RESUMO
BACKGROUND AND AIMS: Radiofrequency ablation (RFA) has replaced percutaneous ethanol injection (PEI) as the treatment of choice for hepatocellular carcinoma (HCC); however, control of local tumor progression (LTP) remains a challenge in perivascular HCC. The aim of this study was to determine whether PEI added to RFA can reduce the LTP rate in perivascular HCC patients. METHODS: We retrospectively analyzed 167 patients, with 197 newly diagnosed HCC nodules with peritumoral vessels, who underwent either RFA plus PEI or RFA monotherapy as the first-line treatment between June 2001 and April 2015. Ethanol was injected inside the tumor close to the peritumoral vessels in the combination therapy group. Patients were matched 1:1 according to their propensity scores to reduce selection bias; cumulative LTP was then analyzed using log-rank tests and Cox proportional hazard regression analyses. RESULTS: The two matched groups comprised 62 tumors each. The overall median follow-up period was 34 months (range, 1-140 months). In the RFA plus PEI group, the cumulative LTP rates were 5.7%, 15.5%, and 20.4% at 1, 3, and 5 years, respectively; in the RFA monotherapy group, the rates were 13.2%, 32.0%, and 40.2%, respectively. The rates were significantly lower in the RFA plus PEI group (p = 0.032). Cox proportional hazard regression analysis showed that PEI combination treatment was significantly associated with a reduced risk of local HCC recurrence (hazard ratio, 0.44; 95% confidence interval, 0.19-0.93; p = 0.031). DISCUSSION/CONCLUSION: The risk of LTP after RFA for perivascular HCC can be significantly reduced by injecting ethanol close to the peritumoral vessels.
Assuntos
Carcinoma Hepatocelular , Ablação por Cateter , Neoplasias Hepáticas , Ablação por Radiofrequência , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Etanol , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Pontuação de Propensão , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Little research has been done on post-exposure prophylaxis (PEP) for COVID-19. This study was done to determine if maoto, a traditional herbal medicine commonly used for diseases with symptoms similar to those of COVID-19, can be repurposed for post-exposure prophylaxis to prevent the spread of nosocomial infection with SARS-CoV-2. METHODS: A cohort analysis was done of the data of 55 health care workers (HCWs) whether to get infected with SARS-CoV-2 in a Japanese hospital experiencing a COVID-19 cluster in April of 2021. Of these subjects, maoto granules for medical use were prescribed for PEP to 42 HCWs and taken for three days in mid-April. Controls were 13 HCWs who rejected the use of maoto. Polymerase chain reaction was performed routinely once or twice a week or when a participant presented with symptoms of COVID-19. RESULT: There were no background differences between the maoto and control groups by profession, sex, or mean age. No severe adverse reactions were observed. During the observation period of 1 week, significantly fewer subjects were diagnosed with COVID-19 in the maoto group (N = 3, 7.1%) than in the control group (N = 6, 46.2%). The prophylactic effectiveness of maoto was 84.5%. CONCLUSION: Oral administration of maoto is suggested to be effective as PEP against nosocomial COVID-19 infection.
Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , COVID-19/prevenção & controle , Pessoal de Saúde , Medicina Herbária , Humanos , Japão , Profilaxia Pós-Exposição , SARS-CoV-2RESUMO
Hepatic ATP-binding cassette A1 (ABCA1) transporter is the modulator of intrahepatic cholesterol levels via the efflux of cholesterol into plasma. This study aimed to determine the expression of hepatic ABCA1 levels in a cholestatic rat model and patients with primary biliary cholangitis (PBC). A cholesterol efflux study was conducted with Abca1 knock down using siRNA in WIF9 cells. Cholesterol levels in the ABCA1 siRNA cells in the medium were significantly decreased compared with those in controls (P < 0.05). Hepatic ABCA1 mRNA levels were significantly higher in BDL rats than in control rats (P < 0.05). Furthermore, the protein expression level of hepatic ABCA1 was also significantly increased by 200% in BDL rats (P < 0.05). In PBC patients, expression of hepatic ABCA1 mRNA was 2.2-fold higher than that in controls (P < 0.05). The level of hepatic liver X receptor (LXR)ß mRNA was correlated with ABCA1 mRNA levels in PBC patients. The expression of hepatic ABCA1 transporter was upregulated in both the cholestatic rat model and PBC patients. Upregulated hepatic ABCA1 may lead to efflux of cholesterol into plasma, thus explaining the mechanism of cholestasis leading to hypercholesterolemia.
Assuntos
Transportador 1 de Cassete de Ligação de ATP/genética , Colestase Intra-Hepática/genética , Colesterol/metabolismo , Hipercolesterolemia/genética , Cirrose Hepática Biliar/genética , Fígado/metabolismo , Transportador 1 de Cassete de Ligação de ATP/antagonistas & inibidores , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Animais , Transporte Biológico , Linhagem Celular Tumoral , Colestase Intra-Hepática/metabolismo , Colestase Intra-Hepática/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Hipercolesterolemia/metabolismo , Hipercolesterolemia/patologia , Fígado/patologia , Cirrose Hepática Biliar/metabolismo , Cirrose Hepática Biliar/patologia , Receptores X do Fígado/genética , Receptores X do Fígado/metabolismo , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Wistar , Transdução de SinaisRESUMO
BACKGROUND/AIMS: Radiofrequency ablation (RFA) has been applied for hepatocellular carcinoma (HCC) up to 3 nodules, within 3 cm in size. However, the scientific rationale of the treatment criteria for RFA has not been well analyzed. We compared the number and size of tumors with recurrence rates and survival rates. METHODOLOGY: The study participants retrospectively were enrolled 625 consecutive cases of naïve HCC treated with RFA. We analyzed recurrence rates and survival of 472 for the patients with HCC ≤ 3 nodules, ≤ 3 cm in size (Group A), and 153 for the patients exceeding limits (Group B). RESULTS: Median follow-up was 2.97 years. The survival rate of Group A was significantly higher than that of Group B (5 years: 55.6% vs. 44.2%, 10 years: 27.4% vs. 15.7%; P<0.05). Multivariate analysis of predictors for prognostic factors demonstrated that meeting the RFA criteria, Child-Pugh score A, and lower levels of des-gamma carboxy prothrombin (DCP) were independent factors significantly affecting prognosis. CONCLUSIONS: The present study is the firstto elucidate the scientific rationale for RFA treatment criteria for HCC regarding tumor number and size. We confirmed that the RFA treatment criteria select patients who stand to gain the most from RFA.
Assuntos
Carcinoma Hepatocelular/cirurgia , Ablação por Cateter , Neoplasias Hepáticas/cirurgia , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Ablação por Cateter/efeitos adversos , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND/AIMS: Recent studies have confirmed that iron overload is involved not only in liver carcinogenesis, but in its progression. Results in studies using liver cancer cell lines have suggested a relationship between transferrin receptor (TfR) expression and liver carcinogenesis, but TfR expression has not yet been analyzed in human hepatocellular carcinoma (HCC) tissues. METHODOLOGY: We immunohistochemically assessed the expression of TfR1 and TfR2 in tumor tissues and adjacent non-tumorous liver tissues from 41 HCC patients who underwent partial hepatectomy. We evaluated uptake of iron in hepatocytes and HCC cells using iron staining. RESULTS: The expression TfR was significantly higher in HCC samples than in adjacent non-tumor tissue (p < 0.001). TfR expression was significantly related to serum alpha-fetoprotein (p < 0.05) and des-gamma carboxy prothrombin (p < 0.05) concentrations. We also found iron deposition in non-tumor tissue from 25 patients, but in only two HCC samples, consistent with findings that hepatocellular iron uptake decreases with liver carcinogenesis. CONCLUSIONS: We investigated the expression of TfR1 and TfR2 in human HCC tissues by immunohistochemistry, the first report demonstrating TfR2 expression immunohistochemically in human HCC. These results suggest that TfR is expressed in response to iron deficiency during liver carcinogenesis.
Assuntos
Antígenos CD/análise , Carcinoma Hepatocelular/química , Neoplasias Hepáticas/química , Receptores da Transferrina/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/biossíntese , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Membrana Celular/química , Membrana Celular/metabolismo , Feminino , Hepatócitos/metabolismo , Humanos , Imuno-Histoquímica , Ferro/análise , Ferro/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Receptores da Transferrina/biossínteseRESUMO
BACKGROUND/AIMS: The present pilot study aimed to evaluate the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) with interferon-beta (IFN-ß) and 5-fluorouracil (5-FU) in patients with advanced hepatocellular carcinoma (HCC). METHODOLOGY: We studied 10 patients with advanced HCC and who were unresponsive to previous HAIC using low-dose 5-FU and cisplatin. The median age was 67 years. Eight patients had portal vein tumor thrombosis and four patients had extrahepatic metastasis. Using a drug delivery system, patients were treated with HAIC of IFN-ß (600 MIU/body, three times/week) and 5-FU (250 mg/body, five times/week). Chemotherapy was repeated consecutively for 2 weeks every 4 weeks. RESULTS: Six (60%) patients had a decrease in tumor markers alpha-fetoprotein (APP) or des-gamma-carboxy prothrombin (DCP). The median overall survival was 108 days and the 1-year survival rate was 10.0%. Univariate analysis showed two significant prognostic factors related to long-term survival for more than 60 days: a decrease in APP or DCP 4 weeks after treatment (P = 0.035) and no extra hepatic metastasis (P = 0.035). Severe hepatic injury was not observed. CONCLUSIONS: HAIC with IFN-ß and 5-PU exerts modest antitumor effects and poses no particular safety concerns. This may be a new promising strategy for treatment of advanced HCC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/secundário , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Artéria Hepática , Humanos , Infusões Intravenosas , Interferon beta/administração & dosagem , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Precursores de Proteínas/sangue , Protrombina , Fatores de Tempo , Resultado do Tratamento , alfa-Fetoproteínas/metabolismoRESUMO
The clinical course of patients with chronic hepatitis B (CH-B) was greatly changed by the introduction of nucleoside analogues. We often encounter patients where the serum level of albumin recovers quickly following the treatment. In this study, we focused carefully on the changes in serum albumin level noted during nucleoside analogue therapy, in an effort to clarify the mechanism behind the restoration of albumin production. We observed changes in serum albumin levels during nucleoside analogue therapy in 12 patients with CH-B and studied the mechanism behind the restoration of albumin production following the therapy. The serum level of albumin was significantly increased very soon after the treatment was started. Prior to treatment with nucleoside analogues, the albumin signal for mRNA was only slightly seen in the peri-portal area, whereas 12 months after the treatment, the liver tissue presented an obvious signal of albumin mRNA. Serum levels of hepatocyte growth factor (HGF) were significantly decreased 12 months after the treatment. In this study, we demonstrated that nucleoside analogues decrease HGF through the suppression of hepatocyte damage, leading to the restoration of albumin production in patients with CH-B.
Assuntos
Antivirais/uso terapêutico , Guanina/análogos & derivados , Hepatite B Crônica/sangue , Lamivudina/uso terapêutico , Albumina Sérica/metabolismo , Adulto , Idoso , Antivirais/farmacologia , Feminino , Expressão Gênica , Guanina/farmacologia , Guanina/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Fator de Crescimento de Hepatócito/sangue , Humanos , Lamivudina/farmacologia , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Albumina Sérica/genética , Fator de Crescimento Transformador beta1/sangue , Adulto JovemRESUMO
Hepatocellular carcinoma (HCC) is frequently associated with paraneoplastic hypercholesterolemia. However, cholesterol overproduction in HCC tissue has never been demonstrated. An aim of this study is to prove cholesterol overproduction in the HCC tissue of patients with paraneoplastic hypercholesterolemia. Six patients with HCC associated with paraneoplastic hypercholesterolemia and three control patients with HCC who did not have hypercholesterolemia were investigated regarding the expression of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase in HCC tissue by means of immunohistochemical technique. In HCC associated with paraneoplastic hypercholesterolemia, HMG-CoA reductase was clearly stained in cancer cells whereas surrounding non-tumorous hepatocytes showed only slight expression of HMG-CoA reductase. In contrast, HCC tissues derived from patients without paraneoplastic hypercholesterolemia showed only slight expression of HMG-CoA reductase whereas surrounding non-tumorous hepatocytes showed a clear expression of HMG-CoA reductase. We morphologically proved cholesterol overproduction in HCC tissue derived from patients with paraneoplastic hypercholesterolemia. Immunohistochemistry for HMG-CoA reductase thought to be useful in the diagnosis of paraneoplastic hypercholesterolemia.
Assuntos
Carcinoma Hepatocelular/enzimologia , Hidroximetilglutaril-CoA Redutases/metabolismo , Hipercolesterolemia/enzimologia , Neoplasias Hepáticas/enzimologia , Síndromes Paraneoplásicas/enzimologia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica , Hepatócitos/enzimologia , Humanos , Hidroximetilglutaril-CoA Redutases/genética , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Regulação para CimaRESUMO
BACKGROUND AND AIM: Percutaneous radiofrequency ablation (RFA) has been shown to be a highly effective treatment for hepatocellular carcinoma (HCC). We investigated the controllability of HCC and explored the algorithm of therapeutic strategy for HCC in patients who met the RFA criteria. METHODS: We enrolled 472 patients with HCC who met the RFA criteria (≤ 3 nodules, ≤ 3 cm) and underwent RFA for initial therapy. Patients who underwent repeated RFA were evaluated retrospectively when HCC exceeded the RFA criteria, or the functional hepatic reserve progressed to Child-Pugh grade C. RESULTS: Overall survival rates were: 1 year, 96%; 3 years, 79%; and 5 years, 56%. In 5 years, 14% of patients progressed to Child-Pugh grade C. Meanwhile, 47% of patients exceeded the RFA criteria. Annually, 8% of patients deviated from the RFA criteria. The percentage of patients who were able to receive RFA significantly decreased at the fourth session compared with up to the third session. The survival rates decreased at the rate of 7% annually until the third year after the initial RFA. Afterwards, it shifted to a decrease at the rate of 12% annually. In a multivariate analysis, the presence of hepatitis C virus infection and the existence of a single tumor were identified as significant independent factors contributing to probabilities exceeding the RFA criteria. CONCLUSIONS: HCC was controlled by RFA up to three RFA treatments and 3 years from the initial therapy. On this basis, we propose a "three (times) × 3 (years) index" for considering a shift from RFA to other treatment modalities.
Assuntos
Carcinoma Hepatocelular/cirurgia , Ablação por Cateter/métodos , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Carcinoma Hepatocelular/patologia , Progressão da Doença , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND/AIMS: We have evaluated the effectiveness of systemic chemotherapy for patients with extrahepatic metastasis from hepatocellular carcinoma. METHODOLOGY: We examined the background, survival rates, median survival time and side effects of 15 cases in which systemic chemotherapy using carboplatin and 5-fluorouracil was done (chemotherapy group) and 59 cases in which chemotherapy was not done (non-chemotherapy group) out of a total of 74 cases of patients with extrahepatic metastasis from hepatocellular carcinoma. RESULTS: The prognoses of the 15 chemotherapy cases and the 59 non-chemotherapy cases were as follows: 66.0%, 33.3%, 20.0% at 6 months, 12 months, 18 months respectively for the chemotherapy cases and 44.0%, 18.2%, 7.1% respectively for the non-chemotherapy cases. Median survival periods were 10.7 months for the chemotherapy group and 5.1 months for the non-chemotherapy group. A significantly better prognosis of survival (p=0.037) was identified in the chemotherapy group and no serious side effects were observed. CONCLUSIONS: The present research preceded the approval of sorafenib. This systemic combination chemotherapy will provide an extended survival prognosis and is thus considered to be comparatively safe and effective in those patients.
Assuntos
Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Neoplasias das Glândulas Suprarrenais/secundário , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/secundário , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Neoplasias das Glândulas Suprarrenais/mortalidade , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Ósseas/mortalidade , Carboplatina/administração & dosagem , Carcinoma Hepatocelular/mortalidade , Distribuição de Qui-Quadrado , Feminino , Fluoruracila/administração & dosagem , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Neoplasias Pulmonares/mortalidade , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
To examine the mRNA expression of hepatobiliary transporters in primary biliary cirrhosis (PBC) patients and to compare bile acid absorption, synthesis, and efflux in patients with non-end-stage and end-stage PBC, we obtained liver samples from PBC patients by percutaneous needle biopsy. End-stage PBC was defined as follows: histological stage IV; cirrhosis; serum total bilirubin, ≥4.0 mg/dl; and Child-Pugh Class C. The mRNA expression levels of sodium taurocholate cotransporting polypeptide (NTCP), bile salt export pump (BSEP), and hepatic cholesterol 7α-hydroxylase (CYP7A1) were significantly higher in the PBC patients than in the controls (P < 0.01). The mRNA levels of NTCP and BSEP were significantly higher in the end-stage PBC patients than in the controls (P < 0.01). However, hepatic CYP7A1 mRNA expression decreased significantly (by 70%) in the patients with end-stage PBC as compared to the controls and the patients with non-end-stage PBC (P < 0.01). The hepatic expression of transporters mediating bile acid influx and efflux showed sustained elevation, whereas that of the rate-limiting enzyme for bile acid biosynthesis was attenuated in the end-stage PBC patients. Thus, mechanisms may be present preventing the accumulation of toxic bile acids in the hepatocytes of end-stage PBC patients.
Assuntos
Transportadores de Cassetes de Ligação de ATP/biossíntese , Colesterol 7-alfa-Hidroxilase/biossíntese , Doença Hepática Terminal/metabolismo , Cirrose Hepática Biliar/metabolismo , Fígado/metabolismo , Transportadores de Ânions Orgânicos Dependentes de Sódio/biossíntese , Simportadores/biossíntese , Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Ácidos e Sais Biliares/metabolismo , Colesterol 7-alfa-Hidroxilase/genética , Regulação para Baixo , Humanos , Transportadores de Ânions Orgânicos Dependentes de Sódio/genética , RNA Mensageiro/biossíntese , Simportadores/genética , Regulação para CimaRESUMO
BACKGROUND/AIMS: The hepatic expression of bile acid transporters is altered in experimental cholestasis and it is unclear whether regulation exists in human cholestatic diseases. We investigated the expression of genes involved in bile acid detoxification, basolateral export and nuclear factor regulation in untreated primary biliary cirrhosis (PBC). METHODS: Liver tissues were obtained from patients with early-stage and late-stage PBC. The hepatic expression levels of messenger RNAs were determined by the real-time reverse transcription polymerase chain reaction. RESULTS: The hepatic expression of multidrug-resistance protein 4 messenger RNA was significantly upregulated in early-stage and late-stage PBC patients compared with controls. The hepatic expression of multidrug-resistance protein 2 and multidrug-resistance protein 3 messenger RNAs was significantly elevated only in early-stage PBC patients. The hepatic expression levels of farnesoid X receptor, fetoprotein transcription factor and constitutive androstane receptor mRNAs were correlated with those of multidrug-resistance protein 2, multidrug-resistance protein 3 and multidrug-resistance protein 4 respectively. CONCLUSIONS: The hepatic expression of multidrug-resistance protein 4 was enhanced in patients with untreated PBC at all stages. However, the hepatic expression of multidrug-resistance protein 2 and multidrug-resistance protein 3 was enhanced only in early-stage patients. The lack of upregulation of these proteins might contribute to the progression of PBC.
Assuntos
Proteínas de Transporte/metabolismo , Regulação da Expressão Gênica/fisiologia , Cirrose Hepática Biliar/metabolismo , Fígado/metabolismo , Glicoproteínas de Membrana/metabolismo , Southwestern Blotting , Receptor Constitutivo de Androstano , Proteínas de Ligação a DNA/metabolismo , Humanos , Microscopia de Fluorescência , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Sondas de Oligonucleotídeos/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND AND AIM: Fulminant hepatitis is still a fatal liver disease, and no specific treatment for it has been available. Vascular endothelial growth factor (VEGF) is the focus of attention because of its various actions. We investigated the effect of vascular endothelial growth factor (VEGF) on Fas-induced fulminant hepatic failure (FHF). METHOD: Male Balb/c mice were treated with an intraperitoneal injection of an anti-Fas antibody (Jo-2 Ab) with or without premedication with intraperitoneally administered human recombinant VEGF. RESULTS: The serum level of alanine aminotransferase (ALT) was up to 300 times higher that of normal mice following the Jo-2 Ab injection, and histological analysis revealed hepatic injury and massive hepatocyte apoptosis. The VEGF significantly suppressed an elevation in serum ALT levels and hepatocyte apoptosis. Immunohistochemically, VEGF-treated mice showed that Bcl-xL in hepatocytes was strongly expressed. CONCLUSIONS: Since hepatocytes do not express VEGF receptors, we speculated that VEGF acts on sinusoidal endothelial cells (SECs) and promotes production of cytokines such as hepatocyte growth factor in SECs, resulting in reducing apoptosis through an increase expression of Bcl-xL in hepatocytes. We suggest that VEGF has a potent antiapoptotic effect on hepatocytes through cell-cell interaction between SECs and hepatocytes.
Assuntos
Falência Hepática Aguda/prevenção & controle , Fígado/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor fas/metabolismo , Alanina Transaminase/sangue , Animais , Anticorpos , Apoptose , Modelos Animais de Doenças , Fator de Crescimento de Hepatócito/metabolismo , Humanos , Injeções Intraperitoneais , Fígado/imunologia , Fígado/patologia , Falência Hepática Aguda/imunologia , Falência Hepática Aguda/metabolismo , Falência Hepática Aguda/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Recombinantes/metabolismo , Fator A de Crescimento do Endotélio Vascular/administração & dosagem , Proteína bcl-X/metabolismo , Receptor fas/imunologiaRESUMO
BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is frequently associated with paraneoplastic hypercholesterolemia. In familial hypercholesterolemia, genetic mutation of the low-density lipoprotein (LDL) receptor gene has been recognized as being a pathogenesis of the disease. We investigate the expression of a LDL receptor protein and gene abnormalities of a LDL receptor in HCC cells in cases with paraneoplastic hypercholesterolemia. METHODS: Eleven patients with HCC associated with paraneoplastic hypercholesterolemia and seven patients with HCC who did not have hypercholesterolemia were studied. Paraffin-embedded tissues were obtained at operative resection, autopsy, or biopsy. Immunohistochemistry was performed using a monoclonal antibody against human LDL receptors. Confocal laser-scanning microscopy was used to observe the FITC-labeled LDL receptor. DNA samples were extracted from paraffin-embedded tissues. Since a LDL receptor gene is located on chromosome 19p13.2, a microsatellite marker, D19S413, was used to analyze the chromosomes. RESULTS: Immunoreactive LDL receptors were observed all over the surface of non-tumorous hepatocytes. However, expression of the LDL receptor was significantly decreased in all HCC cells derived from the 11 patients with hypercholesterolemia. In contrast, the expression was retained in the HCC cells of all patients without hypercholesterolemia. In two patients with hypercholesterolemia, DNA analysis revealed a loss of heterozygosity on chromosome 19p13.2. CONCLUSION: We demonstrated reduced expression of the LDL receptor in HCC cases with paraneoplastic hypercholesterolemia. LDL receptor genes with genomic disorders may cause decreased expression of the LDL receptor protein, leading to feed-back failure of the cholesterol regulation system, as seen in familial hypercholesterolemia. This is the first report considering the mechanism behind the development of paraneoplastic hypercholesterolemia in HCC.
Assuntos
Carcinoma Hepatocelular/química , Hipercolesterolemia/metabolismo , Neoplasias Hepáticas/química , Síndromes Paraneoplásicas/metabolismo , Receptores de LDL/análise , Adulto , Idoso , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Cromossomos Humanos Par 19 , Cromossomos Humanos Par 5 , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Hipercolesterolemia/genética , Hipercolesterolemia/patologia , Imuno-Histoquímica , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Perda de Heterozigosidade , Masculino , Pessoa de Meia-Idade , Síndromes Paraneoplásicas/genética , Síndromes Paraneoplásicas/patologia , Reação em Cadeia da Polimerase , Receptores de LDL/genéticaRESUMO
BACKGROUND: Gamma-glutamyltranspeptidase (GGT) has been recognized as an enzyme that converts glutathione into cysteine, and it is localized predominantly within the liver. Serum GGT is clinically recognized as the most useful marker for diagnosis of alcoholic liver disease (ALD). METHODS: GGT localization within the liver was examined immunohistochemically using an anti-GGT antibody and was visualized by confocal laser scanning microscopy in ALD and normal livers. Double immunostaining for GGT and dipeptidylpeptidase-IV (DPP-IV) was carried out to evaluate GGT localization in greater detail. RESULTS: Expression of GGT protein and mRNA was studied with immunoblot analysis and in situ hybridization, respectively. Immunohistochemically, the expression of GGT in the normal liver was faintly demonstrated in the bile canaliculi of hepatocytes and in biliary epithelial cells. In ALD livers, GGT was clearly demonstrated at the same sites. Double immunostaining demonstrated that GGT and DPP-IV were colocalized in hepatocytes in the ALD liver. In situ hybridization clearly demonstrated GGT-mRNA within the cytoplasm of hepatocytes and biliary epithelial cells. Immunoblot analysis revealed that GGT protein expression was increased in the ALD livers compared with that seen in the normal livers. CONCLUSION: These findings indicate that GGT in control and alcoholic livers is synthesized in hepatocytes and biliary epithelial cells, and is localized within the bile canalicular membrane and the luminal membrane in those cells, respectively. In conclusion, GGT synthesis and protein expression are increased in ALD livers, leading to the elevation of serum levels of GGT that are commonly noted in patients with the disease.
RESUMO
A 57 year-old woman was admitted to our hospital because of large hepatocellular carcinoma (HCC). Laboratory data showed hypercholesterolemia, thrombocytosis and hypoglycemia. Based on several examinations and the clinical course, we diagnosed HCC with paraneoplastic syndrome. It is rare that 3 paraneoplastic phenomena occur in a patient with HCC. In particular, paraneoplastic thrombocytosis is very rare in paraneoplastic syndrome associated with HCC.
Assuntos
Carcinoma Hepatocelular/complicações , Hipercolesterolemia/complicações , Hipoglicemia/complicações , Neoplasias Hepáticas/complicações , Síndromes Paraneoplásicas , Trombocitose/complicações , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Serum alkaline phosphatase (ALP) is a representative marker of cholestasis, in diseases such as primary biliary cirrhosis (PBC). However, the hepatic localization of ALP in patients with cholestatic liver diseases has not been fully clarified. Accordingly, we studied the expression of ALP in the liver of PBC, chronic hepatitis C and controls. By immunohistochemistry, in the liver tissue of controls and chronic hepatitis C patients, ALP was found to be localized in the canalicular membrane of hepatocytes and the apical area of the cytoplasm of bile duct epithelial cells. In PBC, ALP was localized in both the canalicular and baso-lateral membranes of hepatocytes and in the whole cytoplasm of the remaining bile duct epithelial cells. The expression of ALP in liver tissues evaluated by Western blotting was increased to 3.6-fold in PBC compared with that in the controls and chronic hepatitis C patients, while the expression of mRNA of ALP evaluated by RT-PCR was increased to 7.0-fold in PBC compared with that in the controls and chronic hepatitis C patients. The present study is the first study to reveal altered localization and increased expression of ALP which may result in the elevation of serum ALP in PBC.
RESUMO
AIM: Recently percutaneous ethanol injection (PEI) turned into percutaneous radiofrequency ablation (PRFA), and it has become widely used for the treatment of hepatocellular carcinoma (HCC). The present study was to compare the incidence in postoperative HCC recurrence between these two therapeutic approaches. METHODS: One hundred and sixty-eight first-time HCC in patient cases were chosen for PEI (n=94) and PRFA (n=74). The localized recurrence rate based on the operator's experience in percutaneous treatment for HCC (on <5 years versus >/=5 years experience) was examined. RESULTS: The PRFA group demonstrated a significantly lower localized recurrence rate within 2 years than the PEI group (8% and 22%, respectively, P<0.01). The local recurrence rate of HCC within 2 years after PEI was significantly lower in those for whom the operator's experience was more than 5 years compared to those for whom it was less than 5 years (12% versus 24%, respectively, P<0.05). In contrast, after PRFA there was no significant difference between these two groups of <5 years and of >/=5 years experience (8% versus 8%, respectively, P=0.98). CONCLUSION: The present study demonstrated that PRFA resulted in a lower rate of local recurrence in comparison to conventional PEI, regardless of the operator's experience.
RESUMO
A 54-year-old woman was admitted to our hospital because of acute liver injury. Since she had a history of having used a diet product, drug-induced liver injury (DILI) was initially considered. However, the patient was subsequently diagnosed as suffering from primary biliary cirrhosis (PBC) based on the findings of liver histology and serum anti-mitochondrial antibody positivity. Overlap syndrome between PBC and autoimmune hepatitis (AIH) was also suspected, however, serum levels of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase became normal three months later, after treatment with combination therapy comprising ursodeoxycholic acid plus bezafibrate. We therefore concluded that the liver disease in this patient was actually PBC, but that it resembled overlap syndrome or DILI. In cases of PBC, a rapid onset, as frequently seen in the case of DILI, viral hepatitis or AIH, is not common. We herein report a rare case of PBC which resembled DILI.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Suplementos Nutricionais/efeitos adversos , Cirrose Hepática Biliar/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Preparações de Plantas , Fatores de TempoRESUMO
A 73-year-old female with hepatocellular carcinoma (HCC) received percutaneous transhepatic portal vein embolization (PTPE) before extensive right lobe hepatectomy. Serum levels of des-gamma-carboxy-prothrombin (DCP) were increased and remained at a high level until hepatectomy. Immunohistochemical examination revealed that an increased expression of DCP was demonstrated not only in HCC tissues, but also in the non-cancerous liver of the right lobe, where portal blood flow was blocked off as a result of PTPE. The serum level of DCP is known to be greatly increased in patients with HCC accompanied by portal vein invasion. We speculate that this increased DCP level is caused by both increased DCP production in HCC tissue and the surrounding non-cancerous liver, where portal flow is blocked off as a result of portal invasion by HCC.