Safety of interferon β treatment for chronic HCV hepatitis

Hepatitis C is a major cause of liver-related morbidity and mortality worldwide. In fact, chronic hepatitis C is considered as one of the primary causes of chronic liver disease, cirrhosis and hepatocellular carcinoma, and is the most common reason for liver transplantation. The primary objectives for the treatment of HCV-related chronic hepatitis is to eradicat einfection and prevent progression of the disease. The treatment has evolved from the use of m-interferon (IFNα) alone to the combination of IFNα plus ribavirin, with a significant improvement in the overall efficacy, and to the newer PEG-IFNs which have further increased the virological response, used either alone or in combination with ribavirin. Despite these positive results, in terms of efficacy, concerns are related to the safety and adverse events. Many patients must reduce the dose of PEG-IFN or ribavirin, others must stop the treatment and a variable percentage of subjectsare not suitable owing to intolerance toward drugs. IFNβ represents a potential therapeutic alternative for the treatment of chronic viral hepatitis and in some countries it plays an important role in therapeutic protocols. Aim of the present paper was to review available data on the safety ofIFNβ treatment in HCV-related chronic hepatitis. The rates of treatment discontinuation and/or dose modification due to the appearance of severe side effects during IFNβ are generally low and in several clinical studies no requirements for treatment discontinuation and/or dose modifications have been reported. The most frequent side effects experienced during IFNβ treatment are flu-like syndromes, fever, fatigue and injection-site reactions. No differences in terms of side-effect frequency and severity between responders and non-responders have been reported.A more recent study, performed to compare IFNβ alone or in combination with ribavirin, confirmed the good safety profile of both treatments. Similar trends of adverse event frequency have been observed in subpopulations such as patients with genotype-lb HCV hepatitis unresponsive to IFNα treatment or with HCV-related cirrhosis and patients with acute viral hepatitis. If further studies will confirm the efficacy of combined IFNβ and ribavirin treatment, this regimen could represent a safe and alternative therapeutic option in selected patients.     

Safety of interferon β treatment for chronic HCV hepatitis

Hepatitis C is a major cause of liver-related morbidity andmortality worldwide.In fact,chronic hepatitis C is consideredas one of the primary causes of chronic liver disease,drrhosisand hepatocellular carcinoma,and is the most commonreason for liver transplantation.The primary objectives forthe treatment of HCV-related chronic hepatitis is to eradicateinfection and prevent progression of the disease.Thetreatment has evolved from the use of α-interferon (IFNα)alone to the combination of IFNα plus ribavirin,with asignificant improvement in the overall efficacy,and to thenewer PEG-IFNs which have further increased the virologicalresponse,used either alone or in combination with dbavirin.Despite these positive results,in terms of efficacy,concernsare related to the safety and adverse events.Many patientsmust reduce the dose of PEG-IFN or ribavirin,others muststop the treatment and a variable percentage of subjectsare not suitable owing to intolerance toward drugs.IFNβrepresents a potential therapeutic alternative for thetreatment of chronic viral hepatitis and in some countries itplays an important role in therapeutic protocols.Aim of thepresent paper was to review available data on the safety ofIFNβ treatment in HCV-related chronic hepatitis.The rates of treatment discontinuation and/or dosemodification due to the appearance of severe side effectsduring IFNβ are generally low and in several clinical studiesno requirements for treatment discontinuation and/or dosemodifications have been reported.The most frequent sideeffects experienced during IFNβ treatment are flu-likesyndromes,fever,fatigue and injection-site reactions.Nodifferences in terms of side-effect frequency and severitybetween responders and non-responders have been reported.A more recent study,performed to compare IFNβ alone or incombination with ribavirin,confirmed the good safety profileof both treatments.Similar trends of adverse event frequencyhave been observed in subpopulations such as patients withgenotype-1b HCV hepatitis unresponsive to IFNα treatmentor with HCV-related cirrhosis and patients with acute viralhepatitis.If further studies will confirm the efficacy of combinedIFNβ and ribavirin treatment,this regimen could represent asafe and alternative therapeutic option in selected patients.     

Treatment of chronic viral hepatitis with nitazoxanideand second generation thiazolides

Nitazoxanide, the first thiazolide, was originally developed for the treatment of Cryptosporidium parvum. More recently, antiviral activity of nitazoxanide against hepatitis B virus （HBV） and hepatitis C virus was recognized in in vitro systems. These basic studies led to phase Ⅱ clinical trials that demonstrated the safety and efficacy of nitazoxanide in combination with peginterferon, with or without ribavirin, in the treatment of chronic hepatitis C genotype 4. The sustained virologic response rate was 79% and 80% in two studies, which was higher than the response rate of 50% with the standard of care with peginterferon plus ribavirin. In very preliminary studies of patients with chronic hepatitis B, nitazoxanide suppressed serum HBV DNA and led to loss of hepatitis B e antigen in the majority of patients and hepatitis B surface antigen in approximately a quarter of patients. Randomized controlled studies of naive and nonresponder patients with chronic hepatitis C genotype 1 are underway, new second generation and controlled release thiazolides are being developed, and future studies of patients with chronic hepatitis B are planned.     

SEN virus does not affect treatment response in hepatitis C virus coinfected patients but SEN virus response depends on SEN virus DNA concentration

AIM: To clarify the effect of SEN virus (SENV) infection on a combination therapy including interferon alfa (IFN-α) or pegylated-IFN with ribavirin in patients with chronic hepatitis and the effect of a combination therapy on SENV.METHODS: SENV DNA was determined by polymerase chain reaction in serum samples from 95 patients with chronic hepatitis C. Quantitative analysis was done for SENV H DNA.RESULTS: Twenty-one (22%) of 95 patients were positive for SENV DNA. There was no difference in clinical and biochemical parameters between patients with HCV infection alone and coinfected patients. The sustained response rate for HCV clearance after combination therapy did not differ between patients with SENV (52%) and without SENV(50%, n.s.). SENV DNA was undetectable in 76% of the initially SENV positive patients at the end of follow-up. SENV H response to combination therapy was significantly correlated with SENV DNA level (P=-0.05).CONCLUSION: SENV infection had no influence on the HCV sustained response rate to the combination therapy.Response rate of SENV to the combination therapy depends on SENV DNA level.     

Treatment of genotype 2 and 3 chronic hepatitis C virus-infected patients

AIM: Before pegylated interferon alpha (IFN) was introduced for the therapy of chronic hepatitis C virus (HCV)-induced hepatitis, conventional thrice weekly IFN therapy was supplemented by ribavirin. Also, at that time, higher and more frequent doses of IFN were expected to be more effective than the standard regimen of 3 MU thrice weekly. As ribavirin significantly increases side effects and negatively influences the quality of life particularly in young patients, we started a prospective non-randomized study with a daily IFN-2a monotherapy as an initial treatment for chronic hepatitis C. METHODS: Forty-six consecutive chronic HCV-infected patients received 3 MU IFN-2a per day as an initial treatment. Patients with genotype 2 or 3 (n = 12) were treated for 24 wk, and patients with genotypes other than 2 or 3 (n = 34) for 48 wk. Treatment outcome was followed up for 48 wk after the end of treatment (EOT). Virological response was defined as the absence of detectable serum HCV-RNA. Patients without virological response at 12 wk after the start of treatment received low-dose ribavirin (10 mg(kg·d)) additionally. RESULTS: During treatment, three genotype 3 patients were excluded from the study due to incompliance. The remaining patients (n = 9) infected with genotype 2 or 3 showed an initial virological response rate of 100%. Six patients (66.7%) were still found to be virus-free at the end of follow-up period. In these patients, initial virological response was evident already after 2 wk of treatment. In contrast, initial virological response occurred first after 4 wk of treatment in the three patients who relapsed (33.3%). In comparison, patients infected with genotypes other than 2 or 3 (n = 34) showed an initial virological response rate of only 23.5% (n = 8), and even in combination with ribavirin a sustained virological response (SVR) rate of only 11.8% (n = 4) could be achieved. CONCLUSION: In chronic HCV-infected patients with genotype 2 or 3, a SVR can be expected after 24 wk of daily dose IFN-2a treatment without ribavirin, if initial virological response develops early. This finding is worth to be confirmed in a prospective randomized study with pegylated IFN.     

Ribavirin monotherapy increases sustained response rate in relapsers of end treatment virologic responders

AIM: To assess the efficacy of ribavirin monotherapy in patients with biochemical relapse after combination therapy. METHODS: Twenty-four weeks of ribavirin monotherapy was given to biochemical relapsers of end treatment biochemical responders within 6 mo after combination therapy, including non-responders with HCV-RNA level ≤0.2 Meq/mL and end treatment virologic responders (ETVRs) with or without reappearance of HCV-RNA. RESULTS: Sixty-two chronic HCV-infected patients completed 24 wk of interferon-α plus ribavirin combination therapy. Fifty patients (80%) achieved end treatment biochemical response including 16 non-responders and 34 of 36 ETVRs. Twenty-six patients (41.9%) were non-responders. Ribavirin monotherapy was given to 20 biochemical relapsers including 12 non-responders with HCV-RNA levels ≤0.2 Meq/mL, four of eight HCV-RNA reappearing ETVRs, and four HCV-RNA negative ETVRs. After 24 wk of ribavirin monotherapy, one of 12 non-responders, two of four HCV-RNA reappearing ETVRs and all four RNA-negative biochemical relapsers of ETVRs showed sustained virologic response. Two of 12 monotherapy treated non-responders showed persistent normalization of liver function test. In total, 50% (31/62) of patients achieved sustained virologic response. CONCLUSION: Resumption of ribavirin monotherapy in ETVRs at signs of viral rebound and recurrent biochemical abnormalities rather than continuation of monotherapy appears to be the key to success of ribavirin monotherapy after interferon-related combination therapy.     

Retinal vein thrombosis associated with pegylated-interferon and ribavirin combination therapy for chronic hepatitis C

An estimated 300 million people worldwide suffer from chronic hepatitis C with a prevalence of 0.8%-1.0% of the general population in Canada. An increasing pool of evidence exists supporting the use of pegylatedinterferon (peglFN) and ribavirin combination therapy for hepatitis C. We report a 49-year old male of North American aboriginal descent with chronic hepatitis C (genotype 2b). Biopsy confirmed that he had cirrhosis with a 2-wk history of left eye pain and decreased visual acuity. He developed retinal vein thrombosis after 16 of 24 wk of peglFN-α2a and ribavirin combination therapy. He was urgently referred to a retinal specialist and diagnosed with non-ischemic central retinal vein occlusion of the left eye. PeglFN and ribavirin combination therapy was discontinued and HCV RNA was undetectable after 16 wk of treatment. Hematologic investigations revealed that the patient was a factor V Leiden heterozygote with mildly decreased protein C activity. Our patient had a number of hypercoagulable risk factors, including factor V Leiden heterozygosity, cirrhosis, and hepatitis C that alone would have most likely remained clinically silent. We speculate that in the setting of peglFN treatment, these risk factors may coalesce and cause the retinal vein thrombosis.     

Co-treatment with pegylated interferon alfa-2a and entecavir for hepatitis D: a randomized trial

AIM: To investigate the efficacy of pegylated interferon alfa(PEG-IFNα) therapy with and without entecavir in patients with chronic hepatitis D. METHODS: Forty hepatitis D virus(HDV) RNA positive patients were randomized to receive either PEG-IFNα-2a 180 μg weekly in combination with entecavir 0.5 mg daily(n = 21) or PEG-IFNα alone(n =19). Patients who failed to show 2 log reduction in HDV RNA level at 24 wk of treatment, or had detectable HDV RNA at 48 wk of therapy were considered as treatment failure. Treatment was continued for 72 wk in the rest of the patients. All the patients were followed for 24 wk post treatment. Intention to treat analysis was performed.RESULTS: The mean age of the patients was 26.7 ± 6.8 years, 31 were male. Two log reduction in HDV RNA levels at 24 wk of therapy was achieved in 9(43%) patients receiving combination therapy and 12(63%) patients receiving PEG-IFNα alone(P = 0.199). Decline in hepatitis B surface antigen(HBs Ag) levels was insignificant. At the end of treatment, HDV RNA was negative in 8 patients(38%) receiving combination therapy and 10 patients(53%) receiving PEG-IFNα-2a alone. Virological response persisted in 7(33%) and 8(42%) patients, respectively at the end of the 24 wk follow-up period. One responder patient in the combination arm lost HBs Ag and became hepatitis B surface antibody positive. Six out of 14 baseline hepatitis B e antigen reactive patients seroconverted and four of these seroconverted patients had persistent HDV RNA clearance.CONCLUSION: Administration of PEG-IFNα-2a with or without entecavir, resulted in persistent HDV RNA clearance in 37% of patients. The addition of entecavir did not improve the overall response.     

Treatment of hepatitis C virus infection

Acute and chronic hepatitis C virus （HCV） infection remains a serious health problem worldwide, however, there has been advancement in the treatment of HCV infection due to standard treatment using pegylated interferon and ribavirin. The literature indicates that therapy for HCV is becoming more individualized. In addition to considering genotype and viral RNA levels before treatment, achievement of an early virologic response （EVR） and a rapid virologic response （RVR） is now possible during therapy. Moreover, problem patients, such as non-responders, relapsers, HIV or HBV coinfected patients, patients with liver cirrhosis, and preor post-liver transplantation patients are an increasing fraction of the patients requiring treatment. This article reviews the literature regarding standard treatments and problem patients with acute and chronic HCV infection. It also includes discussion on contraindications and side effects of treatment with interferon and ribavirin, as well as new drug development.     

Retreatment with peginterferon and ribavirin in chronic hepatitis C

The development of boceprevir and telaprevir was a major step forward in the treatment of chronic hepatitis C.In addition,the treatment of these infections has been recently revolutionized by the approval of sofosbuvir and simeprevir.However,there are several challenges associated with the application of noveldrugs,such as new and more frequent adverse events,new drug interactions,and excessively high treatment costs.An additional concern is viral resistance.These considerations highlight the fact that direct-acting antiviral agents are not a panacea and may not be the best option for all patients who are in need of therapy.This retrospective study revealed that the sustained virologic response was not significantly reduced following peginterferon and ribavirin retreatment compared with the new therapy.We suggest that patients who experience relapse shortly after completing treatment with peginterferon and ribavirin have a reasonable chance of achieving a sustained virologic response when retreated with these drugs alone.     

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 bloodmononuclear cells (PBMC) with interferon (IFN) couldefficiently decrease hepatitis C virus-RNA (HCV-RNA) amountand to analyze whether this effect was associated with clinicalresponse to IFN.METHODS:Twenty-seven patients with histologically provenchronic hepatitis C were given intravenous administrationof 6 million units (MU) IFN-β daily for 6 weeks followed bythree times weekly for 20 weeks.PBMC collected beforeIFN therapy were incubated with IFN-β and HCV-RNA inPMBC was semi-quantitatively determined.RESULTS:Twenty-five patients completed IFN therapy.Eight patients (32%) had sustained loss of serum HCV-RNAwith normal serum ALT levels after IFN therapy (completeresponders).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 ofHCV-RNA in PMBC in 18 patients (72%).Eight of thesepatients obtained complete response.On the other hand,none of the patients whose HCV-RNA in PBMC did notdecrease by IFN-β was complete responders.Multiple logisticregression analysis revealed that the decrease of HCV-RNAamount in PBMC by IFN-β was the only independent predictorfor complete response (P<0.05).CONCLUSION:The effect of in vitro IFN-β on HCV in PBMCreflects clinical response and would be taken into accountas a predictive marker of IFN therapy for chronic hepatitis C.     

Interferon-λ3 polymorphisms in pegylated-interferon-α plus ribavirin therapy for genotype-2 chronic hepatitis C

AIM: To evaluate interferon-λ3(IFNL3) polymorphisms in response-guided pegylated interferon-α plus ribavirin(Peg-IFNα/RBV) therapy for genotype 2(G2) chronic hepatitis C.METHODS: Between January 2006 and June 2012, a total of 180 patients with chronic infections of G2 hepatitis C virus(HCV) were treated with responseguided Peg-IFNα/RBV therapy. The treatment duration was 24 wk for patients who achieved rapid virologic response(RVR), and 36 or 48 wk for patients who did not. Then, the impact of the IFNL3 single nucleotide polymorphism genotype(TT/non-TT at rs8099917) on treatment outcomes was evaluated in the 180 patients, and between patients infected with either HCV subgenotype 2a or 2b.RESULTS: Of the 180 patients evaluated, 111 achieved RVR, while the remaining 69 patients did not. In RVR patients, the sustained virologic response(SVR) rate was 96.4%, and the IFNL3 genotype did not influence the SVR rate(96.6% vs 95.8% in IFNL3 genotype TT vs non-TT). However, in non-RVR patients, the SVR rate decreased to 72.5%(P 0.0001), and this rate was significantly different between the IFNL3 genotype TT and non-TT groups(80.0% vs 42.9%, P = 0.0146). Multivariate regression analysis in non-RVR patients identified the IFNL3 genotype TT as the only baseline-significant factor associated with SVR(OR = 5.39, 95%CI: 1.29-22.62; P = 0.0189). In analysis according to HCV sub-genotype, no significant difference in the SVR rate was found between HCV sub-genotypes 2a and 2b.CONCLUSION: In response-guided Peg-IFNα/RBV combination therapy for chronically HCV G2-infected patients, the impact of the IFNL3 genotype on SVR was limited to non-RVR patients.     

Simeprevir with peginterferon and ribavirin induced interstitial pneumonitis:First case report

The effectiveness of hepatitis C treatment has improved with the development of interferon(IFN),and it has drastically improved with the development of peg-interferon-α(PEG-IFN) in combination with ribavirin(RBV) and,more recently,with the addition of a protease inhibitor.Simeprevir,which is a secondgeneration protease inhibitor,has shown clinically favorable safety and tolerability profiles.Simeprevir received its first global approval in Japan in September 2013 for the treatment of genotype 1 chronic hepatitis C in combination with PEG-IFN and RBV.One serious adverse event associated with IFN therapy is interstitialpneumonitis,which can be fatal.We experienced a patient with interstitial pneumonitis that was induced by simeprevir with PEG-IFN and RBV therapy for chronic hepatitis C in the early stages of therapy(8 wk after initiating therapy).This is the first case report of interstitial pneumonitis with simeprevir with PEG-IFN and RBV in the world.In addition,it is very interesting that the onset of interstitial pneumonitis was earlier than that in conventional PEG-IFN and RBV therapy.This finding suggests that simeprevir augments the adverse event.We present this case report in light of relevant literature on interstitial pneumonitis with conventional PEG-IFN and RBV therapy.     

Extended-therapy duration for chronic hepatitis C, genotype 1： The long and the short of it

With pegylated interferon and ribavirin, more than half of all chronically-infected hepatitis C patients can achieve a sustained virologic response; however, patients with genotype 1 infections and those with other poor prognostic factors have relatively inferior treatment response rates. Since new therapies are still years away from approval, it is incumbent upon providers to maximize the therapeutic efficacy of today＇s treatment. The later the virus is undetectable in serum during treatment, the less likely it will be eradicated. Patients with a delayed or slow virologic response to therapy （at least a 2-1og10 decrease in baseline hepatitis C RNA yet detectable viremia at 12 wk of therapy and undetectable virus 12 wk subsequently） may, therefore, benefit from an extended therapy course beyond one of standard duration. Although higher rates of treatment discontinuation may plague this approach, 72 wk of treatment for genotype 1-infected slow-responders may improve response rates and diminish relapse rates relative to those of 48 wk. Based on data from both viral kinetic and clinical studies, therapy prolongation in slow responders may be a reasonable strategy to improve response rates in these treatment-refractory 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.     

程序性细胞凋亡基因单核苷酸多态性与慢性乙型肝炎患者干扰素早期病毒学应答的相关性

Objective To investigate the relationship between the single nucleotide polymorphisms (SNP) of programmed cell death-1 (PD-1) gene and early virologic response of interferon-α (IFN-α) in patients with chronic hepatitis B (CHB). Methods A total of 135 CHB patients were prospectively enrolled in this study. SNP of PD-1.1 and PD-1.2 genes were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in these patients.Then its relationship with early virologic response to IFN-α treatment was analyzed. The data were analyzed by x2 test. Results Among the 135 patients, 33 (24.4%) achieved early virologic response to IFN-α. There were 35, 77, and 23 patients with AA, AG, GG genotgpe of PD-1.1. The early virologic response was achived in 5(14.3%), 25(32.5%) and 3(13.0%) among patients with AA,AG, GG genotypes of PD-1.1, respectively. There were statistically different (x2 = 6. 258, P =0. 044). The subjects with AG genotype showed higher response rate than those with AA or GG genotypes (x2 = 6. 246, P= 0. 012). However, the early virologic response rates were not significant different among subjects with AA, AG or GG genotype of PD-1. 2 ( x2= 3.957, P= 0. 138).Conclusion SNP of PD-1.1 gene may be used as a marker to predict the early virologic response to IFN-α treatment in Chinese CHB patients.     

Serum concentration of sFas and sFasL in healthy HBsAg carriers, chronic viral hepatitis B and C patients

AIM: To estimate the amount of apoptosis among healthy HBsAg carriers, patients with chronic HBV infection treated with lamivudine and patients with chronic HCV infedJon treated with interferon alpha and ribavirin. Activity of apoptosis was evaluated by serum sFas/sFasL concentration measurement.Moreover dependence between apoptosis and HBV-DNA or HCV-RNA levels was studied.METHODS: Eighty-six persons were included into study: 34 healthy HBsAg carriers, 33 patients with chronic HBV infection and 19 patients with chronic HCV infection. Serum levels of sFas/sFasL were measured by ELISA assay. HBV-DNA and HCV-RNA were measured by RT-PCR assay. Levels of sFas/sFasL were determined before and 2 and 12 wk after therapy in patients with chronic hepatitis B and C infection.HBV-DNA or HCV-RNA was detected before treatment and 6 mo after treatment.RFSULTS: Twenty-four (71%) healthy HBsAg carriers showed HBV-DNA over 10^5/mL, which was comparable to the patients with chronic hepatitis B. Independently from HBV-DNA levels,the concentration of sFas among healthy HBsAg carriers was comparable to healthy persons. Among patients with chronic hepatitis B and C, the concentration of sFas was significantly higher in comparison to healthy HBsAg carriers and healthy persons. In chronic hepatitis B patients the concentration of sFas was decreased during lamivudine treatment. Among chronic hepatitis C patients the concentration of sFas was increased during IFN alpha and ribavirin treatment, sFasL was not detected in control group. Furthermore sFasL oo:urred more frequently in chronic hepatitis C patients in comparison to chronic hepatitis B patients.CONCLUSION: There are no correlations between apoptosis and HBV-DNA levels. However ther is an association between apoptosis and activity of inflammation in patients with chronic HBV infection. Apoptosis can be increased in patients with chronic hepatitis C by effective treatment which may be a result of apoptosis stimulation by IFN-α.     

Is interferon-beta an alternative treatment for chronic hepatitis C？

The treatment of chronic hepatitis C (CMC) is still far from optimal, particularly for those subpopulations that do not respond to the standard combination therapy with Interferon-α(IFNα) plus ribavirin. Although in some cases the use of higher doses or longer treatment periods may be effective, these approaches are generally associated with a higher incidence of adverse events, which may either lead to a reduction in patient compliance or require drug withdrawal. IFNβcould represent an interesting alternative for treating CMC patients. Controversial data about IFNp efficacy in CMC exist, the main reason being that many results stem from pilot studies with small cohorts of patients. However, promising results have been obtained in some subgroups of patients that fail to respond to IFNa. Additionally, the good tolerability of IFNβrepresents an important advantage of the drug. The rates of dropouts in controlled clinical trials, as well as the need for dose reductions or treatment discontinuation are very low. It might be worth assessing the value of IFNβplus ribavirin in randomized studies with a larger cohort of patients, not eligible or not tolerating standard therapy, and for non-responders.     

SEN virus does not affect treatment response in hepatitis C virus coinfected patients but SEN virus response depends on SEN virus DNA concentration

AIM:TO clarify the effect of SEN virus (SENV) infection on acombination therapy including interferon alfa (IFN-α) orpegylated-IFN with ribavirin in patients with chronic hepatitisand the effect of a combination therapy on SENV.METHODS:SENV DNA was determined by polymerase chainreaction in serum samples from 95 patients with chronichepatitis C.Quantitative analysis was done for SENV H DNA.RESULTS:Twenty-one (22%) of 95 patients were positivefor SENV DNA.There was no difference in clinical andbiochemical parameters between patients with HCV infectionalone and coinfected patients.The sustained response ratefor HCV clearance after combination therapy did not differbetween patients with SENV (52%) and without SENV(50%,n.s.).SENV DNA was undetectable in 76% of theinitially SENV positive patients at the end of follow-up.SENVH response to combination therapy was significantlycorrelated with SENV DNA level (P=0.05).CONCLUSION:SENV infection had no influence on the HCVsustained response rate to the combination therapy.Response rate of SENV to the combination therapy dependson SENV DNA level.     

Ombitasvir,paritaprevir, ritonavir,dasabuvir and ribavirin in cirrhosis after complete destruction of hepatocellular carcinoma

We observed a sustained viral response(SVR) of ombitasvir/paritaprevir/ritonavir, dasabuvir and ribavirin therapy, for 12 wk, in two cases with compensated liver cirrhosis and fully destroyed early hepatocellular carcinoma(HCC). Patients were infected with hepatitis C virus(HCV) genotype 1b and were previous null responders/relapsers to interferon-alpha/ribavirin(IFN/RBV). There was a rapid suppression of HCV RNA to undetectable levels within the first two treatment weeks. SVR was achieved even after marked reduction of the RBV dose. The treatment was well tolerated. Both subjects experienced worsening of liver disease during therapy, in different patterns: severe, transient, predominantly direct hyperbilirubinemia without cytolysis(case 1) or progressive increase of aminotransferases(grade 4) without severe hyperbilirubinemia(case 2).Adverse events spontaneously resolved. The patients remained in a good clinical condition without hepatic decompensation. There was no re-occurrence of HCC. This is the first report for treatment of HCV cirrhosis after complete HCC destruction.