RESUMO
Patients with advanced non-small cell lung cancer (NSCLC) generally require second-line treatment although their prognosis is poor. In this multicenter study, we aimed to detect the characteristics related to patients and disease that can predict the response to second-line treatments in advanced NSCLC. Data of 904 patients who have progressed after receiving first-line platinum-based chemotherapy in 11 centers with the diagnosis of stage IIIB and IV NSCLC and who were evaluated for second-line treatment were retrospectively analyzed. The role of different factors in determining the benefit of second-line treatment was analyzed. Median age of patients was 57 years (range 19-86). Docetaxel was the most commonly used (20.9 %, n = 189) single agent, while gemcitabine-platinum was the most commonly used (6.7 %, n = 61) combination chemotherapy regimen in second-line setting. According to survival analysis, median progression-free survival after first-line treatment (PFS2) was 3.5 months (standard error (SE) 0.2; 95 % confidence interval (CI), 3.2-3.9), median overall survival (OS) was 6.7 months (SE 0.3; 95 % CI, 6.0-7.3). In multivariate analysis, independent factors affecting PFS2 were found to be hemoglobin (Hb) level over 12 g/dl and treatment-free interval (TFI) longer than 3 months (p = 0.006 and 0.003, respectively). Similarly, in OS analysis, Hb level over 12 g/dl and time elapsed after the first-line treatment that is longer than 3 months were found to be independent prognostic factors (p = 0.0001 and 0.045, respectively). In light of these findings, determining and using the parameters for which the treatment will be beneficial prior to second-line treatment can increase success rate.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Prognóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Docetaxel , Feminino , Hemoglobinas/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Masculino , Oncologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxoides/administração & dosagem , Resultado do Tratamento , GencitabinaRESUMO
OBJECTIVES: To investigate the predictive role of serum uric acid (SUA) levels measured in the emergency department (ED) to monitor contrast-induced nephropathy (CIN) and correlation with severity of nephropathy in patients undergoing primary percutaneous coronary intervention (PCI). METHOD: The patients who were admitted to our ED and underwent primary PCI were enrolled retrospectively. Their baseline characteristics including SUA and creatinine levels in the ED and their creatinine levels 48 hours after PCI were noted. Nephropathy was graded as follows: grade 0, ΔCr ≤25% and ≤0.5 mg/dL; grade 1, ΔCr >25% but ≤0.5 mg/dL; and grade 2, ΔCr >0.5 mg/dL. A multiple logistic regression analysis was used to define the independent predictors of CIN. RESULTS: Of a total of 744 patients, CIN was observed in 12.5% (n = 93). Serum uric acid levels were significantly higher in the CIN (+) group compared with the CIN (-) group (6.09 ± 2.01 mg/dL vs 4.89 ± 1.32 mg/dL, respectively; P < .001). Patients with grade 0 CIN had significantly lower SUA levels than did those with grades 1 and 2 (4.89 ± 1.32 mg/dL vs 5.88 ± 1.99 and 6.41 ± 2.02 mg/dL, respectively; P < .001), but there was no significant difference between grade 1 and grade 2 CIN cases in terms of SUA levels (5.88 ± 1.99 mg/dL vs 6.41 ± 2.02 mg/dL, P = .10). The cutoff value for SUA was 5.05 mg/dL for the prediction of CIN (area under the curve, 0.685; P < .001; sensitivity, 66%; specificity, 60%) in the population. CONCLUSIONS: The SUA level is a simple independent early predictor of CIN in patients who underwent primary PCI, and early detection may help prevent the progression of CIN.
Assuntos
Meios de Contraste/efeitos adversos , Nefropatias/induzido quimicamente , Intervenção Coronária Percutânea/efeitos adversos , Ácido Úrico/sangue , Fatores Etários , Creatinina/sangue , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Taxa de Filtração Glomerular , Humanos , Nefropatias/sangue , Nefropatias/prevenção & controle , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/cirurgia , Valor Preditivo dos Testes , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
OBJECTIVES: Increased platelet activation contributes to cardiovascular mortality in chronic kidney disease patients (CKD). Larger platelets are more active and this increased activity had been suggested as a predictive biomarker for cardiovascular disease. In this study, we aimed to evaluate mean platelet volume (MPV) as an inflammatory marker in a broadened group of CKD patients. Our study is unique in literature as it covers all types of CKD including renal replacement therapies. MATERIALS AND METHODS: 200 patients (50 renal transplanted, 50 hemodialysis, 50 peritoneal dialysis, 50 chronic renal failure stages 3-4) were investigated who were between 18 and 76 years of age. The collected data included demographic properties, platelet count, MPV, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and hemoglobin. All of the patients had at least 12 month of therapy of either renal replacement modality. RESULTS: The mean CRP value was detected statistically significantly higher in hemodialysis (HD) patients compared to the resting three groups of patients (p < 0.01). Mean CRP level was detected significantly higher in the pre-dialysis group compared to transplanted and peritoneal dialysis (PD) patients (p < 0.01). There is no statistically significant difference detected among the mean MPV values of all patient groups (p > 0.05). CONCLUSIONS: ESR and CRP were significantly increased in hemodialysis patients compared to the other groups. We did not detect a significant difference among MPV between the groups. ESR was detected lowest in transplanted patients. Transplantation is coming forward as the favorable choice of renal replacement therapy which decreases inflammation.
Assuntos
Falência Renal Crônica/sangue , Transplante de Rim , Volume Plaquetário Médio , Complicações Pós-Operatórias/sangue , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Sedimentação Sanguínea , Proteína C-Reativa/metabolismo , Feminino , Humanos , Inflamação/sangue , Inflamação/etiologia , Inflamação/patologia , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia , Valor Preditivo dos Testes , Diálise Renal , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: Primary gastrointestinal non-hodgkin lymphomas (PGI-NHL) are uncommon diseases with treatment modalities including chemotherapy, surgery, and radiotherapy. Our aim is to analyze the demographic and clinical features and treatment results of PGI-NHL. MATERIALS AND METHODS: 286 patients diagnosed with lymphoma who referred to Ataturk University Medical Faculty Hospital between July 2001 and April 2014 were surveyed retrospectively and 22 (7.6%) PGI-NHL cases whose primary lesions were in gastrointestinal system were included. RESULTS: Mean age was 47 (min.25-max.77) and 14 (63.6%) of them were men. The origin was determined as small intestines (50%), stomach (31.8%) and colon (18.2%), respectively. The most common complaint and pathologic subtype were abdominal pain (68.2%) and diffuse large B cell lymphoma (86.4%), respectively. The Lugano Classification was as follows: stage 1 (18.2%), stage 2 (59.1%), and stage 4 (22.7%). Surgery and chemotherapy were administered to 40.9% of patients. Complete and partial response and disease progression were established in 72.1%, 4.5% and 13.6% of the patients, respectively. Mean survival time was 99.6±16 months. Mean overall survival time was determined significantly longer in small bowel group than gastric group (119±15 vs. 50±24 months) (p=0.039). Age, gender, Eastern Cooperative Oncology Group performance status, International Prognostic Index, stage, histological type, tumor size, LDH level, albumin level, Hemoglobin level and treatment options were not associated with survival. CONCLUSION: Demographic and clinical characteristics of our series were similar with Middle Eastern and African countries. Optimal treatment options or prognostic factors for PGI-NHL are not clear. There is a need for randomized prospective studies including large number of patients and long follow-up period.
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Retinal vein occlusion is an important cause of visual loss. Several ocular and systemic conditions have been reported for retinal vein occlusion. The pathogenesis of thrombus formation in the retinal vein, which results in retinal vein occlusion, is unclear. The aim of this study was to investigate the correlation between increased serum leptin levels and the occurrence of retinal vein occlusion (RVO). The study group consisted of 40 patients with RVO (58.1 +/- 6 years old; 17 males and 23 females): 15 patients with central RVO, 23 with branch RVO, and 2 with hemispheric RVO. The patients who had any ocular or systemic pathology were not included in the study. The control group consisted of 40 healthy individuals of similar gender, age, date and type of health survey, and geographic region. The blood samples of the RVO patients (n = 40) and controls (n = 40) were obtained antecubitally. Leptin levels were measured by an enzyme-linked immunosorbent assay (ELISA) method, and Student's t-test was used to determine differences between the groups. The mean serum leptin levels were 12.5 +/- 1.64 ng/ml in patients with RVO and 8.4 +/- 1.22 ng/ml in the control subjects; namely, the mean serum leptin levels were significantly higher in the patients with RVO (p < 0.001). These results suggest that leptin may be involved in the pathogenesis of venous thrombosis in the retina probably through its effects on homeostasis of the vessel wall.
Assuntos
Leptina/sangue , Oclusão da Veia Retiniana/metabolismo , Veia Retiniana/fisiologia , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Veia Retiniana/metabolismo , Veia Retiniana/fisiopatologia , Oclusão da Veia Retiniana/classificação , Trombose Venosa/etiologiaRESUMO
The aim of this study was to evaluate the lipid peroxidation, nitric oxide (NO), and free radical scavenging enzyme activities in erythrocytes of zinc (Zn)-deficient rats and to investigate the relationship among these parameters in either group. Sixteen male rats with a weight of 40-50 g were used for the experiment. The rats were divided into control (n = 8) and Zn-deficient groups. At the end of the experiment, the animals were anesthetized with ketamine-HCl (Ketalar, 20 mg/kg(-1), i.p.), and the blood was collected by cardiac puncture after thoracotomy. Blood samples were collected in vacutainer tubes without and with K(3)-EDTA as anticoagulant. Erythrocyte catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GRD), glutathione-S-transferase (GST), superoxide dismutase (SOD) activities, total (enzymatic plus nonenzymatic) superoxide scavenger activity (TSSA), nonenzymatic superoxide scavenger activity (NSSA), antioxidant potential (AOP), and serum zinc (Zn) values in the Zn-deficient group were significantly lower than those of the control group, whereas NO and malondialdehyde (MDA) levels were significantly higher than those of the control group. The results show that Zn deficiency causes a decrease in antioxidant defense system and an increase in oxidative stress in erythrocyte of rats.
Assuntos
Antioxidantes/metabolismo , Eritrócitos/metabolismo , Estresse Oxidativo , Zinco/deficiência , Animais , Catalase/metabolismo , Dieta , Eritrócitos/enzimologia , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Glutationa Transferase/metabolismo , Peroxidação de Lipídeos , Malondialdeído/metabolismo , Óxido Nítrico/sangue , Ratos , Ratos Sprague-Dawley , Espectrofotometria Atômica , Superóxido Dismutase/metabolismo , Zinco/administração & dosagemRESUMO
PURPOSE: To assess the tolerability of two different biopsy methods for thyroid nodules in a patient with nodular thyroid disease (NTD). MATERIALS AND METHODS: The study included 58 consecutive patients who had NTD from June 2014 to October 2015. Each patient had, at least, two thyroid nodules were located in two lobes. Parallel and perpendicular fine-needle aspirations (FNAs) were performed. RESULTS: The mean maximum diameters of the assessed thyroid nodules using ultrasound (US) in parallel and perpendicular techniques were 23 ± 7 and 22 ± 6 mm, respectively. Nodule sizes were not significantly different (p > 0.05). For the parallel and perpendicular techniques, the mean numeric rating scale (NRS), verbal rating scale (VRS), and visual analog scale (VAS) values were 3.6 ± 1.9, 2.6 ± 1.1, and 17.2 ± 13 with 6.6 ± 1.7, 3.4 ± 0.5, and 37.8 ± 18, respectively. All these values were statistically significant (p < 0.001); there were no statistical differences between females and males in terms of three pain scales (p < 0.001). CONCLUSION: Patients experienced significantly less pain when undergoing FNA of NTD using the parallel technique as opposed to the perpendicular technique. Therefore, we believe that FNA using parallel technique is preferable for NTD patients.
Assuntos
Dor/prevenção & controle , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologia , Adolescente , Adulto , Idoso , Biópsia por Agulha Fina/efeitos adversos , Biópsia por Agulha Fina/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Medição da Dor/métodos , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/diagnóstico por imagem , Ultrassonografia de Intervenção , Adulto JovemRESUMO
OBJECTIVE: Our aim is to evaluate the frequency and characteristics of cancer in the population of patients with solid organ transplant who are under immunosuppressive medication. In this study we aimed to emphasize the importance of early diagnosis of cancer in solid organ transplant recipients. An aging population began to receive solid organ transplantation and survival times prolonged. But this had a cost and new problems came forward. Especially de novo cancers because of immunosuppressive therapy took notice. Risk of malignancy increases after organ transplantation and cancer incidence was about 2.3-3.1% in these patients including skin cancer, lung cancer, malign lymphoma, cervix cancer, kaposi sarcoma, and hepatobiliary cancer. MATERIALS AND METHODS: The files of 328 organ transplant recipients followed from January 2004 to April 2015 at Atatürk University Medical Faculty were retrospectively reviewed. RESULTS: Eight patients developed cancer (2.4%). There were six males and two females. Age at cancer diagnosis ranged from 42 to 79 years old with average of 55 years. The interval from solid organ transplantation to cancer diagnosis ranged from 6 months to 30 years. Among the patients, five were renal transplant recipients and two were liver transplant recipients. Four patients had stage IV disease, one patient stage IIIB, and three patients had stage I disease. For none of the patients a diagnosis with screening methods was used for cancer before any complaints of tumor emerged. CONCLUSION: To diagnose cancer at early stages in solid organ transplant recipients, earlier and detailed cancer screening is very important. The association between diagnosis of cancer at early stages and prolonged overall survival time is well known. Detailed and careful evaluation for occult malignancies in pre-transplantation period is also important.
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BACKGROUND: Docetaxel, cisplatin, 5-fluorouracil (DCF) given every three weeks is an effective, but palliative regimen and significantly toxic especially in patients who have a low performance score. Here, we aimed to evaluate the efficacy and tolerability of a weekly formulation of DCF in locally advanced and metastatic gastric cancer patients. MATERIALS AND METHODS: 64 gastric cancer patients (13 locally advanced and 51 metastatic) whose ECOG (Eastern Cooperative Oncology Group) performance status (PS) was 1-2 and who were treated with at least two cycles of weekly DCF protocol as first-line treatment were included retrospectively. The weekly DCF protocol included 25mg/m2 docetaxel, 25mg/m2 cisplatin, and 24 hours infusion of 750mg/m2 5-fluorouracil, repeated every week. Disease and patient characteristics, prognostic factors, treatment response, grade 3-4 toxicity related to treatment, progression free survival (PFS) and overall survival (OS) were evaluated. RESULTS: Of the patients, 41 were male and 23 were female; the median age was 63 (29-82) years. Forty-one patients were ECOG-1 and 23 were ECOG-2. Of the total, 81.2% received at least three cycles of chemotherapy. Partial response was observed in 28.1% and stabilization in 29.7%. Overall, the disease was controlled in 57.8% whereas progression was noted in 42.2%. The median time to progression was 4 months (95%CI, 2.8-5.2 months) and median overall survival was 12 months (95%CI, 9.2-14.8 months). The evaluation of patients for grade 3-4 toxicity revealed that 10.9% had anemia, 7.8% had thrombocytopenia and 10.9% had neutropenia. Non-hematologic toxicity included renal toxicity (7.8%) and thrombosis (1.6%). CONCLUSIONS: In patients with locally advanced or metastatic gastric cancer who were not candidates for DCF administered every-3-weeks, a weekly formulation of DCF demonstrated modest activity with minimal hematologic toxicity, suggesting that weekly DCF is a reasonable treatment option for such patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/secundário , Cisplatino/administração & dosagem , Docetaxel , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/secundário , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Taxoides/administração & dosagemRESUMO
BACKGROUND: We aimed to investigate the prognostic value of baseline neutrophil, lymphocyte, and platelet counts along with the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) in local and advanced gastric cancer patients. MATERIALS AND METHODS: In this retrospective cross-sectional study, a total of 103 patients with gastric cancer were included. For all, patient characteristics and overall survival (OS) times were evaluated. Data from a complete blood count test including neutrophil, lymphocyte, monocyte, white blood cell (WBC) and platelet (Plt) count, hemoglobin level (Hb) were recorded, and the NLR and PLR were obtained for every patient prior to pathological diagnosis before any treatment was applied. RESULTS: Of the patients, 53 had local disease, underwent surgery and were administered adjuvant chemoradiotherapy where indicated. The remaining 50 had advanced disease and only received chemotherapy. OS time was 71.6±6 months in local gastric cancer patients group and 15±2 months in the advanced gastric cancer group. Univariate analysis demonstrated that only high platelet count (p=0.013) was associated with better OS in the local gastric cancer patients. In contrast, both low NLR (p=0.029) and low PLR (p=0.012) were associated with better OS in advanced gastric cancer patients. CONCLUSIONS: This study demonstrated that NLR and PLR had no effect on prognosis in patients with local gastric cancer who underwent surgery and received adjuvant chemoradiotherapy. In advanced gastric cancer patients, both NLR and PLR had significant effects on prognosis, so they may find application as easily measured prognostic factors for such patients.
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Adenocarcinoma/secundário , Plaquetas/patologia , Linfócitos/patologia , Neutrófilos/patologia , Neoplasias Gástricas/patologia , Adenocarcinoma/mortalidade , Adenocarcinoma/terapia , Adulto , Idoso , Terapia Combinada , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/terapia , Taxa de SobrevidaRESUMO
Cisplatin (CDDP) is one of the most active cytotoxic agents in the treatment of cancer and has adverse side effects such as nephrotoxicity and hepatotoxicity. The present study was designed to determine the effects of royal jelly (RJ) against oxidative stress caused by CDDP injury of the kidneys and liver, by measuring tissue biochemical and antioxidant parameters and investigating apoptosis immunohistochemically. Twenty-four Sprague Dawley rats were divided into four groups, group C: control group received 0.9% saline; group CDDP: injected i.p. with cisplatin (CDDP, 7 mg kg(-1) body weight i.p., single dose); group RJ: treated for 15 consecutive days by gavage with RJ (300 mg/kg/day); group RJ + CDDP: treated by gavage with RJ 15 days following a single injection of CDDP. Malondialdehyde (MDA) and glutathione (GSH) levels, glutathione S-transferase (GST), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) activities were determined in liver and kidney homogenates, and the liver and kidney were also histologically examined. RJ elicited a significant protective effect towards liver and kidney by decreasing the level of lipid peroxidation (MDA), elevating the level of GSH, and increasing the activities of GST, GSH-Px, and SOD. In the immunohistochemical examinations were observed significantly enhanced apoptotic cell numbers and degenerative changes by cisplatin, but these histological changes were lower in the liver and kidney tissues of RJ + CDDP group. Besides, treatment with RJ lead to an increase in antiapoptotic activity hepatocytes and tubular epithelium. In conclusion, RJ may be used in combination with cisplatin in chemotherapy to improve cisplatin-induced oxidative stress parameters and apoptotic activity.
Assuntos
Apoptose/efeitos dos fármacos , Cisplatino/farmacologia , Ácidos Graxos/farmacologia , Rim/citologia , Fígado/citologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Transferase/metabolismo , Imuno-Histoquímica , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Malondialdeído/metabolismo , RatosAssuntos
Cardiotoxicidade/tratamento farmacológico , Doxorrubicina/toxicidade , Eletrocardiografia/efeitos dos fármacos , Eritropoetina/análogos & derivados , Coração/efeitos dos fármacos , Ramipril/administração & dosagem , Animais , Cardiotoxicidade/fisiopatologia , Darbepoetina alfa , Quimioterapia Combinada , Eritropoetina/administração & dosagem , Coração/fisiopatologia , Masculino , Ratos , Ratos Sprague-Dawley , Volume Sistólico/efeitos dos fármacos , Volume Sistólico/fisiologia , Resultado do TratamentoRESUMO
OBJECTIVE: The present study was undertaken to examine the correlation between the severity of liver disease and the presence and severity of bone disease in patients with hepatic cirrhosis. MATERIALS AND METHODS: Between January 2005 and February 2006, 40 patients with cirrhosis and 22 healthy controls were enrolled in a cross-sectional study. All subjects underwent standard laboratory testing and bone densitometric studies of the lumbar spine and femoral neck using dual X-ray absorptiometry (DEXA). RESULTS: Cirrhotic patients had lower serum follicle-stimulating hormone (FSH) levels than controls. Male patients had lower serum free testosterone (fT) levels than male controls. 25-hydroxyvitamin D (25-OHD3) levels were significantly higher in the controls as compared to patients with cirrhosis. In the cirrhotic group, 25-OHD3 concentrations did not differ significantly between patients with Child B and C class cirrhosis. As compared to the control group, cirrhotic patients had significantly elevated levels of urinary deoxypyridinoline (DPD). The cirrhotic patients also had a significantly lower mean spinal (SD) bone mineral density (BMD) than the control group. BMD of the lumbar spine (LS) was noted to be significantly lower in the Child C group than in the Child B group. In the cirrhotic patients, there was a positive correlation between the BMD T score of the femoral neck (FN) and albumin levels whereas there was a negative correlation between BMD T scores of the FN and age, bilirubin and prothrombin time (PT). CONCLUSION: Osteopenia and osteoporosis are highly prevalent in individuals with liver cirrhosis. Cirrhotic patients should undergo routine bone densitometric assessment and, if necessary, be treated for osteoporosis.