACS variables. Of 59 298 adults waitlisted for LT, 30% resided in LOEq Q5 compared with only 14% in Q1. Q1 neighborhoods with worse SDOH were disproportionately concentrated in transplant regions with low median Model for End-Stage Liver Disease at transplant (MMAT) and shorter wait times. Five years cumulative incidence of waitlist mortality was 33% in Q1 in high MMAT regions versus 16% in Q5 in low MMAT regions. Despite this allocation advantage, LOEq Q1-Q4 were independently associated with elevated risk of waitlist mortality compared with Q5, with highest increased hazard of waitlist deaths of 19% (95% CI, 11%-26%) in Q1. This disparity persisted in the AC era, with 24% (95% CI, 10%-40%) increased hazard of waitlist deaths for Q1 versus Q5. CONCLUSIONS: Neighborhood SDOH independently predicts waitlist mortality in adult LT.
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Skeletal muscle index (SMI) remains a strong predictor of mortality in cirrhosis patients. However, the extent to which SMI varies by race/ethnicity has not been fully evaluated. Among 317 patients, 55% identified themselves as non-Hispanic White (NHW), 26% Hispanic White (HW), 13% Asian, and 6% Black. There was significant variation in SMI by race/ethnicity; median SMI was lowest in Asian and highest in Black patients. There were significant differences of sarcopenia by race/ethnicity using established SMI cutpoints: 48% NHW, 33% HW, 67% Asian, and 37% Black (P = 0.003). Using these cutpoints, SMI was significantly associated with waitlist mortality only in NHW patients but not in other racial/ethnic groups.
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BACKGROUND & AIMS: Tofacitinib is associated with sustained steroid-free remission in patients with ulcerative colitis (UC), with the lowest effective dose recommended for maintenance therapy. However, there are limited real-world data to guide decisions on the optimal maintenance regimen. We aimed to evaluate predictors and outcomes of disease activity after tofacitinib dose de-escalation in this population. METHODS: Included were adults with moderate-severe UC treated with tofacitinib between June 2012 and January 2022. The primary outcome was evidence of UC disease activity-related events: hospitalization/surgery, corticosteroid initiation, tofacitinib dose increase, or therapy switch. RESULTS: Among 162 patients, 52% continued 10 mg twice daily while 48% underwent dose de-escalation to 5 mg twice daily. Cumulative incidence rates of UC events at 12 months were similar in patients with and without dose de-escalation (56% vs 58%; P = .81). In univariable Cox regression among patients with dose de-escalation, an induction course with 10 mg twice daily for more than 16 weeks was protective of UC events (hazard ratio [HR], 0.37; 95% CI, 0.16-0.85) while ongoing severe disease (Mayo 3) was associated with UC events (HR, 6.41; 95% 95% CI, 2.23-18.44), which remained significant after adjusting for age, sex, duration of induction course, and corticosteroid use at dose de-escalation (HR, 6.05; 95% CI, 2.00-18.35). Twenty-nine percent of patients with UC events had their dose re-escalated to 10 mg twice daily, with only 63% able to recapture clinical response at 12 months. CONCLUSIONS: In this real-world cohort, we observed a 56% cumulative incidence of UC events at 12 months in patients with tofacitinib dose de-escalation. Observed factors associated with UC events after dose de-escalation included induction course for fewer than 16 weeks and active endoscopic disease 6 months after initiation.
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Corticoesteroides , Colitis Ulcerosa , Inhibidores de las Cinasas Janus , Piperidinas , Adulto , Humanos , Corticoesteroides/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Piperidinas/uso terapéutico , Resultado del Tratamiento , Inhibidores de las Cinasas Janus/uso terapéuticoRESUMEN
Frailty, a clinical phenotype of decreased physiological reserve, is a strong determinant of adverse health outcomes in patients with cirrhosis. The only cirrhosis-specific frailty metric is the Liver Frailty Index (LFI), which must be administered in person and may not be feasible for every clinical scenario. We sought to discover candidate serum/plasma protein biomarkers that could differentiate frail from robust patients with cirrhosis. A total of 140 adults with cirrhosis awaiting liver transplantation in the ambulatory setting with LFI assessments and available serum/plasma samples were included. We selected 70 pairs of patients on opposite ends of the frailty spectrum (LFI>4.4 for frail and LFI<3.2 for robust) who were matched by age, sex, etiology, HCC, and Model for End-Stage Liver Disease-Sodium. Twenty-five biomarkers with biologically plausible associations with frailty were analyzed using ELISA by a single laboratory. Conditional logistic regression was used to examine their association with frailty. Of the 25 biomarkers analyzed, we identified 7 proteins that were differentially expressed between frail and robust patients. We observed differences in 6 of the 7 proteins in the expected direction: (a) higher median values in frail versus robust with growth differentiation factor-15 (3682 vs. 2249 pg/mL), IL-6 (17.4 vs. 6.4 pg/mL), TNF-alpha receptor 1 (2062 vs. 1627 pg/mL), leucine-rich alpha-2 glycoprotein (44.0 vs. 38.6 µg/mL), and myostatin (4066 vs. 6006 ng/mL) and (b) lower median values in frail versus robust with alpha-2-Heremans-Schmid glycoprotein (0.11 vs. 0.13 mg/mL) and free total testosterone (1.2 vs. 2.4 ng/mL). These biomarkers represent inflammatory, musculoskeletal, and endocrine/metabolic systems, reflecting the multiple physiological derangements observed in frailty. These data lay the foundation for confirmatory work and development of a laboratory frailty index for patients with cirrhosis to improve diagnosis and prognostication.
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Carcinoma Hepatocelular , Enfermedad Hepática en Estado Terminal , Fragilidad , Neoplasias Hepáticas , Trasplante de Hígado , Adulto , Humanos , Fragilidad/diagnóstico , Fragilidad/etiología , Enfermedad Hepática en Estado Terminal/complicaciones , Carcinoma Hepatocelular/complicaciones , Trasplante de Hígado/efectos adversos , Índice de Severidad de la Enfermedad , Neoplasias Hepáticas/complicaciones , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/cirugía , Biomarcadores , Proteínas Sanguíneas , GlicoproteínasRESUMEN
Sarcopenic obesity is associated with higher rates of morbidity and mortality than seen with either sarcopenia or obesity alone. We aimed to define sarcopenic visceral obesity (SVO) using CT-quantified skeletal muscle index and visceral-to-subcutaneous adipose tissue ratio and to examine its association with waitlist mortality in patients with cirrhosis. Included were 326 adults with cirrhosis awaiting liver transplantation in the ambulatory setting with available abdominal CT within 6 months from enrollment between February 2015 and January 2018. SVO was defined as patients with sarcopenia (skeletal muscle index <50 cm 2 /m 2 in men and <39 cm 2 /m 2 in women) and visceral obesity (visceral-to-subcutaneous adipose tissue ratio ≥1.21 in men and ≥0.48 in women). The percentage who met criteria for sarcopenia, visceral obesity, and SVO were 44%, 29%, and 13%, respectively. Cumulative incidence of waitlist mortality was higher in patients with SVO compared to patients with sarcopenia without visceral obesity or visceral obesity without sarcopenia at 12 months (40% vs. 21% vs. 12%) (overall logrank p =0.003). In univariable Cox regression, SVO was associated with waitlist mortality (HR: 3.42, 95% CI: 1.58-7.39), which remained significant after adjusting for age, sex, diabetes, ascites, encephalopathy, MELDNa, liver frailty index, and different body compositions (HR: 2.64, 95% CI: 1.11-6.30). SVO was associated with increase waitlist mortality in patients with cirrhosis in the ambulatory setting awaiting liver transplantation. Concurrent loss of skeletal muscle and gain of adipose tissue seen in SVO quantified by CT may be a useful and objective measurement to identify patients at risk for suboptimal pretransplant outcomes.
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Trasplante de Hígado , Sarcopenia , Masculino , Adulto , Humanos , Femenino , Sarcopenia/complicaciones , Sarcopenia/diagnóstico por imagen , Sarcopenia/epidemiología , Obesidad Abdominal/complicaciones , Obesidad Abdominal/diagnóstico por imagen , Factores de Riesgo , Trasplante de Hígado/efectos adversos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/cirugía , Músculo Esquelético/diagnóstico por imagen , Obesidad/complicaciones , Tomografía Computarizada por Rayos XRESUMEN
"Sarcopenic obesity" refers to a condition of low muscle mass in the context of obesity, though may be difficult to assess in patients with cirrhosis who are acutely ill. We aimed to define sarcopenic visceral obesity (SVO) using CT-based skeletal muscle index (SMI) and visceral-to-subcutaneous adipose tissue ratio (VSR) to examine its association with post-transplant mortality. We analyzed 116 adult inpatients with cirrhosis who were urgently listed and transplanted between 1/2005 and 12/2017 at 4 North American transplant centers. SVO was defined as patients with sarcopenia (SMI <50 cm2 /m2 in men and <39 cm2 /m2 in women) and visceral obesity (VSR ≥ 1.54 in men and ≥1.37 in women). The percentage who met criteria for sarcopenia, visceral obesity, and SVO were 45%, 42%, and 20%, respectively. Cumulative rates of post-transplant mortality were higher in patients with SVO compared to patients with sarcopenia or visceral obesity alone at 36 months (39% vs. 14% vs. 8%) [logrank p = .01]. In univariable regression, SVO was associated with post-transplant mortality (HR 2.92, 95%CI 1.04-8.23) and remained significant after adjusting for age, sex, diabetes, encephalopathy, hepatocellular carcinoma, and MELD-Na (HR 3.50, 95%CI 1.10-11.15). In conclusion, SVO is associated with increased post-transplant mortality in acutely ill patients with cirrhosis.
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Neoplasias Hepáticas , Trasplante de Hígado , Sarcopenia , Adulto , Femenino , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/cirugía , Neoplasias Hepáticas/patología , Masculino , Músculo Esquelético/patología , Obesidad/complicaciones , Obesidad Abdominal/complicaciones , Estudios Retrospectivos , Factores de Riesgo , Sarcopenia/complicacionesRESUMEN
BACKGROUND AND AIMS: Accumulation of visceral adipose tissue is associated with hepatic inflammation and fibrosis, suggestive of its metabolic and inflammatory properties. We aimed to examine the histologic findings of visceral and subcutaneous adipose tissue and to associate these findings with clinical and radiologic characteristics in patients with cirrhosis. METHODS: Included were 55 adults with cirrhosis who underwent liver transplantation from 3/2017-12/2018 and had an abdominal computed tomography (CT) scan within 6 months prior to transplant. Visceral-to-subcutaneous adipose tissue ratio (VSR) was calculated using visceral (VATI) and subcutaneous adipose tissue index (SATI) quantified by CT at the L3-vertebral level and normalized for height (cm2/m2). VAT (greater omentum), SAT (abdominal wall), and skeletal muscle (rectus abdominis) biopsies were collected at transplant. RESULTS: Majority of patients had VAT inflammation (71%); only one patient (2%) had SAT inflammation. Patients with VAT inflammation had similar median VATI (42 vs 41 cm2/m2), lower median SATI (64 vs 97 cm2/m2), and higher median VSR (0.63 vs 0.37, p = 0.002) than patients without inflammation. In univariable logistic regression, VSR was associated with VAT inflammation (OR 1.47, 95%CI 1.11-1.96); this association remained significant even after adjusting for age, sex, BMI, HCC, or MELD-Na on bivariable analyses. CONCLUSION: In patients with cirrhosis undergoing liver transplantation, histologic VAT inflammation was common, but SAT inflammation was not. Increased VSR was independently associated with VAT inflammation. Given the emerging data demonstrating the prognostic value of VSR, our findings support the value of CT-quantified VSR as a prognostic marker for adverse outcomes in the liver transplant setting.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Tejido Adiposo/patología , Adulto , Carcinoma Hepatocelular/patología , Humanos , Inflamación/metabolismo , Grasa Intraabdominal/diagnóstico por imagen , Grasa Intraabdominal/patología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/cirugía , Neoplasias Hepáticas/patología , Grasa Subcutánea/diagnóstico por imagen , Grasa Subcutánea/metabolismo , Grasa Subcutánea/patologíaAsunto(s)
Adenocarcinoma/tratamiento farmacológico , Catéteres/efectos adversos , Enfermedades Duodenales/etiología , Hemorragia Gastrointestinal/etiología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias del Colon Sigmoide/patología , Adenocarcinoma/secundario , Angiografía , Antimetabolitos Antineoplásicos/administración & dosificación , Enfermedades Duodenales/diagnóstico por imagen , Endoscopía Gastrointestinal , Floxuridina/administración & dosificación , Hemorragia Gastrointestinal/diagnóstico por imagen , Humanos , Bombas de Infusión Implantables , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana EdadRESUMEN
In the United States, non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and associated with higher mortality according to data from earlier National Health and Nutrition Examination Survey (NHANES) 1988-1994. Our goal was to determine the NAFLD prevalence in the recent 1999-2012 NHANES, risk factors for advanced fibrosis (stage 3-4) and mortality. NAFLD was defined as having a United States Fatty Liver Index (USFLI) > 30 in the absence of heavy alcohol use and other known liver diseases. The probability of low/high risk of having advanced fibrosis was determined by the NAFLD Fibrosis Score (NFS). In total, 6000 persons were included; of which, 30.0% had NAFLD and 10.3% of these had advanced fibrosis. Five and eight-year overall mortality in NAFLD subjects with advanced fibrosis was significantly higher than subjects without NAFLD ((18% and 35% vs. 2.6% and 5.5%, respectively) but not NAFLD subjects without advanced fibrosis (1.1% and 2.8%, respectively). NAFLD with advanced fibrosis (but not those without) is an independent predictor for mortality on multivariate analysis (HR = 3.13, 95% CI 1.93-5.08, p<0.001). In conclusion, in this most recent NHANES, NAFLD prevalence remains at 30% with 10.3% of these having advanced fibrosis. NAFLD per se was not a risk factor for increased mortality, but NAFLD with advanced fibrosis was. Mexican American ethnicity was a significant risk factor for NAFLD but not for advanced fibrosis or increased mortality.
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Cirrosis Hepática/epidemiología , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Adulto , Anciano , Femenino , Humanos , Hígado/patología , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/mortalidad , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/mortalidad , Encuestas Nutricionales , Prevalencia , Factores de Riesgo , Índice de Severidad de la Enfermedad , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Given their high efficacy, entecavir (ETV) and tenofovir (TDF), are the recommended first-line therapies for chronic hepatitis B, but it is not clear whether the efficacy reported from pivotal trials is similar to the outcomes seen in routine practice. GOALS: Our goal was to examine the treatment outcomes of antiviral therapy in such setting. PATIENTS AND METHODS: We conducted a retrospective study of 557 consecutive treatment-naive patients who started either ETV (n=443) or TDF (n=114) at 3 US liver clinics between January 2005 and 2012. Primary study endpoint was complete viral suppression (CVS) rate (hepatitis B virus DNA<40 IU/mL). RESULTS: The majority of patients in both ETV and TDF groups were Asians, hepatitis B e antigen (HBeAg) negative, male, and with similar pretreatment alanine aminotransferase and hepatitis B virus DNA levels. Similar proportions of patients in the ETV and TDF groups achieved CVS at 24 months: 87.7% versus 87.0%, respectively. Cumulative rates of virological breakthrough in the ETV and TDF groups were 1.0% versus 4.8% (P=0.26) and 3.7% versus 9.8% (P=0.04) at month 12 and 24, respectively; and all were associated with medication nonadherence. Cumulative rate of medication nonadherence was lower in the ETV than TDF group: 4.6% versus 7.8% at month 12 and 8.9% versus 16.9% at month 24, respectively. CONCLUSIONS: Patients treated with either ETV or TDF achieve a similar rate of CVS at 24 months. The primary contributor to suboptimal response was medication nonadherence. Attention to medication adherence is needed in a routine clinical setting.
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Antivirales/uso terapéutico , Guanina/análogos & derivados , Hepatitis B Crónica/tratamiento farmacológico , Tenofovir/uso terapéutico , Adulto , Antivirales/efectos adversos , Biomarcadores/sangre , ADN Viral/sangre , Farmacorresistencia Viral , Femenino , Guanina/efectos adversos , Guanina/uso terapéutico , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/sangre , Hepatitis B Crónica/diagnóstico , Humanos , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Inducción de Remisión , Estudios Retrospectivos , Tenofovir/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos , Carga ViralRESUMEN
BACKGROUND: Entecavir (ETV) is a first-line, oral antinucleoside agent for the treatment of chronic hepatitis B patients. Despite its high potency, some patients may still be viremic after prolonged therapy with ETV monotherapy. Long-term outcome data comparing maintained ETV monotherapy to alternative therapies in persistently viremic patients are limited. Our goal was to compare complete viral suppression (CVS) rates [hepatitis B DNA (HBV DNA)<40 to 60 IU/mL] with alternative therapies to continued ETV monotherapy in ETV partial responders. METHODS: This is a retrospective cohort study consisting of 86 consecutive treatment-naive, ETV=0.5 mg partial responders (detectable HBV DNA after ≥12 mo on ETV) who maintained ETV=0.5 mg daily (n=29) or switched to either ETV=1.0 mg daily (n=32) or ETV/tenofovir (TDF)=0.5 mg/300 mg (n=25) in 3 US GI/liver clinics from January 2005 to January 2012. Patients were identified by International Classification of Diseases, Ninth Revision query and data were collected by individual chart review. For those who remained on ETV=0.5 mg, comparison at regimen "switch time" was done using values at 12 months from initial ETV therapy. Rates of CVS were evaluated using Kaplan-Meier methods. Multivariate Cox proportional hazard models were used to estimate hazard ratio (HR) relating to potential predictors to the desirable outcomes of CVS. RESULTS: In all therapy groups, the majority of patients were Asian (93.1% to 100.0%), male (64.0% to 68.8%), and hepatitis B e antigen-positive (95.8% to 100.0%) and had similar baseline alanine aminotransferase (ALT) levels. However, baseline HBV DNA (7.0 vs. 7.9 vs. 7.8 log10 IU/mL, P=0.05) and HBV DNA at regimen switch point (2.9 vs. 3.7 vs. 3.6 log10 IU/mL, P=0.0014) were lower in the ETV=0.5 mg cohort compared with those switched to ETV=1.0 mg or ETV/TDF, respectively. The ETV=0.5 mg cohort also had the shortest duration of ETV=0.5 mg therapy before switch (11.8 vs. 13.5 vs. 19.2 mo, P<0.0001). After the switch point, more patients on ETV/TDF achieved CVS compared with those on ETV=0.5 mg or ETV=1.0 mg at month 6 (77.3% vs. 13.8% vs. 9.4%), month 12 (86.4% vs. 40.5% vs. 25.0%), and month 18 (100% vs. 70.2% vs. 33.3%). Compared with the ETV=0.5 mg and ETV=1.0 mg groups, the ETV/TDF group also had higher rates of ALT normalization at month 6 (73.0% vs, 46.4% vs. 63.0%), month 12 (79.7% vs. 69.5% vs. 77.9%), and month 18 (100.0% vs. 69.5% vs. 86.8%), respectively. The multivariate analyses, inclusive of baseline age and treatment duration on initial therapy with ETV=0.5 mg, indicated that the ETV/TDF combination (HR=12.19, P<0.0001) was independently and positively associated with CVS, whereas high HBV DNA levels at baseline (HR=0.77, P=0.02) and at switch point (HR=0.46, P=0.002) were negatively associated with CVS. ETV=1.0 mg dose was not a predictor for CVS compared with ETV=0.5 mg. CONCLUSIONS: Following adjustments for HBV DNA levels and prior treatment duration, ETV/TDF combination therapy independently predicted superior viral suppression and ALT normalization in partial responders to ETV=0.5 mg daily compared with ETV=0.5 mg or ETV=1.0 mg monotherapy. In patients who continued to be viremic after 12 months of ETV=0.5 mg, one third were still viremic after another 18 months on the same therapy. Alternative therapies should be considered for these patients.
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Antivirales/administración & dosificación , Sustitución de Medicamentos , Guanina/análogos & derivados , Virus de la Hepatitis B/efectos de los fármacos , Hepatitis B Crónica/tratamiento farmacológico , Tenofovir/administración & dosificación , Adulto , Biomarcadores/sangre , Distribución de Chi-Cuadrado , ADN Viral/sangre , Esquema de Medicación , Combinación de Medicamentos , Femenino , Guanina/administración & dosificación , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/sangre , Hepatitis B Crónica/diagnóstico , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos , Carga ViralRESUMEN
OBJECTIVES: It is unclear whether patients with chronic hepatitis B with partial response to entecavir (ETV) who have achieved complete viral suppression (CVS) with ETV plus tenofovir (TDF) combination therapy maintain CVS if switched to TDF or ETV. Our goal was to examine virologic outcomes in such patients. METHODS: This is a retrospective cohort study of 57 ETV partial responders with chronic hepatitis B who showed CVS on ETV+TDF combination therapy, who were switched back to monotherapy with either ETV (n=16) or TDF (n=18), or continued on combination therapy (n=23). The majority of patients were Asian (91%) and male (65%), with a mean age of 41±12 years. RESULTS: The patients switched back to ETV had significantly higher rates of virologic breakthrough by 6 months after the switch compared with their TDF counterparts (88 vs. 39%, P=0.004). Patients who remained on ETV+TDF also had virologic breakthrough, due to either confirmed or suspected nonadherence. On multivariate analysis inclusive of age, sex, and hepatitis B virus DNA levels at initiation of combination therapy, ETV (compared with TDF) was found to be an independent predictor for virologic breakthrough (odds ratio 112.7, P=0.03), as well as duration of CVS of less than 12 months while on ETV+TDF (odds ratio 60.2, P=0.03). CONCLUSION: TDF monotherapy, especially in those who have had CVS for at least 12 months on combination therapy, may be considered for some ETV partial responders who have achieved CVS with combination therapy, given the financial advantage and convenience of monotherapy.
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Antivirales/administración & dosificación , Guanina/análogos & derivados , Virus de la Hepatitis B/efectos de los fármacos , Hepatitis B Crónica/tratamiento farmacológico , Tenofovir/administración & dosificación , Adulto , Antivirales/efectos adversos , Biomarcadores/sangre , Distribución de Chi-Cuadrado , ADN Viral/sangre , Esquema de Medicación , Quimioterapia Combinada , Femenino , Guanina/administración & dosificación , Guanina/efectos adversos , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/crecimiento & desarrollo , Hepatitis B Crónica/sangre , Hepatitis B Crónica/diagnóstico , Humanos , Estimación de Kaplan-Meier , Modelos Logísticos , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Tenofovir/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Carga ViralRESUMEN
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.
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Lesión Renal Aguda/inducido químicamente , Antivirales/efectos adversos , Guanina/análogos & derivados , Hepatitis B Crónica/tratamiento farmacológico , Tenofovir/efectos adversos , Lesión Renal Aguda/epidemiología , Adulto , Estudios de Casos y Controles , Femenino , Tasa de Filtración Glomerular , Guanina/efectos adversos , Humanos , Incidencia , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Factores de RiesgoRESUMEN
BACKGROUND: There are limited data analyzing the effectiveness of boceprevir (BOC) or telaprevir (TVR) in combination with pegylated interferon (PEG-IFN) plus ribavirin (RBV) in a real-life patient cohort. AIMS: In clinical trials, patients with chronic hepatitis C (CHC) treated with BOC or TVR plus PEG-IFN and RBV achieved sustained virological response (SVR) rates of 70 %. However, it is not clear whether similar results can be realized in routine practice. Our goal is to examine SVR rates of these triple regimens for CHC in a multicenter real-life patient cohort. METHODS: We retrospectively studied 200 consecutive CHC genotype 1 patients who were initiated on PEG-IFN, RBV, and either TVR (n = 113) or BOC (n = 87) from July 2011 to February 2014 at two US academic liver clinics, a Veterans Affairs liver clinic and a community gastroenterology clinic. RESULTS: Both BOC and TVR treatment groups were similar in regard to comorbidities, BMI, and HCV RNA levels. BOC patients were more likely to have cirrhosis than TVR patients (47 vs. 24 %, P = 0.001). SVR rates were low in both cohorts (40 % for BOC, 53 % for TVR, P = 0.05). On multivariate logistic regression, treatment adherence by the "80/80/80 rule," diagnosis of cirrhosis, and use of erythropoietin were statistically significant predictors for SVR. Of these, treatment adherence was the strongest predictor (OR 4.43, 95 % CI 2.8-6.06, P < 0.001). CONCLUSION: SVR was much lower in a real-life patient cohort than in clinical trials (53 % for TVR and 40 % for BOC, compared to 66-75 % in clinical trials).
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Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Oligopéptidos/uso terapéutico , Prolina/análogos & derivados , Adulto , Anciano , Quimioterapia Combinada , Femenino , Humanos , Interferones/uso terapéutico , Masculino , Cumplimiento de la Medicación/estadística & datos numéricos , Persona de Mediana Edad , Prolina/uso terapéutico , Estudios Retrospectivos , Ribavirina/uso terapéutico , Resultado del Tratamiento , Adulto JovenRESUMEN
GOALS: We aimed to determine the incidence and predictors of recurrent hepatocellular carcinoma (HCC) after partial hepatectomy. BACKGROUND: Liver transplantation is the preferred treatment for selected patients with HCC, but access to donor organs is limited. Partial hepatectomy is another accepted treatment option; however, postoperative recurrence is frequently observed. METHODS: This is a retrospective cohort study of 107 consecutive patients who underwent partial hepatectomy for HCC between January 1993 and February 2011 at a US University Medical Center. Study endpoints were recurrent HCC, death, loss to follow-up, or last visit without HCC. RESULTS: The study cohort was 78% male with a median age of 61 years and 59% Asians. A total of 50 patients developed recurrent HCC (46.7%) after a median follow-up of 12 (1 to 69) months postresection. Recurrent HCC was significantly higher in patients with left-sided resection (41% at year 1, 54% at year 2, 62% at year 3, 81% at year 4, and 90% at year 5) compared with right-sided resection (18% at year 1, 34% at year 2, 36% at year 3, 44% at year 4, and 72% at year 5). In multivariate Cox proportional hazards model also inclusive of anatomic resection and TNM stage 3/4, left-sided resection was significantly associated with increased HCC recurrence (hazard ratio, 2.13; P=0.02; 95% confidence interval, 1.08-4.2) compared with right-sided resection. CONCLUSIONS: HCC recurrence rate is higher among those undergoing left-sided resection: 54% at year 2 and 81% at year 4. Liver transplantation should be considered in patients who are at high risk for recurrence.
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Carcinoma Hepatocelular/cirugía , Hepatectomía/métodos , Neoplasias Hepáticas/cirugía , Recurrencia Local de Neoplasia , Centros Médicos Académicos , Adulto , Anciano , Anciano de 80 o más Años , California , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Distribución de Chi-Cuadrado , Femenino , Hepatectomía/efectos adversos , Hepatectomía/mortalidad , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
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.
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Antivirales/administración & dosificación , Guanina/análogos & derivados , Hepatitis B Crónica/tratamiento farmacológico , Adulto , Femenino , Guanina/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND AND AIMS: The Centers for Disease Control and Prevention recommend screening for hepatitis C virus (HCV) in patients with injection drug use, blood transfusion before 1992, stigmata of liver disease, or born between 1945 and 1965. The purpose of this study was to examine risk factors for HCV acquisition in Asian Americans. METHODS: This was a case-controlled study, with 471 consecutive patients testing positive for anti-HCV between January 2001 and December 2008. Controls included 471 patients with negative HCV matched at a one-to-one ratio for sex, age (±5 years), and ethnicity. RESULTS: For Asian patients, the most common risk factors were blood transfusion and acupuncture or exposure to dirty needles (27 and 20 %, respectively). On multiple logistic regression, potential predictors for a positive anti-HCV test in Asians were acupuncture or exposure to dirty needles (OR = 12.9, P < 0.0001), body tattoo (OR = 12.0, P = 0.001), and history of blood transfusion (OR = 5.7, P < 0.0001). DISCUSSION: Acupuncture and exposure to dirty needles are independent risk factors of HCV infection. Asians coming from endemic areas should be screened for HCV even when commonly-known risk factors for Western patients are not present.
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Asiático , Hepacivirus/aislamiento & purificación , Hepatitis C/epidemiología , Hepatitis C/etiología , Terapia por Acupuntura/efectos adversos , Adulto , Anciano , Anticuerpos Antivirales , Estudios de Casos y Controles , Femenino , Hepatitis C/etnología , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Factores de Riesgo , Tatuaje/efectos adversos , Reacción a la Transfusión , Estados Unidos/epidemiologíaRESUMEN
The incidence of hepatocellular carcinoma (HCC) is higher in Asian Americans than in other ethnicities. While hepatitis B virus (HBV) is common, hepatitis C virus (HCV) is more prevalent in some subgroups. Our goal was to determine the etiology of liver disease associated with HCC in subgroups of Asian Americans. This was an analysis of 510 Asian HCC patients at a US medical center. Patients were identified using ICD9 diagnosis. Multivariate logistic regression was used to study predictors of HCV as the cause of HCC. Patients were Southeast Asian, Chinese, and Korean, with similar gender, age, and foreign-born status. Southeast Asians had a similar proportion of HBV- and HCV-related HCC, while Chinese and Korean patients had a higher proportion of HBV-related HCC. HCC was usually associated with HBV in Chinese and Korean patients, but both HCV and HBV were important associations in Southeast Asians.