Hepatocellular carcinoma: ten years experience among veterans in Puerto Rico

PURPOSE: The aim of our study is to determine the characteristics of hepatocellular carcinoma (HCC) as well as risk factors, demographics, survival rates and the use of diagnostic and therapeutic modalities among veteran patients in Puerto Rico. METHODS: A retrospective study of 114 patients with Hispanic background and biopsy-proven HCC diagnosed at the VA Caribbean Healthcare System from 1992 to 2002 was performed. Demographics data, Child-Turcotte-Pugh (CTP) score, presence of cirrhosis, viral serology, alcohol and/or other liver diseases history, diagnostic modalities, lesion size, therapy, and overall survival were examined. RESULTS: The mean age was 66.6 years old. 82% had known underlying cirrhosis. 60% had alcoholic liver disease (ALD), 33% positive serology for hepatitis C (HCV) and 21% both. 5.3% had chronic hepatitis B virus (HBV) infection. Additional causes were not present. CTP classification was: A (42%), B (44%) and C (14%). Abdominal CT scan demonstrated most of the lesions, while ultrasound only 57%. Alfa-fetoprotein was diagnostic in 32%. Mean survival was 10.3 months, better for those with CTP score A. Only 42% of the patients received any kind of therapy. CONCLUSIONS: ALD is the principal underlying liver disease in our HCC patients, closely followed by chronic HCV infection. Less than half of our patients received treatment mainly due to advanced disease for which the over survival was less than a year. HCC continues to be a dreadful disease with poor prognosis for which aggressive screening should be considered for all patients with cirrhosis and advanced liver disease regardless of the cause.

Patterns of prescription of hypoglycaemic drugs in Gran Canaria (Canary islands, Spain) and estimation of the prevalence of diabetes mellitus.

OBJECTIVE: To study the patterns of hypoglycaemic treatment in our community and to estimate the prevalence of known and drug-treated diabetes mellitus. METHODS: From all the diabetic patients who attended the Healthcare Centers of the National Health Service in Gran Canaria in 1999, a random sample of 2924 diabetic patients > 20 years old was selected. Data on age, gender, clinical onset of diabetes, and hypoglycaemic treatment were obtained. Data on drug consumption were supplied by the National Health Service. RESULTS: Of the DM-2 patients 4.4% (3.65-5.14) 84.2% (82.7785.42), 9.4% (8.34-10.45) and 2.1% (1.58-2.61) received diet only, oral drugs, insulin or combination. The duration of DM-2 was associated with more oral drugs and more insulin treatment, but the duration of DM-1 was not associated with intensive insulin therapy;<50% of the type 1 patients had >or=3 daily injections. The prescriptions of biguanides were scarce; over 1/3 of them were of buformin. DM-1 and DM-2 patients were treated with similar doses of insulin, but DM-1 patients had more insulin injections (2.56 vs 2.07, P<0.001), and more fast-acting insulins (65.2% vs 38.0%, P<0.001). The estimated prevalences of known and drug-treated diabetes in the Gran Canaria island were 5.95% (95% CI: 5.096.80%) and 5.73% (4.88-6.57%). CONCLUSIONS: Our prevalences of known and drug-treated diabetes is among the highest reported in European populations. The prescriptions of metformin and of combined therapy in DM-2, and of intensive insulin therapy in DM-1 are less frequent than expected, but nonetheless insulin therapy in DM-1 is more intensive and uses more fast-acting insulin than in DM-2.

Does Silybum marianum play a role in the treatment of chronic hepatitis C?

OBJECTIVES: The recent boom in patient education on chronic hepatitis C has resulted in a worldwide increase in the diagnosis of this condition. Available treatment is expensive and associated with significant side effects; therefore, many patients seek for alternative medicine. Silybum marianum is a natural herb known to mankind for over 2,000 years that has been used as a liver-protecting agent due to its antioxidant properties. The objective of this study is to evaluate the safety profile and the effects of this herb, using a commercially available extract; in the liver chemistry and viral load of hepatitis C in chronically infected patients. METHODS: Patients aged 21-65 years old with a diagnosis of chronic hepatitis C who were not using antiviral therapy were asked to participate. Patients were randomized to treatment with S. marianum 160 mg orally three times a week for four weeks or to no-treatment (control). Blood tests for viral load and liver enzymes (ALT and AST) were done at randomization and at the end of treatment. Paired-t test was used to measure differences between baseline and week 4 values for ALT, AST and viral load. The percent change for ALT, AST and viral load of both groups was analyzed using the Mann Whitney statistical test. RESULTS: 34 patients were enrolled. Men and women were equally distributed. Mean age was 50 years old. Mean baseline measurements of AST, ALT and viral load in the treatment group were 85 +/- 12.41 IU/ml, 120 +/- 20.57 IU/ml and 8.77 +/- 4.12 copies x 10(6)/ml while for the no-treatment group were 71 +/- 9.46 IU/ml, 97 +/- 15.35 IU/ ml and 1.8 +/- 0.62 copies x 10(6)/ml respectively. For treated subjects the mean values of AST, ALT and viral load demonstrated a decrease from baseline values, but this difference was not statistically significant. For control patients the values of ALT (p= .049), AST (p = .005) and viral load (p = .005) showed a statistically significant increase at week 4. Week 4 measurement chang...

Steatosis as a predictive factor for treatment response in patients with chronic hepatitis C

BACKGROUND: Hepatic steatosis has been described in 31-72% of chronic hepatitis C virus (HCV) liver biopsies. Steatosis has been related to disease progression and suggested as a predictor of treatment response in chronic HCV. This study aims to evaluate the presence and degree of steatosis in liver histology of patients with chronic HCV prior to combination therapy with interferon (INF) and ribavirin (RBV), and how it influences treatment response. METHODS: The medical charts of patients with chronic HCV who received treatment at the San Juan Veterans Affairs (VA) Medical Center from 1998 to 2002 were reviewed. Selected patients completed therapy, had a pre-treatment liver biopsy, genotype determination, and pre and post treatment HCV-RNA levels. Patient's age, sex and body mass index (BMI) were determined. Pre-treatment liver biopsy slides were reviewed and graded for steatosis by a hepatopathologist blinded to the treatment outcome. Steatosis was graded by the presence of fat in total biopsy area as: mild (<33%), moderate (33-66%), severe (>66%) or absent. Treatment response was defined as virological clearance measured by HCV RNA at the end of treatment and 24 weeks after completion of treatment. The presence of steatosis was compared to BMI, HCV genotype and treatment response. RESULTS: 46 patients met the inclusion criteria. All patients were male of Hispanic origin. Mean age: 52.7 years (range: 40-68). Mean BMI: 27.5 kg/m2 (range: 21.1-35.9). HCV genotype 1 was present in 67% of patients. 82.6% (38/46) of the patients had hepatic steatosis: 29 (63%) mild, 7 (15%) moderate and 2(4%) severe. 16.6% (8/46) of the biopsies did not show steatosis. Overall, the response rate for those with steatosis was 31.6% (12/38): 10/29 (34.5%) mild, 1/7 (14.3%) moderate and 1/2 (50%) of severe. 75% (6/8) of those without steatosis responded to treatment. This difference (31.6% vs. 75%) was statistically significant (p=.042). The mean BMI of both groups was similar (27.7)...

Prevalence of chronic hepatitis C virus genotypes among patients between 21 to 65 years old in Puerto Rico

OBJECTIVES: This is the first study done in Puerto Rico to estimate the prevalence of hepatitis C virus (HCV) genotype distribution in patients with chronic infection and to determine the statistical association between the genotype and variables such as age, sex, HCV risk factors, and viral load. METHODS: Chronic HCV infected patients diagnosed with ELISA, RIBA or PCR from 1990 to 2002 who were under follow up with members of the Puerto Rico Gastroenterological Association were asked to participate. Eligible patients were those without evidence of HIV or other viral hepatic infection; had no previous antiviral treatment or if previously treated, therapy ended at least six months prior to their participation in the study; had no history of organ transplant and were willing to participate. All study subjects completed a study questionnaire and had blood samples taken to determine HCV genotype and viral load. RESULTS: 500 patients were recruited. Most of the study subjects were males (68%); 70% were 45 to 65 years old. The principal reported risk factors were: surgeries (75.5%), drug use (46.8%), sexual relationships with intravenous/intranasal drug users (30.3%), blood transfusions (30.2%), multiple sex partners (28.9%), tattoos (22.0%), needle accidents (12.7%), and sexual relationships with an HCV infected partner (9.0%). Most patients had multiple risks factors for infection, only 3.4% (17/500) reported a single risk factor whereas 2.0% (10/500) reported none. 33% of the patients were previously treated (non-responders or relapsers) while 67% were naive. In general, 82% of the HCV patients had genotype 1, while 18% had non-1 genotypes. Among genotype 1 subtypes, genotype la (39.8 %) was more common than 1b (27%). The most common non-1 genotype was genotype 2 of which 2b represented 9.8% of the study population. Similar distribution was observed within the categories of the HCV risk factors, with the exception of those who reported sex with an infected partn...

Prevalence of obesity in a Canarian community. Association with type 2 diabetes mellitus: the Guía Study.

OBJECTIVE: We sought to estimate the prevalence of obesity and central obesity, and their association with type 2 diabetes mellitus in the Canarian community of Guía. DESIGN AND SETTING: Population-based study. SUBJECTS: A random sample of 691 subjects over 30 y old (stratified by age and sex) was studied. DATA AND MEASURES: Age, sex, family history of diabetes and medication use were obtained, height, weight and waist circumference were measured and standard oral glucose tolerance tests were performed RESULTS: The prevalences of obesity/central obesity were 36.5%/66.5% (women) and 23.6%/32.0% (men). The prevalence of diabetes was 21.0% (women) and 18.4% (men). These rank among the highest in Europe. Bivariate analyses show a strong association of both obesity and central obesity with diabetes mellitus (P<0.001), but in a multivariate model, waist circumference (P<0.001) but not body mass index (P=0.212) was retained as an independent predictor of diabetes. CONCLUSION: The prevalences of obesity, central obesity and diabetes in our community are extremely high, and central obesity is a better predictor of diabetes than obesity.

Prevalence and determinants of diabetes mellitus and glucose intolerance in a Canarian Caucasian population - comparison of the 1997 ADA and the 1985 WHO criteria. The Guía Study.

AIMS: To estimate the prevalence of diabetes mellitus, impaired fasting glucose and impaired glucose tolerance in a Canarian population according to the 1997 ADA and the 1985 WHO criteria; and to study the cardiovascular risk factors associated with these categories. METHODS: A total of 691 subjects over 30 years old were chosen in a random sampling of the population (stratified by age and sex). An oral glucose tolerance test was performed (excluding known diabetic patients) and lipids were determined in the fasting state. Anthropometric and blood pressure measurements were performed, and history of smoking habits and medications was recorded. RESULTS: The prevalence of diabetes was 15.9% (1997 ADA) and 18.7% (1985 WHO); the prevalence of impaired fasting glucose and impaired glucose tolerance was 8.8 and 17.1%, respectively. The age-adjusted prevalence of diabetes (Segi's standard world population) for the population aged 30-64 years was 12.4% (1985 WHO). The risk factors significantly associated with diabetes (1997 ADA and 1985 WHO) were age, body mass index; waist-to-hip ratio, systolic and mean blood pressure, triglycerides, total cholesterol and low HDL-cholesterol. Age, body mass index and systolic blood pressure were associated with impaired fasting glucose and impaired glucose tolerance; triglycerides were also associated with impaired fasting glucose. CONCLUSIONS: The prevalence of diabetes mellitus and glucose intolerance in Guía is one of the highest among studied Caucasian populations. The new 1997 ADA criteria estimate a lower prevalence of diabetes. Impaired fasting glucose also had a lower prevalence than impaired glucose intolerance and the overlap of these categories was modest.

Platelet cytosolic calcium, peripheral hemodynamics, and vasodilatory peptides in liver cirrhosis.

BACKGROUND: Platelet cytosolic calcium concentration ([Ca2+]i) has been proposed to reflect changes in vascular smooth muscle cells. This study investigated if the platelet [Ca2+]i is altered in cirrhotic patients and determined its relationship with peripheral hemodynamics and peptide levels. METHODS: Fourteen patients with cirrhosis and 11 healthy, age- and sex-matched controls had blood samples taken for determining platelet [Ca2+]i and glucagon, substance P (SP), and vasoactive intestinal peptide (VIP) values. Mean arterial pressure (MAP) and forearm blood flow (FBF) were measured on the same day of blood sampling. Forearm vascular resistance (FVR) was calculated. RESULTS: Patients with cirrhosis had lower platelet [Ca2+]i (50.1 +/- 2 vs. 73.0 +/- 5 nmol/L; P < 0.001) than normal controls. Glucagon levels were significantly higher in patients with cirrhosis, but there was no difference in SP or VIP levels in both groups. MAP (80.5 +/- 3 vs. 94.7 +/- 3; P < 0.005) and FVR (20.1 +/- 1 vs. 36.3 +/- 2; P < 0.001) were significantly lower in patients with cirrhosis. A significant correlation was observed between platelet [Ca2+]i and MAP in patients with cirrhosis (r = 0.81; P < 0.001), between platelet [Ca2+]i and FVR (r = 0.87; P < 0.001), and between platelet [Ca2+]i and diastolic blood pressure (r = 0.78; P < 0.001). No correlation was found between platelet [Ca2+]i and peptide levels. CONCLUSIONS: Patients with cirrhosis have a significant reduction in the platelet [Ca2+]i. This finding correlates well with peripheral hemodynamics. Platelets may be a useful tool to study the etiologic mechanisms leading to the vasodilation of chronic liver disease.

Pharmacologic treatment of portal hypertension.

Variceal formation and rupture are dreaded complications of chronic liver disease and portal hypertension. The pharmacologic treatment of portal hypertension should be able to stop as well as to prevent variceal hemorrhage. There are two principal types of vasoactive drugs in the treatment of portal hypertension: vasoconstrictors and vasodilators. Vasoconstrictors reduce the splanchnic blood flow, thereby decreasing the portal blood flow and portal pressure. Vasodilators act by different mechanisms, including by relaxation of myofibroblasts in the fibrous septa and presinusoidal areas of the liver and by direct vasodilation of the collateral circulation. In addition, paradoxically, they could decrease portal flow and pressure by inducing a baroreflex-mediated mesenteric arterial vasoconstriction. A miscellaneous group of drugs is also available. These drugs reduce the blood flow and pressure in the gastroesophageal variceal system by mechanisms other than vasoconstriction or vasodilation. The success of these pharmacologic agents is limited once the varices have ruptured. The use of beta-blockers in the prophylaxis of the first variceal bleeding has been proven of benefit in this respect. Future research should be aimed at elucidating the role that humoral and endothelial factors play in development of the hyperdynamic circulatory state that characterizes patients with portal hypertension. Once these etiologic factors have been identified and new knowledge is acquired about their role in the complications of chronic liver disease, the challenge will rest on developing novel pharmacologic therapies specifically targeting these factors.