Usefulness of simple assays for serum concentration of hepatitis C virus RNA and HCV genotype in predicting the response of patients with chronic hepatitis C to interferon alpha 2a therapy (original) (raw)
Related papers
Journal of Medical Virology, 1995
The use of two new assays was evaluated for predicting the response to interferon (IFN) therapy in patients with chronic hepatitis C. The genotype of hepatitis C virus (HCV) was established by an enzyme-linked immunosorbent assay based on genotype-specific recombinant peptides of the NS4 region (genotyping ELISA). The concentration of HCV RNA was measured by a branched DNA assay (bDNA assay). Seventyeight patients received the same regimen of IFNa2a. Of the 74 patients assessed who completed the program, 38 (51.4%) were responders; i.e., their serum aminotransferase levels remained normal for 6 months or longer after stopping IFN, while 36 (48.6%) were nonresponders. The results of the HCV genotype determined by the genotyping ELISA and by the polymerase chain reaction (PCR) assay based on genotypespecific primers were similar. The serum concentrations of HCV RNA as measured by the bDNA assay and by the competitive PCR assay correlated closely and significantly (r = 0.82, P < 0.001 1. Multiple logistic regression analysis showed that the serum concentration of HCV RNA determined by the bDNA assay, the HCV genotype determined by the genotyping ELISA, and the histology activity index (HAI) of the liver were independently associated with IFN efficacy.
International Hepatology Communications
Effects of interferon (IFN) treatment on 91 patients with chronic HCV-related liver diseases in three hospitals were analyzed. HCV-RNA encoding the NS5 region of HCV was detected by the RT-PCR method, and HCV genotyping was performed by slot-blot hybridization using the type-specific cDNA probes on HCV-NS5. HCV titers in blood before treatment with IFN were determined by the multicyclic PCR method. HCV-NS5 was positive in 61 out of 91 patients and the HCV-Kl genotype was found in 40 patients, whereas the HCV-K2 genotype was found in 21. To summarize results from all three hospitals, 52.3% of patients recovered completely and 33.3% recovered partially in the K2 group, in each of these the percentage was significantly higher than in the Kl group. In addition, the percentage of the patients showing no response to IFN treatment was significantly higher in the Kl group than in the K2 group. In the HCV-NSS-negative group, the percentage of patients who did not respond was significantly lower than in the Kl group. In the Kl group, a complete recovery tended to be found more frequently in patients with lower titers of HCV. However, some patients with low titers of HCV did not respond to treatment. The differences of HCV titers between the groups showing different responses to IFN treatment was not statistically significant. In the K2 group, HCV titers were significantly lower than those in the Kl group; however, the effects of IFN were not related to the titers of HCV in K2 group. Two patients with liver cirrhosis in the K2 group had a complete or partial recovery, whereas four patients with liver cirrhosis in the Kl group did not respond to IFN treatment. These results indicate that the HCV genotype is the most important determinant of the effects of IFN treatment.
Liver, 1996
To determine whether pretreatment HCV-RNA level, hepatitis C virus genotypes, alanine aminotransferase and histology correlate with subsequent response to interferon-alpha therapy or not, serum HCV-RNA levels and genotype were determined by branched DNA signal amplification assay and genotype-specific polymerase chain reaction in 43 patients with chronic active hepatitis C. Response to recombinant interferon-alpha 2a (504 million units in total) was defined as complete and sustained CR--&amp;gt;SR, n = 12), complete response followed by relapse (CR--&amp;gt;Rel, n = 17), and no response (NR, n = 10), excluding dropouts (n = 4). Patients who showed CR--&amp;gt;SR had a lower HCV-RNA level (0.438 x 10(6) eq/ml) compared to CR--&amp;gt;Rel (2.452 x 10(6) eq/ml, p = 0.008) and NR (4.882 x 10(6) eq/ml, p = 0.009). A higher proportion of patients with CR--&amp;gt;SR had type 2a HCV (67%) compared to the CR--&amp;gt;Rel (28%) and the NR (0%). There was a trend for type 1b hepatitis C virus infection to have higher serum HCV-RNA levels. There was no correlation between pretreatment HCV-RNA level and alanine aminotransferase. However, no relation between pretreatment HCV-RNA level and liver histology was observed; a high proportion of patients with CAH2a showed CR--&amp;gt;SR, compared to those with CAH2b (p = 0.001). Moreover, the patients with CAH2b who had low level hepatitis C virus viremia did not show CR--&amp;gt;SR. These data indicate that pre-treatment serum HCV-RNA levels, genotype and liver histology are good predictors of subsequent response to interferon-alpha therapy in Japanese patients with chronic hepatitis C virus infection.
Journal of Medical Virology, 1994
Interferon induces remission in about 50% of patients with chronic hepatitis C, but it is difficult to predict which patients will respond. Host and viral factors were evaluated for correlation with response to interferon in patients with chronic hepatitis C. Recombinant interferon alpha-2b with a total dose of 480-560 million units was given to 136 patients, of whom 74 (54%) responded. Genotypes of hepatitis C virus (HCV) in sera, I, II, III, IV, and V, were determined by poly-merase chain reaction (PCR) with type-specific primers. In 72 patients, pretreatment levels of HCV RNA were titrated by PCR in serial tenfold dilutions of RNA extracted from serum. Response to interferon occurred in 34 (40%) of 85 patients infected with HCV of genotype II, less frequently than in 22 (85%) of 26 with genotype III (P < 0.001) or in 7 (70%) of 10 with genotype IV. Of 51 patients with genotype II HCV, 6 of 8 (75%) with HCV RNA titers <106 responded, more frequently than 4 of 43 (9%) with titers ≥ 106 (P < 0.001). Responders were younger than non-responders (45.7 ± 11.7 vs. 50.3 ± 9.6 yr) and had received transfusions less frequently (26/74 or 35% vs. 37/62 or 60%, P < 0.01). Response to interferon correlated inversely with the severity of liver histopathology. These results indicate that response to interferon is influenced by HCV genotypes and pretreatment levels of HCV RNA in serum. © 1994 Wiley-Liss, Inc.
Serial assay of hepatitis C virus RNA in serum for predicting response to interferon-a therapy
Digest Dis Sci, 1995
To determine whether the loss of serum hepatitis C virus RNA (HCV-RNA) early in interferon therapy would indicate a sustained response to this agent, we detected serum HCV-RNA successively during and after therapy. Serum samples for detection of HCV-RNA were obtained serially from 36 patients with chronic hepatitis C treated with interferon-et. In 28 of these patients, results of the assay were compared with genotypes and quantitative levels of HCV-RNA in serum before therapy. HCV-RNA was detected by a reverse transcription polymerase chain reaction using the 5'-noncoding region as a primer. Genotypes were determined by using type-specific primers, and serum levels of HCV-RNA were determined by a competitive reverse transcription polymerase chain reaction (RT-PCR). HCV-RNA disappeared from serum in eight of 10 responders (80%), but in only one of the 26 nonresponders (3.8%) at the second week of therapy (P < 0.0005). The time until the disappearance of HCV-RNA was correlated with the serum level of HCV-RNA present before therapy (P < 0.05). The early disappearance of HCV-RNA from serum during interferon therapy was useful in predicting a sustained response in patients with chronic hepatitis C.
Serial assay of hepatitis C virus RNA in serum for predicting response to interferon-α therapy
Digestive Diseases and Sciences, 1995
To determine whether the loss of serum hepatitis C virus RNA (HCV-RNA) early in interferon therapy would indicate a sustained response to this agent, we detected serum HCV-RNA successively during and after therapy. Serum samples for detection of HCV-RNA were obtained serially from 36 patients with chronic hepatitis C treated with interferon-et. In 28 of these patients, results of the assay were compared with genotypes and quantitative levels of HCV-RNA in serum before therapy. HCV-RNA was detected by a reverse transcription polymerase chain reaction using the 5'-noncoding region as a primer. Genotypes were determined by using type-specific primers, and serum levels of HCV-RNA were determined by a competitive reverse transcription polymerase chain reaction (RT-PCR). HCV-RNA disappeared from serum in eight of 10 responders (80%), but in only one of the 26 nonresponders (3.8%) at the second week of therapy (P < 0.0005). The time until the disappearance of HCV-RNA was correlated with the serum level of HCV-RNA present before therapy (P < 0.05). The early disappearance of HCV-RNA from serum during interferon therapy was useful in predicting a sustained response in patients with chronic hepatitis C.
Journal of Hepatology, 1997
BackgrounuYAims: Interferon therapy has a beneficial effect in patients with chronic hepatitis C who have a low viral load. The aim of this study was to compare the core protein level with HCV RNA levels and to analyze whether virus quantitation predicts the efficacy of interferon therapy. MetkZs: HCV core protein level assessed by the recently developed assay was compared with HCV RNA levels measured by three different methods (Amplicor-HCV monitor, competitive RT(CRT)-PCR, and bDNA probe assay) in 352 patients with chronic hepatitis C in relation to viral serotype. Results: From 91% (320/352) to 93% (299/322) of patients with viremia were detected by Amplicormonitor and CRT-PCR, in contrast to 60% (1871312) and 74% (191/258) by bDNA and HCV core protein assay, respectively. The HCV core protein level was positively correlated with HCV RNA levels measured by the three assays (r=0.680 to 0.731). Serum HCV H EPATITIS C virus (HCV) is a major causative agent of non-A non-B hepatitis (l), and polymerase chain reaction (PCR) is usually applied to detect HCV RNA in serum (2-9) for diagnosis and monitoring of HCV infection. Interferon (IFN) is an effective treatment for some patients with chronic hepatitis C (lo-22). After the development of the competitive reversetranscriptase (RT)-PCR for evaluation of the serum HCV RNA level by Kato et al. (4,7,, recent studies RNA and core protein levels were significantly lower in patients with serotype 2 than in those with serotype 1. Viral eradication after interferon therapy was observed in 60-70% of the patients with<1 X 10" copies/ ml of HCV RNA by Amplicor-monitor assay,<2 x 10' copies/ml by CRT-PCR,<O.S Meq/ml by bDNA assay, and<20 pg/ml of core protein by HCV core protein assay. Viral eradication was uncommon (<ll%) among the patients with higher viral loads. Bivariate analysis revealed that the outcome of interferon therapy was more closely associated with both HCV core protein and RNA levels than the HCV serotype. Conclusions: Quantitation of HCV core protein and HCV RNA is useful for prediction of the interferon response.
Factors predictive of a beneficial response to therapy of hepatitis C
Hepatology, 1997
disease. 2 Many of these studies identified pretreatment pa-Alpha interferon is the only drug that has been shown to tient characteristics that are associated with a greater or lesser be effective in the treatment of chronic hepatitis C, but only likelihood of response to interferon ( ). The most clinihalf of patients respond, either transiently or permanently.
Response to interferon in chronic hepatitis C due to mixed genotype infection
Journal of Gastroenterology and Hepatology, 1996
We examined the response to interferon (IFN) in patients with chronic hepatitis C (CHC) due to two different genotypes of hepatitis C virus (HCV) infection. Among 64 CHC patients studied, one (2%) had HCV-RNA genotype I, 36 (56%) had genotype 11, 19 (30%) had genotype 111, 2 (3%) had genotype IV and 6 (9%) had both genotypes I1 and 111. There was no significant difference in age, sex, history of blood transfusion and liver histology among patients with genotypes 11, I11 and I1 + 111. The HCV-RNA titre of genotype I1 patients was significantly higher than that of genotype I11 patients (P<O.O5). However, there was no significant difference in the HCV-RNA titre between genotype II+III and the other groups. The complete response rate achieved with IFN therapy was significantly higher in genotype I11 patients (74%) than in genotype I1 patients (17%; P< 0.01). Of the six patients with genotype II+III, a complete response to IFN was only achieved by two patients (33%), both of whom had a low HCV-FWA titre (5 copies/mL) and HCV serotype 2. The remaining four patients had HCV serotype 1 and three of the patients had a high HCV-RNA titre (2 lo5 copiesiml). The HCV genotype I11 was lost in two patients after IFN therapy. These data suggest that HCV-RNA titre and HCV serotype are important factors for predicting the efficacy of IFN therapy in patients with mixed genotype infection and show direct evidence of higher susceptibility towards CHC of patients with genotype I11 than genotype 11.