RESUMEN
Portal hypertension is a predictor of liver-related clinical events and mortality in patients with hepatitis C and cirrhosis. The effect of interferon-free hepatitis C treatment on portal pressure is unknown. Fifty patients with Child-Pugh-Turcotte (CPT) A and B cirrhosis and portal hypertension (hepatic venous pressure gradient [HVPG] >6 mm Hg) were randomized to receive 48 weeks of open-label sofosbuvir plus ribavirin at Day 1 or after a 24-week observation period. The primary endpoint was sustained virologic response 12 weeks after therapy (SVR12) in patients who received ≥1 dose of treatment. Secondary endpoints included changes in HVPG, laboratory parameters, and MELD and CPT scores. A subset of patients was followed 48 weeks posttreatment to determine late changes in HVPG. SVR12 occurred in 72% of patients (33/46). In the 37 patients with paired HVPG measurements at baseline and the end of treatment, mean HVPG decreased by -1.0 (SD 3.97) mm Hg. Nine patients (24%) had ≥20% decreases in HVPG during treatment. Among 39 patients with pretreatment HVPG ≥12 mm Hg, 27 (69%) achieved SVR12. Four of the 33 (12%) patients with baseline HVPG ≥12 mm Hg had HVPG <12 mm Hg at the end of treatment. Of nine patients with pretreatment HVPG ≥12 mm Hg who achieved SVR12 and completed 48 weeks of follow-up, eight (89%) had a ≥20% reduction in HVPG, and three reduced their pressure to <12 mm Hg. Patients with chronic HCV and compensated or decompensated cirrhosis who achieve SVR can have clinically meaningful reductions in HVPG at long-term follow-up. (EudraCT 2012-002457-29).
Asunto(s)
Hepacivirus , Venas Hepáticas/fisiopatología , Hepatitis C/complicaciones , Hepatitis C/virología , Hipertensión Portal/etiología , Hipertensión Portal/fisiopatología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/etiología , Presión Portal , Adulto , Anciano , Antivirales/uso terapéutico , Quimioterapia Combinada , Femenino , Genotipo , Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , ARN Viral , Respuesta Virológica Sostenida , Factores de Tiempo , Carga ViralRESUMEN
BACKGROUND: Chronic hepatitis C virus therapy in patients with advanced liver disease remains a clinical challenge. HCV-TARGET collects data in patients treated at tertiary academic and community centres. AIM: To assess efficacy of all-oral HCV therapy in advanced liver disease. METHODS: Between December 2013 and October 2014, 240 patients with a MELD score of ≥10 initiated HCV treatment with an all-oral regimen. Data from the 220 patients who completed 12-week follow-up were analysed. RESULTS: Genotype 1 (GT1) patients had higher sustained virological response (SVR) when treated with sofosbuvir plus simeprevir ± ribavirin than with sofosbuvir plus ribavirin (66-74% vs. 54%); GT1b vs GT1a (84% vs. 64%). SVR for GT2 was 72% with sofosbuvir plus ribavirin, while GT3 patients had a substantially lower response (35%). A decrease in MELD score was not clearly related to SVR over the short course of follow-up although some had improvements in MELD score, serum bilirubin and albumin. A predictor of virological response was albumin level while negative predictors were elevated bilirubin level and GT1a. Most patients with GT1 were treated with approximately 12-week duration of sofosbuvir and simeprevir ± ribavirin therapy while GT2 and GT3 patients were treated with approximately 12 and 24 weeks of sofosbuvir plus ribavirin respectively. CONCLUSIONS: All-oral therapies are effective among patients with advanced liver disease with high levels of success in GT2 and GT1b, and may serve to reduce the severity of liver disease after SVR. Treatment for GT3 patients remains an unmet need. Clinical trial number: NCT01474811.
Asunto(s)
Antivirales/administración & dosificación , Bases de Datos Factuales , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/tratamiento farmacológico , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/tratamiento farmacológico , Administración Oral , Adulto , Quimioterapia Combinada , Femenino , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/epidemiología , Humanos , Internacionalidad , Cirrosis Hepática/epidemiología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Ribavirina/administración & dosificación , Simeprevir/administración & dosificación , Sofosbuvir/administración & dosificaciónRESUMEN
Hepatocellular carcinoma (HCC) represents an increasing fraction of liver transplant indications; the role of living donor liver transplant (LDLT) remains unclear. In the Adult-to-Adult Living Donor Liver Transplantation Cohort Study, patients with HCC and an LDLT or deceased donor liver transplant (DDLT) for which at least one potential living donor had been evaluated were compared for recurrence and posttransplant mortality rates. Mortality from date of evaluation of each recipient's first potential living donor was also analyzed. Unadjusted 5-year HCC recurrence was significantly higher after LDLT (38%) than DDLT (11%), (p = 0.0004). After adjustment for tumor characteristics, HCC recurrence remained significantly different between LDLT and DDLT recipients (hazard ratio (HR) = 2.35; p = 0.04) for the overall cohort but not for recipients transplanted following the introduction of MELD prioritization. Five-year posttransplant survival was similar in LDLT and DDLT recipients from time of transplant (HR = 1.32; p = 0.27) and from date of LDLT evaluation (HR = 0.73; p = 0.36). We conclude that the higher recurrence observed after LDLT is likely due to differences in tumor characteristics, pretransplant HCC management and waiting time.
Asunto(s)
Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/cirugía , Trasplante de Hígado/mortalidad , Trasplante de Hígado/métodos , Recurrencia Local de Neoplasia/patología , Adulto , Cadáver , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Rechazo de Injerto , Supervivencia de Injerto , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Donadores Vivos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Invasividad Neoplásica/patología , Recurrencia Local de Neoplasia/mortalidad , Estadificación de Neoplasias , Complicaciones Posoperatorias/mortalidad , Complicaciones Posoperatorias/fisiopatología , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Tasa de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: The impact of virologic response on hepatic function has not been previously defined. AIM: To determine the relationships of quantitative liver function tests (QLFTs) with virological responses to peginterferon (PEG) +/- ribavirin (RBV) in patients with chronic hepatitis C and to use serial QLFTs to define the spectrum of hepatic improvement after sustained virological response (SVR). METHODS: Participants (n = 232) were enrolled in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial, had failed prior therapy, had bridging fibrosis or cirrhosis and were retreated with PEG/RBV. All 232 patients had baseline QLFTs; 24 patients with SVR and 68 nonresponders had serial QLFTs. Lidocaine, [24-(13)C]cholate, galactose and (99m)Tc-sulfur colloid were administered intravenously; [2,2,4,2-(2)H]cholate, [1-(13)C]methionine, caffeine and antipyrine were administered orally. Clearances (Cl), breath (13)CO(2), monoethylglycylxylidide (MEGX), perfused hepatic mass (PHM) and liver volume were measured. RESULTS: Rates of SVR were 18-26% in patients with good function by QLFTs, but < or =6% in patients with poor function. Hepatic metabolism, measured by caffeine k(elim) (P = 0.02), antipyrine k(elim) (P = 0.05) and antipyrine Cl (P = 0.02) and the portal circulation, measured by cholate Cl(oral) (P = 0.0002) and cholate shunt (P = 0.0003) and PHM (P = 0.03) improved after SVR. CONCLUSION: Hepatic dysfunction impairs the virological response to PEG/RBV. SVR improves hepatic metabolism, the portal circulation and PHM.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Interferones/uso terapéutico , Adulto , Relación Dosis-Respuesta a Droga , Femenino , Hepatitis C Crónica/fisiopatología , Hepatitis C Crónica/virología , Humanos , Pruebas de Función Hepática/métodos , Masculino , Persona de Mediana Edad , Ribavirina , Estadística como AsuntoRESUMEN
BACKGROUND: The spectrum of functional impairment in patients with compensated chronic hepatitis C is incompletely defined. AIM: To define hepatic impairment by quantitative tests (quantitative liver function tests) and correlate results with disease severity in patients with chronic hepatitis C. METHODS: We studied 285 adult patients with chronic hepatitis C prior to treatment in the Hepatitis C Anti-viral Long-term Treatment against Cirrhosis Trial; 171 had Ishak fibrosis stages 2-4 (fibrosis) and 114 had stage 5 or 6 (cirrhosis). None had had clinical decompensation. A battery of 12 quantitative liver function test assessed the spectrum of hepatic microsomal, mitochondrial and cytosolic functions, and hepatic and portal blood flow. RESULTS: Twenty-six to 63% of patients with fibrosis and 45-89% with cirrhosis had hepatic impairment by quantitative liver function test; patients with cirrhosis had the greatest impairment (P-value ranging from 0.15 to <0.0001). Cholate Cl(oral), cholate shunt and perfused hepatic mass correlated with cirrhosis, stage of fibrosis (r = -0.51, +0.49, -0.51), varices and variceal size (r = -0.39, +0.36, -0.41). PHM < 95 and cholate shunt >35% identified 91% of patients with medium- or large-sized varices. CONCLUSIONS: Hepatic impairment is common in compensated patients with fibrosis or cirrhosis because of chronic hepatitis C. Cholate shunt, and cholate Cl(oral) and perfused hepatic mass, identify patients at risk for cirrhosis or varices.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis C Crónica/fisiopatología , Cirrosis Hepática/fisiopatología , Pruebas de Función Hepática/métodos , Adulto , Femenino , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Cirrosis Hepática/etiología , Masculino , Persona de Mediana Edad , Estadística como AsuntoRESUMEN
BACKGROUND: Patients with chronic hepatitis C virus and advanced fibrosis or cirrhosis are at risk for disease progression and hepatic decompensation. AIM: To determine the effects on hepatic histology of treatment with peginterferon alfa-2a (90 or 180 mug/week) or interferon alfa-2a (3 million units three times weekly) for 48 weeks in patients with paired biopsies. METHODS: Liver biopsies were obtained at baseline and 6 months after end of treatment. Histological and virological responses were compared. RESULTS: Patients attaining sustained virological response (n = 40) demonstrated the greatest improvements in fibrosis (-1.0, P < 0.0001) and inflammation (-0.65, P < 0.0001). Patients who cleared hepatitis C virus during treatment, but later relapsed (n = 59), experienced less improvement in fibrosis (-0.04, P < 0.0001) and inflammation (-0.14, P = 0.0768). Nonresponders (n = 85) showed no significant improvement in inflammation or fibrosis. Multiple regression analysis showed that the only factors contributing to improvement in fibrosis were sustained virological response (vs. nonresponder, P = 0.0005; vs. relapse, P = 0.7525) and body mass index < or =30 kg/m2 (P = 0.0995). CONCLUSIONS: These findings indicate that virological response to peginterferon alfa-2a improves inflammation and fibrosis in hepatitis C virus patients with advanced fibrosis or cirrhosis. Improving virological response and maintaining ideal body weight are critical for achieving optimal histological outcomes in hepatitis C virus patients.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis C/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Polietilenglicoles/uso terapéutico , Antivirales/administración & dosificación , Esquema de Medicación , Femenino , Hepacivirus/efectos de los fármacos , Hepatitis C/complicaciones , Hepatitis C/patología , Humanos , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Cirrosis Hepática/complicaciones , Cirrosis Hepática/patología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Polietilenglicoles/administración & dosificación , Proteínas Recombinantes , Resultado del TratamientoRESUMEN
BACKGROUND: Treatment options are limited for patients with hepatitis C virus who do not experience sustained viral eradication with pegylated interferon and ribavirin therapy. AIM: To compare, in an open-label, randomized study, long-term continuous interferon alpha-2b treatment with repeated 24-week courses in patients with chronic hepatitis C virus that relapsed after prior interferon monotherapy. METHODS: A total of 499 patients received 24 weeks of interferon alpha-2b, 3 MIU administered 3 TIW. Responders (normal alanine aminotransferase and negative hepatitis C virus -RNA, n = 244) were then randomized to continuous interferon therapy (1, 2 or 3 MIU TIW depending on response) or cyclical therapy (3 MIU TIW for 24 weeks per relapse). Mean Knodell inflammation (I + II + III) and necrosis (IV) scores at baseline vs. year 2 were compared. RESULTS: Patients receiving continuous low-dose therapy vs. cycled therapy had larger reductions in inflammation (-3.9 vs. -3.1) and fibrosis (-0.49 vs. -0.24). Among both groups, the mean change was -3.4 for inflammation and -0.36 for fibrosis. Overall, 73% (95% CI: 67-79) of patients experienced reduced inflammation and 28% (95% CI: 22-34) had reduced fibrosis. CONCLUSIONS: Our results suggest hepatitis C virus patients experiencing viral suppression during long-term maintenance therapy with interferon demonstrate histological improvement. Further prospective trials testing this hypothesis are in progress.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Adolescente , Adulto , Anciano , Alanina Transaminasa/sangre , Antivirales/efectos adversos , Artralgia/inducido químicamente , Biopsia , Esquema de Medicación , Femenino , Fiebre/inducido químicamente , Cefalea/inducido químicamente , Hepacivirus/genética , Hepatitis C Crónica/sangre , Hepatitis C Crónica/enzimología , Hepatitis C Crónica/patología , Humanos , Interferón alfa-2 , Interferón-alfa/efectos adversos , Hígado/patología , Hígado/cirugía , Masculino , Persona de Mediana Edad , Debilidad Muscular/inducido químicamente , ARN Viral/sangre , Proteínas Recombinantes , Prevención Secundaria , Factores de TiempoRESUMEN
BACKGROUND: Measurement of portal inflow and portal-systemic shunt using cholate clearances could be useful in monitoring patients with liver disease. AIM: To examine relationships of cholate clearances and shunt to cirrhosis and varices and to define minimal sampling requirements. METHODS: Five hundred forty-eight studies were performed in 282 patients enrolled in the Hepatitis C Antiviral Long-term Treatment to prevent Cirrhosis (HALT-C) trial. Stable, non-radioactive isotopes of cholate were administered intravenously and orally, clearances (Cl(iv) and Cl(oral)) were calculated from [dose/area under curve (AUC)] and cholate shunt from [(AUC(oral):AUC(iv)) x (Dose(iv):Dose(oral)) x 100%]. RESULTS: Cholate Cl(oral) and cholate shunt correlated with prevalences of both cirrhosis and varices (P < 0.0001 for all). Peripheral venous sampling at 5, 20, 45, 60 and 90 min defined the minimal model. Linear regression of cholate shunt determined from five points within 90 min vs. the standard method of 14 points over 3 h yielded slope of 1.0 and intercept 0.5% (r(2) = 0.98, P < 0.0001). Results were identical in the 189 validation studies (slope 1.0, intercept 0.5%, r(2) = 0.99, P < 0.0001). CONCLUSIONS: Cholate Cl(oral) and cholate shunt may be useful in monitoring patients with liver disease. The 5-point model enhances application of cholate Cl(oral) and cholate shunt in the non-invasive assessment of the portal circulation.
Asunto(s)
Colatos/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Cirrosis Hepática/tratamiento farmacológico , Derivación Portosistémica Quirúrgica/métodos , Colatos/administración & dosificación , Hepatitis C Crónica/complicaciones , Humanos , Cirrosis Hepática/etiología , Pruebas de Función Hepática/métodosRESUMEN
While transjugular intrahepatic portosystemic shunt (TIPS) is a common therapy for cirrhotic patients with diuretic-resistant or diuretic-refractory ascites, some patients are unsuitable for the procedure for technical or medical reasons. We report our experience with the use of chronic intravenous albumin infusions to achieve diuresis in this difficult patient population and review the historic experience of chronic albumin infusions as a treatment for ascites. Nineteen patients with cirrhosis and diuretic-resistant or diuretic-refractory ascites who were deemed unsuitable for TIPS received outpatient intravenous albumin infusions (50 g) weekly for at least 4 weeks. The following endpoints were retrospectively recorded: serum sodium, serum creatinine, blood urea nitrogen, hematocrit, bilirubin, albumin, international normalized ratio, body weight, and Model for End-stage Liver Disease (MELD) score. The contraindications for TIPS included the following: portal vein thrombosis, two; advanced age, one; encephalopathy, nine; hyperbilirubinemia, five; and other, two. Compared to pretreatment, posttreatment weight decreased in 17 patients, remained unchanged in 0 patients, and increased in 2 patients. The overall mean change in body weight (before vs. after therapy) was 8 lb (P < 0.05). The only significant change in biochemistry was an increase in serum albumin from 2.5 g/dl before therapy to 3.5 g/dl after therapy (P < 0.05). We conclude that (1) recurrent intravenous weekly albumin infusions resulted in significant loss of edema and ascites as measured by loss of body weight, and (2) clinicians may want to consider chronic albumin infusions for selected patients with refractory ascites who are not candidates for TIPS.
Asunto(s)
Albúminas/administración & dosificación , Ascitis/tratamiento farmacológico , Ascitis/fisiopatología , Diuresis/efectos de los fármacos , Derivación Portosistémica Intrahepática Transyugular , Albúminas/historia , Albúminas/uso terapéutico , Ascitis/historia , Contraindicaciones , Esquema de Medicación , Femenino , Historia del Siglo XX , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
The role of laparoscopic surgery in the management of polycystic liver disease (PCLD) is not well defined. The authors hypothesized that laparoscopic fenestration for PCLD relieves symptoms caused by polycystic liver disease. In this study, 11 patients underwent 20 laparoscopic cyst fenestration operations as treatment for symptoms of their PCLD. Symptoms leading to surgery were pain and pressure in 15 (75%) and early satiety in 12 (60%) patients. The median hospital stay was 1 day. The symptoms resolved postoperatively in all the patients. An additional laparoscopic fenestration was required in six (55%) patients for recurrent symptoms. The average time to reoperation was 22 +/- 16 months. Two patients required hepatic transplantation. Initial symptom resolution occurred in all the patients undergoing redo fenestration. The authors conclude that laparoscopic fenestration for PCLD is safe, results in minimal "down" time and relieves the symptoms caused by PCLD. Symptomatic relief usually is temporary, and repeat surgery is required for recurring symptoms in half of the patients.
Asunto(s)
Quistes/cirugía , Laparoscopía , Hepatopatías/cirugía , Cuidados Paliativos , Adulto , Femenino , Humanos , MasculinoRESUMEN
This article highlights the currently available immunosuppressive medications that are used to prevent or treat hepatic allograft rejection. Currently-available immunosuppressive medications are highly effective in prevention of allograft rejection, graft loss, and patient death. However, side effects of medications are common, usually dose-related, and specific to the administered drug. Maintenance immunosuppression which has been primarily based upon calcineurin inhibitors (Cyclosporine, CsA, or tacrolimus, Tac) is commonly modified to reduce metabolic complications of therapy. Toxic consequences of steroids may be ameliorated by steroid withdrawal without risk of acute rejection or immunologic graft loss. Calcineurin-sparing regimens may include use of mycophenolate mofetil (MMF) or sirolimus, and allow reduction in doses and plasma levels of CsA and Tac. Recurrence of hepatitis C is universal after liver transplantation and progresses rapidly, compared to its natural history in non-immunocompromised patients. Unfortunately, no single immunosuppressive agent or strategy has yet been shown to convincingly modify the course of post-transplant recurrence. Most centers manage recurrenc hepatitis C by either steroid avoidance, reduction in immunosuppression, or institution of antiviral therapy. Ongoing advances in immunosuppressive and antiviral medications will allow tailoring of the immunosuppressive prescription, which undoubtedly will benefit current and future liver recipients.
Asunto(s)
Terapia de Inmunosupresión , Trasplante de Hígado/inmunología , Inhibidores de la Calcineurina , Glucocorticoides/uso terapéutico , Hepatitis C/cirugía , Humanos , Recurrencia , Sirolimus/uso terapéuticoAsunto(s)
Arachis/inmunología , Hipersensibilidad/etiología , Trasplante de Hígado/efectos adversos , Adolescente , Adulto , Femenino , Humanos , MasculinoRESUMEN
Adult right hepatic lobe living donor liver transplantation (LDLT) has rapidly gained widespread acceptance as an effective procedure for selected patients with end-stage liver disease. However, there are currently no published data on the effect of this procedure on the quality of life of donors. We report the results of a survey of our living liver transplant donors to determine the effect of right hepatic lobe donation on quality of life. We have performed 30 LDLTs since 1997; 24 of these have a follow-up of 4 months or longer. In August 2000, these patients were sent a questionnaire (including a Medical Outcomes Study 36-Item Short-Form Survey) regarding psychosocial outcomes and symptoms after surgery. Major complications occurred in 4 of 24 patients (16%), and minor complications, in 4 of 24 patients (16%). Complete recovery occurred in 75% of patients at a mean time of 3.4 months. Ninety-six percent of patients returned to the same predonation job after a mean time of 2.4 months, and 66% of patients required a period of light-duty work for a mean of 2.8 months before returning to full-duty work. A change in body image was reported in 42% of patients, and 71% reported mild ongoing symptoms (primarily abdominal discomfort) that they related to the donor surgery for which 29% sought evaluation by a physician. The donor's relationship with the recipient was the same or better in 96% of donors, and the relationship with the donor's significant other was the same or better in 88% of donors. Mean out-of-pocket expenses incurred by donors were $3,660. Sixty-three percent of donors reported experiencing more pain than anticipated. All patients would donate again if necessary, and 96% benefited from the donor experience. In conclusion, (1) all our donors are alive and well after donation; (2) almost all donors were able to return to predonation employment status within a few months; (3) most donors have mild persistent abdominal symptoms, and some donors had a change in body image that they attribute to the donor surgery; and (4) this information should be provided to potential donors so they may better understand the impact of donor surgery.
Asunto(s)
Trasplante de Hígado/métodos , Donadores Vivos , Adulto , Femenino , Estado de Salud , Humanos , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/economía , Trasplante de Hígado/psicología , Donadores Vivos/psicología , Masculino , Dolor Postoperatorio/etiología , Psicología , Calidad de Vida , Encuestas y Cuestionarios , Obtención de Tejidos y Órganos/economíaRESUMEN
OBJECTIVES: Orlistat, an intestinal lipase inhibitor, has recently been approved by the US Food and Drug Administration for treatment of obesity. The effects of orlistat on hepatobiliary function have not been previously defined. A 4 wk study was performed involving modest weight loss in obese subjects to observe any short-term hepatobiliary responses that occur after initiating treatment with orlistat and a hypocaloric diet. METHODS: A total of 23 obese (BMI 30-41 kg/m2) subjects were randomized to a double blind t.i.d. treatment with 120 mg of orlistat or a placebo in conjunction with a hypocaloric diet (1200-1500 kcal/day). The study was designed to achieve similar modest weight loss in both groups in order to be able to directly assess the effects of orlistat. Cholesterol saturation, bile composition, and gallbladder motility were measured. RESULTS: At the end of the treatment period, mean weight loss of 3.8 kg was achieved in the orlistat group (vs 2.3 kg with placebo, p = NS). Total bile acid concentration decreased significantly with placebo (-18.57 +/- 6.99 mmol/L; 95% CI = -32.26 to -4.87), but not with orlistat. Biliary phospholipid concentration decreased significantly with placebo (-4.38 +/- 1.91 mmol/L; 95% CI = -8.13 to -0.64) but not with orlistat. Mean changes from the baseline in cholesterol saturation index and gallbladder motility were similar in both groups. Microscopy of bile failed to reveal cholesterol microcrystals before or after treatment in either group. CONCLUSIONS: Our findings indicate a primary initial effect of weight loss is a reduction in biliary bile acids and phospholipids. Orlistat blocks these adverse changes in biliary lipid composition and maintains hepatobiliary function. We speculate that the risk of formation of gallstones during weight loss may actually be lowered with orlistat.
Asunto(s)
Fármacos Antiobesidad/farmacología , Bilis/química , Inhibidores Enzimáticos/farmacología , Vesícula Biliar/efectos de los fármacos , Lactonas/farmacología , Obesidad/tratamiento farmacológico , Adulto , Fármacos Antiobesidad/efectos adversos , Fármacos Antiobesidad/farmacocinética , Ácidos y Sales Biliares/química , Colesterol/metabolismo , Método Doble Ciego , Ingestión de Energía , Inhibidores Enzimáticos/efectos adversos , Inhibidores Enzimáticos/farmacocinética , Femenino , Vesícula Biliar/fisiología , Humanos , Lactonas/efectos adversos , Lactonas/farmacocinética , Lipasa/antagonistas & inhibidores , Lípidos/análisis , Masculino , Persona de Mediana Edad , Obesidad/metabolismo , Orlistat , Pérdida de PesoRESUMEN
At our center, we have performed liver transplantation since 1995 with a rapid-taper steroid protocol (weaning steroids by day 14 posttransplantation). Beginning in 2000, we further reduced the use of corticosteroids to 3 days and added sirolimus to our immunosuppressive regimen. We report our experience with 39 patients who underwent liver transplantation with either tacrolimus or cyclosporin A (Neoral; Novartis Pharmaceuticals Corp., Summit, NJ) and sirolimus, with a 3-day tapered dose of corticosteroids. Thirty-two patients received a cadaveric graft and 7 patients received a right hepatic lobe from a living donor. All patients initially were administered either tacrolimus (0.1 mg/kg/d) or cyclosporin A (10 mg/kg/d) and sirolimus (6 mg/d for 1 day, followed by 2 mg/d), in addition to methylprednisolone on the first 3 days (1, 0.5, and 0.5 g/d) after transplantation. Patients were administered corticosteroids for presumptive or biopsy-proven evidence of acute cellular rejection (methylprednisolone, 1, 0.5, and 0.5 g on 3 successive days). Seventeen patients were administered tacrolimus and 22 patients were administered cyclosporin A. Six patients were excluded from analysis because they were administered sirolimus for less than 2 weeks. Mean duration of follow-up was 124 days. Patient survival was 36 of 39 patients (92%), and graft survival was 35 of 39 grafts (89%). Ten of 33 patients (30%) experienced 12 episodes of rejection (7 biopsy proven, 5 presumptive) compared with 70% in historical controls (P <.01). OKT3 was required in 1 of 33 patients (3%) compared with 37% in controls (P <.01). Twenty-six of 33 patients (79%) were not administered prednisone, and 7 of 33 patients (21%) were administered prednisone for reasons other than rejection. Posttransplantation, there was no significant change in values for creatinine, glucose, aspartate aminotransferase, bilirubin, cholesterol, and white blood cell counts. Platelet counts were significantly reduced, and hematocrits were significantly elevated (P <.05). Liver transplantation may be successfully performed with minimal use of corticosteroids by using sirolimus and either tacrolimus or cyclosporin A. Despite the absence of prednisone from our immunosuppressive protocol, the incidence of rejection and OKT3 use was lower than in historical controls. Patient and graft survival rates were identical to those of historical controls. The findings in this report will serve as the basis for a formal trial evaluating the efficacy of sirolimus in liver transplantation.
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Ciclosporina/uso terapéutico , Inmunosupresores/uso terapéutico , Trasplante de Hígado/inmunología , Sirolimus/uso terapéutico , Tacrolimus/uso terapéutico , Femenino , Glucocorticoides/administración & dosificación , Rechazo de Injerto , Humanos , Donadores Vivos , Masculino , Metilprednisolona/administración & dosificación , Persona de Mediana Edad , Sirolimus/efectos adversosRESUMEN
This article focuses on the origin, diagnosis, and management of focal benign lesions of the liver. The most common lesions include cavernous hemangioma, focal nodular hyperplasia, hepatic adenoma, and nodular regenerative hyperplasia. A number of less frequent occurring lesions are also discussed. In general, the common lesions can be diagnosed by radiologic imaging, but occasionally biopsies are required, and surgical removal is often needed.
Asunto(s)
Neoplasias Hepáticas/etiología , Lesiones Precancerosas/etiología , Adenoma/diagnóstico , Adenoma/etiología , Adenoma/terapia , Anticonceptivos Orales/efectos adversos , Granuloma de Células Plasmáticas/diagnóstico , Granuloma de Células Plasmáticas/etiología , Granuloma de Células Plasmáticas/terapia , Hamartoma/diagnóstico , Hamartoma/etiología , Hamartoma/terapia , Hemangioma/diagnóstico , Hemangioma/etiología , Hemangioma/terapia , Humanos , Hiperplasia , Hígado/patología , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/terapiaRESUMEN
Combined liver-pancreas transplantation is a relatively uncommon procedure. We report successful combined liver-pancreas transplantation in a patient with primary sclerosing cholangitis and insulin-dependent diabetes mellitus and review the literature on this topic.
Asunto(s)
Colangitis Esclerosante/cirugía , Diabetes Mellitus Tipo 1/cirugía , Trasplante de Hígado , Trasplante de Páncreas , Adulto , Anastomosis en-Y de Roux , Colangitis Esclerosante/complicaciones , Diabetes Mellitus Tipo 1/complicaciones , Humanos , Trasplante de Hígado/métodos , Masculino , Trasplante de Páncreas/métodosRESUMEN
The incidence of hepatocellular cancer (HCC) in the United States and other traditionally "low-incidence" countries is increasing. 2. The rise in incidence of HCC is related to chronic hepatitis C. 3. Timely performance of liver transplantation is curative in patients with early-stage HCC. 4. Cirrhotic patients, especially those with viral hepatitis, should be screened for HCC. 5. The performance characteristics of current tests are suboptimal, but serial ultrasonography and alphafetaprotein are recommended. 6. Estimated medical charges related to screening and treatment suggest that $285,294 is required per "cured" case. Assuming that this cure is associated with a 75% to 85% chance for high-quality 10-year survival, the charges approximate $35,000 to $40,000/quality-adjusted life-year (QALY). This cost-benefit analysis is nearly identical to published rates for breast cancer screening ($30,000/QALY).
Asunto(s)
Carcinoma Hepatocelular/cirugía , Hepatitis Viral Humana/cirugía , Neoplasias Hepáticas/cirugía , Trasplante de Hígado , Algoritmos , Biomarcadores/sangre , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/economía , Carcinoma Hepatocelular/epidemiología , Hepatitis Viral Humana/complicaciones , Hepatitis Viral Humana/epidemiología , Humanos , Incidencia , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/economía , Neoplasias Hepáticas/epidemiología , Trasplante de Hígado/economía , Cuidados Preoperatorios , Precursores de Proteínas/sangre , Protrombina , Factores de Riesgo , Obtención de Tejidos y Órganos , Ultrasonografía , Listas de Espera , alfa-Fetoproteínas/análisisRESUMEN
BACKGROUND: In this report we describe the transfer of malignant melanoma from a single donor to four solid organ transplant recipients, all of whom died from metastatic melanoma. METHODS AND CASE HISTORIES: The donor of a heart, liver, and two kidneys to four separate recipients died of intracerebral hemorrhage. The donor had no history or clinical evidence of melanoma. All four recipients, treated with standard immunosuppression protocols, developed metastatic malignant melanoma within 1 year after transplantation Three patients died within 14 months after transplantation, although the fourth, whose immunosuppressive therapy was discontinued, died of metastatic melanoma 30 months after renal transplantation. FINDINGS: Tumors from all recipients were histologically identical. Donor origin of tumor cells was confirmed by polymerase chain reaction (PCR)-based DNA analysis for polymorphic short tandem tetrameric repeats (Geneprint STR, Promega Corp., Madison, WI). DNAs from nontumorous donor tissue and tumor tissue available from three recipients tested positive for CSF1P0 alleles 10 and 12 and for TH01 alleles 6 and 7, although DNAs from nonneoplastic recipient tissues all exhibited different allelotypes. INTERPRETATION: Transmission of fatal or potentially fatal malignant tumors, notably malignant melanoma, from donor to recipient is an uncommon complication of solid organ transplantation. PCR-based genetic analysis permits definitive assignment of the source of posttransplant tumors.