Barbara Adriana Trovato

Elevation of interleukin 6 levels in patients with chronic hepatitis due to hepatitis C virus

Interleukin 6 (IL-6) is a pleiotropic cytokine produced by a wide variety of lymphoid and nonlymphoid tissues. We studied the relationship between IL-6 and the liver in an attempt to elucidate this cytokines role in hepatitis C-induced liver inflammation. We investigated the behavior of serum IL-6 in 25 patients with chronic hepatitis C (divided into three groups depending on severity) and in 27 healthy controls. Our results showed a significant elevation (P<0.0001) in serum IL-6 levels in the patients with chronic hepatitis C, correlated with the histological activity index (HAI) and their HCV-RNA serum levels. This rise may represent the expression of the hepatitis C virusinduced inflammatory state.

Interferon-α Treatment in Patients with Chronic Hepatitis C

SummaryInterferon-α (IFNα) has been used to treat chronic hepatitis C (non-A non-B) since 1986. We conducted a meta-analytic study to evaluate its efficacy in this form of hepatitis by analysing 27 randomised controlled studies that had been performed between 1989 and 1993 and that included a total of 1579 patients, 661 of whom were controls. The Mantel-Haenszel-Peto method was applied to the extrapolated data. The results of our study demonstrated 275 complete remissions in the treated group and 67 spontaneous remissions in the controls. The overall odds ratio was 4.44 (95% CI of the odds ratio = 3.42 to 5.75). The heterogeneity test applicable to the Mantel-Haenszel-Peto method provided a χ2 of 41.51. Our study demonstrated the validity of IFNα treatment in hepatitis C. Upgrading of the therapeutic protocols may improve the efficacy and reduce the side effects.

Decrease of interferon gamma serum levels in patients with chronic hepatitis C.

Cytokines can play a crucial role in defending the organism from viral infections. One of these, interferon gamma (IFN-gamma), possesses marked immunomodulating activity. As cell immunity seems to be involved in chronic hepatitis C virus (HCV), study of the events regulated by IFN-gamma may be useful in evaluating the hosts immunological response. We studied 63 patients (36 males, 27 females) affected by chronic HCV and 28 (14 males, 14 females) healthy controls. IFN-gamma concentrations were significantly lower in the former, and were positively correlated with the histological activity index, suggesting that low IFN-gamma values play a part in determining chronicity. We believe they may be an unfavorable factor and may be useful in detecting patients who are not capable of eradicating the virus.

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.

A COMPARISON OF FOUR TYPES OF INTERFERON ALPHA IN THE TREATMENT OF CHRONIC HEPATITIS C

Abstract Several clinical trials and meta-analyses have shown that the efficacy of interferon (IFN)-alpha in the treatment of chronic hepatitis C is variable, depending on the type of IFN-alpha used. We randomly assigned 220 patients with hepatitis C to receive a 6-month treatment (3 megaunits three times per week) with lymphoblastoid IFN-alpha (group A), recombinant IFN alpha-2a (group B), leukocyte IFN-alpha (group C), or recombinant IFN alpha-2b (group D). The groups were homogeneous with reference to histologic severity of the disease (chronic persistent hepatitis, 21.4%; mild chronic active hepatitis, 28.2%; moderate chronic active hepatitis, 28.6%; and severe chronic active hepatitis, 21.8%). We used common laboratory techniques to detect and assess all serum variables. Liver biopsy was conducted according to Menghinis modified technique, and administration of IFN alpha was conducted according to a double-masked method. A total of 220 patients were enrolled in the study. Ninety-two patients dropped out because of side effects, comorbidity unrelated to the baseline disease, or voluntary termination and 128 patients (32 patients in each group) completed the treatment course and the follow-up period. At the 6-month end point, 14 of 32 patients were completed responders in group A, 13 of 32 in group B, 14 of 32 in group C, and 8 of 32 in group D. After completion of the follow-up period, 10 of 32 patients had a sustained response in group A, 9 of 32 in group B, 10 of 32 in group C, and 8 of 32 in group D. Treatment failure and relapse rates were higher in the patients treated with recombinant alpha IFNs than in patients treated with leukocyte or lymphoblastoid IFN alpha. We observed no relation between the relapse rate and baseline severity of the disease. Among the recombinant IFNs, a major rate of clinical response was observed in patients treated with recombinant IFN alpha-2a. Although leukocyte IFN-alpha and lymphoblastoid IFN-alpha treatments showed an overlapping efficacy in terms of complete or sustained response, the former achieved a lower rate of treatment failure or relapse.

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.

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).

Impaired Thermal and Tactile Sensitivity during Interferon-α Treatment

Interferon (IFN) is currently the most widely used drug in the treatment of viral chronic hepatitis B, C and D. Despite its proven efficacy, interferon induces numerous adverse effects in diverse organs and systems, all of which disappear upon discontinuation of treatment. One of the best known adverse effects is neurotoxicity, which often requires treatment discontinuation,II-8] and manifests with lethargy, asthenia, delayed ideation, and taste and olfactory deficits. Delayed spontaneous motor activity and behavioural changes have also been reported. EEG reveals delayed rhythm with appearance of theta-delta waves in the frontal regions and reduced alpha waves. IFN treatment only rarely provokes severe peripheral neuronal lesions that fit the picture of atrophy. We report a case of a patient with chronic active hepatitis who had been treated with IFNu for about 3 months and showed disorders in lower limb and upper left limb sensitivity that may have been caused by unfamiliar neurological actions of this drug.

Hepatitis C virus genotypes in elderly patients with chronic hepatitis C

The importance of determination of hepatitis C virus (HCV) genotypes and subtypes has been demonstrated not only as epidemiological characteristics, but also as prognostic factors regarding the seriousness of the disease and response to interferon (IFN) in patients with chronic hepatitis C (CHC). Aim of this study was to determine HCV genotypes in a group of elderly patients with CHC, in order to acquire epidemiological data on the prevalence of HCV genotypes in Eastern Sicily, and to evaluate any relationship with the seriousness of the disease and with the response to IFN. The study was carried out on 22 patients with CHC, aged from 65 to 75 years. The prevalence of HCV-RNA subtypes in elderly patients (Group A) was compared with two other groups: Group B aged from 36 to 64 years; and Group C aged from 20 to 35 years. HCV-RNA proved to be positive in 20 of the 22 patients in Group A, and in 100% of these cases the prevalent subtype was 1b; in the other two groups the occurrence of other subtypes was more frequent, especially in the younger ages. In conclusion, the subtype 1b is indigenous in our region and it cannot be proposed as the only prognostic factor for seriousness of the disease and response to IFN, especially in elderly patients.