Ignazio Giugno

A Meta‐Analysis of Interferon‐α Treatment of Hepatitis D Virus Infection

The severity of chronic hepatitis D infection and its unfavorable progress necessitate research into drugs and protocols capable of changing the natural history of the disease. Over the last few years interferon (IFN)‐α 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‐α, 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.

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.

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 α 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.

Effect of Interferon on Blood Lipids

SummaryInterferons (IFNs) modify lipid metabolism, increasing triglyceride levels and partially reducing cholesterol values. We studied 25 patients (10 males and 15 females; mean age 56.92 ± 7.16 years) with HCV-Ab-positive chronic active hepatitis, who were treated with IFNα, in order to evaluate their serum lipid behaviour during treatment. We also enrolled 25 healthy controls (10 males and 15 females; mean age 51.12 ± 15.34 years) to compare their lipid profiles with those of the patients. The following parameters were determined prior to and after the 6 months’ treatment: alanine aminotransferase, total cholesterol, high density lipoprotein cholesterol (HDL-C), triglycerides, low density lipoprotein cholesterol (LDL-C), apoprotein A1 (apo A1), apoprotein B100 (apo B100), apo B100/apo A1, total cholesterol/HDL-C, LDL-C/HDL-C ratios, and lipoprotein (a) [Lp(a)]. After the 6-month treatment, there was a decrease in total cholesterol, HDL-C, LDL-C and apo A1, while there was a rise in apo B100, apo B100/apo A1, total cholesterol/HDL-C and LDL-C/HDL-C ratios. There was a significant increase in triglyceride levels and Lp(a) concentrations. The increase in total cholesterol/HDL-C and LDL-C/HDL-C ratios, Lp(a) and triglycerides may enhance cardiovascular risk, thus underlining the need for accurate pre- and intratreatment evaluation in patients on IFN therapy.

Fish Oil Treatment of Interferon-Alpha-Induced Dyslipidaemia

AbstractObjective: 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 (IFNα). Design: 52 patients (23 males, 29 females) with chronic hepatitis C were randomly assigned to nonblind treatment with IFNα 3 million units (MU) three times weekly alone (group A) or in combination with OFAs 3 g/day for 6 months (groupB). 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 IFNα-induced hypertriglyceridaemia in patients with chronic hepatitis C.

Lipid Profile in Centenarians

SummaryIn human epidemiological studies the levels of plasma lipids are related to the incidence of atherosclerotic cardiovascular disease. In this study we evaluated and compared lipid profiles in a group of healthy centenarians and a control group of adults. The study included 22 healthy centenarians (mean age 102.81 ± 2.5 years) and a control group of 20 elderly volunteers (mean age 70.35 ± 4.12 years). Total cholesterol (TC), high-density lipoprotein cholesterol (HDLC) and triglycerides were determined by enzymatic methods in all subjects. Low-density lipoprotein cholesterol (LDLC) was determined according to Friede wald’s formula; apolipoproteins A and B (Apo A and B) were determined using the nephelometric method, while lipoprotein (a) [Lp(a)] was determined by the ELISA method. The following ratios, which are considered indices of cardiovascular risk, were calculated: TC/HDLC; LDLC/HDLC; Apo B/Apo A. The lipid profile in centenarians was characterised by a lower total cholesterol level (4.36 ± 0.93 mmol/L), LDLC (974.1 ± 288 mg/L), triglycerides (1.14 ± 0.51 g/L), Apo B (0.92 ± 0.26 g/L), Apo B/Apo A ratio (0.63 ±0.1), TC/HDLC ratio (3.52 ± 0.77), and LDLC/HDLC ratio (2.04 ± 0.66) than that observed in controls. Conversely, Lp(a) [39.04 ± 13.44 mg/dl], HDLC (483.1 ± 73 mg/L) and Apo A (1.47 ± 0.28 g/L) were greater in centenarians than in controls.

The efficacy of interferon alfa in chronic hepatitis B: a review and meta-analysis

Abstract Since 1976, treatment with interferon alfa (IFN-α) has been shown to inhibit viral replication and obtain sustained normalization of biohumoral indices in patients with chronic hepatitis B. The present investigators performed a meta-analysis to evaluate the effectiveness of IFN-α. This was done by examining 26 controlled trials (including 773 treated subjects and 532 control subjects) in which patients with chronic hepatitis B and mutant B virus were treated with IFN-α and which had a posttreatment follow-up period of at least 12 months. The Mantel-Haenszel-Peto method was applied to the extrapolated data. Of the 773 patients treated with IFN-α, 306 (39.6%) were complete responders; spontaneous remission was seen in 74 of the 532 control patients (13.9%). The computed odds ratio was 4.0 (95% confidence interval = 3.09 to 5.18). A heterogeneity test furnished a chi-square value of 44.01. Studies of treatment with lymphoblastoid IFN-α reported the highest remission rate (40.8%). Encouraging results were observed in trials of recombinant IFN-α-2a and recombinant IFN-α-2b (remission rates were 38.3% and 36.4%, respectively). A 5-megaunits schedule was more efficacious than a 3-megaunits schedule (remission rate was 47.5% vs 30.7%, respectively). Even if the efficacy of IFN-α in patient with chronic hepatitis B has been confirmed, more prolonged follow-up periods are needed to obtain more reliable results. Furthermore, the results of IFN-α treatment in patients with mutant B virus can be considered poor. Relapse occurred in 70% to 90% of the responders and the remission rate was low compared with the results observed in the 26 trials examined (mean remission rates were 10.0% to 25.0% vs 39.6%, respectively).

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.