Efficacy Of Interferon Therapy Research Articles

Thyroid autoimmunity and dysfunction associated with type I interferon therapy.

Type I interferons are currently used for the treatment of chronic viral hepatitis, multiple sclerosis and several hematological and solid tumors. Side effects are not uncommon, and include multiple alterations in thyroid function, some of which are unrelated to autoimmunity. Review of the literature revealed an overall mean prevalence of incident thyroid dysfunction of 6.2%, hypothyroidism occurring more frequently (3.9%) than hyperthyroidism (2.3%). Destructive thyroiditis characterized by early transient thyrotoxicosis followed by hypothyroidism has also been described. Thyroid dysfunction was mainly subclinical, and spontaneous resolution occurred in almost 60% of patients with or without withdrawal of interferon. Risk factors for developing thyroid abnormalities were female sex and the presence of pre-existing autoimmune thyroiditis. Whether prolonged interferon therapy will increase the likelihood of experiencing thyroid dysfunction, as well as the relationship between incident thyroid autoimmunity and the efficacy of interferon therapy, are still open questions. Although the most-likely explanation for thyroid disease occurring with type I interferon therapy remains an autoimmune reaction or immune system dysregulation, a direct inhibitory effect on thyrocytes may be presumed in patients who developed hypothyroidism without autoimmunity. However, the mechanisms of thyroid damage induced by type I interferons have not yet been clarified in detail. We recommend routine evaluation of serum thyroid-stimulating hormone during interferon therapy. A systematic thyroid assessment is useful only for those patients with pre-existing thyroiditis or incident dysfunction. Although discontinuation of interferon therapy is seldom required, it may be necessary in patients who develop Graves' disease and overt hyperthyroidism.

Prevention and treatment of hepatocellular carcinoma

Viral hepatitis, by either hepatitis C virus (HCV) or hepatitis B virus (HBV), is the dominant cause of hepatocellular carcinoma (HCC). This is to say that HCC may be prevented by controlling viral infection. Horizontal transmission of HCV has become obsolete owing to the discovery of the virus. Vertical transmission of HBV during delivery has been effectively prevented by vaccination and immunization of neonates. The efficacy of interferon therapy against HCV was recently much improved. We now possess several powerful antiviral drugs against HBV. There has been progress also in the treatment of HCC, and together with advances in diagnostics facilitating HCC detection at an early stage, tumor nodules can often be completely removed either by medical ablation or surgical resection. Nevertheless, recurrence of HCC after apparently curative treatment is extraordinarily frequent, since the remaining liver is still at a particularly high risk of HCC. An effective treatment of HCC should include measures to control de novo carcinogenesis.

Long-Term Outcome, with Monitoring of Platelet Counts, in Patients with Chronic Hepatitis C and Liver Cirrhosis after Interferon Therapy

Objective: Because the determination of the stage of fibrosis depends on rather subjective judgment, more objective parameters are needed. In this study, we followed the long-term outcome, with monitoring of platelet counts, in patients with chronic hepatitis C or liver cirrhosis (LC) who had undergone interferon (IFN) therapy. Methods: 596 patients who were diagnosed at our institute from 1987 to 1998 with chronic hepatitis C and LC were treated with IFNs. A further 58 patients were not treated (NT). The annual rate of changes in platelet counts were calculated and compared for IFN-treated and NT patients. Results: The relationship between the efficacy of IFN therapy and the incidence of hepatocellular carcinoma (HCC) showed that the patients who were virologic sustained responders (VSR) had a significantly lower incidence of HCC than the nonresponders (NR) and NT patients. The change in platelet counts was +4,350/µl/year in the VSR, +1,010/µl/year in the biochemical sustained responders (BSR), –4,540/µl/year in the NR and –6,180/µl/year in the NT patients, indicating a significant platelet increase in the VSR, a decrease of the same magnitude in the NR and NT patients, and no change in the BSR. The cumulative probability of developing HCC and liver failure was significantly higher in groups with decreased platelet counts than in groups with increased platelet counts among patients who had undergone IFN therapy. Multivariate analyses revealed that a decrease in platelet counts was the cardinal risk factor for development of HCC and liver failure in chronic hepatitis C or LC patients. Conclusion: Investigation of platelet counts was useful for determining the long-term outcome of patients who had undergone IFN therapy and for predicting the development of HCC.

Efficacy of long-term interferon therapy in chronic hepatitis B patients with HBV genotype C

Infection with Hepatitis B virus (HBV) genotype C predominates in Japan. We analyzed the efficacy of interferon (IFN) alpha or beta in the treatment of chronic hepatitis B patients with HBV genotype C and the clinical predictors for therapeutic response. Forty-three genotype C-infected, chronic hepatitis B e antigen (HBeAg)-positive patients (32 men and 11 women with a mean age of 35.6+/-10.1 years) who had been treated with IFN therapy were retrospectively studied. The patients were classified into two treatment groups. Short-term therapy group was administered a 5-6 MU dose three times weekly for 4 weeks, and the long-term therapy group for 24 weeks. At the end of the follow-up period, 4 (15%) of 27 short-term therapy group patients and 6 (38%) of 16 long-term therapy group patients had normalized serum ALT levels and seroconversion of HBeAg to anti-HBe (p=0.137). Multivariate analysis for parameters most important for the efficacy of IFN therapy was performed using Cox proportional hazard models in order to investigate the association between baseline characteristics of patients and the response to IFN treatment. As a result, the p-values of IFN treatment group and sex were <0.05, and both factors can be recognized as independent significant factors (relative risk, 2.93 and 2.53; p=0.027 and 0.040, respectively). Furthermore, the cumulative rates of seroconversion of HBeAg to anti-HBe analyzed by the Kaplan-Meier method was significantly higher in the female group (p=0.015) and in the long-term IFN therapy group (p=0.0046). In summary, long-term IFN therapy may be more effective than short-term IFN therapy for patients with chronic HBV genotype C infection.

Analysis of Background Factors Influencing Long-Term Prognosis of Patients with Chronic Hepatitis C Treated with Interferon

Objective: Interferon (IFN) therapy has been used as antiviral therapy for chronic hepatitis C (CH-C); however, complete response to the therapy is observed in only about 30% of patients in Japan. Background factors involved in the responsiveness to IFN therapy, and progression to liver cirrhosis (LC) and hepatocellular carcinoma (HCC) after IFN therapy have not yet been sufficiently investigated. Methods: One hundred twenty-one patients with CH-C who received IFN therapy at Showa University Hospital between 1984 and 1999 were analyzed. Results: At 6 months after the termination of IFN therapy, 53 patients achieved a complete response, 11 patients incomplete response, and 57 patients no response. During a mean follow-up of 52.7 months, 12 patients progressed to LC, and 10 patients developed HCC. Multivariate analysis showed that significant independent factors involved in progression to LC were platelet count and the efficacy of IFN therapy. The significant independent factor involved in the development of HCC was platelet count. The factor involved in the therapeutic effect at 6 months after the termination of IFN administration was the serum hepatitis C virus (HCV) RNA levels before IFN therapy. Conclusion: Patients with high HCV RNA levels and low platelet counts should be considered to be at high risk of progressing to LC and developing of HCC and should be carefully followed after IFN therapy using ultrasonography, CT scan and MRI.

Serum Dipeptidyl Peptidase IV (DPP IV, CD26) Activity in Chronic Hepatitis C

Background: DPP IV is a cell surface ectoenzyme widely distributed in the human body. It has been implicated in T-cell activation, hepatocyte-extracellular-matrix interactions and fibroblast proliferation. Furthermore, upregulated CD26 expression has been found on the surface of human hepatoma cells transfected with hepatitis C virus (HCV) c-DNA. We examined the serum DPP IV activity in a large number of patients with chronic HCV infection in a cross-sectional study. We also investigated whether the activity differs from that in controls and depends upon the response to interferon (IFN) therapy. Methods: Serum DPP IV activity was measured by microplate-based (Multiskan-Plus-MKII, Labsystem) kinetic assay in 144 patients with chronic HCV infection. Seventy-four out of 144 patients (46 nonresponders, 28 responders) were formerly treated with interferon. Sixty healthy blood donors served as controls. Gly-Pro-PNA (Bachem, Torrance, USA) was used as substrate. Results are expressed in nmol/ml/min (U/l). Shapiro-Wilk's test, Mann-Whitney U test and Spearman rank order correlation were used for statistical analysis. Results: Serum DPP IV activity was significantly higher (mean = 20.89 [s 9.6]) in patients with chronic HCV infection than in healthy controls (12.39 [2.76, P < 10-5]). The enzyme activities significantly differed in naive HCV-positive patients (22.2 [9.89, P < 10-5]) and nonresponders (23.28 [9.57, P < 10-5]) from that in the healthy controls and also from that in responders (13.69 [4.21]). Correlation was found between DPP IV activity and AST (r = 0.44, P < 10-5), ALT (r = 0.44, P < 10-5), GGT (r = 0.41, P < 10-5) levels. Conclusion: Serum DPP IV activity seems to be an indicator of HCV induced liver injury. The activity may reflect the efficacy of interferon therapy.

Predictors of the efficacy of interferon therapy for patients with chronic hepatitis C before and during therapy: how does this modify the treatment course?

Antiviral therapy for hepatitis C virus (HCV) infection should be based on the natural history of HCV infection; there is a sequential, but slow, progression from chronic hepatitis to cirrhosis, leading to death from either liver failure or hepatocellular carcinoma (HCC). The risk of HCC development increases in association with the advance of fibrosis, and antiviral therapy can reduce this risk. More than 30 indices have been proposed as 'predictors' of favourable response to IFN therapy: host factors (age, gender, duration of HCV-infection, alcohol intake, hepatic iron stores, platelet count, histological staging of the liver disease), viral factors (HCV RNA levels in serum, HCV subtype, diversity of the hypervariable region, mutation of non-structure 5A gene), and IFN factors (dose, duration of treatment, type, treatment regimens i.e. every day vs three times a week, escalating dose regimen). Before starting IFN therapy, HCV subtype and pretreatment HCV RNA load, as well as the fibrotic stage of the liver, should be determined. The response to IFN therapy should be monitored by the HCV RNA status in serum during therapy, and the treatment regimen modified, or discontinued as required. A sustained virological response should be checked at more than 3 months after the completion of therapy. Even though the risk of HCC is markedly reduced in sustained responders, it is possible to develop HCC several years after completion of IFN therapy.

Sustained viral response is rarely achieved in patients with high viral load of HCV RNA by excessive interferon therapy.

Adequate dosing of interferon (IFN) and its cost-effectiveness for sustained virological response were evaluated in relation to viral load and subtype. Prospective analysis of IFN therapy on 326 patients with chronic hepatitis C free from cirrhosis was performed using 9 or 6 million unit (MU) of IFN for six months daily and/or three times a week. Sustained virological response was achieved in 50-94% of patients with < or =2 x 10(4) copies/ml (competitive RT-PCR) or <100 x 10(3) copies/ml (Amplicor monitor) of HCV RNA by 468-1206 MU of IFN, but response was only 0-25% of the patients with > or =2 x 10(5.5) copies/ml (competitive RT-PCR) or >200 x 10(3) copies/ml (Amplicor monitor), even with 468-1206 MU of IFN. A high sustained rate was demonstrated in patients with 100-200 x 10(3) copies/ml of HCV RNA by 901-1206 MU of IFN, in comparison to that with < or =900 MU of IFN. Multivariate analysis showed that IFN dose had a significant value for the efficacy of IFN therapy in patients presenting 100-200 x 10(3) copies/ml of HCV RNA. Cost efficacy analysis indicated that it cost approximately $10,000, $26,000, and $50,000-227,000 for one person-viral eradication in the patients with <100, 100-200, and >200 x 10(3) copies/ml, respectively. High-dose IFN is only cost effective in patients with intermediate viral loads, and IFN therapy could be recommended in patients with <200 x 10(3) copies/ml of HCV RNA.

The alcoholic patient with Hepatitis C Virus infection

Chronic alcoholism in patients with chronic hepatitis C hastens disease progression toward development of cirrhosis and hepatocellular carcinoma. Approximately 30% of alcoholic patients with liver disease are infected with the hepatitis C virus (HCV), the primary risk factor being a history of injection drug use. The histologic pattern in alcoholics is typically indistinguishable from nonalcoholic patients similarly infected with chronic hepatitis C. The mechanism(s) involved in alcohol-induced enhancement of chronic hepatitis C have not entirely been established but may involve increased viral replication, iron overload, and immune suppression. Still to be determined is the minimum amount of daily alcohol intake, if any, that can be ingested without enhancing progressive liver injury. However, chronic hepatitis C patients undergoing treatment with interferon must abstain from any alcohol intake, because the efficacy of interferon therapy is significantly lower in those who continue to drink. Future research efforts are needed in order to further delineate the epidemiology and pathogenesis of chronic hepatitis C in the alcoholic patient.

Efficacy of interferon therapy on serum fibronectin levels in children with chronic hepatitis B infection

Abstract Background: Fibronectin (FN) is a glycoprotein, the major sources of which are hepatocytes, Kupffer cells and endothelial cells. It has many biological functions including adhesion between cells, immunity, blood coagulation and platelet aggregation. Serum FN levels are generally decreased in pathological blood coagulation and inflammation. In the present study, we evaluated the serum levels of FN in patients with chronic hepatitis B virus (HBV) infection treated with interferon-α 2b. Methods: We studied serum levels of FN in a prospective trial between October 1995 and May 1997. The study included 16 patients with chronic HBV infection before and after interferon therapy, in a period of 6 months, and 17 healthy controls. In total, we had 40 patients with chronic HBV infection. We studied these 16 patients (40%) who recovered with interferon therapy. We could not study the other 24 patients because we did not have enough of the reagents for studying FN. Results: Chronic hepatitis B infection was diagnosed serologically and histopathologically. In mean age and sex, no statistically significant differences were found between patients and healthy subjects. The serum FN concentration before treatment with interferon therapy appeared significantly lower in HBV patients than in healthy control subjects (P=0.026 using the Mann–Whitney confidence interval and test). After treatment with interferon, serum levels of FN were significantly higher than levels obtained before interferon therapy (P= 0.004 using the Wilcoxon Test). Conclusions: These results suggest that a decreased level of serum FN in patients with chronic hepatitis before interferon treatment is related to hepatic injury and inflammation. Because of inflammation, the serum FN level is decreased due to the consumption of FN. Increased levels of serum FN in patients having interferon therapy is important and is related to the effects of interferon including antiviral, antiproliferative, anti-inflammatory and immunoregulatory properties in patients with chronic HBV infection. A Japanese study showed a correlation between development of hepatic fibrosis and decrease of plasma FN concentration in adult patients with chronic liver disease. Therefore, the serum level of FN may be a useful marker of hepatic fibrosis in chronic liver disease and interferon may be an important drug for prevention of liver fibrosis. Fibronectin may be also a useful marker in predicting IFN response.

Genotype distribution of hepatitis C virus infection in Greece: correlation with different risk factors and response to interferon therapy.

The aim of this study was to investigate the prevalence of HCV genotypes among Greek patients with chronic hepatitis C and to assess the influence of genotypes and quasi-species populations on efficacy of interferon therapy. Genotypes were determined in 65 patients (18 patients after kidney transplantation, 16 with thalassemia and 31 with no known risk factor) with elevated ALT for more than 6 months and histologically proven chronic hepatitis, using the Inno-Lipa strip assay. The quasi-species were determined using the fluorescence single-strand conformational polymorphism method. Most patients were infected with genotype 3a, namely 61% of patients with kidney transplants (n = 18), 50% of patients with thalassemia (n = 16) and 48% of patients without known risk factors (n = 31). Other genotypes were found including coinfection with different genotypes. In all patients with mixed infection, genotype 3a was present. Thirty-six patients from the last two groups received interferon (3Mio U 3x week) for 1 year. Biochemical and/or virological and histological responses were found in 11/19 patients with genotype 3a (58%), 3/5 with mixed infection, 2/4 with genotype 1b, 2/5 with genotype 2a, 1/4 with genotype 1a and 1/1 with genotype 4. The virus found in non-responders with genotype 3a was genetically more heterogeneous than in responders. These data indicate that (1) the genotype 3a is prevalent in Greek patients (68% of all patients), (2) there is no significant difference regarding genotypes among patients with different risk factors and (3) although based on a small number of patients, the genotype 3a seems to respond better to interferon therapy. Finally, the number of quasi-species may be a factor predictive of response.

Nucleotide sequence variations in the internal ribosome entry site of hepatitis C virus-1b: no association with efficacy of interferon therapy or serum HCV-RNA levels.

The extreme 5'-proximal sequences of the hepatitis C virus (HCV) genome including the 5'untranslated region (5'UTR) and the first 30 nucleotides of the core region are highly conserved, and serve as an internal ribosome entry site (IRES) that initiates the cap-independent translation of HCV polyprotein. Mutations in the IRES sequence have been shown to cause changes in the efficiency of protein translation in vitro. However, the significance of genetic variations in the IRES is not fully known in clinical settings. Pretreatment sera of 25 patients with HCV-1b infection who were treated with interferon were amplified by polymerase chain reaction (PCR), and the IRES sequence was directly sequenced. Correlation of interferon responses or other clinical features with IRES sequence variability was studied. Eleven of 25 patients were sustained responders (SR) of interferon treatment (negative serum HCV RNA and normal alanine transaminase levels for 6 months after the end of interferon treatment), and the other 14 patients were nonresponders ([NR], defined as any patient with positive serum HCV RNA within 6 months after the end of interferon therapy). In each patient, one to four nucleotide substitutions were found compared with the consensus sequence of HCV-1b genotype. There were no differences in the number of nucleotide substitutions between either SR and NR (mean, 1.8 in SR, 2.1 in NR; P = .30), and no specific variations associated with SR or NR were observed. Although NR had significantly higher serum levels of pretreatment HCV RNA than SR (median, 16 vs. <0.5 Meq/mL; P = .02), there was no correlation between the HCV-RNA level and the number of nucleotide substitutions in the IRES (mean, 1.9 nucleotide substitutions in 12 patients with HCV RNA <0.5 Meq/ mL vs. 2.1 nucleotide substitutions in 13 patients with HCV RNA >0.5 Meq/mL; P = .61). Sequence variability of the IRES has no influence on interferon efficacy or serum HCV-RNA concentrations in patients with chronic HCV-1b infection.

Nucleotide sequence variations in the internal ribosome entry site of hepatitis C virus-1b: No association with efficacy of interferon therapy or serum HCV-RNA levels

The extreme 5'-proximal sequences of the hepatitis C virus (HCV) genome including the 5'untranslated region (5'UTR) and the first 30 nucleotides of the core region are highly conserved, and serve as an internal ribosome entry site (IRES) that initiates the cap-independent translation of HCV polyprotein. Mutations in the IRES sequence have been shown to cause changes in the efficiency of protein translation in vitro. However, the significance of genetic variations in the IRES is not fully known in clinical settings. Pretreatment sera of 25 patients with HCV-1b infection who were treated with interferon were amplified by polymerase chain reaction (PCR), and the IRES sequence was directly sequenced. Correlation of interferon responses or other clinical features with IRES sequence variability was studied. Eleven of 25 patients were sustained responders (SR) of interferon treatment (negative serum HCV RNA and normal alanine transaminase levels for 6 months after the end of interferon treatment), and the other 14 patients were nonresponders ([NR], defined as any patient with positive serum HCV RNA within 6 months after the end of interferon therapy). In each patient, one to four nucleotide substitutions were found compared with the consensus sequence of HCV-1b genotype. There were no differences in the number of nucleotide substitutions between either SR and NR (mean, 1.8 in SR, 2.1 in NR; P = .30), and no specific variations associated with SR or NR were observed. Although NR had significantly higher serum levels of pretreatment HCV RNA than SR (median, 16 vs. <0.5 Meq/mL; P = .02), there was no correlation between the HCV-RNA level and the number of nucleotide substitutions in the IRES (mean, 1.9 nucleotide substitutions in 12 patients with HCV RNA <0.5 Meq/ mL vs. 2.1 nucleotide substitutions in 13 patients with HCV RNA >0.5 Meq/mL; P = .61). Sequence variability of the IRES has no influence on interferon efficacy or serum HCV-RNA concentrations in patients with chronic HCV-1b infection. (Hepatology 1997 Dec;26(6):1616-20)

Effect of Alcohol Intake on the Efficacy of Interferon Therapy in Patients with Chronic Hepatitis C as Evaluated by Multivariate Logistic Regression Analysis

The effect of alcohol intake on the efficacy of interferon (IFN) therapy was evaluated retrospectively in patients with chronic hepatitis C diagnosed by liver histology and positive serum hepatitis C virus (HCV)-RNA. Patients included 119 given IFN therapy and 11 no IFN therapy. Serum HCV-RNA was measured 6 months after discontinuation of IFN therapy in 92 treated patients, 27.2% of whom showed disappearance of serum HCV-RNA. Multivariate logistic regression analysis revealed that this disappearance was affected by alcohol intake, the presence of its history (p < 0.05) or cumulative alcohol consumption (kg) (p < 0.01), and serum HCV-RNA levels (p < 0.001). The odds ratio associated with serum HCV-RNA still positive at 6 months was 7.018 (95% confidence interval: 1.444-34.062) and 1.004 (1.001-1.007) for the presence of alcohol intake history and the cumulative alcohol consumption, respectively. Other predictor variables-such as sex and age of patients, history of blood transfusion, HCV genotype, histological findings of the liver, and types of IFN-had no influence on the efficacy of the therapy. Cumulative alcohol consumption showed a negative correlation with serum HCV-RNA levels pretreatment, when the outcome variable was divided into two categories based on serum HCV-RNA levels: 10(6) copy/ml or less and 10(7) copy/ml or more. Alcohol intake was positively correlated with histological extent of alcoholic fibrosis, but affected neither grading nor staging of chronic viral hepatitis. We conclude that alcohol intake was a risk factor on the efficacy of IFN therapy in chronic hepatitis C patients. This effect was independent of serum HCV-RNA levels and histological findings specific for viral hepatitis in the liver.

Effect of Alcohol Intake on the Efficacy of Interferon Therapy in Patients with Chronic Hepatitis C as Evaluated by Multivariate Logistic Regression Analysis

The effect of alcohol intake on the efficacy of interferon (IFN) therapy was evaluated retrospectively in patients with chronic hepatitis C diagnosed by liver histology and positive serum hepatitis C virus (HCV)-RNA. Patients included 119 given IFN therapy and 11 no IFN therapy. Serum HCV-RNA was measured 6 months after discontinuation of IFN therapy in 92 treated patients, 27.2% of whom showed disappearance of serum HCV-RNA. Multivariate logistic regression analysis revealed that this disappearance was affected by alcohol intake, the presence of its history (p < 0.05) or cumulative alcohol consumption (kg) (p < 0.01), and serum HCV-RNA levels (p < 0.001). The odds ratio associated with serum HCV-RNA still positive at 6 months was 7.016 (95% confidence interval: 1.444-34.082) and 1.004 (1.001-1.007) for the presence of alcohol intake history and the cumulative alcohol consumption, respectively. Other predictor variables–such as sex and age of patients, history of blood transfusion, HCV genotype, histological findings of the liver, and types of IFN– had no influence on the efficacy of the therapy. Cumulative alcohol consumption showed a negative correlation with serum HCV-RNA levels pretreatment, when the outcome variable was divided into two categories based on serum HCV-RNA levels: 106 copy/ml or less and 107 copy/ml or more. Alcohol intake was positively correlated with histological extent of alcoholic fibrosis, but affected neither grading nor staging of chronic viral hepatitis. We conclude that alcohol intake was a risk factor on the efficacy of IFN therapy in chronic hepatitis C patients. This effect was independent of serum HCV-RNA levels and histological findings specific for viral hepatitis in the liver.

Section Review Anti-infectives: Current perspectives on the treatment and prevention of hepatitis C infection

Hepatitis C virus (HCV) is thought to infect 0.5 - 1.5% of the world's population. In the majority of cases the infection is chronic, and in at least 20% hepatic cirrhosis develops within 20 years representing a major public health problem for the 1990s. Effective treatment is of paramount importance. Therapy for chronic HCV infection has been developed either to improve the host's immune response or to prevent virus replication. Presently the only licensed compound for treatment of HCV infection is alpha-interferon. Analysis of controlled trials of alpha-interferon therapy has identified that a sustained response occurs in less than 25% of patients treated. There are, however, several host and viral factors that are known to affect the efficacy of interferon therapy. It is likely that future treatment regimens will incorporate combinations of compounds with different modes of action. This review article examines regimens to improve the efficacy of alpha-interferon therapy, current treatment options avail...

Factors predictive of response to interferon therapy in children with chronic hepatitis B

Background/Aims: The efficacy of interferon therapy in Caucasian children with chronic hepatitis B is similar to the in adults. However, little information is available about factors predicting response to this therapy in children. We have performed a univariate analysis to assess the strength of association between basal variables and response, and a multivariate analysis to determine the combination of basal variables which give the best prediction of response in terms of sensitivity and specificity. Methods: The basal parameters were studied in 50 children included in three different trials of interferon alpha therapy (360–700 MU/square meter of body surface, 2 or 3 times weekly for 12 to 24 weeks). Results: Of these, 18 (36%) were responders. In the univariate analysis, a higher histological activity ( p<0.05), a lower percentage of HBcAg-stained hepatocytes ( p<0.001), aspartate amino transferase and alanine aminotransferase levels ( p<0.05) and alanine aminotransferase peak prior to serum HBV-DNA clearance ( p<0.05), were associated to the response. In the multivariate analysis, the combinations of the percentage of HBcAg stained cells with alanine aminotransferase levels and with the histological activity index were the best variables for predicting response (sensitivity: 100% and specificity: 89% and 86%, respectively). Conclusions: Factors predictive of response in children with chronic hepatitis B are similar to those found in adults, and may help in identifying those children with a better chance of responding.

Influence of low iron diet on the efficacy of interferon therapy in patients with HBV related chronic liver disease: [formula omitted], S K Sarin, S Malhotra, K Banerjee, P Khandekar. Dept. of Gastroenterology, G.B.Pant Hospital, NII, Delhi

Influence of low iron diet on the efficacy of interferon therapy in patients with HBV related chronic liver disease: [formula omitted], S K Sarin, S Malhotra, K Banerjee, P Khandekar. Dept. of Gastroenterology, G.B.Pant Hospital, NII, Delhi

Predictive factors in the response to interferon therapy in chronic hepatitis C.

Factors predicting the efficacy of interferon therapy were statistically analyzed on 111 patients with chronic hepatitis C. Of the treated patients (total doses of interferon; 96-468 MU), 35 (31.5%) had a long-term remission. On multivariate analysis, hepatitis C virus genotype (p < 0.0001), histological diagnosis (p < 0.05), fibrosis score of histological activity index (p < 0.01) and source of infection (p < 0.05) were found useful for predicting the response to interferon therapy. Our findings suggest that the outcome of interferon therapy can be predicted to some degree from pretreatment data, and that a new therapeutic strategy is necessary for the group of patients who are predicted to be nonresponders.

Interferon therapy for hepatitis C

Initial trials indicated that around 50% of patients respond to recombinant alpha interferon by normalizing alanine aminotransferase (ALT) at the end of therapy and that half of these relapsed within 6 months following cessation of treatment. Both dose and duration of treatment are critical in the response to therapy. Higher doses and longer duration have been suggested to be more effective than the current recommendations of 3 MUI thrice weekly for 6 months based on results of these initial studies which used ALT and histological scores to evaluate the efficacy of interferon therapy. Following studies using virological markers have shown that improvements in clinical features of disease are associated with decrease or loss of hepatitis C virus (HCV) from serum and liver. The heterogeneity of the response rates between clinical centers using identical protocol emphasizes that the selection of the patients treated was as important for the outcome that the therapy regimen itself with better responses in cases without cirrhosis and with low levels of HCV RNA. Furthermore, the genotype of HCV seems to be also critical for the response rate. Virological evaluations appears therefore crucial to assess not only HCV infection but also for the indication and monitoring of therapy.