[Chronic hepatitis C: initial treatment in patients without previous treatment].
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Antiviral Agents↗
Biomedical subjects
M Diago
Publications and source records attributed to M Diago.
Multicenter randomized study comparing initial daily induction with high dose lymphoblastoid interferon vs. standard interferon treatment for chronic hepatitis C.
One hundred fifty-five chronic hepatitis C patients were assigned at random to receive natural lymphoblastoid interferon (IFN)alpha-n1, s.c., for 13 months in one of three treatment regimens: initial daily induction with 10 million units (MU) followed (group 1, n = 50) or not (group 2, n = 52) by 1 month of rest and then three times weekly 10 MU (2 months), 5 MU (2 months), and 3 MU (8 months); group 3 (n = 53) received tiw 5 MU (2 months) followed by 3 MU (11 months). By intention-to-treat analysis, ALT normalization at completion of treatment was greater in patients who received continuous IFNalpha-n1 therapy with initial daily induction (group 2: 24/52, 46%) compared with those given intermittent therapy with initial daily induction (group 1: 17/50, 34%) and those who received standard IFNalpha-n1 therapy (group 3, 18/53, 34%; P not significant). The sustained ALT response was 26%, 27% and 21% and the sustained virological response was 20%, 27%, and 19%, in groups 1, 2, and 3, respectively. A trend was observed towards a higher biochemical and virological end-of-treatment response in patients given induction therapy (17%) compared with standard therapy (6%, P = 0.053). Sustained biochemical and virological responses were 20%, 27%, and 17% in groups 1, 2, and 3, respectively. Platelet and leukocyte counts decreased following daily high-dose treatment and remained low until therapy cessation (P < 0.001). The data suggest that daily s.c. induction with 10 MU IFNalpha-n1 followed by intermittent or continuous maintenance therapy for 1 year does not improve the results achieved with the standard 1-year IFNalpha course in the treatment of chronic hepatitis C patients.
Adolescent↗
Long-term response to interferon plus ribavirin in patients with chronic hepatitis C refractory to interferon.
OBJECTIVE: A sustained response (SR) to interferon (IFN) is only observed in 15-20% of patients with chronic hepatitis C (CHC). The aim of this study was to determine the long-term effectiveness and safety of the treatment with IFN plus ribavirin (RIB) over two years in CHC patients without SR to IFN. DESIGN: A prospective and open longitudinal follow-up study was conducted over 3 years. PATIENTS AND METHODS: A total of 77 CHC patients were included: 63 non-responders (NR) and 14 relapsers (R) to IFN. Patients were treated with IFN (3 MU s.c. three times a week) and RIB (1,000-1,200 mg p.o. daily) for 12 months. Treatment tolerance and viral response (HCV-RNA in serum < 1,000 copies/ml) were assessed after 1, 3, 6 and 12 months of treatment. SR and relapsing rates were subsequently evaluated 6, 12 and 24 months after the end of the treatment, together with those variables capable of predicting SR. RESULTS: At the end of the treatment, 19/77 patients responded (24.7%), 9/63 (14.3%) were non-responders and 10/14 (71.4%) relapsers, and these same patients exhibited SR after 6 months. The SR rate two years after treatment was 22.1% [8/63 (12.7%) NR and 9/14 (64.3%) R]. The relapse rate after 6 months and two years was respectively 0 and 10.5% (2/77). Independent variables capable of predicting SR were negative viremia conversion within the first month of treatment, maintenance of such negative viremia after 6 months, and R status to IFN. Side effects were recorded in 90.9% of cases (70/77), the most frequent being pseudoinfluenza syndrome. Treatment had to be discontinued in 33.8% of patients (26/77). CONCLUSIONS: Combined IFN-RIB therapy for 12 months in CHC patients without SR to IFN obtains a long-term SR of 22.1%, this rate being higher in relapsers to prior IFN therapy (64.3% in R versus 12.7% in NR).
Adult↗
Peginterferon alfa-2a in patients with chronic hepatitis C.
BACKGROUND: Covalent attachment of a 40-kd branched-chain polyethylene glycol moiety to interferon alfa-2a results in a compound (peginterferon alfa-2a) that has sustained absorption, a slower rate of clearance, and a longer half-life than unmodified interferon alfa-2a. We compared the clinical effects of a regimen of peginterferon alfa-2a with those of a regimen of interferon alfa-2a in the initial treatment of patients with chronic hepatitis C. METHODS: We randomly assigned 531 patients with chronic hepatitis C to receive either 180 microg of peginterferon alfa-2a subcutaneously once per week for 48 weeks (267 patients) or 6 million units of interferon alfa-2a subcutaneously three times per week for 12 weeks, followed by 3 million units three times per week for 36 weeks (264 patients). All the patients were assessed at week 72 for a sustained virologic response, defined as an undetectable level of hepatitis C virus RNA (<100 copies per milliliter). RESULTS: In the peginterferon group, 223 of the 267 patients completed treatment and 206 completed follow-up. In the interferon group, 161 of the 264 patients completed treatment and 154 completed follow-up. In an intention-to-treat analysis in which patients who missed the examination at the end of treatment or follow-up were considered not to have had a response at that point, peginterferon alfa-2a was associated with a higher rate of virologic response than was interferon alfa-2a at week 48 (69 percent vs. 28 percent, P=0.001) and at week 72 (39 percent vs. 19 percent, P=0.001). Sustained normalization of serum alanine aminotransferase concentrations at week 72 was also more common in the peginterferon group than in the interferon group (45 percent vs. 25 percent, P=0.001). The two groups were similar with respect to the frequency and severity of adverse events, which were typical of those associated with interferon alfa. CONCLUSIONS: In patients with chronic hepatitis C, a regimen of peginterferon alfa-2a given once weekly is more effective than a regimen of interferon alfa-2a given three times weekly.
Adult↗
A phase I/II study of recombinant human interleukin-12 in patients with chronic hepatitis B.
BACKGROUND/AIMS: Interleukin-12 (IL-12) may be active against hepatitis B virus (HBV). The objective of the study was to assess the tolerability, activity, pharmacokinetics, and pharmacodynamics of three dose levels (0.03 microg/kg b.w., n=15; 0.25 microg/kg b.w., n=15; 0.50 microg/kg b.w., n=16) of recombinant human (rHu) IL-12 given s.c. once a week for 12 consecutive weeks. METHODS: Forty-six patients with chronic hepatitis B, HBV DNA positivity and aminotransferase elevation were included in a multicenter prospective randomized phase I/II study. RESULTS: Compared with the baseline, HBV DNA levels had decreased significantly at the end of rHuIL-12 treatment and after the 12-week follow-up period (p<0.001). The response to rHuIL-12 treatment was dose-dependent: at the end of the study HBV DNA clearance was greater in patients treated with 0.50 microg/kg b.w. (25%) or with 0.25 microg/kg b.w. (13%) compared with those given 0.03 microg/kg b.w. (7%). Moreover, HBeAg became undetectable at the end of follow-up in five of the patients given the 0.25microg/kg (2/15) or the 0.50 microg/kg (3/16) dose. The drug pharmacology showed that IL-12 had an estimated half-life of 30 h with levels remaining detectable for more than 48 h after rHuIL-12 administration. The serum levels of IL-12, interferon-gamma, IL-10, neopterin and beta2-microglobulin as well as the area under the curve (AUC) were rHuIL-12 dose-related. Side effects were observed more frequently with higher doses, including moderate decreases in lymphocyte and neutrophil counts; three patients withdrew prematurely from treatment. The local reaction observed at the injection site was unrelated to the drug dose. Only one patient showed detectable antibody levels to rHuIL-12 without clinical impact. CONCLUSIONS: Treatment with rHuIL-12 at the doses investigated is safe and tolerable, and appears to be active against HBV in patients with chronic hepatitis B.
Adjuvants, Immunologic↗
Interferon alfa-2b plus ribavirin for chronic hepatitis C patients who have not responded to interferon monotherapy.
BACKGROUND: The role of combination therapy is poorly defined in chronic hepatitis C patients who are non-responders to interferon. AIM: To assess the efficacy, safety and tolerance of interferon alfa-2b plus ribavirin in chronic hepatitis C patients who do not respond to interferon monotherapy. METHODS: A total of 127 non-responder patients with chronic hepatitis C received 3 mU t.i.w. of interferon alfa-2b plus 1000-1200 mg ribavirin daily for 48 weeks. Effects of therapy were evaluated by serum aminotransferases and hepatitis C virus (HCV) RNA levels. RESULTS: Twenty-nine (23%) patients had an end-of-treatment response. Six months after treatment, 20 (16%) patients were sustained responders. Early loss of HCV RNA was the strongest predictor of a sustained response (P < 0.0001). Remission was also more frequent in patients with genotype 1b (P < 0.02), elevated alanine aminotransferase (P < 0.03) and low gamma glutamiltranspeptidase (P < 0.002). Treatment was discontinued in 21 (17%) patients: in 14 for intolerance and in seven due to side-effects. CONCLUSIONS: Combination therapy with interferon plus ribavirin produced a sustained response in 16% of chronic hepatitis C patients who were non-responders to interferon. This combination was safe and well tolerated.
Adult↗
Retreatment for 24 vs 48 weeks with interferon-alpha2b plus ribavirin of chronic hepatitis C patients who relapsed or did not respond to interferon alone.
We assessed the efficacy of interferon (IFN) plus ribavirin over 24 or 48 weeks for the retreatment of patients with chronic hepatitis C who had relapsed or did not respond to a previous course of IFN. One-hundred and twenty patients (69 non-responders and 51 relapsers) were randomly assigned to receive IFN-alpha2b (3 million units thrice weekly) plus ribavirin (1,000-1,200 mg per day) for 24 weeks (group A: 58 patients) or 48 weeks (group B: 62 patients). Treatment was discontinued at week 12 if the alanine aminotransferase (ALT) level remained elevated. The rate of sustained response was 15.5% in group A and 37.1% in group B (P = 0.013). Relapsers treated for 48 weeks had a sustained response rate of 66.6% compared with a sustained response rate of only 25% in those treated for 24 weeks (P = 0.004). Moreover, a sustained response was seen in 14.3% of non-responders treated for 48 weeks and in 8.8% of those treated for 24 weeks (P = 0.71). Fifty-three per cent of patients with a normal ALT level and undetectable hepatitis C virus (HCV) RNA at week 12 had a sustained response compared with 14% of those who were HCV RNA positive at week 12 (P < 0.001). Independent predictive factors of sustained response were: therapy for 48 weeks (P = 0.0026), relapse after IFN treatment (P = 0.0006), loss of HCV RNA at week 12 (P = 0.0008) and HCV genotype non-1 (P = 0.024). Hence, in patients with chronic hepatitis C who failed to respond to a previous course of IFN monotherapy, combination therapy with IFN plus ribavirin for 48 weeks seems to be more effective than IFN plus ribavirin for 24 weeks.
Adult↗
A phase I/II study of recombinant human interleukin-12 in patients with chronic hepatitis C.
Interleukin-12 (IL-12) plays a central role in mounting an effective cellular immune response directed towards elimination of intracellular pathogens. The present open-label, multicenter, dose-escalation phase I/II study was designed to assess tolerability, pharmacokinetics, pharmacodynamics, and efficacy of subcutaneously administered recombinant human interleukin-12 (rHuIL-12) in the treatment of chronic hepatitis C. Sixty patients (42 men, 18 women, aged 24-60) were treated with 0.03 microgram/kg (n = 16), 0.1 microgram/kg (n = 14), 0.25 microgram/kg (n = 15), or 0.5 microgram/kg rHuIL-12 (n = 15) for 10 consecutive weeks. rHuIL-12 was generally well tolerated, with 2 patients (3.3%) being withdrawn from treatment for adverse events. Treatment was associated with temporary decreases in neutrophils and lymphocyte counts and with elevations in serum transaminases and bilirubin. Serum IL-12 levels observed were higher at 0.5 microgram/kg compared with 0.25 microgram/kg doses, suggesting a dose-related increase in systemic exposure of IL-12. Measurable levels of interferon gamma (IFN-gamma) were also observed at the highest dose of 0.5 microgram/kg. At the end of treatment hepatitis C virus (HCV) RNA was detectable in all patients. A more than 50% decrease in pretreatment HCV RNA levels was observed in 3 of 16 patients of the 0.03-microgram/kg dose group, in 3 of 14 of the 0.10-microgram/kg dose group, in 6 of 15 of the 0.25-microgram/kg dose group, and in 8 of 15 patients of the 0.5-microgram/kg dose group. Although in several cases serum alanine transaminase (ALT) levels decreased either during or after treatment, ALT normalization was observed in only 4 patients at the end of treatment and in 5 patients at the end of follow-up. Significant anti-rHuIL-12 antibody titers were not detectable in any patient. In conclusion, antiviral activity of rHuIL-12 in patients with chronic hepatitis C does not appear advantageous in comparison with other currently available treatments.
Adolescent↗
Retreatment of chronic hepatitis B e antigen-positive patients with recombinant interferon alfa-2a. The European Concerted Action on Viral Hepatitis (EUROHEP).
Fifty-seven patients with chronic hepatitis B, hepatitis B virus (HBV) e antigen (HBeAg) and HBV DNA positivity, and aminotransferase elevation despite a previous course of any type of adequate interferon alfa (IFN-alpha) therapy were included in a multicenter prospective randomized controlled trial. The objective of the study was to compare a second course of IFN-alpha therapy (9 million units [MU] of IFN-alpha-2a, Roferon-A, thrice weekly for 6 months) versus no therapy in terms of loss of HBV DNA and HBeAg. At the end of the study, a sustained clearance of HBV DNA and HBeAg was observed in 9 of the 27 (33.3%) patients who had received retreatment with IFN-alpha compared with 3/30 (10%) patients who spontaneously cleared these markers in the untreated control group (chi2 = 4.66, P =.031; odds ratio: 4.5, 95%; confidence interval: 1.1-18.9). None of the responders lost HBsAg. Patients retreated with IFN-alpha were more likely to have biochemical remission in association with HBV clearance (5/27, 18.5%) compared with untreated patients (1/30, 3. 3%; Fisher's exact test P =.09 ). Histological improvement in the liver necroinflammatory activity was observed among sustained responders to IFN-alpha retreatment, consisting of regression of the portal and periportal inflammation and of the piecemeal necrosis; there was no change in the degree of liver fibrosis. Side effects were similar to those previously reported during IFN-alpha treatment; these were mild and reversible on IFN-alpha discontinuation. None of the baseline features were associated with response by Cox's regression analysis. In summary, viremic patients with chronic HBeAg-positive hepatitis may experience disease remission following retreatment with IFN-alpha. Thus, retreatment with IFN-alpha may be considered a therapeutic option.
Adolescent↗
[Indications and prescription of hepatitis A vaccine in Spain. Report of the Spanish Association for the Study of the Liver].
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Adolescent↗
Preliminary investigation of the association of oral lichen planus and hepatitis C.
OBJECTIVE: The aim of this investigation was to determine if an association exists between hepatitis C virus and oral lichen planus. STUDY DESIGN: Three groups of subjects were selected: 505 patients with hepatitis C virus infection (group 1), 100 patients with oral lichen planus (group 2), and a randomly selected control group (age- and gender-matched) of 100 healthy subjects (group 3). The prevalence of oral lichen planus was determined in groups 1 and 3, and the prevalence of hepatitis C virus infection was established in groups 2 and 3. RESULTS: The prevalence of oral lichen planus was 3.36% (n = 17) in group 1 and 1% (n = 1) in the control group; the prevalence of hepatitis C virus infection was 23% (n = 23) in group 2, and 5% (n = 5) in the control group. No significant differences were observed in the incidence of oral lichen planus in group 1 between those patients who received interferon and those who did not. The 17 patients in group 1 who manifested oral lichen planus and hepatitis C virus infection simultaneously exhibited a marked tendency to have only reticular lesions (70.6%), with involvement of the buccal mucosa in 88.2% of these patients, the tongue in 29.4%, and the gingiva in 11.8%. Analyzing a randomized subgroup of 143 patients from group 1 (subgroup 1) that was matched by age and gender with groups 2 and 3, we found that the incidence of oral lichen planus in patients with hepatitis C virus infection (subgroup 1) was greater than in the control group (5.59% vs 1%), though this was not statistically significant (chi2 = 0.119; p = 0.06). In contrast, group 2 exhibited a statistically significant higher incidence of hepatitis C virus infection (23%) than the controls (5%; chi2 = 0.259, p = 0.0002). CONCLUSIONS: The prevalence of hepatitis C virus infection in patients with oral lichen planus was greater than in the control series. In our opinion this observation warrants the investigation of potential concomitant hepatitis C virus infection in patients with oral lichen planus.
Candidiasis, Oral↗
[Focal nodular liver hyperplasia of atypical presentation].
Focal nodular hyperplasia is a benign hepatic tumor that usually appears in young women. Diagnosis of focal nodular hyperplasia is often incidental when an ultrasonography or computed tomography is performed by other reasons, because its course is generally asymptomatic; the presence of a central fibrous scar is characteristic. Management in focal nodular hyperplasia must be conservative, with ultrasonographic follow-up, and it only must be treated when patients are symptomatics or in case of tumoral enlargement. We report a case of FNH in which symptomatic presentation and the absence of central stellate scar in ultrasonography, computed tomography and magnetic resonance leads to a misdiagnostic of hepatic adenoma, that conditioned a surgical resection. The later examination was diagnostic of focal nodular hyperplasia.
Adenoma↗
Multicenter randomized, controlled study of intramuscular administration of interferon-beta for the treatment of chronic hepatitis C.
The intramuscular administration of interferon-beta (IFN-beta) at a dosage of 6 million units three times per week for 6 months has been evaluated in 90 patients included in a multicenter, randomized, controlled trial for the treatment of chronic hepatitis C. Transaminase levels were significantly reduced in IFN-beta-treated patients (p = 0.015) and were significantly lower with respect to those of the untreated controls (p = 0.040 at 6 months). Four treated (8%) and one untreated (2.5%) patients had normal transaminase values after 6 months. At study end (12 months), three quarters of the IFN-beta-treated patients had sustained transaminase normalization, whereas the untreated case had relapsed. Hepatitis C viremia was cleared in 6 (12%) treated patients but in none of the untreated controls (p = 0.058). Side effects of IFN-beta were infrequent (a mild flu-like syndrome in < 10%, asthenia in 16%, anorexia in 8%, headaches and weight loss in 8%, and hair loss in 4%). Leukocyte and platelet counts decreased during IFN-beta treatment, but no dose modifications were necessary. Such decreases were not statistically significant when compared with the levels in the untreated controls. Intramuscular IFN-beta at the dosage used has little efficacy in the treatment of chronic hepatitis C. Because of IFN-beta tolerance, higher doses and alternate routes of injection might prove beneficial for the treatment of this disease.
Adult↗
Tolerance and efficacy of subcutaneous interferon-beta administered for treatment of chronic hepatitis C.
We studied tolerance to subcutaneous (s.c.) administration of 6 million units of interferon-beta (IFN-beta), given three times per week for 6 months, and its efficacy in the treatment of 15 patients with chronic hepatitis C. At the end of the treatment, alanine aminotransferase (ALT) levels were significantly reduced (p = 0.024) in all patients, and 4 (27%) had a normal ALT value. However, at the end of the study (12 months), only 1 of these 4 had a sustained response. No patient cleared hepatitis C virus (HCV) RNA completely, but the RNA could be detected only by polymerase chain reaction (PCR) in the sustained responder. Adverse side effects to the s.c. IFN-beta were infrequent. Leukocyte (p = 0.012) and platelet (p = 0.013) counts decreased significantly during treatment but did not necessitate dose modifications. Thus, although s.c. IFN-beta at the dosage used had little efficacy in the treatment of chronic hepatitis C, the excellent tolerance to the treatment suggests that the effects of higher doses should be explored.
Adult↗
[Indications and prescription of hepatitis A vaccine in Spain. Report of the Spain Association for the Study of the Liver].
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Adult↗
Intrafamily transmission of hepatitis C virus: sexual and non-sexual contacts.
BACKGROUND/METHODS: As a high number of patients with antibodies to hepatitis C (anti-HCV) do not have a known history of parenteral acquisition, other non-parenteral means of hepatitis C virus transmission must be studied. We investigated 1451 household contacts of 535 anti-HCV positive, human immunodeficiency virus-negative index patients. RESULTS: Overall, the prevalence of anti-HCV in household contacts was 4.5%. Thirty (7.6%) out of the 394 heterosexual stable partners were anti-HCV positive as compared to 35 (3.3%) out of 1057 non-sexual contacts (p < 0.01). The prevalence of anti-HCV was lowest in children of the index cases (1.8%). In this group, the prevalence of anti-HCV was 3% (10/330) when the mother was the index case, as opposed to 0.6% (2/328) when the father was the index case (p < 0.05). The prevalence of anti-HCV increased with age, being highest (18.6%) in family contacts older than 60 years. CONCLUSIONS: Transmission of hepatitis C virus may occur among household contacts of anti-HCV positive patients. Sexual contact or the use of non-disposable medical material in the past might explain the higher prevalence of anti-HCV found in sexual partners and in family contacts older than 60 years of age. Anti-HCV screening should be performed in family contacts of anti-HCV positive patients, particularly in those contacts older than 20.
Adolescent↗
[Physical exercise and gastric acid secretion].
The effects of physical exercise on the basal acid secretion of the stomach has been investigated in 10 healthy individuals and 16 hypersecretors with duodenal ulcer. The gastric basal secretion was collected during 3 hours; during the first hour the patient was at rest, during the second he realized a training exercise, according to Roskamm's formula, and in the third was at rest. While normal subjects showed a significative reduction of the acid secretion during the period of exercise, in the hypersecretory patients with ulcer the acid secretion increased significantly during exercise, from 4.25 +/- 1.52 mEq/h to 7.79 +/- 3.49 mEq/h; these figures reverted to normal values (5.45 +/- 2.21) during the recovery period. We comment the potential mechanisms of these differences in both groups of patients.
Adult↗
[Action of domperidone on dopamine-induced inhibition of gastric secretion].
The inhibitory action of dopamine on basal gastric secretion and that stimulated by pentagastrin with previous administration of domperidone in 26 male patients, between 18 and 48 years of age, suffering duodenal ulcer has been studied. The administration of domperidone (0.25 mg/kg) produces a significant reduction of the inhibitory action of dopamine on basal gastric secretion and that stimulated by pentagastrin at dose 0.15 microgram/kg/h. Besides dopamine shows a minor, non significant, inhibitory action on acid gastric secretion stimulated by maximal doses of pentagastrin, while showing no differences against the group without administration of domperidone.
Adolescent↗