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.

[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.

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.