Biomedical subjects

M J Tong

Publications and source records attributed to M J Tong.

At least 19 recordsLinked to original sources

PubMed2001

Surveillance for hepatocellular carcinoma in patients with chronic viral hepatitis in the United States of America.

BACKGROUND: Measurement of serum alpha-fetoprotein (AFP) and abdominal ultrasound (US) examination are used for the early detection of hepatocellular carcinoma (HCC) in chronic liver disease patients. However, the accuracy and usefulness of these tests in a clinical setting in the United States of America have not been clarified. METHODS: We conducted a 7-year prospective surveillance study by using both AFP and US to detect HCC in 602 patients with chronic viral hepatitis. Our main goal was to determine the optimal test for detection of early HCC. We also assessed the clinical outcome of HCC patients identified during this time period. RESULTS: Thirty-one cases of HCC were detected. Serum AFP levels were elevated in 74% of HCC patients, but was also high in 10% of patients who did not develop HCC. The positive predictive value for AFP to detect HCC was only 12% or less for all AFP cut-off values, and the maximum joint sensitivity and specificity as determined by receiver operator characteristic analysis was approximately 65 and 90%, respectively. Abdominal US identified all 31 cases of HCC. The positive predictive value for US examinations to detect HCC was 78%, while the sensitivity and specificity was 100 and 98%, respectively. After detection of HCC, 24 (77%) patients died within a mean of 16.7 +/- 19.4 months. CONCLUSIONS: Our study indicates that US examination was more accurate in detecting HCC. Because of its poor predictive value and low sensitivity, serum AFP should not be used as the only test for screening and surveillance for HCC.

Abdomen↗

PubMed2000

Inhibition of hepatitis C virus (HCV)-RNA-dependent translation and replication of a chimeric HCV poliovirus using synthetic stabilized ribozymes.

Ribozymes are catalytic RNA molecules that can be designed to cleave specific RNA sequences. To investigate the potential use of synthetic stabilized ribozymes for the treatment of chronic hepatitis C virus (HCV) infection, we designed and synthesized hammerhead ribozymes targeting 15 conserved sites in the 5' untranslated region (UTR) of HCV RNA. This region forms an internal ribosome entry site that allows for efficient translation of the HCV polyprotein. The 15 synthetic ribozymes contained modified nucleotides and linkages that stabilize the molecules against nuclease degradation. All 15 ribozymes were tested for their ability to reduce expression in an HCV 5' UTR/luciferase reporter system and for their ability to inhibit replication of an HCV-poliovirus (HCV-PV) chimera. Treatment with several ribozymes resulted in significant down-regulation of HCV 5' UTR/luciferase reporter expression (range 40% to 80% inhibition, P <.05). Moreover, several ribozymes showed significant inhibition (>90%, P <.001) of chimeric HCV-PV replication. We further show that the inhibitory activity of ribozymes targeting site 195 of HCV RNA exhibits a sequence-specific dose response, requires an active catalytic ribozyme core, and is dependent on the presence of the HCV 5' UTR. Treatment with synthetic stabilized anti-HCV ribozymes has the potential to aid patients who are infected with HCV by reducing the viral burden through specific targeting and cleavage of the viral genome.

Antiviral Agents↗

PubMed2000

Assessment of hepatitis C virus RNA and genotype from 6807 patients with chronic hepatitis C in the United States.

Hepatitis C virus (HCV) RNA status and HCV genotype have become important tools in the diagnosis and monitoring of therapy in chronic HCV infection. To establish a database with respect to HCV genotype and serum HCV RNA concentrations in chronic hepatitis C patients in the United States, we analysed 6807 chronic hepatitis C patients who had HCV RNA and HCV genotype tests conducted at a central laboratory. The HCV RNA concentration cut-off for the lower 25th percentile of this population (low titre) was 0.9 x 106 copies ml-1. The median HCV RNA concentration was 3.5 x 106 copies ml-1 and the cut-off for the upper 25th percentile (high titre) was 5 x 106 copies ml-1. Male patients had a median HCV RNA concentration of 3.9 x 106 copies ml-1, which was significantly higher than the median HCV RNA level for females (2.75 x 106 copies ml-1; P < 0.001). HCV genotype 1 was detected in 73% of patients; genotype 2 in 14%; genotype 3 in 8%; mixed genotype in 4%; and genotypes 4, 5 and 6 with a frequency of < 1%. Patients from the Northeast, Southeast and Midwest had significantly (P < 0.001) more infections with genotype 1 than patients from the Western and Southern regions. African-American patients were more likely to be infected with genotype 1 when compared with Caucasian, Hispanic or Asian Pacific Islanders (P < 0.001). Patients infected with HCV genotype 1 and mixed HCV genotypes had significantly higher serum HCV RNA concentrations when compared with HCV genotypes 2 and 3 (P < 0.001 for all comparisons).

Black People↗

PubMed2000

Autoimmune cholangitis with features of autoimmune hepatitis: successful treatment with immunosuppressive agents and ursodeoxycholic acid.

We report a 42-year-old Chinese female with elevated serum levels of liver aminotransferases, alkaline phosphatase, gamma-glutamyl transpeptidase, cholesterol and immunoglobulin M. Serum antimitochondrial antibody was negative, but antinuclear antibody was strongly positive. Liver histology showed features of both autoimmune cholangitis and autoimmune hepatitis. Combination therapy with immunosuppressive (prednisone and azathioprine) and choleuretic agents (ursodeoxycholic acid) was given. Serum aminotransferases and biliary enzymes showed much improvement after treatment. A follow-up liver biopsy showed improvement of both hepatic necroinflammation and bile duct damage. Biliary enzymes rose after withdrawal of the immunosuppressive agents and declined again with reinstitution of prednisone. This case demonstrates that a combination of immunosuppressive agents and ursodeoxycholic acid may effectively treat patients with features of both autoimmune cholangitis and autoimmune hepatitis.

Adult↗

PubMed2000

Measurement of serum hyaluronic acid in patients with chronic hepatitis C and its relationship to liver histology. Consensus Interferon Study Group.

BACKGROUND AND AIMS: Chronic hepatitis C is a slowly progressing inflammatory disease of the liver that can lead to cirrhosis and its complications. Assessment of liver damage in hepatitis C has been primarily via histological evaluation. Liver biopsy, while useful in determining the extent of liver damage, has associated costs and places patients at a small but finite risk of bleeding. Studies in small patient populations have identified serum markers shown to correlate with liver histology, including procollogen III peptide and hyaluronic acid (HA). To determine whether serum HA was a reliable predictor of cirrhosis and fibrosis, we examined serum HA concentrations from 486 chronic Hepatitis C virus (HCV) patients. METHODS AND RESULTS: Patients were anti-HCV and HCV RNA positive, with elevated alanine aminotransferase values and underwent a liver biopsy. Sera were obtained at the baseline for HA using radioimmunoassay methodology. Patients with cirrhosis had significantly higher serum HA concentrations compared with non-cirrhotic patients (382+/-31 vs 110+/-9 microg/L respectively, P< 0.001). Patients with fibrosis had significantly higher mean serum HA concentrations (179+/-11 microg/L) compared with patients without fibrosis (62+/-20 microg/L; P< 0.001). The correlation between HA concentration and the components of the Knodell histological activity index score revealed no strong associations with the exception of fibrosis, which showed moderate correlation (R=0.5421, P<0.001). The clinical value of HA measurement appears to be its ability to exclude cirrhosis. A HA value of < 60 microg/L excluded the presence of cirrhosis or significant fibrosis with a predictive value of 99 and 93%, respectively. CONCLUSIONS: Serum HA measurement may be clinically useful to non-invasively assess the degree of fibrosis and cirrhosis. Further prospective studies are warranted to determine the clinical utility of HA as a non-invasive marker of liver fibrosis.

Adult↗

PubMed2000

Hepatitis B transplantation: special conditions.

Patients with hepatitis B virus (HBV) infection may be coinfected with other viral diseases, such as hepatitis C virus (HCV) and/or D virus (HDV), or have serious diseases secondary to the hepatitis, such as hepatocellular carcinoma. These coexisting conditions have an impact on the success of treatment and of liver transplantation. Patients with HBV and HDV are at lower risk for HBV recurrence than are patients with HBV alone; likewise, patients with HBV/HCV coinfection appear to have a higher 5-year survival rate posttransplantation. Treatment of coinfection is similar to that used for HBV alone. Hepatitis B immune globulin and interferon have been found to be effective in varying degrees. Recurrence or reinfection of disease after liver transplantation presents many clinical problems that will require new therapeutic approaches. Future studies will help to begin solving these challenges.

Carcinoma, Hepatocellular↗

PubMed1999

The long-term outcomes of patients with compensated hepatitis C virus-related cirrhosis and history of parenteral exposure in the United States.

It is well known that hepatitis C virus (HCV) infection may progress to cirrhosis and is linked to the development of hepatocellular carcinoma (HCC). Previous studies have shown that compensated HCV-cirrhosis is related to a certain morbidity and mortality in European patients, but little is known in regard to the clinical outcomes of a similar group of patients in the United States. This study investigated this category of patients in terms of the incidence of decompensation, development of HCC, mortality, and the predictive risk factors for morbidity and mortality. The potential effects of interferon (IFN) therapy on outcomes of the disease also were assessed. A total of 112 patients with compensated HCV-cirrhosis and a documented history of either intravenous drug abuse (IVDA) or transfusion were consecutively enrolled. The mean follow-up interval was 4.5 (2-7.7) years. The cumulative probabilities for decompensation and development of HCC were 22.2% and 10.1% in 5 years, with an estimated yearly incidence of 4.4% and 2.0%, respectively. The cumulative survival probability was 82.8% from entry and 51.1% from decompensation in 5 years, with estimated yearly events of mortality and liver transplantation of 3.4% and 9. 8%, respectively. It was found that age at entry and initial exposure, initial levels of albumin, platelet count, and prothrombin time (PT) were predictive risk factors for developing decompensation, whereas age at entry and initial exposure, history of transfusion, lower initial levels of albumin, platelet count, and viral load were predictive risk factors for events of mortality and liver transplantation. The incidence of decompensation was significantly lower in patients treated with IFN, but age may have played a contributory role. In contrast, neither HCC development nor mortality was significantly altered by IFN therapy. In conclusion, our study indicated that patients with compensated HCV-cirrhosis in the United States progressed slowly and experienced eventual morbidity and mortality. Once decompensation develops, the disease will be more progressive and result in even higher mortality. Further studies will be required to determine the efficacy of IFN on clinical outcomes in this group of patients.

Adult↗

PubMed1999

Racial differences in responses to therapy with interferon in chronic hepatitis C. Consensus Interferon Study Group.

The likelihood of a sustained response to a course of interferon in patients with chronic hepatitis C correlates with several clinical and viral factors, including age, viral genotype and initial levels of hepatitis C virus (HCV) RNA in serum. The role of race and ethnicity has not been assessed. We evaluated the association of race with response to interferon in a large randomized, controlled trial using either consensus interferon (9 microg) or interferon alfa-2b (3 million units) given three times weekly for 24 weeks. African-American patients participating in the study were similar to white patients in mean age (43 vs. 42 years) and baseline levels of HCV RNA (3.6 vs. 3.0 million copies/mL) but had lower rates of cirrhosis (5% vs. 12%) and more frequently had viral genotype 1 (88% vs. 66%: P =.004). Most strikingly, the rates of end-of-treatment and sustained virological responses were lower among the 40 African-American patients (5% and 2%) than among the 380 white patients (33% and 12%) (P =.04 and.07). Rates of response among Hispanic and Asian-American patients were not statistically different than non-Hispanic white patients. Median viral levels decreased by week 24 of therapy by 2.5 logs in white patients (from 3.0 to 0.012 million copies/mL) but by only 0.5 logs among African- American patients (from 3.6 to 1.8 million copies/mL). Thus, there are marked racial differences in virological responses to interferon in hepatitis C that must be considered in assessing trials of interferon therapy and in counseling patients regarding treatment. The differences in response rates are as yet unexplained.

Adolescent↗

PubMed1999

A predictive model for the development of hepatocellular carcinoma, liver failure, or liver transplantation for patients presenting to clinic with chronic hepatitis C.

OBJECTIVE: Chronic infection with hepatitis C may lead to the development of cirrhosis, liver failure, and hepatocellular carcinoma. However, not all patients progress to these endpoints. Ideally, clinicians could improve their capability of stratifying the risk and the time frame within which their patients will progress to these endpoints. The purpose of the present study was to construct statistical models predicting disease progression for individual patients. METHODS: Study endpoints were the development of hepatocellular carcinoma, liver transplantation, or death due to liver disease. The study cohort was 256 patients with hepatitis C acquired from either blood transfusion or use of intravenous drugs. During follow-up, 17 patients developed hepatocellular carcinoma, seven received liver transplantation, and 12 died from liver disease. RESULTS: On multivariate analysis a history of decompensation (relative risk [RR] 4.321, 95% confidence interval [CI] 1.777-10.511) and the serum albumin (RR 0.253, 95% CI 0.136-0.474) were independently associated with the study endpoints. Patients without a history of decompensation and with a serum albumin > or = 4.1 mg/dl had a 3.2% chance of developing the study endpoints within 5 yr. Patients with a history of decompensation and a serum albumin < 4.1 mg/dl had a 40% chance of developing a study endpoint within 5 yr. Baseline genotype and quantitative RNA were not associated with development of the clinical endpoints, with the exception of patients coinfected with two or more genotypes. CONCLUSION: Thus, the serum albumin and a history of decompensation are useful for predicting the development of hepatocellular carcinoma, liver transplantation, and death due to liver disease among patients with hepatitis C.

Adult↗

PubMed1999

Genotype does not affect pattern of HCV RNA decrease among responders during interferon treatment of chronic hepatitis C. Consensus Interferon Study Group.

We assessed differences in the pattern of HCV RNA decrease for HCV genotypes 1, 2, and 3 during interferon treatment to determine if the lower response rates observed among genotype 1 patients were related to a slower decrease in HCV clearance. Serum HCV RNA values of 472 chronic hepatitis C patients treated with either consensus interferon (CIFN) or interferon alfa-2b (IFN alfa-2b) were evaluated. Neither virological sustained responders nor relapsers differed in the pattern of serum HCV RNA decrease based on genotype. Virological sustained responders infected with genotype 1 cleared HCV RNA as rapidly as sustained responders who were infected with genotype 2 or 3. Relapsers had a slower rate of serum HCV RNA decrease than did virological sustained responders. Nonresponders differed in the pattern of serum HCV RNA decrease based on genotype: HCV genotype 3 patients had the greatest decrease in serum HCV RNA; genotype 2 patients had an intermediate decrease; and genotype 1 patients had the least serum HCV RNA decrease. HCV genotype 1 patients treated with CIFN had a greater decrease in serum HCV RNA during therapy than did patients treated with IFN alfa-2b. However, there was no difference in the magnitude of serum HCV RNA decrease between the two interferon treatments for patients infected with genotype 2 or 3. In summary, both genotype and ultimate response to treatment are determinants of the pattern and rate of serum HCV RNA change during interferon therapy of chronic hepatitis C.

Antiviral Agents↗

PubMed1998

Re-treatment of chronic hepatitis C with consensus interferon .

A multicenter, open-label, phase 3 study was conducted in 337 patients with chronic hepatitis C virus (HCV) infection who had either not responded to previous interferon therapy or had relapsed after discontinuation of therapy with either consensus interferon (9 microg) or interferon alpha-2b (3 million U) three times a week for 24 weeks. Patients were randomized to receive a higher dose of consensus interferon (15 microg) administered subcutaneously three times a week for 24 or 48 weeks and then were observed for an additional 24 weeks. Patients who had relapsed after prior interferon therapy were more likely to have a sustained alanine aminotransferase response and HCV RNA response (as measured by reverse transcription-polymerase chain reaction with a sensitivity of < 100 copies/mL) than were patients who had not responded to prior interferon therapy. For relapsers, the sustained HCV RNA response rate was 58% (48 weeks) and 28% (24 weeks). The sustained alanine aminotransferase response for relapsers was 52% (48 weeks) and 39% (24 weeks). The sustained HCV RNA response rate among prior nonresponders was 13% (48 weeks) and 5% (24 weeks), and the sustained alanine aminotransferase response rate for nonresponders was 17% (48 weeks) and 12% (24 weeks). The administration of 15 microg of consensus interferon was well tolerated and was not associated with an increase in the incidence of side effects. These data demonstrate that re-treatment with 15 microg of consensus interferon is safe and effective therapy for patients with chronic hepatitis C who have either not responded to previous interferon therapy or relapsed after discontinuation of interferon therapy.

Adult↗

PubMed1998

Early hepatitis C virus-RNA responses predict interferon treatment outcomes in chronic hepatitis C. The Consensus Interferon Study Group.

In previous studies employing interferons (IFNs) in the treatment of chronic hepatitis C, there have been few reliable predictors of sustained responses. We retrospectively evaluated the predictive value of hepatitis C virus (HCV)-RNA measurements in the first few months during consensus interferon (CIFN) treatment using a sensitive reverse-transcriptase polymerase chain reaction assay to determine sustained responses. Data from two large treatment trials, one of IFN-naive patients and one of retreated relapsers and nonresponders, were used, including serum samples at 2-week intervals in the naive study and 8-week intervals in the retreatment study. Patients received initial CIFN (9 microgram) treatment for 6 months and were assessed 6 months after treatment. There were 28 sustained viral responders of 232 CIFN-treated patients. Of the sustained responders, 48% had already cleared HCV RNA from serum (<100 copies/mL) by week 2, 78% by week 4, 81% by week 6, and 96% by week 12. Patients with early HCV-RNA clearance were more likely to have sustained responses than those who responded later. Early clearance of HCV from serum was also associated with greater likelihood of a sustained response to 48 weeks of retreatment with 15 microgram CIFN. Ninety-five percent of the sustained responders were HCV-RNA-negative by week 8 of retreatment. Early assessment of HCV RNA may help in the prediction of sustained responses to IFN and allow the value of continued treatment to be determined early in the course of IFN therapy.

Antiviral Agents↗

PubMed1998

Long-term retreatment in chronic hepatitis C patients who were non-responders to an initial course of interferon-alpha 2b.

Nineteen patients with chronic hepatitis C who were virological non-responders (seven responder/relapse and 12 no response) to an initial 24-week course of interferon-alpha 2b (IFN-alpha 2b) at a dose of 3 million units (MU) thrice weekly were retreated for an additional 48 weeks at the same dosing schedule and followed-up for another 24 weeks post-therapy. At the end of follow-up (week 72), six (32%) of the 19 patients were hepatitis C virus (HCV) RNA negative and were virological complete responders to retreatment. The viral genotypes in these six patients included two each with 1b and 3a, one with 2b, and another with 2a/2b; five of the six virological responder patients had cirrhosis. Significant predictors for successful retreatment included lower baseline HCV RNA concentrations prior to the first course of therapy, 2 log10 reductions in serum HCV RNA during the initial treatment and classification into the virological 'responder/relapse' category after the first course of IFN (P < 0.01 for all observations). When the above factors were used to construct a predictive model to determine response to retreatment, it was found that the absence of a 2 log10 drop in HCV RNA concentrations during the first course of IFN therapy was the most reliable indicator of non-response to retreatment (likelihood ratio = 10, P = 0.0014). In addition, the presence of HCV RNA at week 12 of retreatment was 100% predictive of virological non-response to the 48-week course of therapy. Our findings indicate that an additional 48-week course of IFN-alpha 2b therapy at 3 MU thrice weekly will achieve a virological complete response in 60% of patients who had a 2 log10 drop in HCV RNA during their first course of treatment, and measurement of week-12 HCV RNA during retreatment to identify non-responders is beneficial to patients as well as being cost-effective. Thus, a second course of IFN remains a viable option in a subgroup of non-responder patients, regardless of genotype or the presence of compensated cirrhosis.

Adult↗

PubMed1998

Discordance between serum alanine aminotransferase (ALT) and virologic response to IFN-alpha2b in chronic hepatitis C patients with high and low pretreatment serum hepatitis C virus RNA titers.

Although serum alanine aminotransferase (ALT) and hepatitis C virus (HCV) RNA concentrations are primary markers used to assess the clinical benefit of interferon (IFN) therapy in patients with chronic HCV infection, discrepancies between these two variables exist. In this study, 103 patients with chronic hepatitis C were treated with 3 MIU IFN-alpha2b three times weekly for 24 weeks, followed by 24 weeks of observation. ALT and virologic responses were compared in patients with high pretreatment HCV RNA titers (defined as pretreatment HCV RNA concentrations at or above the 75th percentile of the distribution or >5,000,000 copies/ml) and low pretreatment HCV RNA titers (defined as pretreatment concentrations below the 75th percentile or < or =5,000,000 copies/ml). Analysis of the virologic response for the high-titer and low-titer groups demonstrated a significantly greater HCV RNA sustained response in the low-titer group (21%) compared with the high-titer group (7%) (p < 0.05). In contrast, the ALT sustained response was not significantly different between the low-titer group (21%) and the high-titer group (18%). Analysis of the correspondence between biochemical and virologic responses showed that only 38% of patients with high pretreatment HCV RNA titers had both a sustained ALT response and a sustained loss of HCV RNA compared with 75% of patients with low pretreatment HCV RNA titers. The level of agreement between the ALT and HCV RNA responses was greater for the low-titer group compared with the high-titer group (kappa = .6848 and kappa = .4966, respectively). Our results indicate that chronic HCV patients with high pretreatment HCV RNA titers showed greater discordance between sustained ALT and HCV RNA responses compared with patients with low pretreatment HCV RNA titers and that measurement of HCV RNA should be included in the assessment of response to IFN therapy in chronic hepatitis C patients.

Adult↗

PubMed1998

Treatment of chronic hepatitis C virus infection with recombinant consensus interferon.

To assess the safety and efficacy of consensus interferon (IFN-Con-1), 55 patients with chronic hepatitis C infection were treated with either 3, 6, 9, 12, or 15 microg IFN-Con-1 s.c. three times a week for 24 weeks, followed by 24 weeks of observation. There was a dose-response relationship with respect to the number of patients with normalized ALT concentrations or undetectable HCV RNA. At the end of the 24-week treatment period, the serum ALT had normalized in 18% of patients given the 3 microg dose and 42% of patients given the 12 microg or 15 microg doses of IFN-Con-1. At the end of the posttreatment observation period, the serum ALT was still normal in 10% of patients given the 3 microg, 6 microg, or 9 microg doses and in 50% of patients given the 15 microg dose. Also, at the end of the 24-week treatment period, 27% of patients given the 3 microg dose and 75% given the 15 microg dose had undetectable serum HCV RNA. At the end of the posttreatment observation period, the proportion of patients with undetectable HCV RNA ranged from 9% of those given the 3 microg dose to 50% of those given the 15 microg dose. Our study indicates that treatment with IFN-Con-1 appears to be safe and effective. In addition, use of 15 microg of IFN-Con-1 resulted in significantly more patients with sustained ALT normalization and absence of HCV RNA 6 months after cessation of therapy compared with treatment with lower doses of IFN-Con-1. Additional trials are underway to confirm these findings.

Adolescent↗

PubMed1998

The changes in quantitative HCV RNA titers during interferon alpha 2B therapy in patients with chronic hepatitis C infection.

OBJECTIVE: Our aim was to analyze the outcomes and the patterns of response to interferon treatment in patients with chronic hepatitis C using serum HCV RNA as the primary endpoint of therapy. METHODS: Seventy anti-HCV-positive patients were treated with 3 million U of interferon-alpha-2b thrice weekly for 24 wk and followed for an additional 24 wk after cessation of therapy (wk 48). Serum HCV RNA was measured by a reverse transcriptase-polymerase chain reaction method that has a sensitivity of < 100 viral copies per ml. RESULTS: The mean pretreatment HCV RNA was 2.8 +/- 2.2 x 10(6) viral copies per ml. Genotype 1 patients had significantly higher mean baseline viral titers than those with genotype 2 (p = 0.03). At wk 48, 12 (17%) patients were HCV RNA negative and considered virological complete responders (CR) to treatment. The remaining patients were HCV RNA positive at wk 48 and were considered nonresponders to therapy. There were two types of virological nonresponder patients, responder relapse (RR) and no response (NR). The mean baseline HCV RNA level was significantly lower in the virological CR patients (p = 0.0004). At wk 12 and 24 of interferon treatment, both the virological CR and RR patients had lower serum HCV RNA concentrations than the patients in the NR category (p = 0.0001), while at wk 48, only. the virological CR patients had undetectable HCV RNA when compared to the RR and NR patients (p = 0.04). Transient decreases in the HCV RNA titers of > or = 1 log in magnitude were observed in 49% of the NR patients, which rose to pretreatment levels either during or after interferon therapy. CONCLUSIONS: Our findings indicate that measurement of serum HCV RNA precisely defined the responses to interferon therapy. Because the goal is to eliminate virus in patients with chronic hepatitis C infection, then HCV RNA should be used as the primary endpoint of treatment.

Adolescent↗

PubMed1997

Treatment of chronic hepatitis C with consensus interferon: a multicenter, randomized, controlled trial. Consensus Interferon Study Group.

This multicenter, randomized, controlled, double-blind, phase III study in 704 patients with chronic hepatitis C infection compared treatment with consensus interferon (CIFN), a non-natural recombinant type-1 interferon, with a standard regimen of recombinant interferon alfa-2b (IFN-alpha2b). Patients were randomized to receive CIFN at doses of 3 microg or 9 microg, or 15 microg IFN-alpha2b (3 million units), subcutaneously three times weekly for 24 weeks, followed by 24 weeks of observation. Efficacy was assessed by normalization of serum alanine transaminase (ALT) concentration and decrease in serum hepatitis C virus (HCV) RNA concentration below the limit of detection by reverse-transcription polymerase chain reaction (RT-PCR) (100 copies/mL). The beneficial effect of CIFN was greater with the 9-microg dose than the 3-microg dose. The sustained ALT and HCV RNA response rates were 20.3% and 12.1%, respectively, in the 9-microg CIFN cohort and 19.6% and 11.3%, respectively, in the 15-microg IFN-alpha2b cohort. However, patients receiving 9 microg of CIFN had a greater reduction in serum HCV RNA concentrations compared with patients receiving 15 microg IFN-alpha2b over the course of treatment (P < .01). Similarly, analysis of patients infected with HCV genotype 1 showed a greater reduction in serum HCV RNA concentration over the course of treatment for the 9-microg CIFN group when compared with the 15-microg IFN-alpha2b group (P < .01). In addition, a greater percentage of patients infected with HCV genotype 1 treated with 9 microg CIFN had undetectable HCV RNA concentrations when compared with patients in the 15-microg IFN-alpha2b cohort at the end of treatment (24% vs. 15%; P = .04). Improvements in liver histology were noted in all three treatment groups; 52% to 55% of the patients in the three cohorts had at least a 2-unit improvement in the Knodell score at the end of the posttreatment period. The adverse-events profiles were characteristic of treatment with type-1 interferon, and the incidences of anti-interferon antibody formation did not significantly differ among the three treatment groups. These results show that administration of 9 microg CIFN three times weekly for 6 months is safe and is effective in reducing serum HCV RNA concentration.

Adult↗

PubMed1997

Prediction of response during interferon alfa 2b therapy in chronic hepatitis C patients using viral and biochemical characteristics: a comparison.

Patients with chronic hepatitis C (n = 103) were treated for 24 weeks with interferon alfa 2b and followed up for 24 weeks after cessation of therapy (week 48). When hepatitis C virus (HCV) RNA at week 48 was used to assess interferon response, 15 (14.6%) were virological complete responders, and all have remained HCV RNA negative for a mean of 3 years. At week 48, 3 of 15 virological complete responders had elevated alanine transaminase (ALT) values. When serum ALT level was used at week 48 to determine response to interferon, 20 (19.4%) were biochemical complete responders. However, 8 of the 20 patients with normal ALT levels were HCV RNA positive at week 48, and 7 of these individuals have had a recurrence of elevated ALT levels within 3 years after cessation of treatment. These findings indicate that measurement of HCV RNA was more accurate than ALT in determining true responses to interferon therapy. Identification of nonresponders early during the course of interferon treatment showed that an elevated ALT level at week 12 was 92% predictive (odds ratio 3.7) but misidentified 33% (5 of 15) of the patients who were virological complete responders at week 48. In contrast, a positive HCV RNA at week 12 of treatment was 98% predictive (odds ratio 35.5) and misidentified only 6.7% (1 of 15) of the virological complete responders. Thus, positive HCV RNA at week 12 of therapy was more accurate in identifying eventual virological nonresponders than measurement of ALT at this time. Termination of interferon therapy in patients who were HCV RNA positive at week 12 would result in a 27% reduction in the direct medical costs and keep patients from undergoing unnecessary treatment. Therefore, testing for HCV RNA at week 12 to identify nonresponders and then discontinuing their treatment is practical, cost-efficient and beneficial both to patients and to third-party payers.

Adolescent↗