Lipoprotein(a) concentration in patients with chronic active hepatitis C before and after interferon treatment.

Patients with chronic active hepatitis C show low lipoprotein(a) (Lp[a]) values. We studied the changes in Lp(a) levels caused by treatment with interferon in 24 patients (9 men and 15 women; mean age, 56.8 +/- 7.3 years) affected by chronic active hepatitis C. Fifteen healthy subjects (6 men and 9 women; mean age, 57.4 +/- 10.3 years) were used as controls. All of the patients with chronic hepatitis C were treated with intramuscular interferon, 3 million units 3 times per week for 6 months. These patients had lower baseline serum Lp(a) concentrations than the controls (4.8 +/- 3.8 mg/dL vs 13.4 +/- 10.3 mg/dL, respectively; P = 0.0007). A significant increase in Lp(a) levels (6.6 +/- 7.2 mg/dL; P = 0.05) occurred after 6 months of treatment in patients with chronic active hepatitis C. Only complete responders presented a significant increase in Lp(a) values (P = 0.01). We believe that increased Lp(a) levels represent an expression of improved liver functions.

Fish oil treatment of interferon-alpha-induced dyslipidaemia: study in patients with chronic hepatitis C.

OBJECTIVE: Our study was designed to evaluate the role of omega-3 fatty acids (OFAs) in reducing serum triglyceride levels in patients with chronic hepatitis C receiving treatment with interferon-alpha (IFNalpha). DESIGN: 52 patients (23 males, 29 females) with chronic hepatitis C were randomly assigned to nonblind treatment with IFNalpha 3 million units (MU) three times weekly alone (group A) or in combination with OFAs 3 g/day for 6 months (group B). RESULTS: Hepatitis C virus (HCV) RNA serum levels decreased significantly in both groups compared with baseline, but there was no significant difference in HCV RNA levels between the 2 groups. At the end of treatment there was a statistically significant difference in ALT levels between patients in group A and in group B (72.15 vs 50.05 IU/L; p = 0.01). A statistically significant increase in triglyceride levels occurred in group A during treatment (p = 0.03 vs baseline). In contrast, a statistically significant decrease in triglyceride serum levels occurred in group B (p = 0.001 vs baseline). CONCLUSION: Concurrent administration of OFAs reversed IFNalpha-induced hypertriglyceridaemia in patients with chronic hepatitis C.

Lipoprotein(a) in cirrhosis. A new index of liver functions?

Over the last few years, lipoprotein(a) [Lp(a)] levels have been investigated because clinical studies have related it to increased cardiovascular and cerebrovascular risk. Although it is known that serum Lp(a) concentrations are controlled genetically, little is known about its metabolism. We studied changes in the lipid profile and Lp(a) values in 57 patients (34 males and 23 females) affected by cirrhosis of the liver subdivided into Child's classes in order to assess whether this lipoprotein is sensitive to reduced liver protein synthesis. The patients presented with low total cholesterol, normal HDL-cholesterol (HDL-c), LDL-cholesterol (LDL-c), triglycerides, apoprotein A1 (Apo-A1) and apoprotein B100 (Apo-B100) concentrations, while Lp(a) concentrations seemed elevated. Grouping the patients into Child's classes revealed that all the lipid parameters investigated reduced as the disease progressed. Lp(a) reduced significantly between Child's Classes I and II and seems to be correlated with the severity of cirrhosis and the clinical worsening of the patients' conditions. These findings suggest that Lp(a) is not only an index of atherosclerosis risk, but also plays a role in monitoring liver functions.

A meta-analysis of interferon-alpha treatment of hepatitis D virus infection.

The severity of chronic hepatitis D infection and its unfavorable progress necessiate research into drugs and protocols capable of changing the natural history of the disease. Over the last few years interferon (IFN)-alpha has been the drug of choice in the management of this infection. We assessed its long-term efficacy by analyzing 5 controlled and 10 uncontrolled trials conducted between 1987 and 1994. The Mantel-Haenszel-Peto method was used in the former to perform statistical analysis. The odds ratio (0.16, confidence interval 0.058-0.476) confirmed the efficacy of IFN-alpha, even if the coefficient was not significant because of the limited number of spontaneous remissions in the trials. Although IFN treatment is fully beneficial in only a small number of patients with chronic hepatitis D infection, at present it is the only available agent.

Eosinophilic gastroenteritis.

Eosinophilic gastroenteritis is a rare disease of unknown aetiology characterized by eosinophilic infiltration of the gastrointestinal wall and increased peripheral blood eosinophilia. The frequent finding of concomitant extradigestive involvement calls for differential diagnosis to distinguish some multisystemic pathologies, such as connective tissue disease. We recently treated a young woman affected by eosinophilic infiltration of the small and large intestine which spread to other organs. Tests ruled out allergic or parasitic aetiopathogenesis of the disease. The clinical, biological and evolutive findings suggest that eosinophilic gastroenteritis may evolve into idiopathic hypereosinophilic syndrome.

Serum lipoprotein(a) changes in acute myocardial infarction.

BACKGROUND: A strong correlation between high serum Lp(a) levels, a genetic modification of cholesterol-low density lipoproteins (c-LDL), and increased coronary heart disease rate has been found. Transient increased serum levels of this lipoprotein during acute myocardial infarction (AMI) and surgical interventions have been found. EXPERIMENTAL DESIGN: we assessed complete lipidic pattern in a study series composed of 19 patients with AMI. We also evaluated the changes of Lp(a) serum levels within the first week of the disease in order to assess whether a correlation between this parameter and extent of necrotic myocardial area is present. PATIENTS: study series was made up of 19 patients (13 males, 6 females; mean age 57.94+/-10.7 years) with AMI compared to 25 control subjects (12 males and 13 females; mean age 51.12+/-15.34 years). MEASURES: we also withdrew a blood sample on days 1, 3 and 7 from the onset of the AMI. On the first day we evaluated the serum levels of the following parameters: glycaemia, azotemia, creatininemia, urycaemia, total cholesterol, high density lipoprotein cholesterol (c-HDL), low density lipoprotein cholesterol (c-LDL), triglycerides, fibrinogen, creatinphosphokinase, aspartate aminotranspherase, thromboplastine time and prothrombinic activity. Lp(a) has been evaluated on day 1, 3 and 7 and after 6 months from AMI. We performed an ultrasound scanning (US) of the heart in day 7 for evaluation of the extent of necrotic myocardial area by observation of "segmental kinetic area". RESULTS: Mean basal Lp(a) serum level was 28.94+/-29.78 mg/dl (as median 17), (normal values 0 to 25 mg/dl). This value was not changed on day 3 (mean 29.47+/-30.46 mg/dl, median 18), while significantly increased on day 7 (39.84+/-42.77, median 26, p=0.05). Spearman's rank correlation test showed a strong correlation between the increase of Lp(a) serum levels on day 7 and extent of necrotic myocardial area (r=0.696, p=0.001). CONCLUSIONS: The positive correlation between mean Lp(a) values on day 1 and 7, and the size of the necrotic area, suggest that Lp(a) has an atherogenic and prothrombotic role. Moreover, elevated Lp(a) values were related to greater tissue damage. We believe that periodical determination of Lp(a) values in subjects with coronary disease is useful in order to predict further acute vascular events.

Antibodies against ox-LDL serum levels in patients with hepatocellular carcinoma.

AIM: Hepatocellular carcinoma (HCC) is a malignancy with high incidence worldwide. The related cachexia is induced by proinflammatory cytokines, responsible for a wide number of metabolic disorders, essentially including lipidic and oxidative metabolism. Oxidized LDL (ox-LDL), produced by LDL-cholesterol oxidation, are one of the risk factors for atheromatosis. Also, ox-LDL act on the deliverance of some cytokines involved in the development and progression of a lot of human tumours. The removal of ox-LDL from the blood is performed by the liver. The intracellular amount of ox-LDL, through various cytokines, might induce HCC by reduction of the apoptotic mechanism of protection. Our aim was to evaluate the behaviour of serum antibodies against ox-LDL levels in order to study their possible changes and influences on a study series composed of HCC patients. METHODS: We enrolled 41 patients (29 males, mean age 67.45+/-8.28 years and 12 females, mean age 64.62+/-7.2 years) with primitive HCC and 30 healthy control subjects (15 males and 15 females, mean age 61.86+/-2.51 years). Diagnosis of HCC was performed on the basis of clinical, laboratory and instrumental findings (Ultrasonography, Computed Tomography and Magnetic Nuclear Resonance, liver biopsy). Of the 41 HCC patients, 30 were affected by hepatitis C virus (HCV), 5 were HBsAg and HBcAg positive and 6 virus B and C negative but consumers of more than 150 g/day of alcohol. Liver biopsy confirmed the presence of HCC derived from cirrhosis in 10 of HCV positive patients, as well as in the patients with high alcohol consumption. Serum IgG antibodies versus the ox-LDL levels have been evaluated by ELISA method and oLAB reactive by Biomedica-Austria. Data have been analysed by 2 tailed Student's "t" test and a value of p<0.05 was considered significant. RESULTS: Lipid pattern values were within the normal ranges except for the Lp(a), that presented low serum levels in both groups. Twenty-five patients presented HCC as well as severe chronic active hepatitis. Serum mean levels of ox-LDL antibodies (ox-LDL Ab), still being within the normal ranges, were significantly lower than in control subjects (p<0.001) in both sexes. CONCLUSION: We hypothesize that the lower ox-LDL Ab serum levels in our HCC patients may be related to the smaller feeding of HCC patients or to the greater uptake of these modified lipoproteins by the hepatic reticular endothelial system. This phenomenon might result especially in the release of cytokines and growth factors for hepatocytes that may induce HCC development and progression.

Beneficial effects of acarbose on familiar hypertriglyceridemias.

Elevated serum triglyceride levels may be related to the following clinical features: increased blood coagulation and viscosity, increased serum fibrinogen levels, decreased fibrinolysis, and for serum levels over 1000 mg/dl, a strong increase of acute pancreatitis rate. Pharmacological choice among the numerous drugs to treat hypertriglyceridemias is currently debated. Our study was aimed to assess the therapeutic efficacy of acarbose in the treatment of non-diabetic subjects, affected by familiar hypertriglyceridemia (FH). We studied 18 non-diabetic patients (10 males, 8 females; mean age 57.61+/-6.85 years) without family history of diabetes mellitus affected by familiar hypertriglyceridemia. The study protocol planned a treatment period of 20 weeks, divided into five 4-week courses and made up as follows: diet plus acarbose therapy (4 weeks); diet therapy alone (4 weeks) alternatively. In the second and fourth 4-week courses diet plus acarbose were administered, while diet therapy alone was administered in the first, third, and fifth 4-week courses. Acarbose doses consisted of 50 mg (1/2 pill) twice daily. Mean serum triglyceride levels, after first month of dietary treatment, underwent a significant reduction from 481.5 +/- 67.1 mg/dl to 389.5 +/- 62.7 mg/dl, even if they did not reach the optimal levels to keep on the dietary therapy alone. After the first month of treatment with acarbose associated to diet, we observed a further reduction of serum triglycerides levels (p = 0.02). When diet alone was administered, mean triglyceride serum levels underwent a significant enhancement (p = 0.003). Restarting for the second time the association treatment, we observed a noteworthy reduction of mean serum triglyceride levels (p = 0.0001). Acarbose acts on the pathogenesis of FH, lowering the production of endogenous triglycerides. Our data suggested that acarbose can be considered a valid therapeutic tool in the treatment of familiar hypertriglyceridemias, also in non-diabetic patients.

Antiviral drugs in chronic hepatitis B: review and meta-analysis.

Many researchers have attempted to identify the drugs capable of acting on the viral replication cycle and maintaining clinical remission in chronic hepatitis B. We evaluated the efficacy of antiviral drugs in chronic hepatitis B, by examination of 20 controlled and non-controlled trials conducted between 1985 and 1996. In chronic hepatitis B, adenine arabinoside and its monophosphate did not achieve satisfactory results, even though combination therapy with cortisone seemed to achieve very good results (remission rates ranging from 45% to 66% in patients treated). Lamivudine did not seem to furnish lasting effects in chronic hepatitis B, because many patients relapse after suspension of the treatment due to the appearance of HBV variants resistant to the drug. Contrasting results were observed with famciclovir. Treatment of chronic hepatitis B, with this drug seemed capable of reducing HBV-DNA serum levels by a mean of 50% compared to pretreatment values, with normal alanine aminotransferase levels in about 30% of treated patients. Ganciclovir treatment of chronic hepatitis B seemed to furnish good, but transient, results. Even if no antiviral drug represented a valid alternative to interferon, antivirals may become the drugs of choice in chronic hepatitis B, because they are aimed at the etiology of disease.

Lipid profile variations in a group of healthy elderly and centenarians.

Epidemiological and clinical studies have clearly shown a close relationship between plasma cholesterol concentrations and vascular risk. We focused our attention on the phenotypic-biohumoral conditions capable of influencing longevity in relation to different age classes. We evaluated the lipid profile in an elderly institutionalized population of 80 subjects (20 males and 60 females divided into age classes) in the town of Catania. Our results revealed a statistically significant reduction in total cholesterol, triglycerides and LDL-cholesterol concentrations as well as Apolipoprotein B100/Apolipoprotein A1, total cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol ratios, and a significant increase in HDL-cholesterol, Apolipoprotein A1, Apolipoprotein B100 and Lipoprotein (a) values. This changes are progressive with age. We believe that low total cholesterol, LDL-cholesterol and triglyceride concentrations, elevated HDL-cholesterol values, and low ratios protect subjects from ischemic and thrombotic events, thus favouring longevity. These changes are most evident and statistically significant in the most advanced decades of life, especially in centenarians, and may depend on diverse determinants, such as body composition, environmental factors, physical activity, diet and drugs.

Erythropoietin in healthy elderly subjects.

The effects of aging on erythropoiesis and the factors regulating it are not well known. Erythropoietin (Epo) is a specific growth factor for the erythroid line and is mainly produced by the kidney. As data on the effects of aging on Epo are discordant we studied serum Epo concentrations in a group of apparently healthy subjects divided into age classes in order to evaluate age-related modifications and correlations with hemoglobin (Hb) and red blood cells (RBC). Our results revealed that Epo values were correlated with age. Epo was higher in the over 65 years age classes than observed in control subjects. We believe that the elevated Epo values in the latter age class may be required to maintain Hb and RBC within normal range.

[Role of interleukin 6 in hepatocellular carcinoma]. / Rôle de l'interleukine 6 dans le carcinome hépatocellulaire.

Interleukin 6 (IL-6) is a pleiotropic cytokine which possesses a broad spectrum of action in diverse pathological conditions. It is mainly produced and metabolised in the liver where it carries out one of its best known actions in the mediation of the acute phase response. We studied its behaviour in hepatocellular carcinoma to evaluate its clinical prognostic role. We determined serum IL-6 concentrations in 39 patients with hepatocarcinoma (27 males and 12 females) and 25 healthy controls (15 males and ten females). Our results showed a significant increase in serum IL-6 concentrations in hepatocarcinoma subjects compared with controls (P < 0.005) and an elevated positive correlation (r = 0.616) between IL-6 and size of the hepatocarcinoma. Our study demonstrated that IL-6 is able to influence hepatocarcinoma progression by acting as an autocrine tumoral growth factor and depleting immune surveillance.

Treatment of nonresectable hepatocellular carcinoma: review of the literature and meta-analysis.

Many doubts surround the numerous forms of nonsurgical treatment of nonresectable hepatocellular carcinoma (HCC). Our study aimed to reach reliable conclusions on the actual efficacy of these treatments. We examined 85 studies involving a total of 6746 patients: 6113 were treated; the remaining 633 were not. We applied the Mantel-Haenszel-Peto method to the extrapolated data, based on the reported 1- and 3-year survival rates. The results confirm that percutaneous ethanol injection achieved survival exceeding 5 years in many cases of HCC characterized by small nodules (diameter < 3 cm). The most efficacious nonsurgical treatment options were transcatheter arterial embolization and transcatheter arterial chemoembolization. Systemic chemotherapy and hepatic intra-arterial chemotherapy were not very effective.

Lipoprotein (a) behaviour in patients with hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a malignancy representing in Europe the 3-5% of all malignant tumors. Metabolic pathway of Lipoprotein(a) [Lp(a)] is influenced by various cytokines delivered during inflammatory and neoplastic diseases. Liver seems to be the main site of Lp(a) synthesis. METHODS: A group of patients affected by HCC was studied in order to evaluate the changes in serum Lp(a) levels and their significance. PARTICIPANTS: 40 patients (25 males and 15 females) affected by primary HCC and 25 control healthy subjects (12 males and 13 females). In HCC patients we evaluated the following serological parameters: Lp(a), total cholesterol (TC), LDL-Cholesterol (LDL-C), HDL-Cholesterol (HDL-C), triglycerides (TG), albumin, (pseudo)cholinesterase (CHE), aspartate amino-transpeptidase (AST), alanine amino-transpeptidase (ALT), gamma-glutamyl transpeptidase (g-GT), alkaline phosphatase (ALP), ferritin, alpha fetoprotein, partial thromboplastin time (PTT), Quick time, prothrombinic activity (PA) and fibrinogen. Statistical analysis of the data obtained was performed using the variance analysis (ANOVA method) and Student's OtO for non-paired data test. For Lp(a), Wilcoxon's non parametric test was used. The correlations between examined parameters were performed by Pearson's correlation test. RESULTS: In patients with HCC, mean serum TC, LDL-C TG and Lp(a) levels were significantly lower than in controls. HDL-C did not show a statistically significant difference between the two groups studied. Furthermore, we found a positive correlation between: Lp(a) and CHE, Lp(a) and albumin, CHE and LDL-C; while a negative correlation has been found between: Lp(a) and alpha-fetoprotein, Lp(a) and ferritin, CHE and alpha-fetoprotein. CONCLUSIONS: On the basis of the relationship with alfa fetoprotein and ferritin serum levels, Lp(a) seems to represent an indirect index of liver damage. Lp(a) is a risk factor for vascular diseases and seems to have an interesting role in the liver functions. We conclude that the evaluation of Lp(a) serum levels may contribute, among other markers, to a more complete evaluation of the liver function in patients with HCC suggesting a predictive role for this lipoprotein.

[Immunologic diseases and hepatitis C virus]. / Maladies immunologiques et virus de l'hépatite C.

Active chronic hepatitis may be associated with various immunologic diseases. In the Mediterranean area and to a lesser extent elsewhere, hepatitis C virus, has often been detected in patients affected by mixed cryoglobulinemia, membranoproliferative glomerulonephritis, polyarteritis nodosa autoimmune type 2b hepatitis, Hashimoto's disease, Sjögren's syndrome and lichen ruber planus. These findings should not be considered fortuitous due to the elevated prevalence of autoantibodies and immunologic abnormalities observed in hepatitis C patients compared with subjects presenting other liver diseases. The pathogenetic evaluation of the association between these immunologic diseases and chronic hepatitis C has led us to suggest that diverse virus C and host induced factors may play a fundamental role in determining these immunologic diseases.

[Treatment of hypertriglyceridemia. Current aspects]. / Trattamento dell'ipertrigliceridemia. Aspetti attuali.

The hypertriglyceridemia attends the physiopathology of the atherosclerosis by various mechanisms: association of low levels of high density lipoprotein-cholesterol (HDL-c), modification of quality of low density lipoprotein-cholesterol (LDL-c), influence on hemostatic processes, association with other hazard's factors (obesity, hypertension, etc.). The hypertriglyceridemia distinguishes in primary and secondary. In primary forms the origin is essentially genetic, while the secondary ones are metabolic consequence of various pathologies (renal, thyroid, diabetes mellitus etc.). The hypertriglyceridemia's treatment is founded on a correct feeding and/or on eventual use of drugs. Apart from the secondary forms, in which is obligatory to treat at first the basal disease, the pharmacological therapy of the hypertriglyceridemia is suggested only in resistant cases to alone dietetic therapy and overall in presence of other factors of atherothrombotic hazard. The most utilized drugs are: omega-3 fatty acids, the nicotinic acid and its derivatives, the fibrates and the statins. The stronghold of alpha-glucosidases inhibitors is the acarbose. It reduces the biosynthesis of very low density lipoproteins (VLDL) by the reduction of substrata with an improvement of glucidic metabolism. Atorvastatin and cerivastatin develop a greater action to reduce serum levels of triglycerides as to the foregoing ones because of the better selectivity of receptor binding, the greater halflife and inhibition of the apolipoprotein's B100 synthesis.

Treatment of familial hypertriglyceridaemia with acarbose.

AIM: The evaluation of serum triglyceride levels has played an important role as an independent method for assessing the risk factor for coronary atherosclerosis. Fibrates, nicotinic acid, and omega-3 polyunsaturated fish oils are the pharmacological tools most used today against hypertriglyceridaemia. Acarbose is a pseudotetrasaccharide of microbial origin which exerts a competitive, selective and reversible inhibition of the intestinal alpha glucoside-hydrolase. We evaluated the efficacy and side-effects of acarbose as a new and alternative drug in the treatment of hypertriglyceridaemia in non-diabetic patients. METHODS: We enrolled 30 non-diabetic patients (18 men, 12 women; mean age 59.23 +/- 6.27 years) without a family history of diabetes mellitus affected by familial hypertriglyceridaemia. The study covered a total period of 6.5 months: half of the patients were on 1.5 months of 'run in' diet only followed by 5 months of therapeutic diet plus acarbose; and half were on the therapeutic diet plus placebo. We gave 30 dividable pills to all patients. The administration was as follows: half a pill before lunch and half a pill before dinner while on the 'run in' diet. Fifteen patients (group A) took acarbose while the reminder (group B) took a placebo (50 mg of starch); these were distributed randomly and the test was double blind. The 20 weeks of study were divided in five 4-week periods. Fasting serum concentrations of total cholesterol, triglycerides, HDL-cholesterol (HDL-c), LDL-cholesterol (LDL-c) and glucose were determined at the starting of the study and after each treatment cycle. Glucose values were determined 2 h after lunch at the beginning of the study and at the end of the first, third and fifth month of treatment. All parameters assessed have been analysed by anova. RESULTS: The serum total cholesterol, LDL-c levels observed in the two groups did not change during the course of treatment. We observed a noteworthy progressive reduction of mean baseline triglyceride levels until the fourth month (p < 0.05) in acarbose-treated patients, with an increase in HDL-c (p < 0.008). CONCLUSIONS: We maintain that acarbose may be a useful therapeutic tool in addition to the diet in order to reduce triglyceride serum levels in non-diabetic patients.

Acarbose is an effective adjunct to dietary therapy in the treatment of hypertriglyceridaemias.

AIMS: In diabetics, acarbose causes a reduction of blood glucose and triglyceride levels. The aim of this study was to assess the effect of this drug in non diabetic subjects with hypertriglyceridaemia. METHODS: Thirty non diabetic patients with hypertriglyceridaemia type IIb or IV (24 males, six females; mean age 51.1+/-10.2 years) were studied. They were stratified into two groups depending on their basal triglyceride concentration (group A: triglyceride values 4.5 mmol l-1 ). Treatment consisted of 4 week courses of diet plus acarbose (50 mg twice daily) alternating with 4 weeks of diet alone for a total period of 16 weeks. RESULTS: Mean triglyceride values decreased significantly during the first and third cycles of therapy, i.e. diet plus acarbose treatment cycles in both patient groups. Group A also had significant reductions in total cholesterol and HDL cholesterol concentrations after completion of the acarbose treatment. Reduction of triglyceride levels was observed after both acarbose courses in patients affected by hypertriglyceridaemia type IIb. A marked reduction of triglyceride concentrations was achieved by patients affected by hypertriglyceridaemia type IV after the second acarbose course only. CONCLUSIONS: Diet alone did not reduce triglyceride concentrations to normal values in our patients. The data suggest that acarbose is a useful adjunct to dietary control in non-diabetic patients affected by severe hypertriglyceridaemia.