Study Aims and Results: This study was conducted to understand the rates of side effects during and after treatment with direct-acting antiviral (DAA) therapy among Egyptian patients. In this retrospective study, a total of 149,816 patients received DAA treatment. The breakdown of type of DAA treatment received included sofosbuvir plus ribavirin (21,835 patients), sofosbuvir plus simeprevir (24,215 pts), sofosbuvir plus daclatasvir (58,477 pts), sofosbuvir, daclatasvir plus ribavirin (45,188), and paritaprevir, ombitasvir plus ribavirin (101 pts). The treatment period was 12 to 24 weeks. The majority of patients treated were male (53%), HCV genotype 4 (90%), and the mean age was 54 years old.
In the analysis, a total of 1.7% of the 149,816 patients treated reported side effects. Of these, 68% were serious which means that slightly more than 1% had serious side effects. The majority of the serious side effects were anemia (low red blood cells) and hyperbilirubinemia (high levels of bilirubin). The two serious side effects were in the patients treated with sofosbuvir plus ribavirin. The combination of sofosbuvir plus daclatasvir had the lowest rate of side effects.
There were 0.02% of people in the analysis treated who developed liver cancer, and .06% died after treatment completion. Patients with cirrhosis showed the highest risk for serious side effects and death.
Conclusions: In this large group of patients treated with various combinations of direct-acting antiviral (DAA) medications the reported side effects were very low. The most common side effects reported were in the group treated with sofosbuvir plus ribavirin.
Editorial Comments: This very large study reaffirms that DAA medications have relatively few side effects with a couple of important caveats:
The highest rates of side effects were in the therapies that included ribavirin. Anemia is a well-documented side effect of ribavirin. Now, the vast majority of HCV treatment does not include ribavirin.
The current study reinforces the need to closely monitor people with cirrhosis while they are receiving HCV treatment (and afterward).
Patients with advanced hepatitis C infection being treated with direct-acting antivirals(DAAs) may have a reduced risk for being diagnosed with hepatocellular carcinoma (HCC) during the first year and further declines after 1 year, according to results published in the Journal of Hepatology.
The study used data from the NAVIGATORE platform, a prospectively recording database of all patients with hepatitis C infection receiving DAAs in the Veneto region of Italy. Participants who were included had liver fibrosis stage ≥F3.
Of 3917 participants with a mean follow-up of 536.2±197.6 days, 55 were diagnosed with HCC. During the first year, HCC incidence was 0.46% (95% CI, 0.12-1.17) in patients with fibrosis stage F3, 1.49% (95% CI, 1.03-2.08) in participants with Child-Pugh-A, and 3.61% (95% CI, 1.86-6.31) in participants with Child-Pugh-B. In the second year, HCC incidences were 0%, 0.2%, and 0.69%, respectively.
Patients with hepatitis C have an increased risk for disease progression to cirrhosis and potentially hepatocellular carcinoma. Recent studies have focused on defining liver cancer risks related to HCV progression and the rates of liver cancer after HCV clearance with new direct-acting antivirals.
The following include several recent that refute previous data suggesting that DAA therapy may increase the risk for liver cancer. Rather, researchers have found it more likely that any increased risk for HCC after DAA therapy is linked to baseline risk factors. Additional include data on liver cancer incidence among patients with comorbidities.
DAAs for HCV do not increase liver cancer recurrence after local-regional therapy
Recently published data showed no association between direct-acting antiviral therapy and an increased risk for hepatocellular carcinoma recurrence among liver transplantation candidates with hepatitis C who experienced initial complete response to local-regional therapy.
“The majority of recent publications reveal no increased risk of liver cancer in patients treated with DAAs — both in terms of de novo HCC and recurrence after complete response to HCC treatment,” Norah Terrault, MD, from the University of California, San Francisco, told HCV Next. “These studies highlight the limitations of earlier studies that were uncontrolled and thus unable to account for differences in the patients in the current DAA era (older, more advanced cirrhosis) and prior pegylated-interferon era.”
The retrospective cohort study comprised 149 adult patients with HCV-associated cirrhosis and HCC listed for transplantation with MELD exception at UCSF between January 2014 and October 2016. According to Terrault and colleagues, they conducted the study prior to concerns about the adverse consequences of DAA therapy and HCC outcomes.
Article: Direct-Acting Antiviral Sustained Virologic Response: Impact on Mortality in Patients without Advanced Liver Disease—L.I. Backus, et. al. by Alan Franciscus
SOURCE: Hepatology doi: 10.1002/hep.29811
Study Aims and Results: The study was undertaken to understand the improved outcomes (defined as the lower risk of death) among treated patients compared to untreated patients. The treated patients received HCV direct-acting antiviral (DAA) medications.
The Veterans Affairs conducted the study. The patient population was comprised of 103,346 veterans with HCV genotypes 1, 2 and 3. Various HCV direct-acting antiviral (DAA) medications (interferon-free) were used to treat 40,664 Veterans. The overall cure rate in the treated group was 96.8%.
The groups (non-treated group vs. treated group) were compared for overall survival. The authors reported that there was a 69% reduction in all-cause deaths compared to the untreated patients.
Conclusions: DAA treatment and cure of hepatitis C in early stage HCV disease (without cirrhosis) dramatically decreased disease progression and death.
Editorial Comments: This study is the largest yet conducted with DAA HCV medications to show the benefit of being cured. In the analyses, the reduction in deaths is further proof of the effectiveness of DAA therapy.
The study confirms that DAA therapy reduces deaths and should settle the question of whether we should treat everyone with hepatitis C. That answer should be a resounding YES!
Alan Franciscus is the Executive Director of the Hepatitis C Support Project and the Editor-in-Chief of the HCV Advocate Website
Read the entire March HCV Advocate newsletter here
Direct acting antivirals (DAA) are a novel and completely oral hepatitis C therapy that is associated with a high response rate. DAAs are used in most patients being treated for hepatitis C, including those with decompensated cirrhosis.
This type of treatment has now completely replaced interferon-based therapy for patients with hepatitis C, a therapy which was also associated with a decrease in hepatocellular carcinoma (HCC) incidence in 40% to 50% of patients
Initially, it was thought that DAAs would also decrease HCC recurrence, but a multicenter, single-arm, retrospective study out of Spain demonstrated an increase in the early recurrence of HCC following treatment with DAAs. Among 58 patients with a history of HCC and a complete response early recurrence was observed in 16 patients (27.6%) when treated with DAA.
Direct-acting antiviral use resulted in high rates of sustained virologic response and were safely tolerated in patients with chronic hepatitis C and mixed cryoglobulinemia, according to a recently published study. Researchers observed that most patients did not have a complete clinical or immunological response, however, suggesting a delayed response.
“Our study showed that achievement of SVR was necessary but not sufficient to obtain a complete immunological or clinical response,” Joel S. Emery, MD, from the University of Toronto, and colleagues wrote. “Although the viral trigger for lymphocyte clonal expansion may be removed (virological response), time-dependent clearance or downregulation of autoimmune B-cell populations is likely necessary before significant immunological or clinical improvements are seen.”
Between August 2011 and December 2015, 83 patients with hepatitis C and mixed cryoglobulinemia received treatment at the researchers’ center. Baseline characteristics were mostly similar between the 65 asymptomatic patients and 18 symptomatic patients. Sixty-six patients received interferon-free treatment.
For the first time, a large study has demonstrated that treatment with direct-acting antivirals (DAAs) significantly reduces mortality rates among people with hepatitis C virus (HCV) monoinfection. The study – published in Clinical Infectious Diseases – matched people who received therapy with all-DAA regimens with untreated controls. Mortality rates in the first 18 months after therapy were significantly lower among individuals who received DAAs. After controlling for other factors, treatment with DAAs was associated with a 57% reduction in the risk of death.
“To our knowledge, this is the first large-scale study to demonstrate the effect of newer DAA regimens upon survival,” write the authors. “Treatment with 2 commonly used DAA regimens…was associated with significant improvements in survival within the first 18 months of treatment, compared with demographically and clinically similar untreated HCV-infected controls.”
DAAs have revolutionised the treatment of people with HCV, with all-oral regimens achieving sustained virologic response (SVR) – or cure – rates in excess of 90% in clinical trials. Successful treatment with DAAs in routine care has already been shown to be associated with a lower risk of fibrosis progression. However, the survival benefit from successful DAA therapy has never been examined in a large study.