RESUMEN
With improvements in surgical technique and the advent of new and more effective immunosuppressive agents, survival rates in liver transplant recipients have dramatically improved. However, hyperlipidemia frequently develops in patients administered cyclosporine-based immunosuppression long-term, although it appears to occur less often with newer, tacrolimus-based regimens. We sought to determine whether an isolated change in the baseline immunosuppressive regimen (cyclosporine to tacrolimus) would improve hyperlipidemic states in these patients. Twenty-one long-term stable liver transplant recipients with hyperlipidemia, manifested by elevated cholesterol and/or triglyceride levels, were offered conversion to tacrolimus from cyclosporine A therapy. Lipid profiles were monitored at baseline (while on cyclosporine therapy) and at 1 and 3 months after conversion to tacrolimus therapy. There were no other medication manipulations. After conversion to tacrolimus therapy, mean cholesterol levels decreased from 251 to 202 mg/dL at 1 month (P <.001) and 194 mg/dL at 3 months (P <.001). Similarly, triglyceride levels decreased from 300 to 207 mg/dL by 1 month (P =.011) and 203 mg/dL by 3 months (P <.001). There was also a statistically significant decrease for very low-density lipoprotein levels at 3 months (P =.005) and low-density lipoprotein levels at 1 and 3 months (P =.013 and P =.014, respectively). High-density lipoprotein levels did not significantly change after conversion to tacrolimus therapy. Conversion was not accompanied by adverse side effects, and patients tolerated the change well. In conclusion, simple conversion from cyclosporine to tacrolimus-based immunosuppression therapy is safe and improves posttransplantation hyperlipidemia in a subgroup of liver transplant recipients.
Asunto(s)
Hiperlipidemias/etiología , Inmunosupresores/uso terapéutico , Trasplante de Hígado/efectos adversos , Tacrolimus/uso terapéutico , Colesterol/sangre , Estudios de Cohortes , Ciclosporina/efectos adversos , Ciclosporina/uso terapéutico , Humanos , Hiperlipidemias/sangre , Hiperlipidemias/inducido químicamente , Inmunosupresores/efectos adversos , Lipoproteínas LDL/sangre , Retratamiento , Triglicéridos/sangreRESUMEN
BACKGROUND: The critical shortage of transplantable organs necessitates utilization of unconventional donors. We describe a successful experience of controlled non-heart-beating donor (NHBD) liver transplantation. METHODS: Controlled NHBDs had catastrophic head injury, prognosis for no meaningful recovery, decision to withdraw life support, and subsequent consent for donation. After stopping mechanical ventilation in the operating room, death determination by a nontransplant caregiver, and rapid aortic cannulation, liver and kidneys were recovered. RESULTS: Controlled NHBDs contributed 5% of hepatic allografts (8/164) from August 1996 through June 1999 (9% in 1998). Sixteen NHBDs afforded 8 livers and 24 kidneys. Liver donors (n=8) were 11-66 years old; half were >50 years old. Premortem alanine aminotransferase was 25-157 U/L. Arrest occurred 3-27 min after stopping ventilation. Perfusion started 3-5 min after incision, and <22 min after hypotension (mean arterial pressure: <50 mmHg). Patient and graft survivals are 100% at 18+/-12 months follow-up. There was no intraoperative complication, reperfusion syndrome, poor graft function, primary nonfunction, arterial thrombosis, biliary complication, or serious infection. Postoperative day 2 prothrombin time was 13+/-1 sec. Peak alanine aminotransferase was 980+/-601 U/L. Intensive care unit and posttransplant lengths of stay were 2+/-2 and 10+/-7 days, respectively. Soon after transplantation there was frequent temporary hyperbilirubinemia (five of eight recipients; bilirubin peak: 7-29 mg/dl, 2-3 weeks after transplantation) and rejection (4/8 recipients, <3 weeks after transplantation). CONCLUSIONS: NHBDs significantly and safely expanded our donor pool. NHBD surgeons must be capable of rapid procurement. Cautious liberalization of criteria for accepting livers from NHBDs with confounding risk factors is justified. Refined ethics guidelines would broaden approval of NHBDs.
Asunto(s)
Trasplante de Hígado , Donantes de Tejidos , Adolescente , Adulto , Anciano , Cadáver , Niño , Femenino , Humanos , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Perfusión , Respiración Artificial , Tasa de Supervivencia , Obtención de Tejidos y Órganos , Resultado del TratamientoRESUMEN
A hepatic rupture case in a pregnancy is reported. A bibliographic revision during the last fifteen years has been carried out in which: epidemiology, risk factors, etiopatogenia, clinic, complementary exams, presage and treatment.
Asunto(s)
Hepatopatías/diagnóstico , Complicaciones del Embarazo/diagnóstico , Adulto , Femenino , Hematoma/diagnóstico por imagen , Humanos , Embarazo , Rotura Espontánea , Tomografía Computarizada por Rayos X/métodosRESUMEN
The clinical and pathological findings of idiopathic ductopenia were studied in a 30-year-old woman who initially manifested jaundice and pruritus. Serum biochemical tests of liver function indicated severe and progressive cholestasis. Viral hepatitis markers and circulating autoantibodies were absent. The patient had a normal cholangiogram and lacked evidence of inflammatory bowel disease. Histological examination of a liver specimen showed severe cholestasis and absence of interlobular bile ducts. Severe jaundice and intractable pruritus developed in the patient and served as the indications for liver transplantation 4 months after initial examination. Transplantation resulted in prompt and complete resolution of the jaundice and pruritus. Two types of idiopathic adulthood ductopenia associated with different prognoses are recognized. Patients with type 1 idiopathic adulthood ductopenia are asymptomatic or manifest symptoms of cholestatic liver disease. They tend to have less destruction of the intrahepatic bile ducts on liver biopsy specimens. Their clinical course ranges from spontaneous improvement to progression to biliary cirrhosis. In contrast, patients with type 2 idiopathic adulthood ductopenia generally manifest initial symptoms of decompensated biliary cirrhosis, have extensive destruction of the intrahepatic bile ducts on liver biopsy, and frequently require orthotopic liver transplantation.
Asunto(s)
Colestasis Intrahepática/diagnóstico , Cirrosis Hepática Biliar/diagnóstico , Trasplante de Hígado , Adulto , Colestasis Intrahepática/complicaciones , Colestasis Intrahepática/patología , Colestasis Intrahepática/cirugía , Femenino , Humanos , Cirrosis Hepática Biliar/complicaciones , Cirrosis Hepática Biliar/patología , Cirrosis Hepática Biliar/cirugía , Prurito/etiologíaRESUMEN
The mechanisms by which hepatitis C virus (HCV) induces chronic infection in the vast majority of infected individuals are unknown. Sequences within the HCV E1 and E2 envelope genes were analyzed during the acute phase of hepatitis C in 12 patients with different clinical outcomes. Acute resolving hepatitis was associated with relative evolutionary stasis of the heterogeneous viral population (quasispecies), whereas progressing hepatitis correlated with genetic evolution of HCV. Consistent with the hypothesis of selective pressure by the host immune system, the sequence changes occurred almost exclusively within the hypervariable region 1 of the E2 gene and were temporally correlated with antibody seroconversion. These data indicate that the evolutionary dynamics of the HCV quasispecies during the acute phase of hepatitis C predict whether the infection will resolve or become chronic.
Asunto(s)
Evolución Molecular , Hepacivirus/genética , Hepatitis C Crónica/virología , Hepatitis C/virología , Proteínas del Envoltorio Viral/genética , Enfermedad Aguda , Adulto , Anciano , Anticuerpos Antivirales , Progresión de la Enfermedad , Femenino , Genes Virales , Variación Genética , Hepacivirus/inmunología , Hepacivirus/fisiología , Hepatitis C/inmunología , Anticuerpos contra la Hepatitis C/biosíntesis , Hepatitis C Crónica/inmunología , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Filogenia , Estudios Prospectivos , Selección Genética , Factores de Tiempo , Proteínas del Envoltorio Viral/inmunología , Replicación ViralRESUMEN
Clinical prediction of portopulmonary hypertension (PPHTN) is critical in the preoperative evaluation of candidates for orthotopic liver transplantation (OLT) because of its association with significant morbidity and mortality. To determine the clinical, laboratory, and echocardiographic predictors of PPHTN, we retrospectively evaluated 55 candidates before OLT. From those, 8 candidates had pulmonary hypertension ([HTN] group A) and 47 candidates did not (group B). Pulmonary HTN was defined as a mean pulmonary artery pressure (PAP) of 25 mm Hg or greater and either elevated pulmonary vascular resistance or normal pulmonary artery wedge pressure. The significant predictors of PPHTN were (1) systemic arterial HTN (63% in group A v 9% in group B; P <.001), (2) loud pulmonary component of the second heart sound (38% v 2%; P =. 001), (3) right ventricular (RV) heave (38% v 4%; P =.002), (4) RV dilatation by echocardiogram (63% v 0%; P <.001), (5) RV hypertrophy by echocardiogram (38% v 0%; P =.001), and (6) echocardiogram-estimated systolic PAP (SPAP) greater than 40 mm Hg (63% v 2%; P <.001). The sensitivity of these variables for the detection of pulmonary HTN ranges from 37% to 63%, and their specificity from 91% to 100%. We conclude that several clinical and echocardiographic features are significantly associated with pulmonary HTN in patients with cirrhosis. In particular, echocardiogram-estimated SPAP greater than 40 mm Hg is strongly associated with pulmonary HTN and is specific. These predictors, however, are not sensitive enough to identify all the patients with PPHTN. Therefore, the evaluation of a combination of these variables may be useful for the preoperative identification of pulmonary HTN in liver transplant candidates.
Asunto(s)
Hipertensión Pulmonar/epidemiología , Trasplante de Hígado , Estudios de Casos y Controles , Ecocardiografía , Femenino , Humanos , Hipertensión/epidemiología , Hipertensión Portal/diagnóstico , Hipertensión Portal/epidemiología , Hipertensión Pulmonar/diagnóstico , Hipertrofia Ventricular Derecha/diagnóstico por imagen , Hipertrofia Ventricular Derecha/epidemiología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Cuidados Preoperatorios , Presión Esfenoidal Pulmonar , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
Many liver transplant recipients are now reaching survival beyond 5 years from the liver transplant procedure, and many others are alive more than a decade from acquiring their new liver. Orthotopic liver transplant recipients enjoy the benefits of normal liver function, but a variety of metabolic and other medical problems often develop that require diagnosis and adequate management. These problems include hyperlipidemia, obesity, diabetes mellitus, renal disfunction, arterial hypertension, bone disease and neuropsychiatric syndromes. The gastroenterologist, internist, or local family physician is frequently called on to identify and treat these postoperative complications in conjunction with physicians at the transplant center.
Asunto(s)
Trasplante de Hígado , Cuidados a Largo Plazo , Humanos , Complicaciones Posoperatorias/terapiaRESUMEN
A hepatic rupture case in a pregnancy is reported. A bibliographic revision during the last fifteen years has been carried out in which: epidemiology, risk factors, etiopatogenia, clinic, complementary exams, presage and treatment.
RESUMEN
The frequency with which florid duct lesions are seen in needle-biopsy specimens of the liver was assessed in patients with primary biliary cirrhosis (PBC) enrolled in a 2-year randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid (UDCA) versus placebo. Paired biopsy specimens obtained at entry and after 2 years on medication were reviewed blindly and mostly simultaneously by a panel of 5 hepatopathologists who, earlier, had characterized the florid duct lesion, which has been well described in the pathology literature. Florid duct lesions at entry were identified in approximately 36%. Patients with earlier disease showed florid duct lesions much more frequently than those with more advanced disease. The prevalence of florid duct lesions in 60 patients receiving placebo medication fell from 38.3% to 21.7%, P =. 025, over the period of 2 years. The prevalence of florid duct lesions also decreased in the 55 patients receiving UDCA, from 32.7% to 18.2%, P =.046. The prevalences of these lesions in the placebo and UDCA patients at entry and at 2 years were not significantly different from each other. The findings suggest that UDCA does not prevent ongoing bile duct destruction in patients with PBC. Instead, they support the impression that UDCA exerts its beneficial effects by protecting against the consequences of bile duct destruction.
Asunto(s)
Conductos Biliares/efectos de los fármacos , Cirrosis Hepática Biliar/tratamiento farmacológico , Ácido Ursodesoxicólico/uso terapéutico , Conductos Biliares/patología , Método Doble Ciego , Humanos , Cirrosis Hepática Biliar/patologíaRESUMEN
Excluding acute hepatic failure caused by drugs, the etiology of fulminant hepatitis (FH) remains unknown in many patients. There are conflicting data about a possible pathogenic role for the hepatitis G virus (HGV) in patients with cryptogenic fulminant hepatitis (non-A-E FH). We investigated the presence of circulating HGV in 36 patients with well-documented non-A-E fulminant and 5 patients with subfulminant hepatitis from 3 geographic locations in the United States. Serum HGV RNA was determined by reverse transcriptase-polymerase chain reaction using primers from the NS5 region of the HGV genome. HGV RNA was also measured before and after liver transplantation in 5 patients and at different time points in 7 patients. Serum samples were recoded and reanalyzed for HGV RNA using different primer sets to assess the validity of the HGV RNA assay. HGV was present in serum of 14 of the 36 patients (38.8%) with non-A-E fulminant hepatitis. Twenty percent of patients from the Northeast, 11% of the patients from the Southeast, and 50% from the Mid-Atlantic regions of the United States had circulating HGV RNA. The use of therapeutic blood products was significantly associated with the presence of serum HGV RNA (P <.02). Retesting for HGV RNA with different primers was positive in all but 1 case. HGV RNA is not causally related to non-A-E fulminant hepatitis. The finding of HGV RNA in serum from these patients is likely related to the administration of blood product transfusion after the onset of fulminant hepatitis.
Asunto(s)
Flaviviridae/aislamiento & purificación , Encefalopatía Hepática/virología , Hepatitis Viral Humana/virología , Adolescente , Adulto , Femenino , Encefalopatía Hepática/sangre , Hepatitis Viral Humana/sangre , Hepatitis Viral Humana/complicaciones , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Reacción a la TransfusiónRESUMEN
Hepatitis C virus (HCV) was transmitted from a patient with fulminant hepatitis C to a chimpanzee. The patient had developed two episodes of fulminant hepatitis C, each occurring after a separate liver transplantation. Serial serum and liver samples from the patient and the chimpanzee were analyzed for HCV replication, genotype, quasispecies heterogeneity, and antibodies. In the patient, the levels of HCV replication in serum and liver correlated with the degree of hepatocellular necrosis and the clinical expression of fulminant hepatitis. The same HCV strain, genotype 1a, was recovered from both episodes of fulminant hepatitis. An unusually severe acute hepatitis was also observed in the chimpanzee. The viruses recovered from the patient and the chimpanzee were almost identical and displayed relatively little quasispecies heterogeneity. Thus, the same HCV strain induced two episodes of fulminant hepatitis in a single patient and severe hepatitis in a chimpanzee, suggesting that the pathogenicity or virulence of a specific HCV strain may be important in the pathogenesis of fulminant hepatitis C.
Asunto(s)
Encefalopatía Hepática/etiología , Hepatitis C/transmisión , Pan troglodytes/virología , Adulto , Secuencia de Aminoácidos , Animales , Femenino , Hepacivirus/patogenicidad , Humanos , Datos de Secuencia Molecular , ARN Viral/sangre , VirulenciaRESUMEN
Chronic hepatitis B virus infection is endemic in Asian communities in the United States. The purpose of the current study was to compare the antiviral efficacy of interferon-alpha2b in a group of adult Asian patients chronically infected with hepatitis B with active replication compared to a control group of Caucasian patients treated with the same regimen. Patients with entry aminotransferase (ALT) levels greater than three times the upper limit of normal received interferon-alpha2b, 5 million units, subcutaneously daily for 16 weeks. Patients with pretreatment ALT levels 1.5-3 times the upper limit of normal received prednisone for a total of six weeks prior to interferon starting at 60 mg daily with reduction in dosage by 20 mg every two weeks with a two-week period between finishing prednisone and starting interferon-alpha2b. Eight (62%) of the 13 Asians and six (60%) of the 10 Caucasians cleared HBeAg and HBV DNA from serum (NS). By the end of one year of follow-up after therapy, four (67%) of six Caucasian responders but none of the Asian responders had cleared hepatitis B surface antigen from serum (P < 0.05). Loss of serum markers of active replication appeared less durable in the Asian responders compared to the Caucasians with reappearance of serum HBeAg in two (25%) of eight of the former but only one (17%) of the latter group. Three other Asian patients subsequently redeveloped HBeAg in serum. It is concluded that adult Asian-Americans have an identical initial response rate to antiviral therapy with interferon-alpha2b; however, the response may be less durable and does not usually lead to loss of HBsAg.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis B Crónica/etnología , Hepatitis B Crónica/terapia , Interferón-alfa/uso terapéutico , Adulto , Alanina Transaminasa/sangre , Asiático , ADN Viral/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Hepatitis B Crónica/sangre , Humanos , Interferón alfa-2 , Prednisona/uso terapéutico , Estudios Prospectivos , Proteínas Recombinantes , Resultado del Tratamiento , Estados Unidos/epidemiología , Población BlancaRESUMEN
Despite the potential medical problems described here, the vast majority of liver transplant recipients report a remarkable improvement in the quality of their lives. Many, in fact, have normal lifestyles, in marked contrast to their disability before liver transplantation. Maintenance of this status, however, requires compliance with regular medical follow-up to implement preventive measures and early detection of complications. A basic knowledge of these issues should enable the internist, general practitioner, and gastroenterologist to diagnose and manage many of the problems unique to liver transplant recipients. The liver transplant center should encourage communication and be readily accessible to the primary care physician. This team approach is responsible for measuring the survival of liver transplant recipients in decades, rather than years.
Asunto(s)
Trasplante de Hígado/rehabilitación , Humanos , Inmunización , Terapia de Inmunosupresión , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/psicología , Cuidados a Largo Plazo , Fenómenos Fisiológicos de la Nutrición , Factores de RiesgoRESUMEN
Interferon is currently the only approved medication in the United States for treatment of chronic hepatitis B and C infections. The mechanism of action of interferon and guidelines for its administration are reviewed. Important clinical studies involving its use in hepatitis B and C infections are discussed, and investigational therapies for chronic viral hepatitis are highlighted.
Asunto(s)
Hepatitis B/terapia , Hepatitis C/terapia , Interferones/uso terapéutico , Enfermedad Crónica , Humanos , Trasplante de HígadoRESUMEN
Outcomes from 48 pregnancies in 34 female liver transplant recipients were analyzed. Data were collected via interviews, questionnaires, and hospital records. All recipients were treated with cyclosporine-based immunosuppression except 2 patients treated with FK506 and 2 treated with no immunosuppression. The age at conception was 26.1 +/- 5.9 years (mean +/- SD) with a transplant interval (time from transplantation to conception) of 2.9 +/- 2.5 years. There were 49 outcomes (1 set of twins): miscarriage 9 (18%), therapeutic abortion 4 (8%), and live birth 36 (74%). No stillbirths or ectopic pregnancies were reported. Of the 36 live births, the gestational age was 36.9 +/- 3.5 weeks, the birthweight was 2,604 +/- 698 grams, 39% were premature (< 37 weeks), and 31% had low birthweight (< 2,500 grams). No birth defects or neonatal deaths (< 28 days) were reported. The newborn complication rate was 17% (n = 6), 5% in premature infants. The incidence of drug-treated hypertension was 46%; pre-eclampsia 21%; infectious complications 26%; and Caesarean section 47%. Recipients with hypertension had a higher proportion of premature infants (71%) than normotensive patients (38%) (P = .04 by Fisher's exact test). Acute rejection was diagnosed in 6 pregnancies, 2 of which were ended by therapeutic abortion. Four recipients who continued their pregnancies were treated with increased immunosuppression for rejection, and all delivered livebirths. There were two grafts lost within 6 months of pregnancy. The only maternal death occurred in a patient who required retransplantation for recurrent C hepatitis 3 months afte therapeutic abortion and died 6 months later. The other recipient with graft loss was successfully retransplanted for chronic rejection 6 months after delivery. We draw the following conclusions: (1) female liver transplant recipients can safely undergo pregnancy, although there is a high rate of premature and low birthweight infants; (2) pregnancies in this population should be considered high-risk and require close monitoring of liver function; and (3) altered graft function during pregnancy should be thoroughly investigated.
Asunto(s)
Trasplante de Hígado , Complicaciones del Embarazo/epidemiología , Resultado del Embarazo , Sistema de Registros , Adulto , Femenino , Estudios de Seguimiento , Edad Gestacional , Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Registros de Hospitales , Humanos , Inmunosupresores/uso terapéutico , Incidencia , Recién Nacido , Trasplante de Hígado/inmunología , Trasplante de Hígado/fisiología , Embarazo , Embarazo de Alto Riesgo , Encuestas y Cuestionarios , Estados UnidosAsunto(s)
Enfermedad Coronaria , Hiperlipidemias , Trasplante de Hígado/efectos adversos , Animales , Anticolesterolemiantes/uso terapéutico , Enfermedad Coronaria/diagnóstico , Enfermedad Coronaria/tratamiento farmacológico , Enfermedad Coronaria/etiología , Quimioterapia Combinada , Humanos , Hiperlipidemias/diagnóstico , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/etiología , Hipolipemiantes/uso terapéutico , Lípidos/sangre , Complicaciones Posoperatorias , Factores de RiesgoRESUMEN
One hundred fifty-one patients with primary biliary cirrhosis (PBC) grouped into four strata based on entry serum bilirubin ( < 2 mg/dL vs. 2 md/dL or greater) and liver histology (stages I, II vs. stages III, IV-Ludwig criteria) were randomized within each stratum to ursodiol or placebo given in a single dose of 10 to 12 mg/kg at bedtime for 2 years. Placebo- (n = 74) and ursodiol- treated (n = 77) patients were well matched at baseline for demographic and prognostic factors. Ursodiol induced major improvements in biochemical tests of the liver in strata 1 and 2 (entry bilirubin < 2), but had less effect on laboratory tests in patients with entry serum bilirubin of > or +2 (strata 3 and 4). Histology was favorably affected by ursodiol in patients in strata 1 and 2 but not in strata 3 and 4. Ursodiol enrichment in fasting bile obtained at the conclusion of the trail was approximately 40% and comparable in all strata. Thus, differences in ursodiol enrichment of the bile acid pool do not explain better responses of laboratory tests and histology found in patients with less advanced PBC. Patients treated will ursodiol tended to develop a treatment failure less frequently that those who received placebo, particularly in strata 1 and 2 (ursodiol 42%, placebo 60%, P = .078). Development of severe symptoms (fatigue/pruritus) and doubling of serum bilirubin were reduced significantly in ursodiol-treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)