Interferon alfa-2b alone or in combination with ribavirin for the treatment of relapse of chronic hepatitis C. International Hepatitis Interventional Therapy Group

BACKGROUND: Interferon alfa is the only effective treatment for patients with chronic hepatitis C. Forty percent of patients have an initial response to this therapy, but most subsequently relapse. We compared the effect of interferon alone with that of interferon plus oral ribavirin for relapses of chronic hepatitis C. METHODS: We studied 345 patients with chronic hepatitis C who relapsed after interferon treatment. A total of 173 patients were randomly assigned to receive standard-dose recombinant interferon alfa-2b concurrently with ribavirin (1000 to 1200 mg orally per day, depending on body weight) for six months, and 172 patients were assigned to receive interferon and placebo. RESULTS: At the completion of treatment, serum levels of hepatitis C virus (HCV) RNA were undetectable in 141 of the 173 patients who were treated with interferon and ribavirin and in 80 of the 172 patients who were treated with interferon alone (82 percent vs. 47 percent, P<0.001). Serum HCV RNA levels remained undetectable 24 weeks after the end of treatment in 84 patients (49 percent) in the combination-therapy group, but in only 8 patients (5 percent) in the interferon group (P<0.001). Sustained normalization of serum alanine aminotransferase concentrations and histologic improvement were highly correlated with virologic response. Base-line serum HCV RNA levels of 2 x 10(6) copies per milliliter or less were associated with higher rates of response in both treatment groups. Viral genotypes other than type 1 were associated with sustained responses only in the combination-therapy group. Combined therapy caused a predictable fall in hemoglobin concentrations but otherwise had a safety profile similar to that of interferon alone. CONCLUSIONS: In patients with chronic hepatitis C who relapse after treatment with interferon, therapy with interferon and oral ribavirin results in higher rates of sustained virologic, biochemical, and histologic response than treatment with interferon alone.     

Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group

BACKGROUND: Only 15 to 20 percent of patients with chronic hepatitis C have a sustained virologic response to interferon therapy. We compared the efficacy and safety of recombinant interferon alfa-2b alone with those of a combination of interferon alfa-2b and ribavirin for the initial treatment of patients with chronic hepatitis C. METHODS: We randomly assigned 912 patients with chronic hepatitis C to receive standard-dose interferon alfa-2b alone or in combination with ribavirin (1000 or 1200 mg orally per day, depending on body weight) for 24 or 48 weeks. Efficacy was assessed by measurements of serum hepatitis C virus (HCV) RNA and serum aminotransferases and by liver biopsy. RESULTS: The rate of sustained virologic response (defined as an undetectable serum HCV RNA level 24 weeks after treatment was completed) was higher among patients who received combination therapy for either 24 weeks (70 of 228 patients, 31 percent) or 48 weeks (87 of 228 patients, 38 percent) than among patients who received interferon alone for either 24 weeks (13 of 231 patients, 6 percent) or 48 weeks (29 of 225 patients, 13 percent) (P<0.001 for the comparison of interferon alone with both 24 weeks and 48 weeks of combination treatment). Among patients with HCV genotype 1 infection, the best response occurred in those who were treated for 48 weeks with interferon and ribavirin. Histologic improvement was more common in patients who were treated with combination therapy for either 24 weeks (57 percent) or 48 weeks (61 percent) than in those who were treated with interferon alone for either 24 weeks (44 percent) or 48 weeks (41 percent). The drug doses had to be reduced and treatment discontinued more often in patients who were treated with combination therapy. CONCLUSIONS: In patients with chronic hepatitis C, initial therapy with interferon and ribavirin was more effective than treatment with interferon alone.     

Combination therapy with interferon alpha and ribavirin for chronic hepatitis C virus infection in thalassaemic patients

Hepatitis C virus (HCV) infection is common in multi-transfused thalassaemic patients, and, in combination with transfusional iron overload, can result in progressive liver disease. Therapy with interferon-alpha causes a sustained loss of HCV in only 15-25% of patients, and there is as yet no established effective therapy for those who fail to respond. We have conducted a pilot study of combination anti-viral therapy for patients who failed to respond, or relapsed after an initial response to single-agent interferon-alpha. Patients were treated for 6 months with interferon-alpha 2b, given subcutaneously three mega units thrice weekly, together with ribavirin, orally 1 g daily. 11 patients were enrolled, their median age was 24.9 years. 8/10 evaluable patients had cirrhosis on biopsy, five were infected with HCV type 1 and all but one had initial HCV RNA titres > 10(6) genomes/ml. Five patients (45.5%) had a sustained virological response with loss of serum HCV RNA for > 6 months after finishing therapy. There was no clear association between response to therapy and age, histology, HCV genotype, or HCV RNA titre. Transfusion requirements were significantly increased during the treatment phase, probably due to ribavirin-induced haemolysis, and this necessitated intensification of iron chelation therapy. Serum ferritin levels decreased significantly in those who responded. These results suggest that combination therapy is potent in clearing HCV infection, and may provide effective second-line therapy for thalassaemic patients who have failed to respond to interferon-alpha monotherapy.     

Interferon alpha with ribavirin for the treatment of chronic hepatitis C in non-responders or relapsers to interferon monotherapy

The ability of different serotypes of group B streptococci (GBS) to induce septic arthritis in mice was compared. Types II, III, IV, V, VI and VII GBS were investigated. A highly capsulate strain of type III GBS, COH1, and its mutants, COH1-11 (lacking capsular sialic acid) and COH1-13 (non-capsulate), obtained by transposon insertional mutagenesis, were used to assess the role of type-specific polysaccharide on the induction of arthritis. At an intravenous dose of 10(7) cfu/mouse, reference strains of types II, III, IV, VI and VII and type III strain COH1 induced arthritis with an incidence ranging from 70 to 90%. For type V and strain COH1-11, 10(8) cfu/mouse was required to obtain a 50% incidence of arthritis; lesions were not evident with strain COH1-13. The presence of the capsule played a major role in the induction of GBS septic arthritis. The presence and amount of sialic acid in capsular polysaccharide influenced the incidence of articular lesions. The bacterial dose affected the manifestations of arthritis; the less virulent strains of GBS also induced articular lesions when an adequate number of micro-organisms reached the joints.     

Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients. CHIB 201 International Study Group

BACKGROUND: Currently available immunosuppressive regimens for cadaver-kidney recipients are far from ideal because acute-rejection episodes occur in about 30% to 50% of these patients. In the phase III study described here we assessed the ability of basiliximab, a chimeric interleukin (IL)-2 receptor monoclonal antibody, to prevent acute-rejection episodes in renal allograft recipients. METHODS: 380 adult recipients of a primary cadaveric kidney transplant were randomly allocated, in this double-blind trial, to receive a 20 mg infusion of basiliximab on day 0 (day of surgery) and on day 4, to provide IL-2-receptor suppression for 4-6 weeks (n=193), or to receive placebo (n=187). Both groups received baseline dual immunosuppressive therapy with cyclosporin and steroids throughout the study. The primary outcome measure was incidence of acute-rejection episodes during the 6 months after transplantation. Safety and tolerability were monitored over the 12 months of the study. FINDINGS: 376 patients were eligible for intention-to-treat analysis (basiliximab, n=190; placebo, n=186). No significant differences in patient characteristics were apparent. The incidence of biopsy-confirmed acute rejection 6 months after transplantation was 51 (29.8%) of 171 in the basiliximab group compared with 73 (44.0%) of 166 in the placebo group (32% reduction; 14.2% difference [95% Kaplan-Meier CIs 3% to 24%], p=0.012). The incidence of steroid-resistant first rejection episodes that required antibody therapy was significantly lower in the basiliximab group (10% vs 23.1%, 13.1% difference [5.4% to 20.8%], p<0.001). At weeks 2 and 4 post-transplantation, the mean daily dose of steroids was significantly higher in the placebo group (p<0.001 with one-way analysis of variance). The incidence of graft loss at 12 months post-transplantation was 23 (12.1%) of 190 in the basiliximab group and 25 (13.4%) of 186 in the placebo group (1.3% difference [-5% to 9%], p=0.591). The incidence of infection and other adverse events was similar in the two treatment groups. The acute tolerability of basiliximab was excellent, with no evidence of cytokine-release syndrome. 14 deaths (basiliximab n=9; placebo n=5; -2.0% difference [-6% to 2%], p=0.293) occurred during the 12-month study and a further three deaths (basiliximab n=1; placebo n=2) occurred within the 380-day cut-off period. One post-transplantation lymphoproliferative disorder was recorded in each group. INTERPRETATION: Prophylaxis with 40 mg basiliximab reduces the incidence of acute rejection episodes significantly, with no clinically relevant safety or tolerability concerns.     

Interferon antibodies in patients with chronic hepatitic C virus infection treated with recombinant interferon alpha-2 alpha

Patients treated with alpha-2a interferon for chronic hepatitis C may produce anti-interferon antibodies whose effect, if any, on the individual response to therapy has not been fully clarified. The prevalence and kinetics of anti-interferon, including those of neutralizing type, have been studied in 60 patients with chronic hepatitis C enrolled in a randomized controlled trial of recombinant alpha-2a interferon. Thirty patients received interferon while 30 were untreated controls. Two different methods, an enzyme immunoassay and an antiviral neutralization bioassay, were used and serial serum samples from each patient were analyzed. Enzyme immunoassay-positive anti-interferon appeared in 60.7% of treated patients within 6 months of therapy; antiviral neutralization bioassay-positive anti-interferon appeared in 52.9% of these enzyme immunoassay-positive patients, and was associated with high enzyme immunoassay reactivity and long-term persistence. Anti-interferon was detected in 75% of patients showing no response to interferon. Antibodies were also detected in three out of six patients who showed alanine aminotransferase normalization persisting up to the end of treatment and in 8 out of 14 patients who showed an initial marked reduction or even normalization of alanine aminotransferase, followed by reactivation of liver damage during treatment. Interestingly, patients who became anti-interferon positive before complete alanine aminotransferase normalization later showed reactivation of liver damage independently of interferon dose reduction, while patients who became positive for anti-interferon after complete alanine aminotransferase normalization either did not reactivate or did so only after interferon dose reduction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of hepatitis C virus genotypes and HIV infection on histological severity of chronic hepatitis C. The Hepatitis/HIV Spanish Study Group

OBJECTIVES: The factors influencing the histological severity of chronic hepatitis C (CHC) have not been well established. We therefore investigated the effect of hepatitis C virus (HCV) genotypes and human immunodeficiency virus (HIV) infection on histological liver damage in a cohort of intravenous drug users with CHC. METHODS: We analyzed the histological activity score and the HCV genotypes in 59 HCV-RNA-positive patients with biopsy-proven CHC. Forty-eight (81%) of them had concomitant HIV infection with a CD4+ cell count above 200 x 10(6) cells/L and an absence of AIDS-defining conditions. Multivariate analysis was performed to determine the features associated with the histological severity. RESULTS: Minimal/mild hepatitis was found in 16 patients (27%), moderate chronic hepatitis in 29 (49%), and severe chronic hepatitis in 14 (24%). Patients with HCV subtype 1b had a higher histological score than others (8.7 +/- 3.3 vs. 6.5 +/- 3.2, p = 0.012), either as single or mixed infections. In multivariate analysis, HIV-infected individuals had a higher score of piecemeal necrosis (OR = 21.7, p = 0.002) and a higher stage of fibrosis (OR = 17.9, p = 0.004) than patients without HIV infection. HIV infection and HCV genotype 1b were found to be independent factors of histological severity. CONCLUSIONS: Liver damage in patients with CHC seems to be directly influenced by HCV subtypes. Infection by HCV subtype 1b is closely associated with more severe forms of liver pathology. Furthermore, the presence of HIV infection is an independent factor associated with more aggressive histological damage. In these patients, higher degrees of piecemeal necrosis and fibrosis are commonly seen.     

A multicenter controlled, randomized, open trial of interferon alpha2b treatment of anti-human immunodeficiency virus-negative hemophilic patients with chronic hepatitis C. Hepatitis Study Group of the Association of Italian Hemophilia Centers

There is limited information about the long-term efficacy of prolonged therapy (more than 6 months) with interferon alpha in hemophilic patients with chronic hepatitis C who are not coinfected with the human immunodeficiency virus (HIV-1). One hundred and seven hemophiliacs were randomly assigned to 3 million U of interferon alpha2b three times weekly for 12 months or no therapy. The patients were followed up for at least 12 months posttreatment. Response was assessed by both serial alanine aminotransferase (ALT) levels and hepatitis C virus (HCV)-RNA measured by reverse transcribed polymerase chain reaction (RT-PCR) method. Before treatment, serum levels of HCV-RNA were measured quantitatively by second-generation branched-DNA assay and the HCV genotype was determined by RT-PCR. Serum HGV-RNA, a marker of infection with the hepatitis G virus, was also measured by RT-PCR. Normalization of ALT was sustained and serum HCV-RNA was cleared in 6 of 45 treated patients, compared with none of the 50 untreated controls (13% v 0% P < .01). Low pretreatment viremia was the only feature that was associated with an increased likelihood of sustained response (P < .01). This study shows that multitransfused hemophiliacs with chronic hepatitis C not coinfected with HIV-1 respond at low rates to prolonged interferon therapy.     

A randomized, controlled trial of a 24-month course of interferon alfa 2b in patients with chronic hepatitis B who had hepatitis B virus DNA without hepatitis B e antigen in serum

Short-term interferon treatment of serum hepatitis B e antigen (HBeAg)-negative carriers with serum hepatitis B virus (HBV) DNA and histological features of chronic hepatitis B has been largely unsuccessful. In a pilot study of long-term treatment, 42 such patients were randomly assigned to 6 million units of interferon alfa 2b (IFN-alpha2b) three times per week for 24 consecutive months (n = 21, 4 with cirrhosis) or to no therapy (n = 21, 3 with cirrhosis). Five patients (24%) discontinued therapy because of treatment-related adverse reactions. Serum levels of alanine transaminase (ALT) became persistently normal and HBV DNA undetectable by dot-blot assay in 8 patients receiving interferon and in 2 untreated controls (38% vs. 10%; P = .03). Hepatitis flare-ups disappeared in 17 patients during therapy compared with 6 controls (81% vs. 29%; P < .001). During a median period of 22 months after interferon was stopped, 2 treated patients (10%) lost serum hepatitis B surface antigen (HBsAg) and seroconverted to antibodies to hepatitis B surface antigen (anti-HBs). Serum ALT remained persistently normal and HBV DNA undetectable by dot-blot assay in 6 initial responders and 1 initial nonresponder, compared with none of the 21 untreated controls (sustained response: 33% vs. 0; P < .001). Comparative analysis of pre- and posttreatment liver biopsies showed that mean Knodell scores dropped in the treated group (10.3 to 5.3; P = .01), but not in the untreated group (9.3 to 9.8; not significant). In conclusion, a 24-month course of treatment with 6 MU IFN-alpha2b was well tolerated by most patients, led to sustained suppression of HBV in one third, and attenuated hepatitis in 81% of patients.     

Combination therapy with thymosin alpha1 and interferon for the treatment of chronic hepatitis C infection: a randomized, placebo-controlled double-blind trial

Hepatitis C is a major cause of liver disease leading to cirrhosis. Although interferon (IFN) is the only approved therapy, treatment is characterized by low response rates and dose-limiting side effects. We evaluated the addition of thymosin alpha1 (TA1), an immunomodulatory peptide, to the standard treatment regimen for hepatitis C to determine if combination therapy shows biological activity using outcome measures including normalization of alanine aminotransferase levels, histological activity, and viral load during treatment. We performed a randomized, double-blind, placebo-controlled trial to compare the biological activity of a combination TA1 and IFN with that seen for IFN alone in patients with chronic hepatitis C infection. One hundred nine patients were randomized for intention to treat and received 1.6 mg of TA1 subcutaneously twice weekly and 3 MU of IFN three times weekly; 3 MU of IFN three times weekly and placebo TA1; or placebo for both agents. All patients had chronic HCV infection with confirmation of chronic hepatitis on liver biopsy. Biochemical responders were followed up until alanine aminotransferase (ALT) levels became abnormal or for 26 weeks, and relapsers were retreated for 26 weeks in the same treatment arm. One hundred three patients completed treatment for 26 weeks, and six patients dropped out. The groups were similar with regard to sex, gender distribution, baseline histological activity index (HAI) score, risk factors, and viral titers. End-of-treatment biochemical response was seen in 37.1% of patients treated with combination therapy, 16.2% of patients treated with IFN alone, and 2.7% of untreated controls by intent-to-treat analysis (IFN/TA1 vs. IFN, chi2 = 4.05, P = .04). HCV RNA clearance was seen in 37.1% of IFN/TA1-treated patients and 18.9% of IFN-treated subjects. Mean HCV RNA titers were significantly lower than baseline at weeks 8, 16, and 24 after drug initiation among patients treated with IFN/TA1 but not in the other treatment arms. Histological improvement, as evidenced by a decrease in HAI of more than two points, occurred in the combination therapy arm more frequently than in comparison groups. Cumulative sustained biochemical responses were 14.2% and 8.1% in the IFN/TA1 and IFN arms, respectively, based on an intention-to-treat model. The combination of TA1 and standard IFN treatment for chronic hepatitis C showed evidence of biological activity at the completion of treatment by biochemical, histological, and virological outcome measures. Further research involving longer duration and varied dosing is needed.     

Efficacy of high dose of recombinant alpha 2b interferon on long term response in chronic hepatitis C and cirrhosis: prospective randomized multicentre study

There is large variability in the rate and extent of fetal damage from cocaine in humans; however, the sources of such variability are not presently known. In order to study the relationship between maternal cocaine pharmacokinetics at the end of pregnancy and maternal or infant cocaine and benzoylecgonine hair concentrations at birth, ten rhesus monkeys were administered cocaine intramuscularly throughout pregnancy. Cocaine and benzoylecgonine hair concentrations were determined at birth and correlated with maternal pharmacokinetics during pregnancy. There were no correlations between either maternal cocaine Cmax or AUC0-infinity and maternal and infant hair cocaine or benzoylecgonine concentrations. There were no significant correlations between maternal hair benzoylecgonine concentrations and either maternal benzoylecgonine AUC0-120 (r = 0.60; P = 0.07) or benzoylecgonine Cmax (r = 0.60; P = 0.07). No correlations existed between infant hair benzoylecgonine concentrations and either maternal benzoylecgonine AUC0-120 (r = 0.30; P = 0.40) or benzoylecgonine Cmax (r = 0.30; P = 0.40). Also, no correlation was found between maternal cocaine dose and maternal or infant cocaine and benzoylecgonine hair concentrations. In comparison to toxicants such as nicotine and carbon monoxide for which there is a good correlation between maternal systemic exposure and neonatal concentrations, the lack of a similar relationship for cocaine is consistent with the role of the placenta in contributing to the variability in the amounts of cocaine reaching the fetus and hence, potentially to the risk of adverse fetal outcome.     

The treatment of chronic hepatitis C with interferon in patients infected with the human immunodeficiency virus. The Spanish Group for the Study of Viral Hepatitis in HIV+ Patients

BACKGROUND: Alfa-interferon (aIFN) is widely recommended for the treatment of chronic hepatitis C (CHC). Hepatitis C virus (HCV) infection is very common in injecting drug users (IDUs), which in Spain represent the large number of HIV-infected persons. Interaction between human immunodeficiency virus (HIV) and HCV in coinfected patients might accelerate the clinical course of HCV-associated liver disease. The efficacy and safety of aIFN therapy in HIV-infected patients with CHC is not well known. PATIENTS AND METHODS: In a multicenter, prospective, open, non randomized and partially controlled study, we compared the efficacy and safety of aIFN therapy in 119 patients with CHC, of whom 90 were HIV-positive and 29 HIV-negative. Interferon was started at 5 mega U tiw for 3 months, followed in responders by 3 megaU tiw for additional 9 months. RESULTS: One hundred seven patients completed the study. A normalization of the aminotransferase values at the end of treatment (complete response, CR) was observed in 26/80 (32.5%) HIV-positive and 10/27 (37.0%) HIV-negative individuals (p = 0.666). Relapses at 12 months of stopping aIFN were seen in 30.8% of HIV-positive subjects and 12.5% of HIV-negatives (p = 0.403). Side effects were uncommon and did not have severity; only one patient required to stop the medication. However, 3 HIV-positive subjects treated with aIFN (3.5% of them) showed an irreversible fall of CD4+ T-cells below half the baseline values. CONCLUSION: HIV-infected patients with CHC seems to respond to aIFN with a similar rate than HIV-negatives. Moreover, the drug is similarly well tolerated in both groups of patients, although a fall of CD4+ T-cells is an unusual side effect of particular relevance observed in HIV-infected patients.     

Importance of pretreatment viral load and monitoring of serum hepatitis C virus RNA in predicting responses to interferon-alpha2a treatment of chronic hepatitis C. Hanshin Chronic Hepatitis C Study Group

In order to investigate the conformational structure of isolated human gastric mucus gel pretreated with or without ethanol, gel samples were determined by attenuated total reflection/Fourier transform-infra-red (ATR/FT-IR) microspectroscopy. The result indicates that the secondary structure-dependent amide I band and the glycoprotein region were significantly different in the gastric mucus gels pretreated with and without 40% ethanol. The structural composition of beta-sheet structure (1640-1600 cm-1) increased from 38.48 to 55.08% (+16.6%) after 6-hour pretreatment with 40% ethanol, but the beta-turn structure, (1660-1700 cm-1) decreased from 41.38 to 24.29% (-17.05%). The peak area ranging from 1180 to 1000 cm-1, assigned to the glycoprotein region, was also different after pretreatment with ethanol for 6 h. The higher peak area of the carbohydrate band was obtained in the frequency region between 1000 and 1040 cm-1 and 1100 and 1180 cm-1 for mucus gel pretreated with 40% ethanol. However, the peak area ranging from 1100 to 1040 cm-1 mainly due to the symmetric phosphate stretching mode of proteins was somewhat lower for the ethanol-pretreated mucus gel than the native mucus gel. This result strongly reveals that ethanol significantly modified the conformational structure of proteins and carbohydrates of gastric mucus gel. We propose that the dehydration and interference of hydrophobic interactions in the isolated mucus gel after pretreatment with ethanol might be responsible for this conformational change.     

Quantitative assessment of IgM antibodies towards an immunodominant B-cell epitope within the preS2 domain of HBV in the natural course and during combined prednisone/interferon alpha 2b treatment of chronic hepatitis B virus infection

A direct binding enzyme-linked immunosorbent assay (ELISA) was established for quantitative determination of serum IgM antibodies towards a synthetic peptide corresponding to a selected segment (14-21) of the preS2-gene product containing an immunodominant linear B-cell epitope. The prevalence of IgM anti-preS2 (14-21) antibody titers > 1,000 for hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B virus (HBV) infection was 38% (22/58) and 10% (2/21) for HBeAg-negative subjects (P < 0.005). IgM anti-preS2 (14-21) reactivity was detected during the clinical course of chronic HBV infection and IgM anti-peptide antibody titers declined and disappeared before spontaneous HBe/anti-HBe seroconversion. Recombinant interferon (IFN)-alpha 2b with an antecedent short course of corticosteroids was administered to eight Chinese patients with chronic HBV infection. The IgM anti-preS2 (14-21) reactivity was monitored consecutively during treatment and patients were followed for more than 1 year. A close association between the presence of pretreatment IgM anti-preS2 (14-21) in serum and the capacity to respond favorably to the combined prednisone/IFN-alpha 2b therapy was detected. The IgM anti-preS2 (14-21) titers decreased during treatment with subsequent loss of detectable antibodies 8-16 weeks after the initiation of therapy. This decrease was concomitant with an alanine aminotransferase (ALT) augmentation preceding the disappearance of HBV-DNA and anti-HBe seroconversion. Long-term remission was not observed in treated patients who lacked detectable levels of pretreatment IgM anti-preS2 (14-21) in the circulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mother to child transmission of hepatitis C virus: prospective study of risk factors and timing of infection in children born to women seronegative for HIV-1. Tuscany Study Group on Hepatitis C Virus Infection

OBJECTIVE: To determine the risk factors for and timing of vertical transmission of hepatitis C virus in women who are not infected with HIV-1. DESIGN: Follow up for a median of 28 (range 24-38) months of babies born to women with antibodies to hepatitis C virus but not HIV-1. SUBJECTS: 442 mothers and babies, of whom 403 completed the study. MAIN OUTCOME MEASURES: Presence of antibodies to hepatitis C virus and viral RNA and alanine aminotransferase activity in babies. Presence of viral RNA, method of infection with hepatitis C, method of delivery, and type of infant feeding in mothers. RESULTS: 13 of the 403 children had acquired hepatitis C virus infection at the end of follow up. All these children were born to women positive for hepatitis C virus RNA; none of the 128 RNA negative mothers passed on the infection (difference 5%, 95% confidence interval 2% to 7%). 6 children had viral RNA immediately after birth. 111 women had used intravenous drugs and 20 had received blood transfusions. 11 of the infected children were born to these women compared with 2 to the 144 with no known risk factor (difference 7%, 2% to 12%). CONCLUSIONS: This study suggests that in women not infected with HIV only those with hepatitis C virus RNA are at risk of infecting their babies. Transmission does seem to occur in utero, and the rate of transmission is higher in women who have had blood transfusions or used intravenous drugs than in women with no known risk factor for infection.     

Better efficacy of a 12-month interferon alfa-2b retreatment in patients with chronic hepatitis C relapsing after a 6-month treatment: a multicenter, controlled, randomized trial. Le Groupe D'étude et De Traitement du Virus De L'hépatite C (Get.Vhc)

We studied the efficacy of three interferon alfa-2b (IFN-2b) regimens for the retreatment of patients with chronic hepatitis C (CHC) with prior complete response followed by relapse. Consecutive patients with CHC who had a complete biochemical response but relapse after a first course of 6 months of IFN with 3 million units (MU) given subcutaneously three times per week were enrolled in the study. Six to 24 months after the end of the first treatment, the patients were randomly assigned to receive IFN with either the same regimen (group 1), a regimen of 12 months with 3 MU (group 2), or a regimen of 6 months with 10 MU (group 3). Sustained biochemical response was defined as normal serum alanine transaminase (ALT) values during the follow-up and sustained virological response as a clearance of hepatitis C virus (HCV) RNA from the serum at the end of follow-up (6 months' posttreatment). Histological improvement was defined as a decrease of 1 point in Metavir score between the first liver biopsy and a biopsy performed at 6 months' postretreatment. Two hundred forty-seven patients were randomized: 75 to group 1, 91 to group 2, and 81 to group 3. In an intent-to-treat analysis, 12%, 36.3%, and 18.5% of patients had a sustained biochemical response after retreatment in groups 1, 2, and 3, respectively (P <.001); 13. 8%, 32.4%, and 17.2% of patients had a sustained virological response after retreatment in groups 1, 2, and 3, respectively (P <. 05). A low viral load and patients in group 2 were independently associated with a sustained biochemical response. A low Knodell score index before treatment, patients with a high level of ALT before retreatment, genotype 3, low viral load, and patients in group 2 were independently associated with sustained virological response. Younger age, a high level of ALT, a low level of gamma-glutamyl transferase before retreatment, low viral load, and patients in group 2 were independently associated with sustained biochemical and virological response. Among the 80 patients with repeated liver biopsies, 47.6% had improved histological activity scores; this improvement was associated with a sustained biochemical and virological response. In patients with CHC initially treated with 3 MU of IFN given subcutaneously three times per week over a 6-month period, and who subsequently developed a relapse after a biochemical response, retreatment with a regimen of 3 MU of IFN given three times per week for 12 months produced better biochemical and virological sustained response rates than regimens involving a higher dose or a shorter duration of retreatment. The biochemical and virological sustained response was associated with histological improvement.