Interferon therapy for patients more than 60 years of age with chronic hepatitis C

Abstract Nineteen patients aged > 60 years with chronic hepatitis C (CHC) received interferon (IFN) therapy and a complete response (CR) was achieved by five of them (26%). The incidence of CH with severe fibrosis in this elderly group was significantly higher than in another 52 patients with CHC who were < 60 years of age (the younger group; P < 0.05). There was no significant difference in the hepatitis C virus (HCV) genotype distribution between the elderly group and the younger group. However, the HCV-RNA titre was significantly higher in the elderly group than in the younger group ( P < 0.05). There was no significant difference in the efficacy rate of IFN in the elderly and younger groups after standardization of the background factors. In the elderly group, the HCV-RNA titre was significantly lower in the patients achieving CR than in those with no response ( P < 0.05). These data suggest that elderly patients with a low HCV-RNA titre can still respond well to IFN therapy.     

Response to interferon in chronic hepatitis C due to mixed genotype infection

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 II, 19 (30%) had genotype III, 2 (3%) had genotype IV and 6 (9%) had both genotypes II and III. There was no significant difference in age, sex, history of blood transfusion and liver histology among patients with genotypes II, III and II + III. The HCV-RNA titre of genotype II patients was significantly higher than that of genotype III patients (P < 0.05). 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 III patients (74%) than in genotype II 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-RNA titre (≦ 10^4,5 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 (≧ 10⁵ copies/mL). The HCV genotype III 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 III than genotype II.     

Poor response to interferon treatment for chronic hepatitis C in human immunodeficiency virus-infected haemophiliacs.

We performed a pilot study to evaluate the factors associated with response to interferon (IFN) therapy for chronic hepatitis C (CHC) with human immunodeficiency virus (HIV) coinfected haemophiliacs. Seven haemophiliacs, coinfected with HIV and hepatitis C virus (HCV), received 9 mega-units (MU) of natural IFN-alpha daily during the first 2 weeks and then three times a week for 22 weeks, all injected subcutaneously. Six patients were receiving zidovudine (AZT) 600 mg day-1 and didanosine (ddI) 200 mg day(-1) during IFN therapy. This treatment was safe and well tolerated. Four patients had no detectable serum HCV-RNA at the end of therapy, but long-term, none of the seven patients achieved a sustained response, i.e. undetectable serum HCV-RNA with persistently normal serum alanine aminotransferase (ALT) 6 months after therapy. IFN did not affect CD4-positive cell counts. Most of our patients had high HCV-RNA loads and/or low CD4 counts, both unfavourable markers for IFN therapy. In conclusion, IFN therapy did not eradicate HCV from haemophiliacs coinfected with HIV.     

Interferon signaling and treatment outcome in chronic hepatitis C

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide. The current standard therapy for chronic hepatitis C (CHC) consists of a combination of pegylated IFN alpha (pegIFNalpha) and ribavirin. It achieves a sustained viral clearance in only 50-60% of patients. To learn more about molecular mechanisms underlying treatment failure, we investigated IFN-induced signaling in paired liver biopsies collected from CHC patients before and after administration of pegIFNalpha. In patients with a rapid virological response to treatment, pegIFNalpha induced a strong up-regulation of IFN-stimulated genes (ISGs). As shown previously, nonresponders had high expression levels of ISGs before therapy. Analysis of posttreatment biopsies of these patients revealed that pegIFNalpha did not induce expression of ISGs above the pretreatment levels. In accordance with ISG expression data, phosphorylation, DNA binding, and nuclear localization of STAT1 indicated that the IFN signaling pathway in nonresponsive patients is preactivated and refractory to further stimulation. Some features characteristic of nonresponders were more accentuated in patients infected with HCV genotypes 1 and 4 compared with genotypes 2 and 3, providing a possible explanation for the poor response of the former group to therapy. Taken together with previous findings, our data support the concept that activation of the endogenous IFN system in CHC not only is ineffective in clearing the infection but also may impede the response to therapy, most likely by inducing a refractory state of the IFN signaling pathway.     

A fresh look at interferon-alpha signaling and treatment outcomes in chronic hepatitis C

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide. The current standard therapy for chronic hepatitis C (CHC) consists of a combination of pegylated IFN alpha (pegIFNalpha) and ribavirin. It achieves a sustained viral clearance in only 50-60% of patients. To learn more about molecular mechanisms underlying treatment failure, we investigated IFN-induced signaling in paired liver biopsies collected from CHC patients before and after administration of pegIFNalpha. In patients with a rapid virological response to treatment, pegIFNalpha induced a strong up-regulation of IFN-stimulated genes (ISGs). As shown previously, nonresponders had high expression levels of ISGs before therapy. Analysis of posttreatment biopsies of these patients revealed that pegIFNalpha did not induce expression of ISGs above the pretreatment levels. In accordance with ISG expression data, phosphorylation, DNA binding, and nuclear localization of STAT1 indicated that the IFN signaling pathway in nonresponsive patients is preactivated and refractory to further stimulation. Some features characteristic of nonresponders were more accentuated in patients infected with HCV genotypes 1 and 4 compared with genotypes 2 and 3, providing a possible explanation for the poor response of the former group to therapy. Taken together with previous findings, our data support the concept that activation of the endogenous IFN system in CHC not only is ineffective in clearing the infection but also may impede the response to therapy, most likely by inducing a refractory state of the IFN signaling pathway.     

Chronic hepatitis C in elderly patients: clinical, histological and virological features

Some clinical, histological and virological features, efficacy and safety of interferon (IFN) therapy were evaluated in elderly patients with chronic hepatitis C (CHC). We enrolled 22 patients aged 65-75 (mean age: 68.3 +/- 3.17 years); 15 males and 7 females. In all cases the hepatitis C virus RNA (HCV-RNA) was determined before, during and after the therapy, and HCV sub-types were established; 15 patients underwent hepatobiopsy. At entry, the duration of disease was: 6 patients 1-3 years, 2 patients 4-10 years, 14 patients 11-30 years; alanine-aminotransferase (ALT) = (3.17 +/- 1.15) x N (N = normal value); aspartate-transaminase (AST) = 2.28 +/- 1.6 x N; gamma-glutamyl-transpeptidase (gGT) = 1.4 +/- 1.1 x N; platelets = 164,000 +/- 66,000/mm(3); histological pattern: 2 mild chronic active hepatitis (CAH), 5 CAH, 2 severe CAM, 6 CAH with liver cirrhosis (LC); histological activity index (HAI) (14 patients) = 11.14 +/- 4.5 (range 5-17); scores according to Scheuer: lobular 2.28 +/- 1.13, portal 2.71 +/- 0.99, fibrosis 2.35 +/-1.33; HCV-RNA +ve: 20 patients, HCV-RNA -ve: 2 patients; HCV-subtypes: 1b 20/20 (100%), 1b+1a 1/20 (5%), 1b+ 2a 1/20 (5%). Treatment was applied to 18 patients, for 3-12 months; 5 received alpha-IFN2a; 5 received alpha-IFN2b, 3 lymphoblastoid IFN, all at a dose of 3 mU thrice per week; 3 patients received 6 mU beta-IFN thrice per week. Therapy over 6 months was applied to 16 patients: Complete response (CR) was observed in 8 patients (50%), one of them was with long-term CR (over 12 months after therapy); 5 have had relapse and 2 patients are still under treatment. Partial response (PR) was observed in 4 patients (25%), no response (NR) in 4 patients (25%). Side effects were moderate and self-limited. Loss of HCV-RNA was shown in some patients with PR and in all patients with CR, but only temporarily.     

Long-term follow up of chronic hepatitis C patients after alpha-interferon treatment: a functional study

AIM: To evaluate the long-term functional outcome of chronic hepatitis C (CHC) patients treated with interferon (IFN) therapy. METHODS: Thirty-six patients with CHC were followed up for a mean of 36 months (+/- 19, SD) after a course of IFN therapy. Biochemical, virological (qualitative hepatitis C virus (HCV)-RNA and HCV genotype), and functional (monoethylglycinexylidide (MEGX) test) evaluations were carried out at the time of liver biopsy. Patients were divided into long-term responders (LTR), relapsers (RR), or non-responders (NR) according to IFN therapy outcome. At the end of follow up, patients were non-invasively re-evaluated by means of biochemistry, qualitative HCV-RNA, MEGX test, and liver ultrasonography. RESULTS: A significant decrease in MEGX values was observed in all patients. However, when patients were examined according to treatment outcome, only NR and RR showed a significant decrease in liver function as compared to pretreatment levels (MEGX30, 80.5 +/- 26.8-62.9 +/- 24.2 ng/mL, P< 0.01; MEGX60, 72.9 +/- 18.1-60.5 +/- 19.7 ng/mL, P< 0.05; MEGXAUC, 3,816 +/- 1,243-3,095 +/- 1,205 ng/mL per h, P< 0.05). On the contrary, LTR patients showed no significant modifications in MEGX values at each sampling time (MEGX,5, 72.9 +/- 31.4-70.3 +/- 29.7 ng/mL; MEGX30, 84.0 +/- 27.6-71.5 +/- 21.8 ng/ mL; MEGX60, 69.5 +/- 26.8-63.2 +/- 14.4 ng/mL; MEGXAUC 4028 +/- 1,378-3,620 +/- 1,041 ng/mL per h). At the end of follow up, LTR patients showed normal liver biochemistry and negativity of serum HCV-RNA, while NR and RR patients showed a significant decrease in platelets. CONCLUSIONS: In CHC patients long-term response to IFN therapy, besides favoring positive clinical and virologic long-term outcome, results in maintaining preserved liver function. Furthermore, IFN therapy seems to determine a decrease in the rate of functional disease progression, even in NR and RR. The MEGX test may be considered as a useful tool for performing serial follow up of CHC patients.     

Effect of in vitro interferon-beta administration on hepatitis C virus in peripheral blood mononuclear cells as a predictive marker of clinical response to interferon treatment for chronic hepatitis C

AIM:To test whether in vitro incubation of peripheral blood mononuclear cells (PBMC) with interferon (IFN) could efficiently decrease hepatitis C virus-RNA (HCV-RNA) amount and to analyze whether this effect was associated with clinical response to IFN.METHODS:Twenty-seven patients with histologically proven chronic hepatitis C were given intravenous administration of 6 million units (MU) IFN-β daily for 6 weeks followed by three times weekly for 20 weeks. PBMC collected before IFN therapy were incubated with IFN-β and HCV-RNA in PMBC was semi-quantitatively determined.RESULTS: Twenty-five patients completed IFN therapy.Eight patients (32%) had sustained loss of serum HCV-RNA with normal serum ALT levels after IFN therapy (complete responders).HCV-RNA in PBMC was detected in all patients,whereas it was not detected in PBMC from healthy subjects.In vitro administration of IFN-β decreased the amount of HCV-RNA in PMBC in 18 patients (72%). Eight of these patients obtained complete response. On the other hand,none of the patients whose HCV-RNA in PBMC did not decrease by IFN-β was complete responders. Multiple logistic regression analysis revealed that the decrease of HCV-RNA amount in PBMC by IFN-β was the only independent predictor for complete response (P&lt;0.05).CONCLUSION:The effect of in vitro IFN-β on HCV in PBMC reflects clinical response and would be taken into account as a predictive marker of IFN therapy for chronic hepatitis C.     

Individualisation of antiviral therapy for chronic hepatitis C

The combination of pegylated‐interferon (PEG‐IFN)/ribavirin is currently the standard of care antiviral treatment for chronic hepatitis C (CHC), but optimal results require an individual approach. Key issues are to deliver doses that confer optimal antiviral efficacy against hepatitis C virus (HCV) for a time sufficient to minimise relapse. Viral monitoring during therapy guides the subsequent treatment course, particularly HCV RNA results at 4 weeks (rapid viral response [RVR]) and 12 weeks (complete early viral response [cEVR]). There is strong evidence that for most patients with genotypes 2 or 3 HCV infection, RVR allows truncation of treatment to 16 weeks, provided ribavirin dose is weight‐based. However, those patients with cirrhosis, insulin resistance/diabetes or older than 50 years need 6–12 months treatment. For “difficult‐to‐treat” CHC (genotypes 1 and 4), RVR is infrequent (～15% in European studies), but allows treatment to be truncated from 48 to 24 weeks. Without RVR, there is some evidence that longer treatment (72 weeks) improves sustained viral response (SVR). However, “induction dosing” first 12 weeks of PEG‐IFN clearly does not improve SVR. To prevent dose reductions and complete therapy, it is critical to detect and treat depression and other disabling side‐effects, including judicious use of growth factors for severe anemia or neutropenia and possibly, thrombocytopenia. Another potentially important aspect may be attempts to counter central obesity and insulin resistance, which confer suboptimal antiviral response with any HCV genotype. Treatment partnerships with specialist nurses, psychological therapists and other healthcare workers are also essential for optimal individual management of patients with CHC.     

Urgency to treat patients with chronic hepatitis C in Asia

Chronic hepatitis C (CHC) infection poses a global healthcare burden, being associated with serious complications if untreated. The prevalence of hepatitis C virus (HCV) infection is highest in areas of Central, South, and East Asia; over 50% of HCV patients worldwide live in the region, where HCV genotypes 1b, 2, 3, and 6 are the most prevalent. Treatment outcomes for chronic hepatitis C vary by ethnicity, and Asian patients achieve higher sustained virologic response rates following interferon (IFN)‐based therapy than non‐Asians. However, low efficacy, poor safety profile, and subcutaneous administration limit the use of IFN‐based therapies. Superior virologic outcomes have been observed with different classes of direct‐acting antivirals (DAAs) alone or in combination, and several all‐oral DAA regimens are available in Asia. These regimens have shown excellent efficacy and favorable tolerability in clinical trials, yet there is a need for further studies of DAAs in a real world context, particularly in Asia. Furthermore, IFN‐free treatment may not be accessible for many patients in the region, and IFN‐based regimens remain an option in some countries. There is a need to improve current clinical practices for HCV management in Asia, including effective screening, disease awareness, and prevention programs, and to further understand the cost‐effectiveness of IFN‐free regimens. The evolution of potent treatments makes HCV eradication a possibility that should be available to all patients. However, access to these therapies in Asian countries has been slow, primarily because of economic barriers that continue to present a hurdle to optimal treatment.     

Distribution of the different subtypes of hepatitis C virus in Japan and the effects of interferon: A nationwide survey

Interferon (IFN) is now commonly used for the treatment of type C hepatitis; however, its effects differ depending upon the subtype of hepatitis C virus (HCV) being treated. It has been recently confirmed in many studies in Japan that the effectiveness of IFN treatment is poor in patients having type 1b and better in patients having type 2a HCV. However, the effects of IFN treatment on other subtypes of HCV were not clear because of the small number of patients in each hospital. In the present study, the effects of IFN treatment in patients with other HCV subtypes were analysed from nationwide data collected in Japan using a standard questionnaire. From this questionnaire, local differences in the distribution of HCV subtypes in Japan were also analysed. A standard questionnaire, consisting of questions about the number of patients with chronic type C hepatitis with different HCV subtypes and the number of patients showing different responses to IFN treatment, was sent to over 40 study groups in Japan, Answers to the questionnaire concerning HCV subtyes and the effects of IFN treatment were obtained from 26 and 22 hospitals, respectively, throughout Japan. The incidence of HCV type 1b was highest in the Kinki area (south-central Japan). The incidence of type 1b HCV decreased in parallel with distance from this area. The mortality rates of hepatic cancer in different areas were significantly corrclated with the incidence of HCV type 1b. The efficacy of IFN treatment was significantiy better for both types 2a and 2b HCV than for type 1b HCV; the efficacy of IFN treatment was poor in the mixed type of 1b and 2a and tended to be better in type 1a. The efficacy of IFN treatment for other types of HCV was also better. These results indicate that there are local differences in the distribution of HCV subtypes in Japan and that these differences may be closely associated with the clinical features of HCV-related liver disease. The efficacy of IFN treatment was significantly poorer in patients with the 1b-related type HCV than in patients with other types of HCV.     

Effect of mutation in the hepatitis C virus nonstructural 5B region on HCV replication

Background We have reported that the presence of a mutation at the hepatitis C virus (HCV) nonstructural protein 5B (NS5B), defined as a change in amino acids at sites specific for a different reported genotype, was related to complete response (CR) to interferon (IFN) therapy in patients with chronic hepatitis C (CHC) with genotype 1b. The present study assessed the impact of the NS5B mutation on the replication of HCV in these patients.Methods Genotype-specific mutations of HCV NS5B were determined by direct sequencing. We measured HCV-RNA titers in serum by real-time detected polymerase chain reaction (PCR), and serum HCV core protein levels (as a marker of HCV-RNA replication) were measured using an enzyme immunoassay in patients with CHC genotype 1b. RNA-dependent RNA polymerase (RdRp) activity was measured by Behrens method in liver cirrhosis patients infected with HCV (n = 13) and in those infected with hepatitis B virus (HBV; n = 2).Results The titers of HCV-RNA (n = 44) and the levels of HCV core protein (n = 41) were significantly lower in patients with the HCV genotype 1b mutant compared with wild-type HCV (P < 0.05). RdRp activity in liver tissue did not show any correlation with the HCV NS5B mutation.Conclusions HCV NS5B genotype-specific mutations in HCV genotype 1b may influence HCV replication.     

High serum leptin is an independent risk factor for non-response patients with low viremia to antiviral treatment in chronic hepatitis C

AIM:To determine whether body weight and/or serumleptin were independent predictors of response toantiviral treatment in patients with chronic hepatitis C.METHODS:A retrospective evaluation was performedin 139 patients with chronic hepatitis C treated withinterferon(IFN)from 1996 to 2000.Sustained responsewas defined as negative by hepatitis C virus(HCV)RNAanalysis using PCR and normal transaminase at 24 wkafter cessation of IFN therapy.Patients who remainedpositive for HCV RNA at the end of IFN treatment weredefined as resistant to IFN therapy.Sex,age,body massindex(BMI)(≥25 vs<25),complication of diabetesmellitus,serum leptin level(≥8.0 μg/L vs<8.0 μg/L),and the stage of liver fibrosis by needle biopsy(F1/F2 vsF3/F4)were examined.RESULTS:Sustained response was achieved in 33patients(23.7%),while others failed to show a responseto IFN therapy.Overall,the factors associated withsustained antiviral effects were HCV-RNA load,HCVgenotype,serum leptin level,and stage of liver fibrosisevaluated by univariate analysis.BMI was not associatedwith any therapeutic effect of IFN.Multivariate analysisindicated that HCV-RNA load was a significant risk factor,but among the patients with low viremia(HCV-RNA<100 MU/L),leptin level was an independent risk factorfor IFN resistance.Namely,a high level of serum leptinattenuated the effect of IFN on both male and femalepatients with low viremia.CONCLUSION:High serum leptin level is a negative predictor of response to antiviral treatment in chronichepatitis C with low viremia.     

Rapid clearance of hepatitis C virus RNA in peripheral blood mononuclear cells of patients with clotting disorders and chronic hepatitis C treated with alpha-2b interferon is not a predictor for sustained response to treatment

Summary. Thirteen patients with congenital coagulation disorders and chronic hepatitis C were treated with alpha-interferon (IFN). Serum transaminases (ALT) and hepatitis C virus (HCV)-RNA in plasma and peripheral blood mononuclear cells (PBMC) were followed during and after treatment. During IFN treatment ALT levels normalized in 8/13 patients. In all patients HCV-RNA disappeared from PBMC. In 9/13 HCV-RNA also became undetectable from plasma; in six of these nine this occurred earlier in PBMC than in plasma; in the remaining three the disappearance of HCV-RNA occurred simultaneously in plasma and PBMC. All but two patients relapsed within 3 weeks after cessation of IFN, one relapsed after 6 weeks and one patient remains in remission after 6 months. HCV-RNA reappeared either earlier in plasma (3/12) or simultaneously in plasma and PBMC (9/12). Viral replication in PBMC thus can easily be suppressed by IFN, whereas longer treatment is needed for the eradication of HCV-RNA in plasma. The detection of HCV-RNA in PBMC cannot be used as a prognostic marker for the identification of patients with chronic hepatitis C who will have a sustained response to IFN treatment.     

Early hepatitis C virus changes and sustained response in patients with chronic hepatitis C treated with peginterferon alpha-2b and ribavirin.

BACKGROUND: Interferon-based therapy induces changes in viral dynamics in chronic hepatitis C (CHC) patients. AIMS: The aim of this study was to assess early hepatitis C virus (HCV)-RNA changes and evaluate its predictive value to achieve sustained viral response (SVR) in patients with CHC treated with peginterferon alpha-2b weekly plus ribavirin daily for 48 weeks. METHODS: HCV-RNA was measured at baseline, 48 h, 4, 12, 24 and 48 weeks of treatment and 24 weeks after treatment. RESULTS: Eighteen HCV genotype 1 patients were included (13 male, five female) with a mean age of 44.4+/-11.9 years. Nine patients achieved SVR (50%). Viral decline occurred as early as 48 h; the magnitude of decline was statistically different between both groups (P<0.01). Responders had a > or =1 log(10) drop in HCV-RNA at 48 h (positive predictive value (PPV) of 89% to achieve SVR) that persisted at week 4. By week 12, serum HCV-RNA was undetectable (PPV 100%). CONCLUSIONS: Our data indicate that peginterferon alpha-2b plus ribavirin treatment produces significant changes in HCV dynamics that can be detected as early as 48 h after the first dose of peginterferon alpha-2b and that these changes are useful in predicting response to therapy in CHC patients.     

Hepatitis C virus (HCV) relapses after anti-HCV therapy are more frequent in HIV-infected patients

The response to standard or pegylated interferon (IFN) plus ribavirin (RBV) seems to be lower in hepatitis C virus (HCV)/HIV-coinfected subjects than in HCV-monoinfected patients. Thus, the principles guiding anti-HCV therapy in HIV-negative patients may not apply in the setting of HIV infection. We examined the rate of HCV relapse in 58 HCV/HIV-coinfected subjects who showed undetectable HCV-RNA (<600 IU/ml) at the end of anti-HCV combination therapy. Overall, 19 (32.8%) patients relapsed after discontinuing treatment, a rate significantly higher than that seen in HIV negatives, which is in the range of 15-20%. There were no significant differences between HCV genotypes (33.3% for HCV genotypes 2-3 versus 31.8% for HCV genotypes 1-4) and/or the use of either standard or pegylated IFN (37% versus 29%, respectively). Thus, extended periods of anti-HCV therapy might reduce HCV relapses in HIV-coinfected patients initially responding to therapy.     

Natural Interferon α Treatment and Interferon α Receptor 2 Levels in Acute Hepatitis C

Efficacy of interferon (IFN) therapy during the acute phase of hepatitis C infection is promising, although the optimal regimen has yet to be determined. It is not known whether the known prognostic factors for chronic hepatitis C (CHC) influence the effect of IFN in acute hepatitis C (AHC). Seventeen patients with AHC were analyzed for hepatic IFN alpha receptor 2 (IFNAR2) prior to IFN treatment. All patients were subsequently treated with either 168 million units (MU) or 336 MU of natural IFN alpha. Seventeen age-matched samples of CHC were provided as controls. The overall sustained response rate was 64.7% (11/17). In patients who received a total dose of 168 MU IFN, the sustained response rate was 28.6% (2/7), and in those who received 336 MU of IFN, the sustained response rate was 90.0% (9/10). The peaks of ALT and HCV-RNA quantity were not associated with the response to IFN. The hepatic IFNAR2 levels were 1.52 +/- 0.34 densitometry units and 0.92 +/- 0.16 in AHC and CHC, respectively (P = 0.042). There was no difference in hepatic IFNAR2 levels between sustained virological responders (SVR) and nonsustained virological responders (NR). The hepatic receptor levels were higher in AHC than in CHC patients. The levels of hepatic IFNAR2 did not differ in SVR and NR, indicating that high-dose natural IFN alpha treatment is effective for AHC, irrespective of the levels of hepatic IFNAR2.     

Effect of treatment with interferon α-2b and ribavirin in patients infected with genotype 2 hepatitis C virus

Aim:  Nearly 20% of chronic hepatitis C (CHC) patients with genotype 2 hepatitis C virus (HCV) infection are not curable, even by interferon (IFN)–ribavirin combination therapy. The aim of this study is to investigate the factors that determine the efficacy of combination therapy in patients with genotype 2 HCV infection.
Methods:  Fifty patients with CHC who underwent a treatment of 6 MU IFN α-2b with ribavirin for 24 weeks were retrospectively analyzed.
Results:  All the patients showed no serum HCV-RNA within 12 weeks after starting the therapy. Forty-one of the 50 patients (82%) achieved a sustained virological response (SVR). The age, sex, genotype (2a vs. 2b) and grade/stage of the liver by histopathology and pretreatment viral load werenot different between the sustained responders and relapsers. Univariate analysis showed that an earlier viral clearance from blood and a larger number of amino acid substitutions in the interferon sensitivity determining region (ISDR) were predictors of SVR. Multivariate analysis showed that a large number of amino acid substitutions in the ISDR was a predictor of SVR.
Conclusion:  The characterization of the amino acid sequences of ISDR may be helpful for predicting a relapse after combination therapy in patients with genotype 2 HCV infection.