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BACKGROUND: During 2009 and 2010, 2 clusters of organ transplant-transmitted Balamuthia mandrillaris, a free-living ameba, were detected by recognition of severe unexpected illness in multiple recipients from the same donor. METHODS: We investigated all recipients and the 2 donors through interview, medical record review, and testing of available specimens retrospectively. Surviving recipients were tested and treated prospectively. RESULTS: In the 2009 cluster of illness, 2 kidney recipients were infected and 1 died. The donor had Balamuthia encephalitis confirmed on autopsy. In the 2010 cluster, the liver and kidney-pancreas recipients developed Balamuthia encephalitis and died. The donor had a clinical syndrome consistent with Balamuthia infection and serologic evidence of infection. In both clusters, the 2 asymptomatic recipients were treated expectantly and survived; 1 asymptomatic recipient in each cluster had serologic evidence of exposure that decreased over time. Both donors had been presumptively diagnosed with other neurologic diseases prior to organ procurement. CONCLUSIONS: Balamuthia can be transmitted through organ transplantation with an observed incubation time of 17-24 days. Clinicians should be aware of Balamuthia as a cause of encephalitis with high rate of fatality, and should notify public health departments and evaluate transplant recipients from donors with signs of possible encephalitis to facilitate early diagnosis and targeted treatment. Organ procurement organizations and transplant centers should be aware of the potential for Balamuthia infection in donors with possible encephalitis and also assess donors carefully for signs of neurologic infection that may have been misdiagnosed as stroke or as noninfectious forms of encephalitis.
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Amebiasis , Balamuthia mandrillaris , Encefalitis , Trasplante de Riñón/efectos adversos , Trasplante de Hígado/efectos adversos , Adulto , Amebiasis/diagnóstico por imagen , Amebiasis/patología , Amebiasis/transmisión , Encéfalo/diagnóstico por imagen , Encéfalo/parasitología , Encéfalo/patología , Niño , Preescolar , Encefalitis/diagnóstico por imagen , Encefalitis/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Donantes de Tejidos , Receptores de TrasplantesRESUMEN
Hepatitis C virus (HCV) infection is the leading reason for liver transplantation and a common cause of hepatocellular carcinoma, the most rapidly increasing cause of cancer-related deaths in the United States. Of the approximately 3 million persons living with HCV infection in the United States, an estimated 38% are linked to care, 11% are treated, and 6% achieve cure. Recent development of highly effective and well-tolerated medications, such as sofosbuvir and simeprevir, to treat chronic HCV infection shows promise in curbing rising HCV-related morbidity and mortality, with the potential to cure >90% of patients. To fully benefit from these new treatments, improvement in linkage to care and treatment is urgently needed.* Lack of provider expertise in HCV treatment and limited access to specialists are well-documented barriers to HCV treatment. In September 2012, CDC funded programs in Utah and Arizona to improve access to primary care providers with the capacity to manage and treat HCV infection. Both programs were modeled on the Extension for Community Healthcare Outcomes (Project ECHO), developed by the University of New Mexico's Health Sciences Center in 2003 to build primary care capacity to treat diseases among rural, underserved populations through videoconferencing and case-based learning in "teleECHO" clinics. To assess the effectiveness of these programs in improving primary care provider capacity and increasing the number of patients initiating treatment, process and patient outcome data for each state program were analyzed. In both states, Project ECHO was successfully implemented, training 66 primary care clinicians, predominantly from rural settings. Nearly all (93%) of the clinicians had no prior experience in care and treatment of HCV infection. In both states combined, 129 (46%) of HCV-infected patients seen in teleECHO clinics received antiviral treatment, more than doubling the proportion of patients expected to receive treatment. These findings demonstrate Project ECHO's ability to expand primary care capacity to treat HCV infection, notably among underserved populations.
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Medicina Basada en la Evidencia , Hepatitis C/terapia , Atención Primaria de Salud/organización & administración , Arizona , Humanos , Modelos Organizacionales , UtahRESUMEN
BACKGROUND/AIM: Thrombocytopenia is a common complication of chronic liver disease. The theory of portal decompression to improve thrombocytopenia due to hypersplenism has led to the study of transjugular intrahepatic portosystemic shunt (TIPS) as a potential therapy. However, there is a paucity of data and results have been conflicting. The aim of this study was to determine whether platelet counts improved in cirrhotic patients after placement of the new polytetrafluoroethylene (PTFE)-coated TIPS, developed in 2004. METHODS: This is a retrospective cohort study of 68 patients with chronic liver disease who underwent a TIPS procedure. One-hundred twenty controls who did not undergo a TIPS procedure were matched on average for age, sex, race, model for end-stage liver disease (MELD) score, and etiology of liver disease. Platelet and hemoglobin counts were recorded during the month prior to the TIPS procedure (baseline) and over the following 12-14 months or until transplanted or death. RESULTS: While platelet counts improved during the first 3 months after TIPS with a mean increase of 11.25 × 103/µL (p = 0.064), they returned to baseline (pre-TIPS) with mean platelets of 91.31 × 103 µL by 12-14 months in comparison with a mild decrease of 10.2 × 103 µL in platelet counts in the control group from 100.4 × 103 µL to 90.2 × 103 (p = 0.119). There was also no significant correlation between platelet counts and etiology of liver disease, age, race, gender, or MELD score. Hemoglobin counts were found to have a small increase of 0.657 g/dL over the 12-14 month course in the TIPS group, which was statistically significant (p = 0.003). CONCLUSION: There does not appear to be a significant improvement in thrombocytopenia in cirrhotic patients after TIPS placement, despite advances in TIPS stents. However, there may be a mild improvement in anemia after TIPS implantation.
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Cirrosis Hepática/complicaciones , Cirrosis Hepática/cirugía , Derivación Portosistémica Intrahepática Transyugular , Stents , Trombocitopenia/etiología , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Politetrafluoroetileno , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND AND AIMS: This article provides expert guidance on the management of pruritus symptoms in patients receiving obeticholic acid (OCA) as treatment for primary biliary cholangitis (PBC). PBC is a chronic, autoimmune cholestatic liver disease that affects intrahepatic bile ducts. If not adequately treated, PBC can lead to cholestasis and end-stage liver disease, which may require transplant. Timely treatment is therefore vital to patient health. Pruritus is a common symptom in patients with PBC. Additionally, the use of OCA to treat PBC can contribute to increased pruritus severity in some patients, adding to patient discomfort, decreasing patient quality of life (QoL), and potentially affecting patient adherence to OCA treatment. METHODS: In May 2018, a group of physician experts from the fields of gastroenterology, hepatology, and psychiatry met to discuss the management of pruritus in OCA-treated patients with PBC. Recognizing the importance of optimizing treatment for PBC, these experts developed recommendations for managing pruritus symptoms in the OCA-treated PBC patient based on their experience in clinical practice. RESULTS: These recommendations include a comprehensive list of management strategies (including over-the-counter, prescription, and alternative therapies), guidance on titration of OCA to minimize pruritus severity, and an algorithm that outlines a practical approach to follow up with patients receiving OCA, to better assess and manage pruritus symptoms. CONCLUSIONS: Pruritus associated with OCA therapy is dose dependent and often manageable, and with the proper education and tools, most pruritus cases can be effectively managed to minimize treatment discontinuation.
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BACKGROUND: Treatment for chronic hepatitis C virus (HCV) has rapidly evolved to simple, well-tolerated, all-oral regimens of direct-acting antivirals (DAAs). There are few data on the epidemiology of HCV in American Indians/Alaska Natives (AI/ANs), a population disproportionately affected by HCV. METHODS: In this retrospective cohort study, all HCV-infected AI/AN patients treated with DAA therapies between January 1, 2014, and February 24, 2016, in specialty clinics or by primary care clinicians participating in Extension for Community Healthcare Outcomes (ECHO) were included. Demographic, clinical, and virologic data on all patients treated for HCV from pretreatment through sustained virologic response at 12 weeks (SVR12) were collected. RESULTS: Two hundred eighty patients were included; 71.1% of patients (n = 199) were infected with genotype 1 (GT1), 18.2% (n = 51) with GT2, and 10.7% with (n = 30) GT3. At baseline, 26.1% (n = 73) patients had cirrhosis and 22.6% (n = 56) had active substance use disorder; eighty-eight percent (n = 232) of patients achieved SVR12. Among the 165 GT1 patients treated with sofosbuvir (SOF)/ledipasvir for 8, 12, and 24 weeks, SVR12 was achieved by 91.5% (n = 54), 92.2% (n = 71), and 100% (n = 13), respectively. Among GT2 patients, 87.2% (n = 34) and 71.4% (n = 5) treated with 12 and 16 weeks of SOF/ribavirin (RBV) achieved SVR12, respectively. Among GT3 patients, 100% (n = 2) and 83.3% (n = 20) treated with 12 and 24 weeks of SOF/RBV achieved SVR12, respectively. SVR12 rates remained high among patients with active substance use disorder. CONCLUSIONS: DAA therapies are highly efficacious in HCV-infected AI/ANs. SVR12 rates remained high among patients with active substance use disorder. More steps must be taken to increase access to treatment for this underserved, vulnerable population.
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OBJECTIVE: To assess the safety and efficacy of a protocol to support management of intracerebral pressure in patients with fulminant liver failure (FLF). DESIGN AND SETTING: A prospective series was conducted between May 2004 and September 2006 at Banner Good Samaritan Medical Center, a 650-bed teaching hospital in Phoenix, Arizona. PATIENTS: We recruited consecutive patients with FLF and stage 3 or 4 encephalopathy. INTERVENTIONS: We placed an intracranial pressure monitor in each patient and employed a protocol to support decisions regarding hemostatic management and prevention and treatment of intracranial hypertension (IHTN). Treatment modalities included hypothermia, hypocarbia, intravenous pentobarbital, intravenous mannitol and vasopressor titration for maintenance of cerebral perfusion pressure. The main outcome measure was survival in transplant candidates. MEASUREMENTS AND MAIN RESULTS: Twenty-two patients entered the study and 21 (95%) had at least one episode of IHTN. Eighty-two discrete episodes of IHTN occurred, and 78 of these (95%) resolved with treatment. Overall survival was 55%. Eleven of 18 (61%) of transplant candidates survived with good neurologic outcome. No patient died from isolated cerebral edema. Three patients had intracranial hemorrhages related to the intracranial pressure monitor. CONCLUSIONS: Protocol-driven management of intracranial pressure in FLF can result in good clinical outcomes in most transplant candidates, even if IHTN occurs.
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Hipnóticos y Sedantes/uso terapéutico , Hipertensión Intracraneal/etiología , Hipertensión Intracraneal/terapia , Fallo Hepático Agudo/complicaciones , Pentobarbital/uso terapéutico , Adolescente , Adulto , Edema Encefálico/etiología , Femenino , Hemostáticos/uso terapéutico , Mortalidad Hospitalaria , Humanos , Hipotermia Inducida , Hipertensión Intracraneal/prevención & control , Presión Intracraneal , Fallo Hepático Agudo/clasificación , Fallo Hepático Agudo/terapia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico/métodos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: The Simeprevir ObservatioNal Effectiveness across practice seTtings (SONET) study evaluated the real-world effectiveness of simeprevir-based treatment for hepatitis C virus (HCV) infection. METHODS: The SONET study was a phase 4, prospective, observational, United States-based study enrolling patients ≥18 years of age with chronic genotype 1 HCV infection. The primary endpoint was the proportion of patients who achieved sustained virologic response 12 weeks after the end of treatment (SVR12), defined as HCV ribonucleic acid undetectable ≥12 weeks after the end of all HCV treatments. RESULTS: Of 315 patients (intent-to-treat [ITT] population), 275 (87.3%) completed the study. Overall, 291 were treated with simeprevir + sofosbuvir, 17 with simeprevir + sofosbuvir + ribavirin, and 7 with simeprevir + peginterferon + ribavirin. The majority of patients were male (63.2%) and white (60.6%); median age was 58 years, 71.7% had genotype/subtype 1a, and 39.4% had cirrhosis. The SVR12 was achieved by 81.2% (255 of 314) of ITT patients (analysis excluded 1 patient who completed the study but was missing SVR12 data); 2 had viral breakthrough and 18 had viral relapse. The SVR12 was achieved by 92.4% (255 of 276) of patients in the modified ITT (mITT) population, which excluded patients who discontinued treatment for nonvirologic reasons before the SVR12 time point or were missing SVR12 assessment data. Among mITT patients, higher SVR12 rates were associated with factors including age ≥65 years, non-Hispanic/Latino ethnicity, and employment status, but not genotype/subtype nor presence of cirrhosis. Simeprevir-based treatment was well tolerated; no serious adverse events were considered related to simeprevir. CONCLUSIONS: In the real-world setting, simeprevir + sofosbuvir treatment was common and 92% of mITT patients achieved SVR12. Simeprevir-based treatment was effective and well tolerated in this cohort, including patients with cirrhosis.
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Chronic hepatitis C (CHC) is associated with multiple extrahepatic manifestations that may impact infected patients. The mechanisms through which these develop include those which are immunological, in which the chronic persistence of virus leads to the circulation of immune complexes (mixed cryoglobulinemia) and other autoimmune phenomena, and those which are virological and related to the extrahepatic tropism of the virus to other tissues. It is estimated that 40-74 % of patients with CHC may develop at least one extrahepatic manifestation during the course of the disease. Extrahepatic syndromes may represent the first signal of hepatitis C infection in some patients. CHC is associated with a four-fold increased risk of insulin resistance and type 2 diabetes mellitus; with cardiovascular disease in 17-37 % of patients; and with increased risk for cerebrovascular deaths, with a biological gradient of cerebrovascular mortality correlating with an increasing serum viral load. CHC is also associated with lymphoproliferative disorders, particularly non-Hodgkin B-cell lymphoma. The kidney is involved in 35-60 % of patients with CHC-associated mixed cryoglobulinemia. The prevalent type of glomerulonephritis associated with mixed cryoglobulinemia is membranoproliferative glomerulonephritis. In 30 % of cases, renal involvement begins with a nephritis syndrome and acute renal failure, while in 55 % there is only mild hematuria, microalbuminuria, proteinuria and renal insufficiency. CHC is also associated with cognitive impairment, especially in memory and concentration. Thus, extrahepatic CHC manifestations involve multiple organ systems outside the liver linked to a variety of comorbidities which may lead to significantly increased mortality from non-liver-related events.
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Hepatitis C/complicaciones , Trastornos Cerebrovasculares/etiología , Crioglobulinemia/etiología , Diabetes Mellitus Tipo 2/etiología , Glomerulonefritis/etiología , Hepacivirus , Hepatitis C/inmunología , Humanos , Resistencia a la Insulina , Trastornos Linfoproliferativos/etiologíaRESUMEN
In this review we critically assess the literature to evaluate the level of risk posed by alcohol as both a primary etiology of hepatocellular carcinoma (HCC) and as a cofactor in its development. Although there have been conflicting findings, based on the body of evidence to date, it appears that the linkage between compensated alcoholic liver disease-associated cirrhosis and HCC is best characterized as medium-high risk, with the risk increasing with age and with quantity and duration of alcohol consumption and is more pronounced in females. While abstinence is the most effective way to reduce HCC risk, its effect seems largely dependent on the severity of liver damage at the point of cessation. Alcohol clearly interacts with other etiologies and conditions including viral hepatitis B and C, hereditary hemochromatosis, diabetes, and obesity to increase the risk for developing HCC, either synergistically or additively. Continued progress in genetics, especially through mechanistic-based and genome-wide association studies may ultimately identify which single nucleotide polymorphisms are risk factors for the onset of alcoholic liver disease and its progression to HCC and lead to the development of targeted therapeutics which may help providers better manage at-risk patients.
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Carcinoma Hepatocelular/etiología , Hepatopatías Alcohólicas/complicaciones , Neoplasias Hepáticas/etiología , Abstinencia de Alcohol , Consumo de Bebidas Alcohólicas , Complicaciones de la Diabetes/etiología , Femenino , Hemocromatosis/complicaciones , Hepatitis B Crónica/complicaciones , Hepatitis C Crónica/complicaciones , Humanos , Cirrosis Hepática Alcohólica/complicaciones , Masculino , Obesidad/complicaciones , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
UNLABELLED: This review summarizes published data on sofosbuvir-based regimens for patients infected with HCV GT1 with a focus on evaluating the optimal and possible durations of treatment. METHODS: PubMed and conference abstract books published between 2011-2015 were searched. RESULTS: HCV treatment has decreased from 24 week regimens to studies done as short as 4 weeks. History of prior treatment or cirrhosis have consistently shown lower SVR12 rates with shorter duration therapies. Low cure rates have been seen in patients within 4 week trials, however, select patients with low fibrosis scores, low HCV VL and HCV GT-1b have moderate cure rates. CONCLUSION: Most patients will require 12-24 weeks of therapy. Further studies are needed to elucidate the predictors of treatment response to short duration therapies and optimal combination of DAAs.
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Antivirales/uso terapéutico , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/tratamiento farmacológico , Cirrosis Hepática/prevención & control , ARN Viral/antagonistas & inhibidores , Sofosbuvir/uso terapéutico , Bencimidazoles/uso terapéutico , Manejo de la Enfermedad , Esquema de Medicación , Quimioterapia Combinada , Fluorenos/uso terapéutico , Genotipo , Hepacivirus/patogenicidad , Hepacivirus/fisiología , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/virología , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/etiología , Cirrosis Hepática/virología , ARN Viral/biosíntesis , Ribavirina/uso terapéutico , Factores de Tiempo , Resultado del Tratamiento , Carga Viral/efectos de los fármacosRESUMEN
All-oral, direct-acting antivirals (DAAs) have significantly improved the efficacy and safety of chronic hepatitis C (CHC) treatment but their effectiveness and safety among patients with chronic kidney disease (CKD) remains poorly understood. Our aim was to assess the efficacy and safety of DAAs for treatment of CKD patients. The National Library of Medicine through PubMed was searched for studies evaluating the efficacy of DAAs for the treatment of patients with CKD stages 4 or 5, as defined by the Kidney Disease Outcomes Quality Initiative guidelines [i.e. glomerular filtration rate (GFR) 15-29 ml/min per 1.73 m2 and GFR <15 ml/min per 1.73 m2, respectively, or hemodialysis or peritoneal dialysis]. Randomized clinical trials (RCTs) and relevant cohort studies were included if they were published in English and included sustained viral response after 12 weeks (SVR12) as a primary or secondary endpoint. After applying inclusion and exclusion criteria, eight studies (one RCT and seven cohort studies) following 350 patients were selected. For patients with CKD stage 4 or 5, ± hemodialysis, the overwhelming majority of DAA regimens were well-tolerated and resulted in SVR12 rates of 90-100%. Most studies were small, with the exception of one RCT evaluating elbasvir and grazoprevir. Overall, treatment of CHC in patients with CKD is highly effective with SVR12 rates similar to those seen in patients without CKD and with acceptable adverse event profiles. In patients with hepatitis C virus (HCV) genotype (GT) 1a, 1b or 4 and Stage 4 or 5 CKD, the best evidence available is for the use of elbasvir and grazoprevir. This combination as well as the combination of paritaprevir/ritonavir/ombitasvir/dasabuvir for HCV GT-1b are recommended. More studies are needed to assess efficacy and adverse effects of DAAs and their impact on CKD patients and to fully elucidate the effect of curing CHC on the natural history and sequelae of renal disease in CHC patients with CKD.
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BACKGROUND: Historically, chronic hepatitis C virus (HCV) treatment was response-guided. Clinical trials with sofosbuvir indicated on-treatment virologic response was not predictive of sustained virologic response (SVR) and hence response-guided therapy (RGT) was abandoned. The purpose of this study is to examine the association between on-treatment 4-week HCV RNA and SVR in patients treated in real-world practice. METHODS: The study is a retrospective analysis of consecutive patients started on treatment with a sofosbuvir-containing regimen, January 1, 2014 through August 20, 2014, for HCV genotype 1-6 infection. Patients were treated by HCV specialists at 6 centers in the Project ECHO (Extension for Community Healthcare Outcomes) HCV Collaborative or in the community by primary care clinicians mentored by HCV specialists through Project ECHO. Patients were included if they were over 18 years, had evidence of chronic HCV, and were started on a sofosbuvir-containing regimen. The aspartate aminotransferase:platelet ratio index (APRI) was used to estimate fibrosis. The main outcome measures were 4-week HCV RNA and SVR. RESULTS: Overall SVR was 82.5 %. At week 4, HCV RNA was detected in 27.4 % of patients. Stepwise multivariable logistic-regression analyses identified APRI > 1.0, male sex, genotype 3, and detectable on treatment 4-week HCV RNA as independent predictors of failure to achieve SVR. CONCLUSIONS: In a real-world setting, a significant proportion of sofosbuvir treated patients have detectable on-treatment 4-week HCV RNA. Detectable on-treatment 4-week HCV RNA is associated with virologic failure. More data are needed to formulate guidance for RGT with newly available HCV therapies.