Shock wave and mesenchymal stem cells as treatment in the acute phase of spinal cord injury: A pilot study / Ondas de choque y células madre mesenquimales como tratamiento en la fase aguda de la lesión medular: un estudio piloto

Introduction: Spinal cord injury (SCI) is a complex pathology with thousands of patients worldwide. During the acute early phase, neural tissue shows some regenerative properties that disappear at the chronic phase. Shock Waves and Stem Cells have been proposed as a possible therapy. Methods: Here, we analyse Shock Waves’ immediate effect over spinal cord genetic response in the injured and healthy spinal cord and the effect of Shock Waves and combined Shock Waves plus Stem Cells distally grafted to treat the first month after spinal cord injury. Results: The immediate application of shock waves increases VEGF (Vascular Endothelial Growth Factor) but reduces the BDNF (Brain-Derived Growth Factor) RNA (Ribonucleic acid) response. Shock wave therapy increases GFAP (Glial fibrillary acidic protein) positive cells and vascularity during the treatment's acute phase. Conclusion: Shock wave treatment seems to be enough to produce benefits in the acute phase of spinal cord injury, with no accumulative positive effects when mesenchymal stem cell graft is applied together.(AU)

Introducción: La lesión medular es una afección compleja con miles de pacientes repartidos a lo largo del mundo. Durante la fase aguda temprana de la lesión, el tejido neural muestras ciertas propiedades regenerativas que desaparecen durante la fase crónica. Las ondas de choque y las células madre han sido propuestas como posibles terapias. Metodología: En este estudio analizamos el efecto inmediato de una sesión de ondas de choque sobre la médula espinal, tanto sana como lesionada, y si su efecto es sumatorio al que produce un tratamiento de células madre mesenquimales inyectadas distalmente, como se ha observado en estudios previos. Resultados: Se observa un efecto inmediato con las ondas de choque que promueve un incremento del efecto trófico vascular endotelial, y una disminución del factor trófico derivado del cerebro. La terapia prolongada con ondas de choque en la fase aguda incrementa la presencia de astrocitos y la vascularización local. No parece haber efecto sumatorio con el tratamiento de células madre, produciéndose efectos similares con o sin las células madre mesenquimales. Conclusiones: Las ondas de choque parecen tener un efecto positivo durante la fase aguda de una lesión medular por compresión, sin que el tratamiento distal de células madre mesenquimales parezca implicar un efecto sumatorio.(AU)

Shock wave and mesenchymal stem cells as treatment in the acute phase of spinal cord injury: A pilot study.

INTRODUCTION: Spinal cord injury (SCI) is a complex pathology with thousands of patients worldwide. During the acute early phase, neural tissue shows some regenerative properties that disappear at the chronic phase. Shock Waves and Stem Cells have been proposed as a possible therapy. METHODS: Here, we analyse Shock Waves' immediate effect over spinal cord genetic response in the injured and healthy spinal cord and the effect of Shock Waves and combined Shock Waves plus Stem Cells distally grafted to treat the first month after spinal cord injury. RESULTS: The immediate application of shock waves increases VEGF (Vascular Endothelial Growth Factor) but reduces the BDNF (Brain-Derived Growth Factor) RNA (Ribonucleic acid) response. Shock wave therapy increases GFAP (Glial fibrillary acidic protein) positive cells and vascularity during the treatment's acute phase. CONCLUSION: Shock wave treatment seems to be enough to produce benefits in the acute phase of spinal cord injury, with no accumulative positive effects when mesenchymal stem cell graft is applied together.

Enfermedad de Sinding-Larsen-Johansson: análisis de factores asociados / Sinding-Larsen-Johansson disease: analysis of the associated factors

Objetivo. Analizar los factores clínicos, etiológicos biomecánicos asociados a la enfermedad de Sinding-Larsen-Johansson (SLJ). Material y método. Estudio de casos-control valorando los siguientes parámetros: edad, sexo, tiempo de evolución clínica, lateralidad, nivel de actividad deportiva, grado radiológico, existencia de patela alta, existencia de retracción de isquiotibiales y aumento de la caída posterior de la tibia. Resultados. Presentamos 15 rodillas en 14 pacientes (un caso de afectación bilateral). El porcentaje de varones es del 85,7% y la edad media de afectación es de 10,86 años (d.t. 1,61). Todos ellos presentaban un nivel de actividad física y deportiva elevado con una duración de los síntomas muy variable (1-36 meses). Sin tendencia clara en cuanto a la lateralidad, la mayoría se incluyen en un grado radiológico tipo ii (53,3%). El análisis de los datos no muestra diferencias significativas (p>0,05) entre los grupos respecto al índice de Caton ni de Insall modificado. En la medición del ángulo poplíteo en las rodillas lesionadas, sí encontramos diferencias significativas (media: 32,50 d.t.:8,90) con respecto al grupo control (17,67; 8,21). La diferencia en la medición del ángulo de caída posterior en las rodillas lesionadas también ha resultado estadísticamente significativo (10,47; 2,82) con respecto a las rodillas de los casos control (8,33; 1,40). Conclusiones. Los pacientes con la enfermedad tienen un aumento de la pendiente tibial y retracción de isquiotibiales respecto al grupo control y esta diferencia es estadísticamente significativa (AU)

Aim. To analyse the clinical symptoms, aetiology and biomechanical aspects related to Sinding-Larsen-Johansson (SLJ) disease. Material and method. A case control study was conducted, analysing the following variables: age, gender, clinical follow up, side of body with the symptoms, sporting activity, radiological stage, presence of patella alta, presence of short hamstring tendons, and increased posterior tibial slope. Results. A total of 15 knees in 14 patients were studied; one case with bilateral disease. The large majority of cases were 85.7% were male, and the mean age was 10.86 (standard deviation 1.61). All of them practised sport and physical activity at a high level with a variable duration of symptoms (1-36 months). There was predominance in side. The majority were radiological grade II (53.3). The data analysis did not show any significant difference (P>.05) between the study groups regarding the Caton and modified Insall indexes. There was a significant difference in the popliteal angle measured in the affected knees (mean: 32.50, SD: 8.9) compared with the control group (mean: 17.67, SD: 8.21). The difference in the posterior slope angle in the affected knees was also statistically significant (mean: 10.47, SD: 2.82) compared with the control (mean: 8.33, SD: 1.4). Conclusions. According to our data, patients have short hamstring tendons and increased posterior tibial slope compared to the control group, and this difference is statistically significant (AU)

[Sinding-Larsen-Johansson disease: analysis of the associated factors]. / Enfermedad de Sinding-Larsen-Johansson: análisis de factores asociados.

AIM: To analyse the clinical symptoms, aetiology and biomechanical aspects related to Sinding-Larsen-Johansson (SLJ) disease. MATERIAL AND METHOD: A case control study was conducted, analysing the following variables: age, gender, clinical follow up, side of body with the symptoms, sporting activity, radiological stage, presence of patella alta, presence of short hamstring tendons, and increased posterior tibial slope. RESULTS: A total of 15 knees in 14 patients were studied; one case with bilateral disease. The large majority of cases were 85.7% were male, and the mean age was 10.86 (standard deviation 1.61). All of them practised sport and physical activity at a high level with a variable duration of symptoms (1-36 months). There was predominance in side. The majority were radiological grade II (53.3). The data analysis did not show any significant difference (P>.05) between the study groups regarding the Caton and modified Insall indexes. There was a significant difference in the popliteal angle measured in the affected knees (mean: 32.50, SD: 8.9) compared with the control group (mean: 17.67, SD: 8.21). The difference in the posterior slope angle in the affected knees was also statistically significant (mean: 10.47, SD: 2.82) compared with the control (mean: 8.33, SD: 1.4). CONCLUSIONS: According to our data, patients have short hamstring tendons and increased posterior tibial slope compared to the control group, and this difference is statistically significant.

Relationship between insulin resistance, inflammation and liver cell apoptosis in patients with severe obesity.

BACKGROUND: In obesity, insulin resistance appears frequently after activation of proinflammatory molecules. Caspase-generated cytokeratin-18 (CK-18) fragments are produced during the apoptosis of hepatic cells. The main objective in the present study is to investigate the relationship between insulin resistance and caspase-generated CK-18 fragments in patients with severe obesity. METHODS: Sixty-two patients selected for bariatric surgery were clinically studied (sex, age, weight, waist diameter, body mass index, arterial pressure and type 2 diabetes mellitus) and analytic parameters were measured in blood (glucose concentration, cholesterol, triglycerides, insulin, glycosylated hemoglobin, aspartate aminotransferase, alanine aminotransferase, high-sensitivity C-reactive protein, adiponectin, interleukin 6, interleukin 18 and CK-18 fragments). Patient group division was based on 70th percentile of insulin resistance as measured by homeostasis model assessment (HOMA) and also according to liver histology. RESULTS: Patients with greater insulin resistance (percentile > 70th) showed higher values of CK-18 fragments, interleukin 6 and transaminases. A positive correlation between the HOMA score, value of CK-18 fragments and triglyceride level was found. A correlation between CK-18 fragments with interleukin 6, triglycerides and transaminases was also observed. HOMA score and value of CK-18 fragments correlated with the degree of liver fibrosis. CONCLUSIONS: Greater degree of insulin resistance induces apoptosis of hepatic cells as measured by the serum levels of CK-18 fragments.

Administración de carboxipeptidasa tras altas dosis de metotrexato. Tratamiento e interacciones medicamentosas / Carboxypeptidase-G2 administration after high-dose methotrexate. Treatment and drug interactions

El metotrexato es un antineoplásico muy utilizado y eficaz en neoplasias como las leucemias, los linfomas y los osteosarcomas. La toxicidad renal es un efecto secundario indeseable que se pretende evitar con una alcalinización urinaria e hiperhidratación eficaz. En caso de intoxicación aguda se establece el uso de carboxipeptidasa G2, una enzima que provoca la hidrólisis del metotrexato en sus metabolitos inactivos. Por su parte, el uso de glutamina durante el tratamiento oncológico previene parte de los efectos indeseables secundarios a éste. Se presenta el caso clínico de un adolescente afectado de linfoma no hodgkiniano en tratamiento con glutamina, que tras la administración de un tercer ciclo de metotrexato (5g/m2) presentó un cuadro de insuficiencia renal que precisó la administración de carboxipeptidasa, con descenso no satisfactorio de las concentraciones de metotrexato en sangre, si bien no se pudo diferenciar la fracción activa del metabolito inactivo por carecer de esta técnica en España. Se revisó la bibliografía sobre la interacción de glutamina y metotrexato y se discutió su fisiopatología sobre un posible papel de la glutamina como favorecedora de la toxicidad por metotrexato (AU)

Methotrexate (MTX) is widely used as anticancer agent in various malignancies, including acute lymphoblastic leukaemia, lymphoma and osteosarcoma. High doses of MTX may cause acute renal dysfunction. Nephrotoxicity is prevented by the use of alkalinization and hydration. More recently Carboxypeptidase-G2, a recombinant bacterial enzyme that rapidly hydrolyzes MTX to inactive metabolites, has become available for the treatment of acute nephrotoxicity. On the other hand, glutamine is usually administered in oncology treatments to avoid other side effects. We report a case of an adolescent who was diagnosed with T lymphoblastic lymphoma. He was receiving treatment with glutamine when the third course of methotrexate was administered (5g/m2) and he suffered a deterioration in his renal function. Carboxypeptidase was used but the methotrexate serum concentration reduction was not satisfactory. The technique to assess the amount of enzyme-inactivated methotrexate by quantification of MTX metabolites is not available in our country, therefore, the concentrations of MTX may be overestimated. The literature was reviewed to study the influence of glutamine on delayed methotrexate elimination which may lead to acute toxicity (AU)

[Carboxypeptidase-G2 administration after high-dose methotrexate. Treatment and drug interactions]. / Administración de carboxipeptidasa tras altas dosis de metotrexato. Tratamiento e interacciones medicamentosas.

Methotrexate (MTX) is widely used as anticancer agent in various malignancies, including acute lymphoblastic leukaemia, lymphoma and osteosarcoma. High doses of MTX may cause acute renal dysfunction. Nephrotoxicity is prevented by the use of alkalinization and hydration. More recently Carboxypeptidase-G2, a recombinant bacterial enzyme that rapidly hydrolyzes MTX to inactive metabolites, has become available for the treatment of acute nephrotoxicity. On the other hand, glutamine is usually administered in oncology treatments to avoid other side effects. We report a case of an adolescent who was diagnosed with T lymphoblastic lymphoma. He was receiving treatment with glutamine when the third course of methotrexate was administered (5 g/m(2)) and he suffered a deterioration in his renal function. Carboxypeptidase was used but the methotrexate serum concentration reduction was not satisfactory. The technique to assess the amount of enzyme-inactivated methotrexate by quantification of MTX metabolites is not available in our country, therefore, the concentrations of MTX may be overestimated. The literature was reviewed to study the influence of glutamine on delayed methotrexate elimination which may lead to acute toxicity.

Incidence of adult form of autoimmune hepatitis in Valencia (Spain).

BACKGROUND AND STUDY AIMS: There is little information on the incidence of autoimmune hepatitis (AIH) because on many occasions the disease can progress asymptomatically, different diagnostic criteria have been proposed during the last 20 years, and many epidemiological studies are based on retrospective clinical series. The aim of this study was to determine the incidence of AIH in the province of Valencia, Spain, during the year 2003. PATIENTS AND METHODS: The Services of Gastroenterology of eight acute-care reference hospitals in the province of Valencia, Spain, covering 1,774,736 inhabitants over 14 years of age, participated in a prospective study. All newly diagnosed patients with AIH between January 1, 2003 and December 31, 2003 were eligible. The diagnosis was based on criteria of the International Autoimmune Hepatitis Group revised in 1999. RESULTS: There were 19 new cases of AIH, 18 females and 1 male [mean (SD) age of 54.3 (11.2) years, range 23-73]. Incidence peaked in the 45-54 year age group. Eighteen cases were classified as AIH type 1 and one case as AIH type 2. The incidence rate of AIH for the year 2003 in people older than 14 years of age was 1.07 new cases per 100,000 inhabitants, with 1.96 cases per 100,000 inhabitants in females and 0.12 cases per 100,000 inhabitants in males. CONCLUSIONS: The 2003 annual incidence of AIH in Valencia, Spain, was similar to that reported in other European countries. AIH occurred more frequently in women and in the 45-54 year age group, type 1 being the most common.

[A clinical study of adult autoimmune hepatitis in Valencia, Spain]. / Estudio clínico de la hepatitis autoinmune del adulto en Valencia.

OBJECTIVE: the clinical phenotype of autoimmune hepatitis (AIH) varies among geographical areas. The aim of this study is to determine the salient features of AIH in adult patients from the province of Valencia, Spain. MATERIAL AND METHODS: eighty-one patients with AIH attended to in eight acute-care hospitals between 1994 and 2003. New patients diagnosed with AIH during year 2003 were evaluated prospectively. Data from patients currently attending follow-up visits and diagnosed before 2003 were collected retrospectively. RESULTS: a total of 94% of patients were females. Forty-three percent were asymptomatic, 27% had acute hepatitis, and 30% had chronic hepatitis. Type 1 AIH was diagnosed in 90% of cases. Type 2 AIH was more frequent in younger patients, and presented with an acute pattern. One third of patients had cirrhosis at onset. Patients with cirrhosis were older than 60 years more frequently. Immunosuppressants were given to 57 patients, with complete or partial remission in 87.7%. There were no significant differences in response to immunosuppression according to presentation pattern or AIH subtype. CONCLUSIONS: AIH in Valencia was predominantly diagnosed in asymptomatic women. Most cases were type 1, and in 25% of patients another autoimmune disease coexisted. At the time of diagnosis one third of patients had cirrhosis, particularly those over 60 years.

Clinical evaluation of drug-induced hepatitis.

OBJECTIVE: To ascertain the epidemiological characteristics, clinical symptoms, and evolution of drug-induced hepatitis over the last 22 years. EXPERIMENTAL DESIGN AND SUBJECTS: An observational, retrospective study between 1982 and 1993, and prospective study between 1994 and 2003. All patients in our department diagnosed with having drug-induced hepatitis were studied analyzing epidemiological (age, sex, cases per year, hospitalization) and clinical features (previous liver disease, hepatic symptoms, laboratory results), and follow-up (complete recovery or chronicity). RESULTS: A total of 61 patients were diagnosed as having drug-induced hepatitis, 26 men and 35 women (57%), mean age 52.4 years +/- 17 years, of which 72.2% were older than 40 years. A total of 43% were admitted to hospital. In 87% of cases, two or more drugs were involved, the most frequent being antituberculosis (19 cases), psychotropic (26 cases), and non-steroidal anti-inflammatory drugs (45 cases). Evolution showed that 94% of patients recovered after the withdrawal of suspected causal drugs. CONCLUSIONS: The incidence of drug-induced hepatitis is higher in patients over 40 years of age, it being more common in females. Non-steroidal anti-inflammatory, psychotropic, and anti-tuberculosis agents were the main drugs involved. Most patients made a complete recovery after withdrawal of the suspected causal drug.

Clinical value of increased serum creatinine concentration as predictor of short-term outcome in decompensated cirrhosis.

BACKGROUND: The purpose of this study was to assess whether serum creatinine concentration alone or associated with other biological parameters was an independent predictor of short-term mortality in patients with decompensated cirrhosis. METHODS: A total of 212 consecutive episodes of decompensated cirrhosis in patients admitted to the hospital between January 1999 and December 2001 were reviewed retrospectively. Depending on a serum creatinine concentration equal to or greater than 1.5 mg/dL at the time of admission, patients were divided into decompensated cirrhosis with renal failure (101 episodes in 59 patients, aged 69.8 +/- 10 years) and without renal failure (111 episodes in 61 patients, aged 64.5 +/- 13 years). Outcome (alive, death) during the episode of decompensation of liver disease and outcome at 90 days after admission were assessed. RESULTS: Differences in the frequency of variables according to outcome in the overall episodes of decompensated cirrhosis with and without renal failure showed significant differences between patients who died and those who were alive both at hospital discharge and at 90 days in serum bilirubin, Child-Pugh score, MELD (model for end-stage liver disease) score, and serum creatinine levels. In the multivariate analysis, serum creatinine was not an independent predictor of outcome. The prediction accuracy according to the area under the ROC (receiver operating characteristic) curve was greater for the MELD scale than for serum creatinine. CONCLUSIONS: Serum creatinine concentration is a parameter that should be included in the prognostic assessment of patients with decompensated cirrhosis, but should be combined with other specific parameters of liver function, such as bilirubin, albumin, and the international normalized ratio (INR) for prothrombin time.

Incidence and epidemiological factors of hepatocellular carcinoma in Valencia during the year 2000.

AIM: to ascertain the incidence and epidemiological factors of hepatocellular carcinoma in the Province of Valencia, Spain. DESIGN: a prospective study was made of hepatocellular carcinoma during the year 2000 collecting all diagnosed cases from four hospitals during that year. RESULTS: a total of 64 cases of hepatocellular carcinoma with a male predominance (42/22) and a mean age of 73.4 years (range of 42-90) were diagnosed. Incidence rate was 8.2 per 100,000, and cirrhosis was known to pre-exist in most cases, half of which were Child-Pugh A. Anti-VHC positive, alone or alcohol or virus B related was detected in 3 of every 4 cases. In the majority of the cases the tumours were located in the right hepatic lobe and the size at first diagnosis was less than 3 cm in 37.3% of the cases. Alpha-fetoprotein levels only exceeded 200 mg/ml in 37.3% of the patients and bore a good size relation to the tumour (R=0.245, p=0.003. No relation vis-à-vis aetiology with age, sex, tumour location or Child-Pugh stage was found. CONCLUSIONS: the incident rate of hepatocellular carcinoma in Valencia province during 2000 was 8.2 per 100,000 individuals. This lesion appeared more frequently in men between the ages of 60-80. Hepatitis C virus was the main etiologic agent found. Key words: Hepatocellular carcinoma. Incidence. Hepatitis C virus. Epidemiology. Child-Pugh grade. Alpha-fetoprotein.

Influence of age and date of infection on distribution of hepatitis C virus genotypes and fibrosis stage.

The objective of this study was to assess the influence of age and date of acquisition of hepatitis C virus (HCV) infection on the distribution of genotypes and the progression of fibrosis in HCV-infected patients who were born in Spain and had their habitual place of residence in this country. Genotypic analysis was performed in 375 patients in whom it was possible to establish the year of HCV infection because the mode of transmission was known (transfusion, injection drug use, blood donor, or epidemic outbreak). In 298 patients with liver biopsy, fibrosis stage was related to age at infection, duration of infection, alcohol consumption, and HCV genotype. HCV subtype 1b was almost exclusively detected among transfusion recipients, but the onset of intravenous drug addiction was associated with the introduction of HCV genotypes other than 1b among injecting users with subsequent spread to other exposure risk groups. Fibrosis progression was influenced by alcohol consumption, increased duration of infection, and older age at infection. In summary, spread of intravenous drug use determined HCV infection by genotypes other than 1b. The risk of fibrosis progression was influenced more by age at viral acquisition and alcohol consumption than by the infecting genotype.

Altered modulation of soluble guanylate cyclase by nitric oxide in patients with liver disease.

The glutamate-nitric oxide-cGMP pathway is impaired in brain in vivo in animal models of chronic moderate hyperammonemia either with or without liver failure. The impairment occurs at the level of activation of soluble guanylate cyclase by nitric oxide (NO). It has been suggested that the impairment of this pathway may be responsible for some of the neurological alterations found in hyperammonemia and hepatic encephalopathy. Soluble guanylate cyclase is also present in lymphocytes. Activation of guanylate cyclase by NO is also altered in lymphocytes from hyperammonemic rats or from rats with portacaval anastomosis. We assessed whether soluble guanylate cyclase activation was also altered in human patients with liver disease. We studied activation of soluble guanylate cyclase in lymphocytes from 77 patients with liver disease and 17 controls. The basal content of cGMP in lymphocytes was decreased both in patients with liver cirrhosis and in patients with chronic hepatitis. In contrast, cGMP concentration was increased in plasma from patients with liver disease. Activation of guanylate cyclase by NO was also altered in liver disease and was higher in lymphocytes from patients with cirrhosis or hepatitis than that in lymphocytes from controls. Successful treatment with interferon of patients with hepatitis C reversed all the above alterations. Altered modulation of soluble guanylate cyclase by NO in liver disease may play a role in the neurological and hemodynamic alterations in these patients.

Multicenter randomized study comparing initial daily induction with high dose lymphoblastoid interferon vs. standard interferon treatment for chronic hepatitis C.

One hundred fifty-five chronic hepatitis C patients were assigned at random to receive natural lymphoblastoid interferon (IFN)alpha-n1, s.c., for 13 months in one of three treatment regimens: initial daily induction with 10 million units (MU) followed (group 1, n = 50) or not (group 2, n = 52) by 1 month of rest and then three times weekly 10 MU (2 months), 5 MU (2 months), and 3 MU (8 months); group 3 (n = 53) received tiw 5 MU (2 months) followed by 3 MU (11 months). By intention-to-treat analysis, ALT normalization at completion of treatment was greater in patients who received continuous IFNalpha-n1 therapy with initial daily induction (group 2: 24/52, 46%) compared with those given intermittent therapy with initial daily induction (group 1: 17/50, 34%) and those who received standard IFNalpha-n1 therapy (group 3, 18/53, 34%; P not significant). The sustained ALT response was 26%, 27% and 21% and the sustained virological response was 20%, 27%, and 19%, in groups 1, 2, and 3, respectively. A trend was observed towards a higher biochemical and virological end-of-treatment response in patients given induction therapy (17%) compared with standard therapy (6%, P = 0.053). Sustained biochemical and virological responses were 20%, 27%, and 17% in groups 1, 2, and 3, respectively. Platelet and leukocyte counts decreased following daily high-dose treatment and remained low until therapy cessation (P < 0.001). The data suggest that daily s.c. induction with 10 MU IFNalpha-n1 followed by intermittent or continuous maintenance therapy for 1 year does not improve the results achieved with the standard 1-year IFNalpha course in the treatment of chronic hepatitis C patients.

Prevalence of hepatitis C virus in patients with lichen planus of the oral cavity and chronic liver disease.

Lichen planus (LP) may represent a mucosal reaction to a variety of factors including hepatitis C virus (HCV) infection. We compared the prevalence of HCV infection in patients with LP of the oral mucosa and chronic liver disease (LP-CLD) with those suffering exclusively from LP or from chronic liver disease (CLD). A total of 267 outpatients participated in a prospective study. There were 41 patients in the LP-CLD group, 128 in the LP group, and 98 in the CLD group. The diagnosis of LP was based on typical macroscopic and histopathologic features and the diagnosis of liver disease on liver histology. Serum samples were screened for anti-HCV antibodies. In 89 patients, serum HCV RNA was also measured. The overall prevalence of anti-HCV antibodies was 29.2% (78/267 patients). Serum HCV RNA levels were positive in 96.2% of anti-HCV-positive patients and in none of anti-HCV-negative subjects. Anti-HCV-positivity was more frequent in the groups of LP-CLD (78%) and CLD (42.8%) than in the LP group (3.1%). It is concluded that HCV infection plays an etiopathogenetic role in CLD associated with oral LP, whereas according to the present findings, the majority of patients suffering exclusively from oral LP are not infected by the HCV.

Predictors of morbidity and mortality after the first episode of upper gastrointestinal bleeding in liver cirrhosis.

BACKGROUND/AIMS: Upper gastrointestinal (GI) bleeding is one of the most frequent causes of morbidity and mortality in the course of liver cirrhosis. The aim of this study was to determine the independent predictors of morbidity, mortality, and survival after the first episode of GI bleeding in patients with liver cirrhosis. METHODS: In a retrospective study of 403 cirrhotic patients who were admitted in the period January 1982 to December 1994 because of a first episode of GI hemorrhage, epidemiological factors, bleeding-related variables and cirrhosis-related variables that may be associated with hepatic and extrahepatic complications, mortality at 48 h and 6 weeks, and survival up to 30 June 1996 were assessed. RESULTS: Forty-five percent of patients developed hepatic and/or extrahepatic complications, with a mortality rate of 7.4% at 48 h and 24% at 6 weeks. Renal failure, rebleeding, hepatocellular carcinoma, and hepatic encephalopathy were independent predictors of mortality. The Kaplan-Meier method showed a median survival of 30.9+/-4.5 months (95% confidence interval 22 to 39.7 months). The cumulative percentage of survivors was 60.2% at 1 year, 33.6% at 5 years, and 14% at 10 years. In a Cox's multiple regression analysis, age, hepatic encephalopathy, hepatocellular carcinoma, Child-Pugh grade, and renal failure were independently associated with long-term survival. CONCLUSIONS: The first episode of GI bleeding in patients with liver cirrhosis is associated with high morbidity and mortality. Renal failure, rebleeding, hepatocellular carcinoma, and hepatic encephalopathy were independent risk factors for early death.

Incidence and risk factors for hepatocellular carcinoma in 967 patients with cirrhosis.

PURPOSE: To determine the incidence of hepatocellular carcinoma in cirrhosis and to examine the influence of age and sex, and the contribution of etiological factors. METHODS: 967 patients with liver cirrhosis and free of hepatocellular carcinoma were enrolled in this longitudinal, retrospective and observational study. Monitoring for hepatocellular carcinoma was scheduled at 3- to 6-month intervals. The mean (+/-SD) length of follow-up was 60.3+/-51.7 months (range 6 258). RESULTS: During the observation period, hepatocellular carcinoma developed in 64 patients. The calculated annual incidence was 2.1%. The probability of being free of liver cancer was 92% at 5 years, 80% at 10 years, and 69% at 15 years. Age was the only independent risk factor for the development of malignancy in the multivariate analysis. There were no differences according to male sex, alcohol abuse, and chronic hepatitis B and C virus infection. CONCLUSIONS: The annual incidence of hepatocellular carcinoma was 2.1%. These results, although confirming that age is a risk factor for hepatocellular carcinoma in cirrhosis, indicate that alcohol abuse, male sex, and concurrent hepatitis B and C virus infection do not involve a higher risk of developing liver cancer.