RESUMEN
BACKGROUND: To assess whether the effectiveness of a combination of transcatheter arterial chemoembolization (TACE) and percutaneous ethanol injection (PEI) is superior to PEI alone in the treatment of patients with small hepatocellular carcinoma (HCC), a randomized controlled study was performed. METHODS: Fifty-two patients with one to three HCC tumors measuring < than 3 cm in greatest dimension were enrolled and underwent the combination TACE-PEI therapy (26 patients with 31 nodules) or PEI alone (26 patients with 34 nodules). There were no significant differences in background between the two groups. The mean follow-up was 30.1 months +/- 17.5 months. RESULTS: The cumulative detection rates of local residual disease in the TACE-PEI group (3.7% at 1 year and 19.3% at 3 years) were significantly lower compared with the detection rates in the PEI alone group (34.2% and 39.3%, respectively; P = 0.013). The cumulative new nodular recurrence rates in the TACE-PEI group (8.7% at 1 year and 19.3% at 3 years) tended to be lower compared with the recurrence rates in the PEI alone group (26.9% and 80.1%, respectively; P = 0.057). The cumulative survival rates were not significantly different between the two groups (TACE-PEI group: 100%, 80.8%, and 40.4% at 1 year, 3 years, and 5 years, respectively; PEI alone group: 91.3%, 65.9%, and 37.7%, respectively; P = 0.458). However, among the patients from each group with HCC tumors measuring < 2 cm, the survival rates in the TACE-PEI group were improved compared with the survival rates in the PEI alone group (P < 0.01) in addition to the detection rates of local residual disease and the new nodular recurrence rates (P < 0.01 and P = 0.047, respectively). The frequency of short-term and long-term adverse effects was not significantly different between the groups. However, only two major complications (biloma and ascites with pleural effusion) were observed, both of which occurred in patients in the TACE-PEI group. CONCLUSIONS: Combination therapy with TACE-PEI was superior to PEI alone in the treatment of patients with small HCC tumors, especially for patients with HCC tumors measuring < 2 cm in greatest dimension.
Asunto(s)
Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Etanol/administración & dosificación , Neoplasias Hepáticas/terapia , Anciano , Carcinoma Hepatocelular/mortalidad , Terapia Combinada , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Masculino , Recurrencia Local de NeoplasiaRESUMEN
Hepatitis virus infection through virus reactivation has a high risk of mortality in patients with hematological malignancies receiving chemotherapy. We examined the incidence of both hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and severe liver dysfunction (alanine aminotransferase >ten times the normal upper limit and total bilirubin >5 mg/dl) during chemotherapy in 268 patients with hematological malignancies. Eight patients (3.0%) were infected with HBV and 22 patients (8.2%) were infected with HCV. One patient (0.4%) was infected with both HBV and HCV. HBV- or HCV-infected patients showed severe liver dysfunction at a significantly higher incidence than non-infected patients (11/31 (35.5%) vs. 0/237 (0%), p<0.0001). Furthermore, the incidence of severe liver dysfunction in HBV-infected patients was significantly higher than in HCV-infected patients (6/8 (75.0%) vs. 4/22 (18.2%), p<0.01). Three of eight HBV-infected patients were initially negative for hepatitis B surface antigen (HBsAg) by latex agglutination and became positive for HBsAg during chemotherapy. Furthermore, all three patients developed severe liver dysfunction and two developed fatal fulminant hepatitis. From an examination of the original stock of serum samples before chemotherapy, two patients were found to be positive for HBV-DNA by polymerase chain reaction (PCR). Although post-transfusion HBV infection was suspected in the one remaining patient, the cause of HBV infection could not be clarified due to the impossibility of examination in blood donors. Since HBV-infected patients develop severe liver dysfunction at a higher incidence than either patients not infected with virus or HCV-infected patients before chemotherapy for hematological malignancies, it is recommended that HBV-DNA should be tested by PCR to detect HBV marker-negative carriers and liver function tests should be carefully monitored.
Asunto(s)
Antineoplásicos/farmacología , Neoplasias Hematológicas/tratamiento farmacológico , Hepacivirus/efectos de los fármacos , Virus de la Hepatitis B/efectos de los fármacos , Hepatitis B/epidemiología , Hepatitis C/epidemiología , Hígado/fisiopatología , Activación Viral/efectos de los fármacos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , ADN Viral/sangre , Femenino , Neoplasias Hematológicas/complicaciones , Hepacivirus/fisiología , Hepatitis B/complicaciones , Hepatitis B/fisiopatología , Hepatitis B/transmisión , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/fisiología , Hepatitis C/complicaciones , Hepatitis C/fisiopatología , Humanos , Incidencia , Japón/epidemiología , Fallo Hepático/etiología , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Reacción a la TransfusiónRESUMEN
We report a case of a 41-year-old man with acute myelogenous leukemia who developed fulminant hepatitis from reactivation of trace hepatitis B virus (HBV) 2 months after complete remission. Although he became positive for HB surface antigen at the onset of fulminant hepatitis, he had been negative for HBV serum markers, and only HBV DNA was detected by polymerase chain reaction (PCR) amplification on admission. The original stocks of serum samples from all blood donors were tested again for HBV DNA by PCR, and all samples were negative. This case demonstrates that testing for HBV DNA by PCR is necessary before chemotherapy, because silent HBV carriers are rare and fulminant hepatitis may be induced by chemotherapy in patients with hematologic malignancies.
Asunto(s)
Antineoplásicos/efectos adversos , Hepatitis B/etiología , Leucemia Mieloide Aguda/complicaciones , Fallo Hepático/virología , Adulto , ADN Viral/sangre , Hepatitis B/inducido químicamente , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/crecimiento & desarrollo , Humanos , Terapia de Inmunosupresión/efectos adversos , Leucemia Mieloide Aguda/tratamiento farmacológico , Masculino , Reacción en Cadena de la Polimerasa , Activación Viral/efectos de los fármacosRESUMEN
BACKGROUND AND AIMS: Previously we found that serum matrix metalloproteinase (MMP)-1 activity decreased with progression of chronic liver disease. Our objectives in the present study were to observe the change in the serum MMP-1 protein concentration using recently developed specific enzyme immunoassays for MMP-1 and MMP-1 complexed with tissue inhibitor of metalloproteinases (TIMP)-1 and to elucidate the clinical usefulness of the serum MMP-1 test in chronic viral hepatitis. We measured the serum concentrations of MMP-1 and MMP-1/TIMP-1 complex using these immunoassays in 64 patients with histologically characterized chronic viral hepatitis. RESULTS: Serum MMP-1 concentration was inversely related to the histological severity of chronic hepatitis (P< 0.0001). It was closely associated with the histological degree of periportal necrosis (P< 0.0001), intralobular necrosis (P< 0.005), portal inflammation (P<0.0001) and liver fibrosis (P< 0.05). The serum concentration of MMP-1/TIMP-1 complex was also related to the histological severity of chronic hepatitis (P< 0.0001). It was associated with the degree of portal inflammation (P< 0.05), but not with the degree of periportal necrosis, intralobular necrosis or liver fibrosis. As serum MMP-1 level was closely associated with the histological degree of necroinflammation, we examined the ability of the serum MMP-1 test to differentiate active and inactive forms of hepatitis with a receiver operating curve. The results were compared with those of serum procollagen type III N-peptide (PIIINP) test. We found that the serum MMP-1 test was superior to the serum PIIINP test in assessing liver necroinflammation. CONCLUSIONS: In addition to the previously reported changes in enzyme activity, MMP-1 proteins in serum decreased during histological progression of chronic hepatitis. The serum MMP-1 test may be useful clinically to differentiate active and inactive types of hepatitis in patients with chronic viral hepatitis.
Asunto(s)
Colagenasas/sangre , Hepatitis B Crónica/enzimología , Hepatitis C Crónica/enzimología , Biomarcadores/sangre , Biopsia , Progresión de la Enfermedad , Femenino , Hepatitis B Crónica/patología , Hepatitis C Crónica/patología , Humanos , Técnicas para Inmunoenzimas , Masculino , Metaloproteinasa 1 de la Matriz , Persona de Mediana Edad , Fragmentos de Péptidos/sangre , Procolágeno/sangre , Curva ROC , Radioinmunoensayo , Índice de Severidad de la Enfermedad , Inhibidor Tisular de Metaloproteinasa-1/sangreRESUMEN
We present 3 patients who developed choledocholithiasis 10, 13, and 12 months after percutaneous ethanol injection and/or transcatheter arterial chemoembolization for hepatocellular carcinoma. Since none of these patients had stones in the gallbladder or in the bile ducts before treatment, bile duct stones might have resulted from local injury in the bile ducts by percutaneous ethanol injection and/or transcatheter arterial chemoembolization. Choledocholithiasis may be a late complication of nonresectional and local therapies for hepatocellular carcinoma tumors.
Asunto(s)
Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/efectos adversos , Etanol/efectos adversos , Cálculos Biliares/inducido químicamente , Neoplasias Hepáticas/terapia , Anciano , Carcinoma Hepatocelular/diagnóstico por imagen , Colangiografía , Endoscopía del Sistema Digestivo , Etanol/administración & dosificación , Femenino , Cálculos Biliares/diagnóstico por imagen , Cálculos Biliares/terapia , Humanos , Inyecciones Intraarteriales , Litotricia , Neoplasias Hepáticas/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
Portal vein thrombosis as a complication of liver cirrhosis has been reported to be extremely rare in Japan, as compared with European countries. There are few reports discussing the correlation of portal vein thrombosis with refractory ascites. Between January 1994 and December 1995, 20 cases (91%) of 22 patients with liver cirrhosis with ascites admitted to our hospital responded well within 2 months to a combination therapy of diuretics and albumin infusion, and the other two cases (9%) with refractory ascites were associated with portal vein thrombosis. The ascites in the first patient continued for 1 year, despite diuretics and albumin infusion therapy, and portal vein thrombosis was confirmed by autopsy. The ascites in the other patient continued for more than 4 months, and portal vein thrombosis was detected by ultrasound. Portal vein thrombosis was not found in the other 20 cirrhotic patients with ascites. These two cases suggest that portal vein thrombosis may be a contributing factor to refractory ascites in patients with decompensated liver cirrhosis.
Asunto(s)
Ascitis/etiología , Cirrosis Hepática/complicaciones , Vena Porta , Trombosis de la Vena/etiología , Ascitis/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia del TratamientoRESUMEN
Transforming growth factor (TGF)-beta 1 is an important cytokine involved in the pathobiology of tissue fibrosis through its stimulation of the production of, and inhibition of the degradation of, extracellular matrix proteins. We examined the clinical usefulness of plasma TGF-beta 1 concentration as a marker of fibrogenesis in patients with chronic viral hepatitis. Thirty-five patients, 11 with minimal chronic hepatitis, 14 with mild chronic hepatitis and 10 with moderate chronic hepatitis and 20 healthy subjects were studied. Transforming growth factor-beta 1 concentrations in platelet-poor plasma were measured with a TGF-beta 1 enzyme-linked immunosorbent assay system kit after acid-ethanol extraction. Plasma TGF-beta 1 levels were significantly elevated in patients with mild and moderate chronic hepatitis, but not in those with minimal chronic hepatitis, compared with the levels in the controls. Plasma TGF-beta 1 levels were increased in parallel with the histological degree of necroinflammation and of liver fibrosis. Plasma TGF-beta 1 levels were positively correlated with blood levels of procollagen type III N-peptide, and 7S fragment and central triple-helix of type IV collagen. These results suggest that plasma TGF-beta 1 level is a useful marker in assessing the situation of liver active fibrogenesis in patients with chronic viral hepatitis.
Asunto(s)
Hepatitis B Crónica/sangre , Hepatitis C Crónica/sangre , Factor de Crecimiento Transformador beta/sangre , Biomarcadores/sangre , Estudios de Casos y Controles , Colágeno/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Hígado/patología , Cirrosis Hepática/sangre , Masculino , Persona de Mediana Edad , Mucinas/sangre , Fragmentos de Péptidos/sangre , Procolágeno/sangre , RadioinmunoensayoRESUMEN
Serum hyaluronan measurement is an option for diagnosing cirrhosis and assessing liver fibrosis, but it is of little use in the diagnosis of chronic hepatitis and compensated liver cirrhosis. It is generally known that intake of food results in elevation of the serum hyaluronan concentration. This work was designed to determine whether a change in the serum hyaluronan concentration after eating might reflect the hepatic sinusoidal endothelial cell impairment in chronic liver diseases. The chronological measurement of serum hyaluronan concentration after eating was performed after an overnight fast in 31 patients with chronic hepatitis, 31 cirrhotic patients, and 8 healthy subjects. The hyaluronan concentration in the loading test increased with the severity of the liver disease in the patients with chronic hepatitis, being significantly higher in the patients with moderate or a higher grade of necroinflammation than in those with a minimal grade, and also significantly higher in patients with stage 3 fibrosis than in those with stage 2 or less. The elevation of the concentration after eating in patients with liver cirrhosis was marked and the range did not overlap with that in patients with chronic hepatitis. Even in 14 patients with compensated liver cirrhosis whose hyaluronan concentration pre-prandially was less than 200 ng/ml, the range of the post-prandial peak concentration did not overlap with that in the chronic hepatitis patients. These results suggest that the evaluation of post-prandial serum hyaluronan concentration is potentially useful for assessing the grading of necroinflammation and staging of fibrosis in patients with chronic hepatitis, as well as for diagnosing compensated liver cirrhosis.
Asunto(s)
Hepatitis Crónica/sangre , Ácido Hialurónico/sangre , Cirrosis Hepática/sangre , Periodo Posprandial , Biomarcadores , Femenino , Hepatitis Crónica/diagnóstico , Humanos , Cirrosis Hepática/diagnóstico , Pruebas de Función Hepática , Masculino , Persona de Mediana EdadRESUMEN
Hyaluronate in tissue and lymph is known to be heterogenous and to show a wide range of molecular weights (10(4) to 10(7) Da). Serum hyaluronate concentrations are increased under various pathophysiological conditions such as liver disease, post-gastrectomy, and after the ingestion of food. To clarify whether the chromatographic patterns of hyaluronate in serum from patients with chronic liver disease are different under these conditions, we subjected sera to chromatography using a Sephacryl S 400 HR column. The chromatograms revealed that the hyaluronate in serum was eluted as a single peak at the position corresponding to the molecular weight of blue dextran, the molecular weight being more than 2 x 10(6) Da. The patterns of the chromatogram were similar among the patients with liver disease and the healthy subject although the heights of the peaks were different. Ingestion of food and a history of gastrectomy for gastric cancer did not influence the elution patterns of serum hyaluronate. These results indicate that hyaluronate in serum has molecular weight of more than 2 x 10(6) Da, and that its elution patterns are not influenced by pathophysiological factors, such as the severity of liver disease, or history of gastrectomy or by food intake in patients with chronic liver disease.
Asunto(s)
Ácido Hialurónico/sangre , Hepatopatías/sangre , Adulto , Cromatografía en Gel , Enfermedad Crónica , Ingestión de Alimentos , Hepatitis C/sangre , Hepatitis C/fisiopatología , Hepatitis Crónica/sangre , Hepatitis Crónica/fisiopatología , Humanos , Cirrosis Hepática/sangre , Cirrosis Hepática/fisiopatología , Hepatopatías/fisiopatología , Masculino , Persona de Mediana Edad , Peso MolecularRESUMEN
BACKGROUND/AIMS: Tissue inhibitor of metalloproteinase (TIMP)-1 is an important regulator of matrix metalloproteinase activity. To clarify the changes in TIMP-1 in diseased livers, we measured TIMP-1 concentrations in liver tissue samples from patients with chronic liver disease. The relationship between serum and liver levels of TIMP-1 was also examined in some patients. METHODS: The subjects were 68 patients who underwent liver biopsy. The liver TIMP-1 concentration was measured using an enzyme immunoassay after the extraction of TIMP-1 with 2 M guanidine. RESULTS: As compared with the controls (n=10), the liver TIMP-1 level was increased 2.2-fold in the 24 chronic active hepatitis 2A patients, 2.9-fold in the 10 chronic active hepatitis 2B patients and 4.1-fold in the six liver cirrhosis patients, but no significant increase was observed among the 18 chronic persistent hepatitis patients. The liver TIMP-1 levels were closely correlated with the histological degrees of periportal necrosis, portal inflammation, and liver fibrosis. When the localization of TIMP-1 was examined immunohistochemically, TIMP-1 was stained mainly in hepatocytes, and the intensity was stronger in the livers of chronic active hepatitis and liver cirrhosis patients than in those of the chronic persistent hepatitis patients. The serum TIMP-1 and liver TIMP-1 levels were significantly correlated, indicating that serum TIMP-1 could reflect the change of liver TIMP-1 in patients with chronic liver disease. CONCLUSION: Liver TIMP-1 concentration increases with progression of the liver disease, when the degradation of extracellular matrix proteins is decreased, resulting in the development of liver fibrosis.