Excellent Sustained Virological Response Research Articles

Effectiveness, tolerability and safety of Direct Acting Antivirals in Mexican individuals with Hepatitis C virus genotype-1 and previous pegylated interferon and ribavirin therapy.

BackgroundDirect Acting Antivirals (DAAs) represent a large improvement in the treatment of chronic hepatitis C, resulting in <90% sustained virological response (SVR). There are no reports on the real-world DAA response for Mexico and few reports exist for Latin America. The aim of the study was to report SVR, and immediate benefits with the DAA treatments sofosbuvir, ledispavir, with/without ribavirin (SOF/LDV ± RBV) and ombitasvir, paritaprevir, ritonavir, dasabuvir with/without RBV (OBV/PTV/r/DSV ± RBV) in patients with viral genotype 1a or 1b, and who did not respond to previous peginterferon/ribavirin (PegIFNα2a+RBV) therapy.MethodsA descriptive, ambispective, longitudinal study was conducted. A cohort of 261 adult patients received PegIFNα2a+RBV therapy before 2014; 167 (64%) did not respond, 83 of these were subsequently treated with SOF/LDV ± RBV or OBV/PTV/r/DSV ± RBV. Child-Pugh-Score (CPS), Fibrosis-4 (FIB-4), and AST to Platelet Ratio Index (APRI) were evaluated before and after treatment.ResultsSVR with PegIFNα2a+RBV was 36%, and 97.5% with DAAs. CPS, FIB-4 and APRI improved significantly after DAA treatment, mainly because of liver transaminase reduction.ConclusionsDAA treatment showed excellent SVR rates in Mexican patients who had not responded to PegIFNα2a+RBV therapy. Improvement in CPS, FIB-4 and APRI without improvement in fibrosis was observed in cirrhotic and non-cirrhotic patients, as well as considerable reduction in liver transaminases, which suggests a reduction in hepatic necroinflammation.

Real-world experience with Grazoprevir/Elbasvir in the treatment of previously "difficult to treat" patients infected with hepatitis C virus genotype 1 and 4.

Grazoprevir/elbasvir (GZR/EBR) was approved for the treatment of chronic hepatitis C virus (HCV) genotype 1 and 4 infected patients with or without compensated liver cirrhosis. The aim of this study was to assess GZR/EBR regimen in the real-world experience, particularly in previously "difficult-to-treat" patients with chronic kidney diseases, human immunodeficiency virus-coinfected, cirrhotics, and treatment-experienced. The analysis included patients treated with GZR/EBR selected from 10 152 individuals from the EpiTer-2 database, large national real-world study evaluating antiviral treatment in 22 Polish hepatology centers between 2015 and 2018. Data were completed retrospectively and submitted online. A total of 1615 patients who started GZR/EBR therapy in 2017 and 2018 with a female predominance (54%) and median age of 54 years were analyzed. The majority were infected with GT1b (89%) and treatment naïve (81%). Liver cirrhosis was diagnosed in 19%, and 70% of patients had comorbidities, of which chronic renal disease was present in 7% and HIV-coinfection in 4%. Overall, a sustained virologic response (SVR) was achieved by 95% according to intent-to-treat (ITT) and 98% after exclusion of lost to follow up (modified ITT). No differences were found in cure rate between all included patients and subpopulations previously considered as difficult-to-treat. Majority of patients completed the treatment course as scheduled, adverse events were mostly mild and did not lead to therapy discontinuation. GZR/EBR treatment carried-out in patients infected with HCV genotype 1 and 4 demonstrated good tolerability and an excellent SVR rate with no effectiveness reduction in so called difficult-to-treat populations.

Direct-acting antiviral therapy for hepatitis C infection among people receiving opioid agonist treatment or heroin assisted treatment

BackgroundTreating chronic hepatitis C virus (HCV) infection among PWID (people who inject drugs) is crucial to achieve the WHO goal of HCV elimination, as this population is highly affected and carries a high risk of transmission.The aim of our study was to provide real-life data on HCV treatment among PWID either in opioid agonist treatment (OAT) or in heroin-assisted treatment (HAT) in a low-threshold access primary care-based addiction medicine institution. MethodsWe conducted a retrospective chart analysis of patients treated with direct-acting antivirals (DAA) between 10/2014 and 08/2017 in the Arud outpatient clinics in Zurich, Switzerland. We reported patient and treatment characteristics and substance use. The outcomes were sustained virological response (SVR) by intention-to-treat (ITT) and modified ITT (mITT) analyses, excluding patients with missing SVR data. ResultsWe included 64 patients in our analysis. Forty-two (66%) were in OAT, and 22 (34%) were in HAT. Twenty-six patients (41%) reported harmful alcohol use, and 9 patients (14%) reported injecting drug use during DAA treatment. Every patient completed the treatment. Fifty-nine out of 64 achieved SVR resulting in an ITT SVR rate of 92.2%. Two patients had virological failure. Three patients were lost to follow-up between the end of treatment and SVR12 visit. Excluding these 3 patients, our study showed an mITT SVR rate of 96.7%. ConclusionPWID can be treated with DAA treatment integrated in OAT and HAT with an excellent SVR rate. OAT and HAT programs should offer integrated HCV treatment to their patients.

Direct-acting Antivirals for HIV/HCV Co-infected Individuals: As Good as it Gets?

Although HIV/HCV co-infected individuals were historically considered a "difficult to treat" population in the era of Interferon (IFN)-based anti-HCV treatment, the introduction of directacting antivirals, characterized by excellent efficacy and good safety profile, has widely revolutionized the HCV treatment scenario. Recent real life studies reported excellent sustained virological response rates in HIV/HCV coinfected subjects, thus confirming data obtained in randomized clinical trials. However, certain issues have recently emerged in this population. In fact, high rates of acute HCV infection and reinfections were documented in several studies, particularly in HIV-positive men who have sex with men. Moreover, drug-drug interactions with ART or other co-medications may require careful considerations as well as the management of HIV/HCV co-infected subjects with chronic kidney disease and advanced liver disease in the course of a DAA-based treatment. Hence, we aim to review DAA efficacy studies performed in HIV/HCV co-infected patients in both randomized clinical trials and real-world cohorts. In addition, current challenges and future perspectives are discussed in order to optimize management strategies for HIV/HCV co-infected subjects and their access to care in clinical practice.

High efficacy of Sofosbuvir plus Simeprevir in a large cohort of Spanish cirrhotic patients infected with genotypes 1 and 4.

Hepatitis C (HCV) therapy with Sofosbuvir (SOF)/Simeprevir (SMV) in clinical trials and real-world clinical practice, showed high rates of sustained virological response (SVR) in non-cirrhotic genotype (GT)-1 and GT-4 patients. These results were slightly lower in cirrhotic patients. We investigated real-life effectiveness and safety of SOF/SMV with or without ribavirin (RBV) in a large cohort of cirrhotic patients. This collaborative multicentre study included data from 968 patients with cirrhosis infected with HCV-GT1 or 4, treated with SOF/SMV±RBV in 30 centres across Spain between January-2014 and December-2015. Demographic, clinical, virological and safety data were analysed. Overall SVR was 92.3%; the majority of patients were treated with RBV (62%) for 12weeks (92.4%). No significant differences in SVR were observed between genotypes (GT1a:94.3%; GT1b:91.7%; GT4:91.1%). Those patients with more advanced liver disease (Child B/C, MELD≥10) or portal hypertension (platelet count≤100×109 /L, transient elastography≥21Kpa) showed significantly lower SVR rates (84.4%-91.9%) than patients with less advanced liver disease (93.8%-95.9%, P<.01 in all cases). In the multivariate analysis, the use of RBV, female gender, baseline albumin≥35g/L, MELD<10 and lack of exposure to a triple therapy regimen were independent predictors of SVR (P<.05). Serious adverse events (SAEs) and SAE-associated discontinuation events occurred in 5.9% and 2.6%. In this large cohort of cirrhotic patients managed in the real-world setting in Spain, SOF/SMV±RBV yielded to excellent SVR rates, especially in patients with compensated liver cirrhosis. In addition, this combination showed to be safe, with low rates of SAEs and early discontinuations.

Treatment of HCV infection in liver transplant recipients with ledipasvir and sofosbuvir without ribavirin.

Ledipasvir and sofosbuvir is a well-tolerated regimen with high sustained virological response (SVR) rates in pre-liver transplant patients infected with chronic hepatitis C virus (HCV), but data in liver transplant recipients outside of clinical trials is limited. To address this knowledge gap and assess SVR rates without the use of ribavirin in liver transplant recipients METHODS: This is a retrospective study examining the treatment of 75 post-liver transplant recipients with ledipasvir and sofosbuvir without ribavirin. Differences between SVR cohorts and predictors of SVR were analysed in an intention-to-treat (ITT) fashion. A total of 408 genotype 1, HCV patients were treated with ledipasvir/sofosbuvir from October 2014 to August 2015 at our centre. Seventy-three patients were post-liver transplant and were treated with a median of 2.9years from transplant. Ledipasvir/sofosbuvir achieved an SVR12 of 95.9%. African Americans made up 28.8% of the cohort. Sixty-three per cent of patients were treated previously, including 13.7% of patients previously treated with direct-acting antivirals. Only 2.7% had recurrent allograft cirrhosis, and the majority (90.4%) was on calcineurin inhibitor based immunosuppressive therapy. Approximately 82% of patients had chronic kidney disease (CKD) stage 2 or 3. In univariate logistic regression, only detectable week 8 viral load was predictive of failure to achieve SVR. Our data confirm excellent SVR outcomes and favourable safety and tolerability profiles with ledipasvir/sofosbuvir without ribavirin in post-liver transplant recipients infected with HCV, despite treatment guidelines to use ribavirin.

Hepatocellular carcinoma decreases the chance of successful hepatitis C virus therapy with direct-acting antivirals

The approval of all-oral direct-acting antiviral (DAA) regimens for the treatment of hepatitis C virus (HCV) has led to the expansion of therapy to include patients with cirrhosis who have hepatocellular carcinoma (HCC). Data on the use of DAAs in HCV+ patients with HCC is limited. The aim of this study was to assess the efficacy of all-oral-DAA regimens in HCV+ cirrhotic patients who have or had HCC compared to those without HCC. A retrospective cohort study was conducted on all cirrhotic patients who were treated for HCV with DAAs at our institution between January 2014 and November 2015. A total of 421 HCV+ patients with cirrhosis were identified, of whom 33% had active or a history of HCC. Failure to achieve sustained virologic response (SVR) occurred in 21% of patients with HCC compared to 12% of patients without HCC (p=0.009). Of the 29 patients with HCC who did not achieve SVR, 27 (93%) occurred when an active tumor was present. DAA therapy in the presence of an inactive tumor or after removal of tumor (resection/transplant) resulted in excellent SVR rates, similar to those without HCC (p<0.0001). In multivariable analysis, the primary predictor of DAA treatment failure was the presence of active HCC at the time of HCV treatment initiation (adjusted odds ratio=8.5, 95% confidence interval=3.90-18.49). The presence of active HCC tumor at the initiation of HCV therapy is significantly associated with all-oral DAA treatment failure. HCV treatment after curative therapies for HCC resulted in excellent SVR. The new medications for hepatitis C have excellent cure rates. However, our study shows that in patients with both liver cancer and hepatitis C, they do not achieve these cure rates. Patients with liver cancer are almost 8 times more likely to fail hepatitis C treatment than patients without liver cancer.

Safety and Efficacy of Sofosbuvir Based Regimens for Treatment of Chronic Hepatitis C Genotype 4: A Community Based Retrospective Cohort Study

Introduction: limited data exists on efficacy of short course therapy with peg interferon, ribavirin and sofosbuvir for chronic hepatitis C genotype 4 infection. We assessed the efficacy and tolerability of combination regimens involving sofosbuvir in patients infected with chronic hepatitis C genotype -4 in a retrospective cohort study. Methods: We retrospectively reviewed medical records of 37 patients with chronic hepatitis c genotype 4 treated between Jan 2013 to June 2015. Twenty-nine of the 37 patients were treated with Peg-Interferon 180mcg subcutaneously weekly with daily weight based ribavirin in combination with fixed dose sofosbuvir for 12 weeks. Three patients each received interferon free sofosbuvir + ribavirin and ledipasvir + sofosbuvir (Harvoni) regimens. Two patients were treated with simeprevir and sofosbuvir at standard doses. Results: Majority of the patients (N=33) were from Middle eastern or Egyptian origin. Eighty percent (N=30) were men and 19% (N=7) were women. Among all patients, 37% (N=14) were treatment experienced and 13% (N=5) had cirrhosis at baseline. Nine patients were co infected with human immunodeficiency virus. End of treatment was not recorded in one patient and sustained virologic response was not available for 4 patients. Two patients discontinued the treatment due to adverse reactions. Excluding patients, who discontinued treatment regimen and who don't have documented ETR and 12 week SVR rate, overall end of treatment response and sustained virologic response rate at 12 weeks post treatment were 100% (34/34) and 93.5% respectively (29/31). Hundred percent of the patients treated with interferon, ribavirin and sofosbuvir, attained 12 week sustained virologic response. One of the two patients who relapsed after treatment was treated with sofosbuvir and ribavirin and the other patient received simeprevir and sofosbuvir regimen. Most common adverse reactions were leukopenia (27%), followed by fatigue (21%), anemia (19%) and thrombocytopenia (16%). One patient developed severe skin reaction after 4 weeks of treatment and the other patient decompensated with esophageal variceal bleeding and both discontinued the treatment.Figure 1Figure 2Conclusion: Our results suggest that short course treatment with peg interferon, ribavirin with direct acting antiviral agent sofosbuvir still a suitable option for treating patients with chronic hepatitis C genotype 4 with excellent sustained virologic response and acceptable adverse events.

Nonzero Risk of Hepatocellular Carcinoma Even after Sustained Virological Response

Approximately 130 to 150 million people are chronically infected with hepatitis C virus (HCV) in the world. HCV infection is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). The existence of hepatitis C— originally identifiable only as a type of non-A, non-B hepatitis— was suggested in the 1970s and proven in 1989. In the treatment of chronic hepatitis C (CHC), antiviral therapy has seen brilliant advances and rapid evolution in efficacy as well as safety and tolerability within recent several years. New antiviral agents now promise excellent sustained virological response (SVR) rates. 1 After the widespread prescription of direct-acting antivirals (DAAs), the incidence of HCC will decrease gradually in the upcoming decades. However, the risk of HCC still remains in patients with advanced fibrosis, even though SVR reduces the progression to HCC. 2 Therefore, current guidelines recommended continued HCC surveillance for patients with liver cirrhosis even after SVR. 3 In a recent meta-analysis of observational studies, SVR is associated with a reduction in the relative risk for HCC for persons at all stages of liver disease (hazard ratio, 0.24; p<0.01). 4 This meta-analysis suggests that interferon (IFN) therapy is beneficial in reduction of HCC development after SVR. However, even if the absolute reduction in risk was 4.6%, approximately 1.5% of the patients with SVR developed HCC. Up to now, there is no data supporting long-term benefits of SVR achieved with DAAs-based regimens in the risk of HCC development because of insufficient follow-up time. In the near future, DAA-based regimens will induce the high SVR rates and increase the numbers of patients with SVR. Consequently, a nonzero risk of HCC development after SVR may be the hot topic in many studies. 5 Furthermore, it is very important to identify patients at high risk for developing HCC. Several markers have been identified to predict the risk of HCC in CHC patients with SVR. For example, the pretreatment platelet count, alkaline phosphatase, and older age were significantly associated with the risk of HCC development. 6

Spotlight on grazoprevir-elbasvir once-daily combination and its potential in the treatment of hepatitis C.

Chronic hepatitis C virus (HCV) infection is a leading cause of health care utilization in the USA. Incidence of cirrhosis from HCV is expected to rise in the near future, further increasing this burden. There is a high medical need for effective, tolerable, safe, all-oral, short-duration therapy. To this end, several new direct-acting antiviral agents have been developed and have shown excellent sustained virologic response rates. However, patients who have previously failed treatment or who have developed cirrhosis, renal failure, or human immunodeficiency virus coinfection remain difficult-to-treat subgroups. An all-oral agent that is effective in many of these subgroups would simplify treatment of HCV greatly. Here we review currently available data on the efficacy, treatment duration, tolerability, and safety of combination of grazoprevir and elbasvir.

Dasabuvir (ABT333) for the treatment of chronic HCV genotype I: a new face of cure, an expert review

ABSTRACTHepatitis C virus (HCV) affects nearly 1.3% of US population and around 2% of people worldwide. It is associated with serious complication of Cirrhosis and Hepatocellular carcinoma leading to significant morbidity and mortality. Until now the only treatment option for this serious disease was interferon based therapy which had poor tolerance and at best SVR (Sustained virological response) in only 50% of cases. With the introduction of other direct – acting antiviral agents the treatment of HCV has been revolutionized with significantly high rates of cure. Among novel Direct acting antivirals are non-nucleoside inhibitor NS5B which is highly effective in treatment of HCV genotype 1 a and 1b including those with compensated cirrhosis achieving high cure rates with SVR more than 97 % in pooled analysis from six different phase 3 trials. This review will discuss the DAA – Dasabuvir, a non – nucleoside NS5B inhibitor, its mechanism of action, efficacy, safety & tolerance, and drug resistance. Dasabuvir is approved by FDA in combination with other DAA agents called as the 3D(Viekira Pak) in various interferon free regimens achieving high cure rates (SVR >95%) with low adverse effects. In Europe, it is approved by European medicines agency for use in combination with Ombitasvir, Paritaprevir, and ritonavir with or without ribavirin. The drug is used in treatment naive as well as previously treated patient with high success rates. It is also approved in patients with compensated cirrhosis, patients with HIV co-infection and liver transplant recipients which were in the past were excluded from treatment with interferon based therapy. Dasabuvir is extensively evaluated in large clinical trials and shown excellent SVR among HCV genotype1 patient population in combination with other oral DAAs, with good safety profile and tolerance. Its drawback is its genotype restriction, need for ribavirin (RBV) for 1a genotype, low resistance barrier and high cost. It is well tolerated with less than 1 % of patients permanently discontinuing treatment and 2% of patient experiencing a serious adverse reaction. It is contraindicated in patients with known hypersensitivity to ritonavir (e.g. Steven – Johnson syndrome) and strong inducers of CYP3A and CYP2CB.

Association of serum vitamin B12 levels with stage of liver fibrosis and treatment outcome in patients with chronic hepatitis C virus genotype 1 infection: a retrospective study.

BackgroundChronic hepatitis C (CHC) is a global health challenge. New therapeutic agents with excellent sustained virological response (SVR) rates are available mainly in developed countries, while the majority of CHC patients live in countries with low health budget. Predictors of therapeutic response are therefore necessary. Vitamin B12 appears to be involved in hepatitis C virus replication.MethodsWe therefore studied retrospectively the relationship between baseline serum vitamin B12 levels and clinical features in 116 CHC genotype 1 infected patients. Logistic regression models with univariate and multivariate analysis were used in the statistical analysis.ResultsBaseline serum vitamin B12 levels were found to be positively associated with serum transaminase activities (AST, p = 0.002, ALT, p = 0.04), baseline viral load (p < 0.0001), stage of fibrosis (p = 0.0001) and favorable interferon-λ3/4 (IFNL3/IFNL4) rs12979860 genotypes (p = 0.04), and inversely with SVR (p < 0.001) as well as with rapid virological response (p = 0.001). Patients with baseline serum vitamin B12 levels below a cut-off value of 570 ng/L achieved a SVR rate of 59% with an odds ratio (OR) of 13.4 [confidence interval (CI) 4.3–41.9, p < 0.0001] compared to patients above the cut-off value. By combining serum vitamin B12 levels and IFNL3/IFNL4 rs12979860 genotypes, patients with baseline serum vitamin B12 levels below the cut-off value of 570 ng/L and IFNL3/IFNL4 rs12979860 CC genotype achieved a SVR rate of even 80% with an OR of 54 (CI 9.9–293, p < 0.0001) compared to patients above the cut-off value and non-CC-genotypes.ConclusionOur data suggest baseline serum vitamin B12 levels as useful noninvasive marker for characterizing CHC patients. They might further help to identify responders to a standard treatment.

Sofosbuvir, a novel nucleotide analogue inhibitor used for the treatment of hepatitis C virus.

To provide an overview of a novel anti-hepatitis C agent, sofosbuvir. Sofosbuvir is a novel nucleotide analogue inhibitor of hepatitis C virus (HCV) NS5B polymerase that has recently been approved by the Federal Drug Administration for the treatment of HCV genotypes 1, 2, 3 or 4 in a variety of patients. The emergence of such a novel treatment provides benefit to previously untreated genotypes and patient populations, with little chance of promoting significant viral resistance. Excellent sustained virologic response rates 12 weeks after the end of treatment (SVR12) were seen in phase II and III clinical trials when sofosbuvir was used with ribavirin. Even more promising are the results from phase II and III clinical trials that evaluated sofosbuvir in combination with other oral direct acting antivirals (DAAs). Data with sofosbuvir in the hepatitis C virus (HCV)/HIV coinfected and in the pre- and post-transplantation populations are still emerging. The drug was very well tolerated in clinical studies, with the most common adverse events of headache, nausea and fatigue. Overall, sofosbuvir presents a new and effective treatment option for HCV-infected patients.

Neurocognitive function and dysfunction after hepatitis C therapy

We read with interest the elegant study by Kraus et al.1 in the August issue of Hepatology. We have some concerns with regard to possible bias due to confounding factors not taken into account in the study. It is well known that not only depression but also the emotional state of the patient and motivation alone can modify neurocognitive function. It is very common for interferon alpha (IFN-α) therapy to induce depression or dysthymia.2 The psychiatric adverse effects of IFN-α can last for a long period after ending therapy, whether the patient achieved sustained virological response (SVR) or not. The authors give no data about such an important and proven factor in cognitive test performance.3, 4 A depressed or dysthymic patient will not perform as well as an euthymic patient in the measured tasks (alertness, attention, vigilance and working memory), no matter how simple. No information is given with regard to the distribution in both groups of this side effect, what medication was used in case it appeared, or if they responded to the antidepressant medication. Furthermore, the study was not blinded and we assume the patients were informed of the progress of their antiviral therapy. This creates an unavoidable psychological bias. The authors explain that their excellent SVR rate (69% versus the usual 40 to 50%) is explained in part due to the motivation of the studied patients. However, they do not consider that the same factor influences the neuropsychological test they performed. Motivated patients, perhaps those who achieved SVR, perform better on the Test for Attentional Performance (TAP) as compared to unmotivated patients.5 Pablo SolÍs-Muñoz, M.D., Ph.D.1,3 Carlos Mingote-Adán, M.D., Ph.D.2 Jose Antonio SolÍs-Herruzo, M.D., Ph.D.3 1Angloamerican Medical Unit Gastroenterology and Hepatology Madrid, Spain 2PAIPSE, Department of Psychiatry University Hospital “12 de Octubre” Madrid, Spain 3Biomedical Research Unit of Gastroenterology and Hepatology University Hospital “12 de Octubre” Madrid, Spain

A review of the current anti-HCV therapy: Are we finally ready for interferon-free regimens

Hepatitis C virus (HCV) continues to be a global problem but with the arrival of new drugs it is expected to move towards exile. The health care community has finally woken up to the need to tackle this infection especially because HCV-induced hepatitis in combination with HIV has turned out to be a formidable foe. So far the management of HCV has concentrated mainly on interferon-based therapies. The focus is now increasingly on drugs targeting various other components of hepatitis C, which are essential for its survival in the host like HCV non-structural (NS) 3/4A serine protease inhibitors: Boceprevir, telaprevir, simeprevir; NS5A inhibitors (daclatasvir, ledipasvir); NS5B polymerase inhibitors (sofosbuvir), cyclophilin inhibitors and many others in the pipeline like the NS4B inhibitors and the micro-RNA122 inhibitors. These new drugs have shown excellent sustained virological response (SVR) compared to the presently available drugs and their combinations. Adding to this is the new HCV vaccine which although facing various hurdles is making good inroads and expected to meet its endpoints in the near future. This review gives a brief overview of epidemiology, pathogenesis, followed by the description of current regimens in the treatment of hepatitis C and the much eagerly awaited future all new oral anti-hepatitis C regimen, which can potentially eliminate the use of painful injections of interferon.

Triple therapy with boceprevir or telaprevir for treatment naïve HCV patients

Boceprevir and telaprevir are the first two protease inhibitors available for the treatment of patients infected with HCV genotype 1. In treatment naïve patients, a sustained virologic response (SVR) of 70–80% is observed when either of these protease inhibitors is used with peginterferon and ribavirin A rapid virologic response (RVR) is observed in 56–60% of them allowing a shorter course of 24–28 weeks of therapy with an excellent SVR rate of 90% or even higher. Patients who do not achieve RVR, and those with cirrhosis should be treated for 48 weeks. Both drugs, boceprevir and telaprevir, achieve similar SVR rates but treatment strategies are completely different for each drug. The decision of which protease inhibitor to utilize should weigh several factors including the treatment strategy, duration of therapy, the likelihood of achieving an RVR, adverse event profile, and cost. Besides, the physician's experience with each drug and the wishes of the patient also have to be considered.

Short duration treatment in genotype 1 chronic hepatitis C patients with rapid virologic response to pegylated interferon plus ribavirin

Background In patients with chronic hepatitis C, rapid HCV-RNA clearance under treatment might allow shorter treatment duration without modifying the sustained virological response (SVR) rate. This study evaluated the impact of rapid virological response (RVR) in HCV genotype 1b infection management. Methods In an open-label trial, 180 patients received standard doses of peginterferon alfa-2a plus ribavirin. Those with undetectable serum HCV-RNA at week 6 (RVR) received 24-week short-course treatment; patients with undetectable HCV-RNA at week 12 (early responders [ER]) received 48-week “standard of care” treatment; patients with positive HCV-RNA at week 12 (non-responders [NR]) stopped the treatment. Study end-point was to determine SVR rate at week 24. Results The following responses were observed: 24% RVR, 44% ER, 32% NR. Among RVR subjects, HCV-RNA baseline levels and age were significantly lower ( P = 0.038 and 0.035 respectively) than in non-RVR patients. At follow-up, 91% of RVR and 33% of ER patients achieved SVR. Among those with RVR, patients experiencing post-therapy relapse were older than those who achieved a SVR ( P = 0.028). Conclusions Chronic HCV-1b patients, achieving RVR with a 24-week treatment regimen, attained excellent SVR rates. In a cost-effective therapeutic approach, all HCV-1b patients eligible for therapy may have a short duration therapy on the basis of RVR.

New direct-acting antivirals in the development for hepatitis C virus infection.

A large number of new therapies are in development for chronic hepatitis C including direct-acting antiviral drugs (DAA), which target specific hepatitis C virus enzymes. Two of these compounds have already advanced into phase 3 development in the USA and EU, and many more are in phase 2 trials and likely to advance. In this review, the results of recent studies on ribavirin analogues, nonstructural (NS) 3/4 serine protease inhibitors, NS5B polymerase inhibitors, cyclophilin inhibitors, silimarin components, and thiazolides have been updated. Each compound includes a brief summary of its proposed mechanism of action, results of early clinical trials, and more advanced trial data where available. These compounds are likely to be the first approved in the USA and EU and will initially be used in combination with the current standard of care. It is possible that future treatment paradigms with these agents will offer the potential of interferon-free regimens. It is most likely that patients for these new therapies will be selected carefully by identifying and treating first those who have excellent sustained virologic response rates with 24 weeks of pegylated interferon and ribavirin, the current standard of care. It is also likely that there will be a need to identify those patients who are not likely to have a sustained virologic response with the addition of a protease inhibitor to the current standard of care and delaying their therapy until combination viral suppression therapy becomes an option. The cost and side effects of the DAA will be important considerations for treating physicians. This review is current through 2009; however, data are rapidly changing.

Antiviral therapy for recurrent hepatitis C after liver transplantation: sustained virologic response is related to genotype 2/3 and response at week 12

Recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) is a major cause of transplant failure in HCV-positive patients. We retrospectively assessed the efficacy and safety of antiviral therapy and determined the factors influencing sustained virologic response (SVR) in LT recipients. Between 1998 and 2007, we treated 36 LT recipients for hepatitis C cirrhosis and subsequent HCV recurrence (27 genotype 1 and 9 genotypes 2/3) with pegylated interferon alpha-2a (180 microg/week), pegylated interferon alpha-2b (1.5 microg/kg per week), or standard interferon alpha-2b (3 MIU 3X/week) plus ribavirin (600-1200 mg/day) for 48 weeks. SVR was achieved in seven of 27 (26%) of genotype 1 patients versus nine of nine (100%) genotype 2/3 patients (P=0.0001). Early virologic response at week 12 was associated with permanent viral clearance. Side effects included cytopenia and acute hearing loss, but rate of therapy withdrawal and dose reduction was low. Combination therapy in patients with HCV reinfection after LT yields an excellent SVR rate in genotype 2/3 patients, but remains unsatisfactory in genotype 1 patients. Virologic response at week 12 (early virologic response) can determine whether therapy should be continued or not.

Extended Treatment Duration for Hepatitis C Virus Type 1: Comparing 48 Versus 72 Weeks of Peginterferon-Alfa-2a Plus Ribavirin

The treatment of patients infected with hepatitis C virus (HCV) type 1 remains a challenge necessitating innovative strategies to improve treatment outcome. The extension of treatment duration beyond 48 weeks is one possible strategy to address this problem. The efficacy and safety of 48 weeks (group A, N = 230) vs 72 weeks (group B, N = 225) of treatment with pegylated-interferon-alfa-2a (180 microg/wk) plus ribavirin (800 mg/day) were studied in treatment-naive patients with HCV type 1 infection. On-treatment and sustained virologic response (SVR) 24 weeks after stopping treatment was assessed by qualitative reverse-transcription polymerase chain reaction (sensitivity 50 IU/mL). Overall, no significant differences could be observed in the treatment outcome between both groups. End-of-treatment and SVR rates in groups A and B were 71% vs 63% and 53% vs 54%, respectively. Patients with undetectable HCV-RNA levels already at weeks 4 and 12 had excellent SVR rates ranging from 76% to 84% regardless of treatment group, whereas patients shown to be still HCV-RNA positive at week 12 achieved significantly higher SVR rates when treated for 72 instead of 48 weeks (29% vs 17%, P = .040). A particular benefit from extended treatment duration was seen in patients with low-level viremia (<6000 IU/mL) at week 12. The frequency and intensity of adverse events was similar between the 2 groups. Extended treatment duration generally is not recommended in HCV type 1 infection and should be reserved only for patients with slow virologic response defined as HCV-RNA positive at week 12 but negative at week 24.