Meeting News Coverage

EASL releases, outlines 2015 HCV recommendations

VIENNA — The goal of HCV therapy is to eradicate infection, according to Jean-Michel Pawlotsky, MD, PhD, Coordinator of the panel that published the 2015 EASL Recommendations on the Treatment of HCV.

Pawlotsky, who is a professor at the University of Paris-Est and director of the French National Reference Centre for Viral Hepatitis B, C and Delta, said that the panel took into consideration the heterogeneity of European countries, populations, policies and medical coverage systems. But regardless of the diversity, clinicians in all countries should aim to prevent cirrhosis, decompensation, hepatocellular carcinoma and death. “The endpoint is undetectable HCV RNA,” he said during a symposium at the International Liver Congress.

Pawlotsky addressed the pressing issue of cost of HCV therapies. “The indication is that treatment-naive and treatment-experienced patients who are compensated or decompensated who are willing to be treated should be considered for therapy,” he said. “Every patient has a right to be treated.”

That said, he was realistic in that certain populations should be prioritized. Those include patients with F3 or F4 fibrosis, HIV or HBV coinfection, those who are indicated for transplantation, those who have had HCV recurrence after transplantation, patients with extrahepatic manifestations, debilitating fatigue and those who are at risk for transmitting HCV.

The indications for patients coinfected with HIV are identical to those for patients monoinfected with HCV. “However, drug-drug interactions should be taken into account,” Pawlotsky said.

Treatment is justified in patients with F2 fibrosis and can be deferred in more mild disease, he added.

Approved, recommended therapies

Key drug approvals in 2015 included the combination of sofosbuvir and ledipasvir (Harvoni, Gilead Sciences) and the ‘3D regimen’ of ombitasvir, paritaprevir and ritonavir with or without dasabuvir (Viekira Pak, AbbVie).

“Drug-drug interactions are complex and difficult to deal with, particularly in patients with comorbidities,” Pawlotsky said. “I would recommend using the web resources the University of Liverpool have set up. It’s a very useful tool when you prescribe drugs.”

He added that the EASL document contains a number of tables outlining which drugs are approved in which populations along with contraindications and warnings.

Most treatments are approved for 12 or 24 weeks, usually depending on the level of compensation. The following are recommended:

  • In genotype 1a: sofosbuvir/ledipasvir, the 3D regimen, Sovaldi/Olysio (sofosbuvir, Gilead Sciences; simeprevir, Janssen) and sofosbuvir/daclatasvir are possible options. These are the therapies that are approved for genotype 1b infection, as well, with slight changes in the treatment regimens.
  • In genotype 2: options are sofosbuvir/ribavirin, sofosbuvir/daclatasvir and, where necessary peginterferon with ribavirin and sofosbuvir (rescue in failing patients).
  • In genotype 3: options are sofosbuvir/ribavirin, sofosbuvir/daclatasvir and peginterferon with ribavirin and sofosbuvir (rescue in failing patients).
  • In genotype 4: sofosbuvir/ledipasvir, sofosbuvir/simeprevir, sofosbuvir/daclatasvir and ritonavir-boosted paritaprevir with ombitasvir (without dasabuvir).
  • In genotype 5 and 6: sofosbuvir/ledipasvir, sofosbuvir/daclatasvir and peginterferon and ribavirin with sofosbuvir.

“These recommendations are based on evidence, but also when no evidence was available, the panel expressed opinions,” Pawlotsky said. “Options are provided.”

He added that the first treatment that is recommended may not be better than the second.

Also, while it would appear that the panel recommends over-treating certain populations, Pawlotsky said there was a rationale for this approach. “Treatment failure has been associated with resistance,” he said. “We want to maximize SVR rates from the beginning.”

Other recommendations

Pawlotsky said that the panel was conservative with regard to treatment monitoring. Visits are recommended at a few points during therapy, then at end of treatment and at 12 or 24 weeks after treatment. “Basically informing the patient that their viral load is going down,” he said.

Treating before transplantation is recommended to prevent graft infection, according to Pawlotsky. “However, the optimal timing of treatment — before or after transplantation — is still up for debate,” he said. “Post-transplant patients should not be treated with peg-riba.”

Clinicians should also be aware of adjustments in immunosuppression among transplant populations with some regimens.

Sofosbuvir has been associated with toxicity in patients with renal insufficiency, including ESLD. “The 3D regimen may be used in patients with severe renal impairment, but it is limited to certain genotypes.” Pawlotsky said.

Regarding retreatment, patients who failed on peginterferon and ribavirin should be treated as treatment-naive patients. “The problem is patients who failed on a DAA regimen,” he said, and noted that NS5A resistant viruses can be persistent. “This recommendation was not easy to make. The regimen should contain sofosbuvir plus one or two other DAAs.”

The clinical community is awaiting the next round of approvals. Namely, the grazoprevir/elbasvir combination (MK-5172, MK-8742; Merck) and the asunaprevir/daclatasvir/beclabuvir (Trio, Bristol-Myers Squibb) combination. “These recommendations will be updated as soon as newly approved therapies become available,” Pawlotsky said.

For More Information:

Pawlotsky JM, et al. Presented at: International Liver Congress; April 22-26, 2015; Vienna.

Disclosure: Pawlotsky reports receiving grant and research support from Gilead; being on the advisory boards of Abbvie, Achillion, Bristol-Myers Squibb, Gilead, Janssen and Merck; and speaking and teaching with Abbvie, Bristol-Myers Squibb, Gilead, Janssen, Merck and Roche.

Editor's note: This article has been updated with clarifications from the presenter.

VIENNA — The goal of HCV therapy is to eradicate infection, according to Jean-Michel Pawlotsky, MD, PhD, Coordinator of the panel that published the 2015 EASL Recommendations on the Treatment of HCV.

Pawlotsky, who is a professor at the University of Paris-Est and director of the French National Reference Centre for Viral Hepatitis B, C and Delta, said that the panel took into consideration the heterogeneity of European countries, populations, policies and medical coverage systems. But regardless of the diversity, clinicians in all countries should aim to prevent cirrhosis, decompensation, hepatocellular carcinoma and death. “The endpoint is undetectable HCV RNA,” he said during a symposium at the International Liver Congress.

Pawlotsky addressed the pressing issue of cost of HCV therapies. “The indication is that treatment-naive and treatment-experienced patients who are compensated or decompensated who are willing to be treated should be considered for therapy,” he said. “Every patient has a right to be treated.”

That said, he was realistic in that certain populations should be prioritized. Those include patients with F3 or F4 fibrosis, HIV or HBV coinfection, those who are indicated for transplantation, those who have had HCV recurrence after transplantation, patients with extrahepatic manifestations, debilitating fatigue and those who are at risk for transmitting HCV.

The indications for patients coinfected with HIV are identical to those for patients monoinfected with HCV. “However, drug-drug interactions should be taken into account,” Pawlotsky said.

Treatment is justified in patients with F2 fibrosis and can be deferred in more mild disease, he added.

Approved, recommended therapies

Key drug approvals in 2015 included the combination of sofosbuvir and ledipasvir (Harvoni, Gilead Sciences) and the ‘3D regimen’ of ombitasvir, paritaprevir and ritonavir with or without dasabuvir (Viekira Pak, AbbVie).

“Drug-drug interactions are complex and difficult to deal with, particularly in patients with comorbidities,” Pawlotsky said. “I would recommend using the web resources the University of Liverpool have set up. It’s a very useful tool when you prescribe drugs.”

He added that the EASL document contains a number of tables outlining which drugs are approved in which populations along with contraindications and warnings.

Most treatments are approved for 12 or 24 weeks, usually depending on the level of compensation. The following are recommended:

  • In genotype 1a: sofosbuvir/ledipasvir, the 3D regimen, Sovaldi/Olysio (sofosbuvir, Gilead Sciences; simeprevir, Janssen) and sofosbuvir/daclatasvir are possible options. These are the therapies that are approved for genotype 1b infection, as well, with slight changes in the treatment regimens.
  • In genotype 2: options are sofosbuvir/ribavirin, sofosbuvir/daclatasvir and, where necessary peginterferon with ribavirin and sofosbuvir (rescue in failing patients).
  • In genotype 3: options are sofosbuvir/ribavirin, sofosbuvir/daclatasvir and peginterferon with ribavirin and sofosbuvir (rescue in failing patients).
  • In genotype 4: sofosbuvir/ledipasvir, sofosbuvir/simeprevir, sofosbuvir/daclatasvir and ritonavir-boosted paritaprevir with ombitasvir (without dasabuvir).
  • In genotype 5 and 6: sofosbuvir/ledipasvir, sofosbuvir/daclatasvir and peginterferon and ribavirin with sofosbuvir.

“These recommendations are based on evidence, but also when no evidence was available, the panel expressed opinions,” Pawlotsky said. “Options are provided.”

He added that the first treatment that is recommended may not be better than the second.

Also, while it would appear that the panel recommends over-treating certain populations, Pawlotsky said there was a rationale for this approach. “Treatment failure has been associated with resistance,” he said. “We want to maximize SVR rates from the beginning.”

Other recommendations

Pawlotsky said that the panel was conservative with regard to treatment monitoring. Visits are recommended at a few points during therapy, then at end of treatment and at 12 or 24 weeks after treatment. “Basically informing the patient that their viral load is going down,” he said.

Treating before transplantation is recommended to prevent graft infection, according to Pawlotsky. “However, the optimal timing of treatment — before or after transplantation — is still up for debate,” he said. “Post-transplant patients should not be treated with peg-riba.”

Clinicians should also be aware of adjustments in immunosuppression among transplant populations with some regimens.

Sofosbuvir has been associated with toxicity in patients with renal insufficiency, including ESLD. “The 3D regimen may be used in patients with severe renal impairment, but it is limited to certain genotypes.” Pawlotsky said.

Regarding retreatment, patients who failed on peginterferon and ribavirin should be treated as treatment-naive patients. “The problem is patients who failed on a DAA regimen,” he said, and noted that NS5A resistant viruses can be persistent. “This recommendation was not easy to make. The regimen should contain sofosbuvir plus one or two other DAAs.”

The clinical community is awaiting the next round of approvals. Namely, the grazoprevir/elbasvir combination (MK-5172, MK-8742; Merck) and the asunaprevir/daclatasvir/beclabuvir (Trio, Bristol-Myers Squibb) combination. “These recommendations will be updated as soon as newly approved therapies become available,” Pawlotsky said.

For More Information:

Pawlotsky JM, et al. Presented at: International Liver Congress; April 22-26, 2015; Vienna.

Disclosure: Pawlotsky reports receiving grant and research support from Gilead; being on the advisory boards of Abbvie, Achillion, Bristol-Myers Squibb, Gilead, Janssen and Merck; and speaking and teaching with Abbvie, Bristol-Myers Squibb, Gilead, Janssen, Merck and Roche.

Editor's note: This article has been updated with clarifications from the presenter.

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