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BACKGROUND: Obeticholic acid (OCA) was recently approved as the only on-label alternative for patients with primary biliary cholangitis (PBC) with intolerance or suboptimal response to ursodeoxycholic acid (UDCA). However, few data are available outside clinical trials. AIM: To assess the effectiveness and safety of OCA in a real-world cohort of patients with non-effective UDCA therapy. METHODS: Open-label, prospective, real-world, multicentre study, enrolling consecutive patients who did not meet Paris II criteria, from 18 institutions in Spain and Portugal. Effectiveness was assessed by the changes in GLOBE and UK-PBC scores from baseline. POISE and Paris II criteria were evaluated after 12 months of OCA . Liver fibrosis was evaluated by FIB-4 and AST to platelet ratio index (APRI). RESULTS: One hundred and twenty patients were eligible, median time since PBC diagnosis 9.3 (4.0-13.8) years, 21.7% had cirrhosis, and 26.7% received had previous or concomitant treatment with fibrates. Seventy-eight patients completed at least 1 year of OCA. The Globe-PBC score decreased to 0.17 (95% CI 0.05 to 0.28; P = 0.005) and the UK-PBC score decreased to 0.81 (95% CI -0.19 to 1.80; P = 0.11). There was a significant decrease in alkaline phosphatase of 81.3 U/L (95% CI 42.5 to 120; P < 0.001), ALT 22.1 U/L (95% CI 10.4 to 33.8; P < 0.001) and bilirubin 0.12 mg/dL (95% CI 0 to 0.24; P = 0.044). FIB-4 and APRI remained stable. According to the POISE criteria, 29.5% (23 out of 78) achieved response. The adverse events rate was 35%; 11.67% discontinued (8.3% due to pruritus). CONCLUSIONS: This study supports data from phase III trials with significant improvement of PBC-Globe continuous prognostic marker score among OCA-treated patients with good tolerability.
Subject(s)
Liver Cirrhosis, Biliary , Ursodeoxycholic Acid , Chenodeoxycholic Acid/analogs & derivatives , Cholagogues and Choleretics/adverse effects , Humans , Liver Cirrhosis, Biliary/drug therapy , Prospective Studies , Spain , Ursodeoxycholic Acid/adverse effectsABSTRACT
Pravastatin has demonstrated anti-tumor activity in preclinical and clinical studies. This multicentric randomized double-blind placebo-controlled phase II study (NCT01418729) investigated the efficacy and safety of sorafenib + pravastatin combination on the overall survival (OS) and time to progression (TTP) of patients with advanced hepatocellular carcinoma (aHCC). A total of 31 patients were randomized. Median OS did not differ between both groups (12.4 months for the sorafenib + pravastatin group vs. 11.6 months for the control group). Of note, however, the radiological TTP was higher in patients treated with sorafenib + pravastatin than in the control group (9.9 months vs. 3.2 months; p = 0.008). Considering all the study population, the presence of portal vein thrombosis (PVT) was associated with worse OS, being lower in patients with PVT compared to patients without PVT (6.3 months vs. 14.8 months; p = 0.026). Data also showed a decrease in OS in patients with vascular invasion (VI) compared to patients who did not present it (6.3 months vs. 14.8 months; p = 0.041). The group of patients without dermatological events (DE) showed lower OS (6.9 months vs. 14.5 months; p = 0.049). In conclusion, combination of sorafenib + pravastatin was safe and well-tolerated, prolonging the TTP of patients with aHCC but not improving the OS compared to sorafenib + placebo. The absence of PVT and VI and the development of DE are positive prognostic factors of sorafenib response.
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BACKGROUND & AIMS: Information on safety and efficacy of systemic treatment in patients with hepatocellular carcinoma (HCC) under dialysis are limited due to patient exclusion from clinical trials. Thus, we aimed to evaluate the rate, prevalence, tolerability, and outcome of sorafenib in this population. METHODS: We report a multicenter study comprising patients from Latin America and Europe. Patients treated with sorafenib were enrolled; demographics, dose modifications, adverse events (AEs), treatment duration, and outcome of patients undergoing dialysis were recorded. RESULTS: As of March 2018, 6156 HCC patients were treated in 44 centres and 22 patients were concomitantly under dialysis (0.36%). The median age was 65.5 years, 40.9% had hepatitis C, 75% had Child-Pugh A, and 85% were Barcelona Clinic Liver Cancer-C. The median time to first dose modification, treatment duration and overall survival rate were 2.4 months (interquartile ranges [IQR], 0.8-3.8), 10.8 months (IQR, 4.5-16.9), and 17.5 months (95% CI, 7.2-24.5), respectively. Seventeen patients required at least 1 dose modification. The main causes of first dose modification were asthenia/worsening of Eastern Cooperative Oncology Group-Performance Status and diarrhoea. At the time of death or last follow-up, four patients were still on treatment and 18 had discontinued sorafenib: 14 were due to tumour progression, 2 were sorafenib-related, and 2 were non-sorafenib-related AE. CONCLUSIONS: The outcomes observed in this cohort seem comparable to those in the non-dialysis population. Thus, to the best of our knowledge, this is the largest and most informative dataset regarding systemic treatment outcomes in HCC patients undergoing dialysis.
Subject(s)
Antineoplastic Agents , Carcinoma, Hepatocellular , Liver Neoplasms , Aged , Antineoplastic Agents/adverse effects , Carcinoma, Hepatocellular/drug therapy , Europe , Humans , Liver Neoplasms/drug therapy , Niacinamide/adverse effects , Phenylurea Compounds/adverse effects , Renal Dialysis , Sorafenib/therapeutic use , Treatment OutcomeABSTRACT
Antecedentes y objetivo: En 2010 publicamos que en España el 53% de los carcinomas hepatocelulares (CHC) se diagnostican fuera de programas de cribado, lo que conlleva una menor supervivencia. El objetivo del presente estudio es evaluar la situación actual y las causas del diagnóstico fuera de cribado. Material y métodos: Registro prospectivo entre el 1 de octubre de 2014 y el 31 de enero de 2015 en 73 centros asistenciales españoles de segundo/tercer nivel. Se registraron las características basales y el primer tratamiento de los tumores primarios hepáticos incidentales de ese período. Resultados: Se incluyeron 720 pacientes: CHC (n=686), colangiocarcinoma intrahepático (n=29), hepatocolangiocarcinoma (n=2), otros (n=3). Los pacientes con CHC fueron varones en el 82% de los casos; media de 67 años; cirrosis en el 87%; etiología: alcohol 35%, VHC 30%, alcohol y VHC 15%, enfermedad hepática por depósito de grasa 6%; estadio tumoral: BCLC-0 11%, A 43%, B 19%, C 16% y D 11%; tratamiento inicial: quimioembolización transarterial (23%), ablación percutánea (22%), tratamiento sintomático (20%), resección (11%), sorafenib (11%). Se diagnosticaron fuera de cribado 356 pacientes (53%). Los motivos principales fueron la ausencia de diagnóstico previo de hepatopatía (76%) y la mala adherencia al cribado (18%). Estos pacientes eran predominantemente varones (p<0,001), de etiología alcohólica (p<0,001), con consumo activo de alcohol (p<0,001) y se diagnosticaron en estadios más avanzados (p<0,001), recibiendo menos tratamientos radicales (p<0,001). Conclusiones: En España, la principal causa del diagnóstico de CHC fuera del cribado es la ausencia de diagnóstico previo de enfermedad hepática, principalmente en varones con consumo de alcohol. La detección de hepatopatía en población asintomática y la mejora de la adherencia al cribado son los principales aspectos para mejorar la detección precoz (AU)
Background and objective: In 2010 we published that 53% of cases of hepatocellular carcinoma (HCC) detected in Spain were diagnosed outside the context of standard screening programs, which consequently leads to lower survival rates. The aim of this study was to analyze the current situation and the causes of diagnosis out of screening programs. Material and methods: Prospective registry of 73 second- and third-level Spanish healthcare centers carried out between October 1, 2014 and January 31, 2015. The baseline characteristics of the disease and the first treatment administered for the incidental primary liver tumors during such period were recorded. Results: A total of 720 patients were included in the study: HCC (n=686), intrahepatic cholangiocarcinoma (n=29), hepatic cholangiocarcinoma (n=2), other (n=3). HCC characteristics: male 82%; mean age 67 years; cirrhosis 87%; main etiologies: alcohol 35%, HCV 30%, alcohol and HCV 15%, non-alcoholic fatty liver disease 6%; tumor stage: BCLC-0 11%, A 43%, B 19%, C 16% and D 11%; first treatment: transarterial chemoembolization (23%), percutaneous ablation (22%), symptomatic treatment (20%), resection (11%), sorafenib (11%). Three hundred and fifty-six patients (53%) were diagnosed outside of screening programs, mainly owing to the fact that they suffered from an undiagnosed liver disease (76%) and to the poor adherence to the screening program (18%). These patients were mainly male (P<.001), with an alcoholic etiology (P<.001) and active alcohol consumption (P<.001). Moreover, the disease was predominantly diagnosed at more advanced stages (P<.001) and was addressed with less radical treatments (P<.001). Conclusions: In Spain, the main cause of diagnosis of a HCC outside the context of a screening program is the absence of a prior diagnosis of a liver disease, particularly in alcohol-consuming men. Detecting a liver disease in asymptomatic populations and improving adherence to screening programs are the main areas that must be subject to improvement in order to improve the early detection of HCC (AU)
Subject(s)
Humans , Carcinoma, Hepatocellular/epidemiology , Liver Neoplasms/epidemiology , Cholangiocarcinoma/epidemiology , Early Detection of Cancer/statistics & numerical data , Prospective Studies , Mass Screening/statistics & numerical data , Incidence , Neoplasm Staging/statistics & numerical data , Practice Patterns, Physicians'ABSTRACT
BACKGROUND AND OBJECTIVE: In 2010 we published that 53% of cases of hepatocellular carcinoma (HCC) detected in Spain were diagnosed outside the context of standard screening programs, which consequently leads to lower survival rates. The aim of this study was to analyze the current situation and the causes of diagnosis out of screening programs. MATERIAL AND METHODS: Prospective registry of 73 second- and third-level Spanish healthcare centers carried out between October 1, 2014 and January 31, 2015. The baseline characteristics of the disease and the first treatment administered for the incidental primary liver tumors during such period were recorded. RESULTS: A total of 720 patients were included in the study: HCC (n=686), intrahepatic cholangiocarcinoma (n=29), hepatic cholangiocarcinoma (n=2), other (n=3). HCC characteristics: male 82%; mean age 67 years; cirrhosis 87%; main etiologies: alcohol 35%, HCV 30%, alcohol and HCV 15%, non-alcoholic fatty liver disease 6%; tumor stage: BCLC-0 11%, A 43%, B 19%, C 16% and D 11%; first treatment: transarterial chemoembolization (23%), percutaneous ablation (22%), symptomatic treatment (20%), resection (11%), sorafenib (11%). Three hundred and fifty-six patients (53%) were diagnosed outside of screening programs, mainly owing to the fact that they suffered from an undiagnosed liver disease (76%) and to the poor adherence to the screening program (18%). These patients were mainly male (P<.001), with an alcoholic etiology (P<.001) and active alcohol consumption (P<.001). Moreover, the disease was predominantly diagnosed at more advanced stages (P<.001) and was addressed with less radical treatments (P<.001). CONCLUSIONS: In Spain, the main cause of diagnosis of a HCC outside the context of a screening program is the absence of a prior diagnosis of a liver disease, particularly in alcohol-consuming men. Detecting a liver disease in asymptomatic populations and improving adherence to screening programs are the main areas that must be subject to improvement in order to improve the early detection of HCC.
Subject(s)
Carcinoma, Hepatocellular/diagnosis , Early Detection of Cancer , Liver Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/therapy , Female , Guideline Adherence/statistics & numerical data , Humans , Liver Neoplasms/etiology , Liver Neoplasms/therapy , Male , Middle Aged , Practice Guidelines as Topic , Practice Patterns, Physicians'/statistics & numerical data , Prospective Studies , SpainABSTRACT
BACKGROUND & AIMS: Sorafenib (SOR) is the standard of care for patients with hepatocellular carcinoma (HCC) and portal vein invasion (PVI), based on the results of phase 3 trials. However, radioembolization (RE) using yttrium-90 microspheres has been shown to achieve higher response rates and better survival in large cohorts and phase 2 trials. This study aimed to compare survival of HCC patients with PVI treated by RE or SOR. METHODS: Survival among patients with HCC and PVI treated with RE or SOR in four Spanish hospitals between 2005 and 2013 was analysed retrospectively. Kaplan-Meier survival curves were plotted and baseline variables tested for prognostic value using the log-rank test. A multivariate prognostic model including variables identified in the univariate analysis and adjusted by a propensity score based on factors that may determine the probability of exposure to RE was generated using Cox regression analyses. RESULTS: After a median follow-up of 6 months, 60 deaths had occurred: 38 and 22 in SOR and RE groups respectively. Median survival was 6.7 months (95%CI 5.2-8.1 months) for the entire cohort, and 8.8 months (95%CI 1.8-15.8) in the RE group and 5.4 months (95%CI 2.7-8.1) in the SOR group (P = 0.047). The difference in survival was still statistically significant when 13 patients in the RE group who started SOR after a median time of 8 months were censored from the analysis. CONCLUSIONS: In a cohort of patients with HCC and PVI treatment with RE was associated with a more prolonged survival compared with SOR.
Subject(s)
Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic , Liver Neoplasms/mortality , Liver Neoplasms/therapy , Niacinamide/analogs & derivatives , Phenylurea Compounds/therapeutic use , Aged , Antineoplastic Agents/therapeutic use , Female , Humans , Logistic Models , Male , Microspheres , Middle Aged , Niacinamide/therapeutic use , Portal Vein/pathology , Propensity Score , Radiopharmaceuticals/therapeutic use , Retrospective Studies , Sorafenib , Spain , Survival Analysis , Yttrium Radioisotopes/therapeutic useABSTRACT
OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of entecavir monotherapy in nucleos(t)ide-naive chronic hepatitis B patients and to analyse the influence of the comorbidity burden on therapy outcome. METHODS: We retrospectively analysed data from 237 nucleos(t)ide-naive chronic hepatitis B white patients treated with entecavir (0.5 mg/day) at 23 Spanish centres. For the efficacy and safety analyses, patients were grouped according to their baseline comorbidities. RESULTS: The mean age of the cohort was 43 years (range: 19-82 years); 73% were male, 83% were white, and 33% were hepatitis B e antigen (HBeAg) positive. At baseline, the median hepatitis B virus DNA level was 6.20 log10 IU/ml. Of the patients, 18% had cirrhosis, 9.7% had diabetes, 16.3% had hypertension, and 15.7% had obesity; 13.4% of patients had more than one comorbid condition. Virological and biochemical responses at month 36 were obtained independently of the patients' baseline comorbid condition. Of 10 HBeAg-positive patients who discontinued treatment after HBeAg seroconversion, those who had not also cleared HBsAg (six) experienced virological recurrence in a median 5.6 months. There were no treatment discontinuations due to adverse events. Three patients were diagnosed with hepatocellular carcinoma at months 12, 30 and 54, and six experienced hepatic decompensation during follow-up. The median serum creatinine levels did not increase after 36 months of treatment, even in patients with comorbidities. CONCLUSION: Entecavir is safe, well tolerated, and highly effective, even in patients with comorbid condition(s). Discontinuation of treatment in patients who have not been cleared of HBsAg may lead to virological recurrence.
Subject(s)
Antiviral Agents/therapeutic use , Guanine/analogs & derivatives , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/drug therapy , Adult , Aged , Aged, 80 and over , Alanine Transaminase/blood , Antiviral Agents/adverse effects , Creatinine/blood , DNA, Viral/blood , Diabetes Mellitus , Female , Follow-Up Studies , Guanine/adverse effects , Guanine/therapeutic use , Hepatitis B Antibodies/blood , Hepatitis B Surface Antigens/immunology , Hepatitis B e Antigens/immunology , Hepatitis B virus/genetics , Hepatitis B, Chronic/blood , Humans , Hypertension/complications , Liver Cirrhosis/complications , Male , Middle Aged , Obesity/complications , Recurrence , Retrospective Studies , White People , Young AdultABSTRACT
BACKGROUND & AIMS: The addition of protease inhibitors (PIs) changed the hepatitis C virus (HCV) treatment standards and improved sustained viral response (SVR) rates in patients with genotype 1 HCV infection. METHODS: Prospective, multicentre, national registry that includes naïve and treatment-experienced patients with HCV genotype 1 infection, who had bridging fibrosis or cirrhosis and were treated with triple therapy (peginterferon alfa-2a or alfa-2b, ribavirin and boceprevir) as compassionate use, and in accordance with the Summary of Product Characteristics. RESULTS: Most of the patients (68.2%) were male, with a mean age of 53 years, 75% (n = 128) had HCV 1b genotype and baseline viral load of 6.2 log. According to prior treatment, 20% of patients were treatment-naïve and 80% had received prior treatment. Approximately 36.5% of patients (n = 62) reported at least one serious adverse events (SAEs) (total SAEs = 103). The most common SAEs were neutropenia (57.6%), anaemia (47.6%) and grade 3 thrombopenia (25.9%). Patients with albumin <3.5 g/dl and bilirubin >2 mg/dl had an increased relative risk (greater than one-fold) for SAEs, including infections and hepatic decompensation. In the intent-to-treat analysis (n = 170), the overall percentage of patients with SVRw12 was 46.5%. In patients with 1 log decrease at week 4 (lead-in phase), the overall SVRw12 rate was 67.0%. In the patients initiating triple therapy with boceprevir (n = 139), the global response rate was 56.4%. In a multivariate analysis, an increased probability of achieving SVR was associated with response to prior treatment (relapsers), >1 log decrease in viral load in the lead-in phase and baseline albumin >3.5 g/dl. CONCLUSIONS: Triple therapy in patients with severe fibrosis/cirrhosis is associated with a higher rate of SAE and a lower rate in comparison with patients with mild disease. However, for patients with intact liver function, it could be considered as a treatment option, when other alternatives would not be available.
Subject(s)
Hepacivirus/genetics , Hepatitis C/drug therapy , Interferon-alpha/therapeutic use , Liver Cirrhosis/drug therapy , Polyethylene Glycols/therapeutic use , Proline/analogs & derivatives , Protease Inhibitors/therapeutic use , Ribavirin/therapeutic use , Compassionate Use Trials , Drug Therapy, Combination/adverse effects , Hepatitis C/complications , Hepatitis C/genetics , Humans , Interferon-alpha/adverse effects , Liver Cirrhosis/etiology , Male , Middle Aged , Polyethylene Glycols/adverse effects , Proline/adverse effects , Proline/therapeutic use , Prospective Studies , Protease Inhibitors/adverse effects , Recombinant Proteins/adverse effects , Recombinant Proteins/therapeutic use , Ribavirin/adverse effects , SpainABSTRACT
IntroducciónLos pacientes cirróticos con frecuencia presentan trastornos nutricionales.ObjetivosValorar en pacientes con hepatopatía crónica los niveles plasmáticos de ácido fólico y vitamina B12 y determinar si estos parámetros pueden ayudar al diagnóstico etiológico de esta enfermedad.Pacientes y métodoSe estudiaron 39 pacientes que ingresan por descompensación de su hepatopatía (29 de etiología alcohólica y 10 por otras causas) y se comparan con 35 controles. Se analizaron, entre otros, los niveles plasmáticos de ácido fólico, vitamina B12, volumen corpuscular medio (VCM), aspartato aminotransferasa (AST), alanino aminotransferasa (ALT), el cociente AST/ALT, la gammaglutamiltransferasa (GGT).ResultadosLos niveles plasmáticos de vitamina B12 en pacientes con hepatopatía crónica descompensada eran de 1.151±568pg/ml y 440±133pg/ml en los controles (p<0,05). Los niveles plasmáticos de ácido fólico fueron de 8,57±3,8ng/ml en los controles y de 6,68±2,74ng/ml en los pacientes con hepatopatía crónica descompensada (p<0,05). Los pacientes con hepatopatía crónica de etiología alcohólica tenían unos niveles plasmáticos de ácido fólico inferiores que los pacientes con hepatopatía no alcohólica (5,7±2,1 frente a 9,3±2.6; p<0,0005). El cociente entre la vitamina B12/ácido fólico discriminaba mejor la etiología alcohólica que otros parámetros analíticos como la AST, ALT, VCM, el cociente AST/ALT y la GGT.ConclusionesLos niveles plasmáticos de vitamina B12 en pacientes con hepatopatía crónica descompensada están altos, mientras que los niveles plasmáticos de ácido fólico están bajos. El cociente entre la vitamina B12 y el ácido fólico podría ser útil en el diagnóstico diferencial de la etiología de la hepatopatía crónica(AU)
BackgroundPatients with liver disease frequently experience changes in their nutritional status.ObjectiveTo determine changes in vitamin B12 and folic acid plasma levels in patients with chronic cirrhosis and to assess whether these parameters may be useful in the etiologic diagnosis of this disease.Patients and methodsThirty-nine patients admitted for decompensated cirrhosis (29 with alcoholic etiology and 10 with non-alcoholic etiology) and 35 controls were prospectively studied. Plasma levels of vitamin B12, folate acid, mean corpuscular volume (MCV), aspartate aminotransferase (AST), alanine aminotransferase (ALT), AST/ALT ratio, and gamma-glutamyltransferase (GGT), among other parameters, were measured.ResultsVitamin B12 levels were 1151±568pg/ml in patients with decompensated cirrhosis and 440±133pg/ml in controls (p<0.05). Plasma folate levels were 8.57±3.8ng/ml in controls and 6.68±2.74ng/ml in patients with cirrhosis (p<0.05). Folate levels were lower in patients with alcoholic cirrhosis (mean value, 5.7±2.1) than in those with non-alcoholic cirrhosis (9.3±2.6; p<0.0005). The vitamin B12/folate ratio discriminated alcoholic etiology better than other parameters such as AST, ALT, MCV, AST/ALT ratio and GGT.ConclusionsPlasma levels of vitamin B12 in patients with decompensated chronic liver disease are high, whereas plasma folate levels are low. The ratio between vitamin B12 and folic acid may be useful in the differential diagnosis of the etiology of chronic liver disease(AU)
Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Liver Cirrhosis/blood , Vitamin B 12/blood , Diagnosis, Differential , Folic Acid Deficiency/blood , gamma-Glutamyltransferase/blood , Homocysteine/blood , Liver Cirrhosis/diagnosis , Liver Cirrhosis/etiology , Liver Failure/etiology , Liver Function Tests , Prognosis , Prospective Studies , Aspartate Aminotransferases/blood , Alanine Transaminase/bloodABSTRACT
Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming a world-wide public health problem. NAFLD represents a spectrum of disease ranging from "simple steatosis", which is considered relatively benign, to nonalcoholic steatohepatitis and to NAFLD-associated cirrhosis and end-stage liver disease. The etiology of NAFLD and its progression is complex and remains incompletely understood. The progression of the disease involves many factors. Apart from the two hits, the accumulation of TG and the development of fibrosis and necroinflammatory processes, exit numerous molecules associated with these two hits. Among them we can highlight the pro-inflammatory molecules and adiponectins. This review focuses on the growing evidence from both experimental and human studies suggesting a central role of cytokines in the pathogenesis of NAFLD. We review the role of cytokines as key regulators of insulin sensitivity and hepatic lipid overloading, liver injury and inflammation, and fibrosis with an emphasis on potential therapeutic implications.
Subject(s)
Fatty Liver/immunology , Inflammation Mediators/immunology , Inflammation/immunology , Animals , Fatty Liver/pathology , Fatty Liver/physiopathology , Fatty Liver/therapy , Humans , Inflammation/pathology , Inflammation/physiopathology , Obesity/physiopathology , Oxidative Stress , Risk FactorsABSTRACT
BACKGROUND: Patients with liver disease frequently experience changes in their nutritional status. OBJECTIVE: To determine changes in vitamin B12 and folic acid plasma levels in patients with chronic cirrhosis and to assess whether these parameters may be useful in the etiologic diagnosis of this disease. PATIENTS AND METHODS: Thirty-nine patients admitted for decompensated cirrhosis (29 with alcoholic etiology and 10 with non-alcoholic etiology) and 35 controls were prospectively studied. Plasma levels of vitamin B(12), folate acid, mean corpuscular volume (MCV), aspartate aminotransferase (AST), alanine aminotransferase (ALT), AST/ALT ratio, and gamma-glutamyltransferase (GGT), among other parameters, were measured. RESULTS: Vitamin B(12) levels were 1151+/-568pg/ml in patients with decompensated cirrhosis and 440+/-133pg/ml in controls (p<0.05). Plasma folate levels were 8.57+/-3.8ng/ml in controls and 6.68+/-2.74ng/ml in patients with cirrhosis (p<0.05). Folate levels were lower in patients with alcoholic cirrhosis (mean value, 5.7+/-2.1) than in those with non-alcoholic cirrhosis (9.3+/-2.6; p<0.0005). The vitamin B(12)/folate ratio discriminated alcoholic etiology better than other parameters such as AST, ALT, MCV, AST/ALT ratio and GGT. CONCLUSIONS: Plasma levels of vitamin B12 in patients with decompensated chronic liver disease are high, whereas plasma folate levels are low. The ratio between vitamin B12 and folic acid may be useful in the differential diagnosis of the etiology of chronic liver disease.
Subject(s)
Folic Acid/blood , Liver Cirrhosis/blood , Liver Function Tests/methods , Vitamin B 12/blood , Adolescent , Adult , Aged , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Diagnosis, Differential , Erythrocyte Indices , Female , Folic Acid Deficiency/blood , Folic Acid Deficiency/epidemiology , Homocysteine/blood , Humans , Liver Cirrhosis/diagnosis , Liver Cirrhosis/etiology , Liver Cirrhosis, Alcoholic/blood , Liver Cirrhosis, Alcoholic/diagnosis , Liver Diseases, Alcoholic/blood , Liver Diseases, Alcoholic/complications , Liver Failure/etiology , Male , Middle Aged , Prognosis , Prospective Studies , Young Adult , gamma-Glutamyltransferase/bloodABSTRACT
BACKGROUND: The prevalence of nonalcoholic fatty liver disease (NAFLD) is high. NAFLD is linked to obesity, diabetes mellitus, and hypertriglyceridemia. Approximately 20% of patients with NAFLD will eventually develop cirrhosis. Our purpose was to investigate whether resveratrol decreased hepatic steatosis in an animal model of steatosis, and whether this therapeutic approach resulted in a decrease in tumor necrosis factor alpha (TNF-alpha) production, lipid peroxidation and oxidative stress. METHODS: Male Wistar CRL: Wi (Han) (225 g) rats were randomized into three groups. A control group (n = 12) was given free access to regular dry rat chow for 4 weeks. The steatosis (n = 12) and resveratrol (n = 12) groups were given free access to feed (a high carbohydrate-fat free modified diet) and water 4 days per week, and fasted for the remaining 3 days for 4 weeks. Rats in the resveratrol group were given resveratrol 10 mg daily by the oral route. All rats were killed at 4 weeks and assessed for fatty infiltration and bacterial translocation. Levels of TNF-alpha in serum, hepatic malondialdehyde (MDA), oxidative stress (superoxide dismutase, glutathione peroxidase, catalase and nitric oxide synthase) and biochemical parameters were measured. RESULTS: Fat deposition was decreased in the resveratrol group as compared to the steatosis group (Grade 1 vs Grade 3, P < 0.05). TNF-alpha and MDA levels were significantly increased in the steatosis group (TNF-alpha; 33.4 +/- 5.2 vs 26.24 +/- 3.47 pg/ml and MDA; 9.08 +/- 0.8 vs 3.17 +/- 1.45 muM respectively, P < 0.05). This was accompanied by increased superoxide dismutase, glutathione peroxidase and catalase and decreased nitric oxide synthase in the liver of resveratrol group significantly (P < 0.05 vs steatosis group). Bacterial translocation was not found in any of the groups. Glucose levels were decreased in the group of rats given resveratrol (P < 0.05). CONCLUSION: Resveratrol decreased NAFLD severity in rats. This effect was mediated, at least in part, by TNF-alpha inhibition and antioxidant activities.
Subject(s)
Antioxidants/therapeutic use , Fatty Liver/drug therapy , Stilbenes/therapeutic use , Animals , Antioxidants/pharmacology , Catalase/metabolism , Disease Models, Animal , Fatty Liver/metabolism , Glucose/metabolism , Glutathione Peroxidase/metabolism , Lipid Peroxidation/drug effects , Male , Malondialdehyde/metabolism , Nitric Oxide Synthase/metabolism , Oxidative Stress/drug effects , Random Allocation , Rats , Rats, Wistar , Resveratrol , Severity of Illness Index , Stilbenes/pharmacology , Superoxide Dismutase/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
BACKGROUND: Colonoscopy is one of the methods of choice for screening relatives of patients with colorectal cancer. OBJECTIVE: To evaluate the rate of adherence to colonoscopy in first-degree relatives of patients with colorectal cancer and describe the lesions found. METHODS: A prospective, cross-sectional, multicentre, nationwide study was conducted. The study population was composed of first-degree relatives of patients with colorectal cancer selected randomly from the EPICOLON study. Seventy-four index patients were included. These had 342 living first-degree relatives (parents, siblings and children), of whom 281 were interviewed. RESULTS: The adherence rate was 38% (107/281). Adherence was greater in families with a higher degree of familial aggregation for colorectal cancer (88.9% for Amsterdam vs 33.3% for Bethesda and sporadic cancer; p<0.05), an index patient aged under 65 years (60% for patients <65 years vs 32.9% for patients >or=65 years; p<0.05) and an index patient who was female (46.2% for women vs 31% for men; p = 0.28). Adherence was also greater in relatives under 65 years (54% in patients <65 years vs 18% in patients >or=65 years; p = 0.05), in female relatives (49% in female relatives vs 27.3% in male relatives; p<0.05) and in siblings and children (40% in siblings and children vs 13% in parents; p<0.05). Lesions were found in 26% (28/107) of the study population. Nine (8.4%) individuals had a total of 18 advanced lesions. CONCLUSIONS: These results indicate that adherence to colonoscopy in our population of first-degree relatives was low. The adherence was more frequently associated with a higher degree of familial aggregation, a relative age of under 65 years, a sibling or offspring relationship, and female sex.
Subject(s)
Colonoscopy/psychology , Colorectal Neoplasms/diagnosis , Mass Screening/psychology , Patient Compliance , Adult , Age Factors , Aged , Colonoscopy/statistics & numerical data , Colorectal Neoplasms/genetics , Colorectal Neoplasms/psychology , Female , Genetic Predisposition to Disease , Humans , Male , Mass Screening/statistics & numerical data , Middle Aged , Prospective Studies , Sex Factors , SpainABSTRACT
BACKGROUND: Resveratrol is a polyphenol with important antiinflammatory and antioxidant properties. We investigated the effect of resveratrol on alcohol-induced mortality and liver lesions in mice. METHODS: Mice were randomly distributed into four groups (control, resveratrol-treated control, alcohol and resveratrol-treated alcohol). Chronic alcohol intoxication was induced by progressively administering alcohol in drinking water up to 40% v/v. The mice administered resveratrol received 10 mg/ml in drinking water. The animals had free access to standard diet. Blood levels were determined for transaminases, IL-1 and TNF-alpha. A histological evaluation was made of liver damage, and survival among the animals was recorded. RESULTS: Transaminase concentration was significantly higher in the alcohol group than in the rest of the groups (p < 0.05). IL-1 levels were significantly reduced in the alcohol plus resveratrol group compared with the alcohol group (p < 0.05). TNF-alpha was not detected in any group. Histologically, the liver lesions were more severe in the alcohol group, though no significant differences between groups were observed. Mortality in the alcohol group was 78% in the seventh week, versus 22% in the alcohol plus resveratrol group (p < 0.001). All mice in the alcohol group died before the ninth week. CONCLUSION: The results obtained suggest that resveratrol reduces mortality and liver damage in mice.
Subject(s)
Alcoholism/mortality , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antioxidants/pharmacology , Chemical and Drug Induced Liver Injury , Liver Diseases/mortality , Stilbenes/pharmacology , Alanine Transaminase/blood , Alcoholism/pathology , Animals , Aspartate Aminotransferases/blood , Drinking , Eating , Interleukin-1/blood , Liver/drug effects , Liver/pathology , Liver Diseases/pathology , Male , Mice , Mice, Inbred BALB C , Resveratrol , Transaminases/blood , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Chronic hepatitis C virus (HCV) infection is generally a slowly progressive disease. A minority of infected patients, however, eventually will develop cirrhosis and its life-threatening complications.Recent development of combination interferon (IFN) and ribavirin(RBV) antiviral therapy has changed the approach to patients infected with the virus. Once cirrhosis develops, treatment is a difficult task and should be done with close monitoring because of numerous adverse effects. In patients with compensated cirrhosis,combination therapy is the most efficient approach and offers the highest sustained virological response. Although data are limited,no significant differences have been reported between the use of pegylated interferon (PEG-IFN) and standard IFN in combination with RBV. Moreover, PEG-IFN has a higher risk of hematological complications, and this should be considered when using in advanced disease. Antiviral therapy for patients with decompensated cirrhosis should be used only in a clinical trial setting because of reported severe adverse effects. After liver transplantation, combination therapy may be an alternative for a limited number of patients. Although definitive recommendations cannot be made because of limited studies, there is a group of very well compensated patients with HCV and cirrhosis who benefited from treatment by clinicians well versed in the use of combination therapy.
Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Liver Cirrhosis/virology , Contraindications , Humans , Liver Cirrhosis/drug therapy , PrognosisABSTRACT
BACKGROUND: The dynamics of hepatitis C virus (HCV) quasi species in the E2 region may correlate with the course of infection after orthotopic liver transplantation (OLT). METHODS: Thirty-four patients who underwent transplantation for HCV-related cirrhosis were studied. Serum and liver samples were available before OLT and at 1 week, 4 months, and 1 year after OLT. Patients were divided into group 1 (Knodell/Ishak fibrosis stage [FS] at 1 year, <2) and group 2 (FS at 1 year, > or =2). Complexity was estimated by the number of bands in a single-strand conformational polymorphism assay, whereas diversity was measured by Shannon entropy (SE) and median mobility shift (MMS) values derived from the heteroduplex mobility assay. Diversity dynamics were measured at transmission (before OLT vs. 1 week after OLT) and after OLT (1 week after OLT vs. 1 year after OLT). RESULTS: Complexity was higher in group 1 patients than in group 2 patients before OLT (P<.02) and at 1 week after OLT (P<.04). Diversity decreased in group 1 at transmission, as measured by either SE (P<.01) or MMS (P<.04). However, diversity increased in this group after OLT, as measured by SE (P<.03) or MMS (P<.02). FS at 1 year after OLT correlated with transmission changes, as measured by SE (r=0.642, P<.0001) and MMS (r=0.443, P<.04), and with post-OLT changes (for SE: r=-0.583, P<.01; for MMS: r=-0.536, P<.01). CONCLUSIONS: HCV complexity and diversity in the E2 region correlated with the severity of recurrence of HCV infection after OLT. Increased diversity of quasi species at transmission correlated with a higher FS at 1 year. However, increased diversity of quasi species in the post-OLT period correlated with a lower FS at 1 year. The dynamics of HCV quasi species in patients who undergo transplantation are predictive of outcome.
Subject(s)
Hepacivirus/physiology , Hepatitis C, Chronic/virology , Liver Cirrhosis/virology , Liver Transplantation , 5' Untranslated Regions/chemistry , 5' Untranslated Regions/genetics , Disease Progression , Electrophoresis, Polyacrylamide Gel , Female , Genetic Variation , Hepacivirus/genetics , Hepacivirus/immunology , Hepatitis C, Chronic/immunology , Hepatitis C, Chronic/surgery , Humans , Liver Cirrhosis/immunology , Male , Middle Aged , Phylogeny , Polymorphism, Single-Stranded Conformational , RNA, Viral/chemistry , RNA, Viral/genetics , Reverse Transcriptase Polymerase Chain Reaction , Viral Envelope Proteins/chemistry , Viral Envelope Proteins/geneticsABSTRACT
1. Liver grafts from hepatitis C virus (HCV)-infected deceased donors can be used safely in HCV-infected recipients. 2. Histological assessment of the graft before orthotopic liver transplantation (OLT) is advised. 3. Recipients of these grafts should give consent accordingly. 4. The course of HCV disease after OLT parallels that in patients who received noninfected organs.
