RESUMEN
BACKGROUND: Sustained virological response (SVR) is the primary objective in the treatment of chronic hepatitis C (CHC). Results from a recent clinical trial of patients with previously untreated CHC demonstrate that the combination of peginterferon alpha-2a and ribavirin produces a greater SVR than interferon alpha-2b and ribavirin combination therapy. However, the cost-effectiveness of peginterferon alpha-2a plus ribavirin in the U.S. setting has not been investigated. METHODS: A Markov model was developed to investigate cost-effectiveness in patients with CHC using genotype to guide treatment duration. SVR and disease progression parameters were derived from the clinical trials and epidemiologic studies. The impact of treatment on life expectancy and costs were projected for a lifetime. Patients who had an SVR were assumed to remain virus-free for the rest of their lives. In genotype 1 patients, the SVRs were 46% for peginterferon alpha-2a plus ribavirin and 36% for interferon alpha-2b plus ribavirin. In genotype 2/3 patients, the SVRs were 76% for peginterferon alpha-2a plus ribavirin and 61% for interferon alpha-2b plus ribavirin. Quality of life and costs were based on estimates from the literature. All costs were based on published U.S. medical care costs and were adjusted to 2003 U.S. dollars. Costs and benefits beyond the first year were discounted at 3%. RESULTS: In genotype 1, peginterferon alpha-2a plus ribavirin increases quality-adjusted life expectancy (QALY) by 0.70 yr compared to interferon alpha-2b plus ribavirin, producing a cost-effectiveness ratio of $2,600 per QALY gained. In genotype 2/3 patients, peginterferon alpha-2a plus ribavirin increases QALY by 1.05 yr in comparison to interferon alpha-2b plus ribavirin. Peginterferon alpha-2a combination therapy in patients with HCV genotype 2 or 3 is dominant (more effective and cost saving) compared to interferon alpha-2b plus ribavirin. Results weighted by genotype prevalence (75% genotype 1; 25% genotype 2 or 3) also show that peginterferon alpha-2a plus ribavirin is dominant. Peginterferon alpha-2a and ribavirin remained cost-effective (below $16,500 per QALY gained) under sensitivity analyses on key clinical and cost parameters. CONCLUSION: Peginterferon alpha-2a in combination with ribavirin with duration of therapy based on genotype, is cost-effective compared with conventional interferon alpha-2b in combination with ribavirin when given to treatment-naïve adults with CHC.
Asunto(s)
Antivirales/administración & dosificación , Antivirales/economía , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/economía , Interferón-alfa/administración & dosificación , Interferón-alfa/economía , Polietilenglicoles/administración & dosificación , Polietilenglicoles/economía , Ribavirina/administración & dosificación , Ribavirina/economía , Análisis Costo-Beneficio , Progresión de la Enfermedad , Quimioterapia Combinada , Genotipo , Costos de la Atención en Salud , Hepacivirus/genética , Hepatitis C Crónica/virología , Humanos , Interferón alfa-2 , Años de Vida Ajustados por Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Proteínas Recombinantes , Estados Unidos , Carga ViralRESUMEN
The aim of this study was to examine the role of interventional radiology (IR) in the pretransplant evaluation of potential living-related liver transplantation (LRLT) donors and in the post-transplant management of pediatric liver transplant recipients. Medical records and procedural reports were reviewed of 12 potential donors and five recipients for left lateral segment liver transplants. Procedures performed by the IR Division, clinical indications, and complications were tabulated. Retrospective calculation of radiation exposure to the skin and gonads of the donors and recipients were made. Three-dimensional ultrasound (3D US) was used in all 12 potential donors to screen for the donor with the most appropriately sized left lateral segment. The four optimal donor candidates underwent contrast angiography in order to measure the diameter and screen for variant arterial supply to the left lateral segment. Pretransplantation, one recipient underwent mesenteric angiography with indirect portography to confirm thrombosis of the portal vein and to prove patency of the splenomesenteric venous confluence. Three children underwent LRLT and two children received split livers from cadaveric donors. Thirty-two IR procedures were performed after transplantation (Tx) in the four transplant survivors (one child died following Tx). These IR procedures included: ultrasound-guided percutaneous liver biopsy to evaluate the pathologic cause of liver dysfunction (seven); placement of nasal jejunal feeding tubes (three) or a peripherally inserted central catheter (four) for nutritional and pharmacologic support; large-volume diagnostic and therapeutic paracentesis (two) and thoracentesis (one); percutaneous catheter drainage of symptomatic large pleural effusions (two), large-volume chylous ascites (one) (with later drain removal [one]), and a large biloma (one); percutaneous biliary drain placement (three), biliary drain replacement (two), and balloon cholangioplasty (four) to relieve obstructive jaundice from biliary enteric anatomic strictures; and mesenteric arteriography (one) for suspected thrombosis of the hepatic artery. No complications occurred. Mean skin and gonadal radiation doses were 193 mGy and 27 mGy, respectively, for donors, and 164 mGy and 60 mGy, respectively, for recipients. Even in a program such as this, with a limited series of pediatric liver Txs, it is apparent that IR plays an integral role in optimizing the clinical outcome and use of resources. Specific benefits included: selection of optimal donors; accurate mapping of the donor and occasionally recipient hepatic vasculature; and, most importantly, providing relatively safe minimally invasive procedures for nutritional support and diagnosis and management of untoward events after Tx. When possible, ultrasound guidance should be used to avoid excessive cumulative fluoroscopic exposure to recipients.
Asunto(s)
Trasplante de Hígado , Radiografía Intervencional , Adolescente , Adulto , Niño , Femenino , Fluoroscopía , Humanos , Trasplante de Hígado/métodos , Donadores Vivos , Masculino , Persona de Mediana Edad , Apoyo Nutricional , Selección de Paciente , Dosificación Radioterapéutica , Estudios RetrospectivosRESUMEN
PURPOSE: To determine if three-dimensional ultrasound (3D US), by nature of its ability to simultaneously evaluate structures in three orthogonal planes and to study relationships of devices to tumor(s) and surrounding anatomic structures from any desired orientation, adds significant additional information to real-time 2D US used for placement of devices for ablation of focal liver tumors. MATERIALS AND METHODS: Sixteen patients underwent focal ablation of 23 liver tumors during two intraoperative cryoablation (CA) procedures, three intraoperative radiofrequency ablation (RFA) procedures, 11 percutaneous ethanol injections (PEI) procedures, and six percutaneous RFA procedures. After satisfactory placement of the ablative device(s) with 2D US guidance, 3D US was used to reevaluate adequacy to device position. Information added by 3D US and resultant alterations in device deployment were tabulated. RESULTS: 3D US added information in 20 of 22 (91%) procedures and caused the operator to readjust the number or position of ablative devices in 10 of 22 (45%) of procedures. Specifically, 3D US improved visualization and confident localization of devices in 13 of 22 (59%) procedures, detected unacceptable device placement in 10 of 22 (45%), and determined that 2D US had incorrectly predicted device orientation to a tumor in three of 22 (14%). CONCLUSIONS: Compared to conventional 2D US, 3D US provides additional relationship information for improved placement and optimal distribution of ablative agents for treatment of focal liver malignancy.
Asunto(s)
Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/cirugía , Ablación por Catéter/métodos , Imagenología Tridimensional , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Ultrasonografía Intervencional , Adulto , Anciano , Carcinoma Hepatocelular/patología , Criocirugía , Femenino , Humanos , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
During a 6-and-a-half month period, we identified 10 human immunodeficiency virus (HIV)-infected men who were receiving antiretroviral regimens, including nucleoside analogues, and who developed unexplained reproducible hyperlactatemia in association with either abdominal symptoms or an unaccounted-for elevated alanine aminotransferase level, or both. After careful consideration of the possible etiologies, antiretrovirals were discontinued; lactate levels normalized in all patients. The estimated incidence of this phenomenon in our clinic was 20.9 cases per 1000 person-years of nucleoside analogue treatment. These observations extend the spectrum of the nucleoside analogue-induced lactic acidosis/hepatic steatosis syndrome by the identification of a subtle and perhaps earlier form, which has characteristic symptoms and laboratory abnormalities, and a favorable prognosis on discontinuation of antiretroviral therapy.
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Acidosis Láctica/inducido químicamente , Fármacos Anti-VIH/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Nucleósidos/efectos adversos , Inhibidores de la Transcriptasa Inversa/efectos adversos , Acidosis Láctica/complicaciones , Adulto , Alanina Transaminasa/análisis , Fármacos Anti-VIH/uso terapéutico , Quimioterapia Combinada , Infecciones por VIH/sangre , Infecciones por VIH/fisiopatología , Humanos , Hepatopatías/complicaciones , Masculino , Persona de Mediana Edad , Nucleósidos/uso terapéutico , Inhibidores de la Transcriptasa Inversa/uso terapéuticoRESUMEN
PURPOSE: To evaluate the usefulness of information provided by three-dimensional ultrasound (3D US) and to determine whether 3D US decreased the number of passes required to obtain portal vein (PV) access during creation of transjugular intrahepatic portosystemic shunts (TIPS). MATERIALS AND METHODS: Intermittent 3D US volume acquisitions were obtained during creation of TIPS in 20 patients. Useful information provided by 3D US was tabulated. The number of passes required to achieve PV access was recorded and results were compared retrospectively to 25 patients who underwent TIPS without 3D US. RESULTS: 3D US documented that the operator's opinion of which hepatic vein had been selected was incorrect in nine patients (45%), detected unfavorable PV anatomy that required modification of equipment or technique in seven patients (35%), permitted estimation of the trajectory required to access the targeted PV in all patients (100%), assisted in selecting the optimal point along the hepatic vein for origination of the needle pass in 11 patients (55%), allowed avoidance of a large hepatocellular carcinoma in one patient (5%), and confirmed that access into the main PV was intrahepatic in four patients (20%). The mean number of needle passes decreased from 10.4 in the historic control group to 4.6 in the 3D US group (P = .0001). CONCLUSION: 3D US provided imaging information that detected technical errors and altered anatomy, and provided positional and directional information to significantly improve needle pass efficiency.
Asunto(s)
Monitoreo Intraoperatorio/métodos , Vena Porta/diagnóstico por imagen , Derivación Portosistémica Intrahepática Transyugular/métodos , Ultrasonografía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Várices Esofágicas y Gástricas/diagnóstico por imagen , Várices Esofágicas y Gástricas/cirugía , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Vena Porta/cirugía , Estudios Prospectivos , Reproducibilidad de los ResultadosRESUMEN
PURPOSE: To evaluate the usefulness of information provided by three-dimensional ultrasound (3D US) and to determine whether 3D US decreased the number of passes required to obtain portal vein (PV) access during creation of transjugular intrahepatic portosystemic shunts (TIPS). MATERIALS AND METHODS: Intermittent 3D US volume acquisitions were obtained during creation of TIPS in 20 patients. Useful information provided by 3D US was tabulated. The number of passes required to achieve PV access was recorded and results were compared retrospectively to 25 patients who underwent TIPS without 3D US. RESULTS: 3D US documented that the operator's opinion of which hepatic vein had been selected was incorrect in nine patients (45%), detected unfavorable PV anatomy that required modification of equipment or technique in seven patients (35%), permitted estimation of the trajectory required to access the targeted PV in all patients (100%), assisted in selecting the optimal point along the hepatic vein for origination of the needle pass in 11 patients (55%), allowed avoidance of a large hepatocellular carcinoma in one patient (5%), and confirmed that access into the main PV was intrahepatic in four patients (20%). The mean number of needle passes decreased from 10.4 in the historic control group to 4.6 in the 3D US group (P = .0001). CONCLUSION: 3D US provided imaging information that detected technical errors and altered anatomy, and provided positional and directional information to significantly improve needle pass efficiency.
Asunto(s)
Imagenología Tridimensional , Vena Porta/diagnóstico por imagen , Derivación Portosistémica Intrahepática Transyugular , Ultrasonografía Intervencional/métodos , Adulto , Anciano , Várices Esofágicas y Gástricas/cirugía , Femenino , Fluoroscopía , Venas Hepáticas/diagnóstico por imagen , Humanos , Hígado/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Vena Porta/anatomía & histología , Estadísticas no ParamétricasRESUMEN
BACKGROUND AND OBJECTIVES: Viral hepatitis due to hepatitis C virus results in chronic liver disease in more than 70% of individuals infected with the virus. Hepatitis C virus is also thought to be the cause of autoimmune chronic hepatitis, type II. The only treatment for chronic hepatitis C is interferon (IFN). IFN is both an antiviral agent and an up regulator of the cellular immune system. The latter effect is non-specific. Thus, IFN diffusely activates the cellular immune system and can initiate new autoimmune diseases in patients treated with it. To determine the prevalence of autoantibodies in patients with chronic hepatitis C and in patients with autoimmune hepatitis and to determine the incidence of new onset autoimmune disease in IFN-treated subjects with chronic hepatitis C, the records of 323 unselected patients with chronic hepatitis were reviewed. MATERIAL AND METHODS: A total of 203 patients with a mean age of 45.7 +/- 0.8, ranging 18-81 with either HCV disease or autoimmune hepatitis, were identified and studied. One hundred sixty-two patients with chronic hepatitis C defined by elevations of serum alanine aminotransferase (ALT) for at least 6 months, the presence of detectable anti-HCV (HCV; second generation enzyme immunoassay [EIA2], a positive recombinant immunoblot assay [RIBA], the presence of HCV-RNA by PCR in serum and an abnormal biopsy consistent with chronic hepatitis C) were identified. Each was also negative for HbsAg, HbeAg and anti-Delta. Forty-one patients with a putative autoimmune chronic hepatitis (AIH) diagnosed on the basis of serologic positivity for classical autoantibodies (ANA and anti-smooth muscle antibodies), tissue typing (B8, Dr3 positive), characteristic liver biopsy findings and the absence of anti-HCV and HCV-RNA in serum were identified. The records of both of these groups of patients were reviewed for the following antibodies: anti-nuclear antibodies (ANA), antimitochondrial antibodies (AMA), anti-liver-kidney microsomal antibody (LKM), anti-smooth muscle antibodies (SMA), anti-microsomal antibodies (MSA). RESULTS: The rate of ANA positivity was 63% in both groups; the rate of SMA positivity was 65% in patients with HCV infection (group I) and 63% in patients with AIH (group II). AMA was positive in 4% of the subjects in group I and 50% of the subjects in group II; anti-LKM antibodies were absent in all 91 HCV cases and were present in 4% of the cases in group II; MSA positivity was present in 17% of group I and 10% of group II. Eighty-one of the one hundred sixty-two patients (50%) with chronic hepatitis C received IFN treatment at a dose of 5 MU SQ daily for 6 months. Thirty-two of these eighty-one patients (42 females and 39 males with a mean age of 45.0 +/- 1.3, ranging from 18 to 81 yr.) had at least two autoantibodies detectable prior to the IFN therapy (subgroup 1) and 49 had one or no identifiable autoantibodies (subgroup 2) present prior to IFN therapy. No significant differences in the interferon response rate defined by HCV-RNA negativity and normalization of serum ALT levels at the end of therapy was noted between those with autoantibodies and those without autoantibodies. Fifteen of the interferon-treated patients developed a clinical manifestation of a new onset autoimmune disease during the course of their interferon treatment. Six of the fifteen patients belonged to subgroup 1 (n = 32) and the remaining 9 patients to subgroup 2 (n = 49) (p > 0.05). None were managed by discontinuing the interferon. Most required some form of specific treatment.(ABSTRACT TRUNCATED)
Asunto(s)
Autoanticuerpos/sangre , Enfermedades Autoinmunes/inmunología , Hepatitis C/inmunología , Hepatitis Crónica/inmunología , Hepatitis/inmunología , Interferones/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alanina Transaminasa/sangre , Anticuerpos Antinucleares/sangre , Femenino , Hepacivirus/genética , Hepatitis C/enzimología , Anticuerpos contra la Hepatitis C/sangre , Hepatitis Crónica/enzimología , Humanos , Inmunidad Celular/inmunología , Incidencia , Riñón/inmunología , Masculino , Microsomas/inmunología , Microsomas Hepáticos/inmunología , Persona de Mediana Edad , Mitocondrias Hepáticas/inmunología , Músculo Liso/inmunología , Prevalencia , ARN Viral/genética , Estudios Retrospectivos , Regulación hacia Arriba/inmunologíaRESUMEN
Fulminant hepatic failure (FHF) is a clinical syndrome with a poor outcome. Survival rates are between 10% and 40% depending on the etiology of hepatic necrosis. Multiple supportive modalities have been tried to improve patient outcome. However, orthotopic liver transplantation has been shown to be the most effective therapy at improving survival. Management of these patients requires invasive monitoring, mechanical ventilation, and infection prophylaxis, all of which are conducted most efficiently in specialized units. The goal is to allow the native liver to regenerate and to prevent the development of complications while maintaining the patient in a condition suitable for orthotopic liver transplantation. Therapeutic plasma exchange improves survival in patients with sufficient residual capacity for regeneration. It is effective in restoring hemostasis, improving neurological function, and prolonging biochemical stability of patients awaiting liver transplantation. Hepatoprotective and hepatotrophic substances are still in the experimental stage. Auxiliary liver grafting and artificial liver support devices have proved to be an adjunct or a bridge to transplantation; however, they are not yet widely available.
Asunto(s)
Encefalopatía Hepática/terapia , Terapia Combinada , Cuidados Críticos/métodos , Encefalopatía Hepática/fisiopatología , Humanos , Trasplante de Hígado/métodos , Selección de Paciente , Plasmaféresis , Desintoxicación por Sorción/instrumentaciónRESUMEN
The effect of FK 506 on regeneration of the liver was studied in rats after a two-thirds partial hepatectomy after 60 min of ischemia of the unresected liver. The animals were divided into three distinct groups of 10 rats each. Group 1 (controls) received 0.5 ml saline solution intravenously 30 min after the induction of ischemia. Groups 2 and 3 were injected with FK 506 (0.3 mg/kg) intravenously 30 min after and 24 min before the induction of hepatic ischemia, respectively. The hepatic content of ATP and serum levels of ALT and lactate dehydrogenase were determined on each animal. In addition, the histological appearance and mitotic activity of the remnant liver was determined at regular 24-hr intervals after hepatic ischemia. All 10 control animals died within 72 hr. Treatment with FK 506 resulted in improved survival in groups 2 and 3 (30% and 80%, respectively). The improved survival seen in the FK 506-treated animals was reflected by a restoration of hepatic ATP content, a reduction in the serum levels of ALT and lactate dehydrogenase, an amelioration of hepatic necrosis and neutrophilic infiltration and an increase in the mitotic activity of the liver. These results suggest that FK 506 ameliorates the hepatic injury associated with ischemia/reperfusion and has a potent stimulatory effect on liver cell regeneration that may make it valuable as a hepatoprotective agent when administered to organ donors before graft harvesting.
Asunto(s)
Antibacterianos/uso terapéutico , Inmunosupresores/uso terapéutico , Hepatopatías/prevención & control , Daño por Reperfusión/prevención & control , Adenosina Trifosfato/análisis , Alanina Transaminasa/sangre , Animales , L-Lactato Deshidrogenasa/sangre , Hígado/química , Hígado/patología , Regeneración Hepática , Masculino , Mitosis , Necrosis , Ratas , Ratas Endogámicas Lew , TacrolimusRESUMEN
The widespread application of hepatic transplantation has created a tremendous demand for donor organs. An assessment of donor parameters is thought to be important in selecting good donors; however, the criteria utilized have not been standardized. This study was performed to determine the effect of a measurable donor blood alcohol level on graft survival. Fifty-two patients who underwent orthotopic liver transplantation at the University of Pittsburgh were included in the study. Twenty-five patients received liver grafts from donors having a blood alcohol level between 0.04 and 0.4 g/l with a mean of 0.17 g/l. Twenty-seven patients received a liver graft from a donor who had no measurable blood alcohol. There were no differences between these two groups of donors regarding the time of initial hospitalization until the time of donation. Graft failure within the first 30 days was 24% for those receiving an organ from an alcohol-positive donor as compared with 22.2% in those receiving an organ from an alcohol negative donor. The recipient mortality rate was 16% and 11%, respectively. No relationships between the donor blood alcohol level and organ performance, frequency of primary graft nonfunction, or number of episodes of acute cellular rejection were evident. Based upon these data, the presence of a measurable blood alcohol level in a donor should not mitigate against organ donation.
Asunto(s)
Etanol/farmacocinética , Supervivencia de Injerto/fisiología , Pruebas de Función Hepática , Trasplante de Hígado/fisiología , Complicaciones Posoperatorias/fisiopatología , Donantes de Tejidos , Adulto , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Bilirrubina/sangre , Estudios de Seguimiento , Supervivencia de Injerto/efectos de los fármacos , Humanos , Tiempo de Protrombina , Estudios RetrospectivosRESUMEN
Ischemic damage of the allograft liver is a major problem in clinical liver transplantation. Therefore the identification of hepatoprotective agents is a high priority at most liver transplantation programs. FK 506, a potent new immunosuppressive agent has been reported to possess hepatotrophic activity. To evaluate the putative hepatotrophic activity of FK 506 on experimental hepatic ischemia, rats were subjected to a subtotal hepatectomy following experimental ischemia and subsequent rat survival was assessed. FK 506 (0.3 mg/Kg) administered intravenously 24 hours prior to the induction of hepatic ischemia, reduced the subsequent mortality rate from 100% among controls given saline to only 20% (P less than 0.001). This observation demonstrates that FK 506 enhances the regenerative response of the liver to ischemic injury and may, in addition to its immunologic activity have hepatotrophic activity as well.