World Hepatitis Day: steps towards elimination

World Hepatitis Day takes place every year on 28 July. News highlights from this year include:

  • Elimination of viral hepatitis by 2030 is a global health target endorsed by the World Health Assembly. World Health Organization (WHO) data on 28 countries representing 70% of the global burden of viral hepatitis show that more than 86% of countries reviewed have set national hepatitis elimination targets and more than 70% have begun to develop national hepatitis plans to enable access to effective prevention, diagnosis, treatment and care services. Furthermore, nearly half of the countries surveyed are aiming for elimination through providing universal access to hepatitis treatment.

Drug prices: time to shift from talking about high prices to low production costs

Dzintars Gotham presenting at IAS 2017. Image credit: Enzo Poultreniez /

Protests against the high cost of hepatitis C drugs may be having the paradoxical effect of discouraging access to treatment rather than promoting access, one of Australia’s leading researchers on hepatitis C told last month’s 9th International AIDS Society Conference on HIV Science (IAS 2017) in Paris.

"One of the most important things we have to do is re-frame [the debate about hepatitis C drug prices]. The focus on $1000 a pill has done us a disservice with donors. We need to be talking about a $150 course of treatment," said Professor Margaret Hellard, Deputy Director of the Burnet Institute, Melbourne.

In fact, research presented at the conference shows that a course of treatment for hepatitis C could be delivered for $47 in countries where generic versions of hepatitis C drugs can be used. Using data on the costs of the raw materials used to manufacture direct-acting antivirals, and on the costs of production, researchers calculated that even including a 10% profit margin, generic manufacturers could make sofosbuvir/daclatasvir available for $47 and sofosbuvir/ledipasvir for $79. Hepatitis B treatment with entecavir would cost $82 a year. What’s missing is funding for treatment and awareness among governments and donors of how affordable treatment for hepatitis C could be.

Awareness of the costs of production might also encourage governments in upper-middle income and higher income countries to adopt a tougher stance in price negotiations and start thinking in terms of their strategic aims for public health, several panellists at a conference symposium on drug costs argued.

"One of the jobs of government should be negotiating hard for the best price and not just accepting the price offered," said Margaret Hellard. "We need our governments to make strong and brave decisions on behalf of their people."

Hepatitis C: DAA treatment and mortality

For the first time, a large study has demonstrated that sustained virologic response 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 a control group of people not receiving therapy. Mortality rates in the first 18 months were significantly lower among people who received DAAs. After controlling for other factors, treatment with DAAs was associated with a 57% reduction in the risk of death. Among those who were treated, cure was associated with a 43% reduction in the risk of death. (Although these figures give the impression that treatment had a greater impact than cure, they are not comparable because they refer to a reduction in risk in two different populations, all people with hepatitis C and all people treated.)

The study appeared shortly after the publication of a systematic review by the Cochrane Collaboration which concluded that there was no evidence that DAA treatment reduced the risk of death or serious illness. That review was strongly criticised by the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD).

A second study, published recently in the journal Gut, found that the risk of several non-liver complications associated with chronic HCV infection is reduced after interferon-based treatment that achieves a sustained virological response.

The study found that curing hepatitis C with interferon-based treatment significantly reduced the risk of developing non-Hodgkin lymphoma, mixed cryoglobulinaemia, glomerulonephritis, porphyria cutanea tarda and type 2 diabetes, and of suffering a stroke.

Treatment was only protective against the risk of glomerulonephritis and stroke if started within one or two years of infection with HCV. Treatment was only beneficial in reducing the risk of non-Hodgkin lymphoma if started within a year of infection.

Vosevi approved in the European Union and United States

On 18 July the US Food and Drug Administration approved Gilead Sciences' Vosevi, a new once-daily combination pill containing sofosbuvir, velpatasvir, and voxilaprevir. Vosevi was approved as "salvage therapy" for people with all hepatitis C virus (HCV) genotypes who were not previously cured with prior direct-acting antiviral (DAA) therapy.

On 28 July the European Commission approved Vosevi for the treatment of adults with genotype 1 to 6 chronic HCV infection.

Vosevi was authorised for marketing in the European Union as:

  • An 8-week regimen for previously untreated people without cirrhosis.
  • An 8-week regimen for previously untreated people with compensated cirrhosis.
  • A 12-week regimen for people with any genotype of chronic HCV infection, without cirrhosis or with compensated cirrhosis (Child-Pugh class A), who have previously experienced treatment failure with a DAA-containing regimen.

Maviret approved in the European Union and United States

The European Commission and the US Food and Drug Administration last month approved AbbVie's new combination pill for people with hepatitis C virus (HCV) genotypes 1 to 6, to be marketed as Maviret in the European Union and as Mavyret in the United States.

Maviret is a fixed-dose co-formulation containing the NS3/4A protease inhibitor glecaprevir and the NS5A inhibitor pibrentasvir; both drugs are being approved for the first time.

Maviret is indicated for previously untreated people, or those treated with prior interferon-based therapy, who have HCV genotypes 1, 2, 3, 4, 5 or 6 and who either do not have liver cirrhosis or have compensated cirrhosis (Child-Pugh class A).

In the European indication, Maviret is not recommended for retreatment of people who previously used NS3A/4A protease inhibitors or NS5A polymerase inhibitors. In the US indication, it is approved for adults with HCV genotype 1 who were previously treated with either an NS3/4A inhibitor or an NS5A inhibitor, but not both. This means that Maviret/Mavyret should not be used after Harvoni or Epclusa.

Maviret is not recommended for people with significant liver function impairment (Child-Pugh class B), and it is contraindicated for those with decompensated cirrhosis (Child-Pugh class C).

In the United States AbbVie has announced that the price of Mavyret will be set at $26,400 for an 8-week course of the drug. This price is lower than the best price negotiated for sofosbuvir/ledipasvir (Harvoni) by one of the largest healthcare payers in the United States, the Veterans Affairs Administration and is likely to stimulate demands by insurers for cuts in the prices of other drugs. Prices for Maviret have not been announced yet for European Union countries.

Epclusa use expanded to people with HIV co-infection in the United States

The US Food and Drug Administration (FDA) announced on 1 August that the indication for use of Epclusa now includes use in people with HIV and genotype 1 to 6 chronic hepatitis C virus co-infection without cirrhosis or with compensated cirrhosis, or with decompensated cirrhosis in combination with ribavirin.

Harvoni licence extended to adolescents aged 12-18 years in European Union

The indication for Harvoni in the European Union has been extended to include the treatment of chronic hepatitis C virus genotype 1, 3, 4, 5 and 6 infection in adolescents aged 12 to < 18 years.

Hepatitis C treatment in Africa

Karine Lacombe of Saint-Antoine Hospital, Paris, at IAS 2017. Photo by Liz Highleyman,

Treatment for hepatitis C in sub-Saharan Africa can produce cure rates as high as those seen in industrialised countries, with high adherence and minimal side-effects, according to a presentation last month at the 9th International AIDS Society Conference on HIV Science (IAS 2017) in Paris, France.

The TAC ANRS 12311 trial, sponsored by the French National Agency for Research on AIDS and Viral Hepatitis (ANRS), assessed the feasibility, efficacy and safety of interferon-free direct-acting antiviral treatment in Cameroon and Ivory Coast. Starting in October 2015, this open-label study enrolled 120 adults who had not previously been treated for hepatitis C.

After 12 weeks of post-treatment follow-up, 89% achieved sustained virological response (SVR12), or continued undetectable hepatitis C virus (HCV) RNA, considered a cure. Cure rates were 88% for genotype 1, 90% for genotype 2 and 89% for genotype 4. The SVR12 rate was a bit lower for those with cirrhosis, at 78%. HIV co-infection had no impact on efficacy, adherence or safety.

Based on these findings, "It is time to scale up HCV screening and advocate for treatment access for those in need in resource-limited countries, to make global HCV elimination a reality for all," the researchers concluded.

Non-alcoholic fatty liver disease in people living with HIV

Liver disease is now a leading cause of serious illness and death in people with HIV. Until now, much of the liver disease occurring in people living with HIV has been associated with co-infection with hepatitis B or C, but non-alcoholic fatty liver disease (NAFLD) is emerging as a new concern in the management of individuals with HIV infection who do not have hepatitis B or C co-infection.

The condition is defined by the accumulation of fat in the liver and the presence of triglycerides in liver cells in the absence of a cause such as excess alcohol consumption. NAFLD may progress to non-alcoholic steatohepatitis (NASH), in which the liver becomes inflamed and liver cells are damaged, and possibly to fibrosis and cirrhosis (death of liver tissue and scarring) or to liver cancer. NAFLD also increases the risk of developing cardiovascular disease.

Numerous pharmaceutical treatments for NASH are being investigated in clinical trials but it is far from clear which types of drugs are likely to prove effective, and if treatment of NASH will have any long-term impact on mortality and serious illness due to liver disease or cardiovascular disease.

In HIV-negative individuals, NAFLD is usually associated with metabolic syndrome including obesity, insulin resistance and elevated lipids. Global prevalence of NAFLD is estimated at 25%, with prevalence higher in people with type 2 diabetes.

Over a third of people with HIV have NAFLD in the absence of hepatitis B or C, according to a new study published last month in the journal AIDS. Metabolic disorders including high body mass index (BMI), diabetes and elevated lipids were key risk factors. The study also revealed high prevalences of NASH and liver fibrosis, possible outcomes of NAFLD, with metabolic disorders once again shown as the most important factors.

The researchers conclude that:

  • NAFLD is common in people with HIV, but more studies with good-quality biopsy data are needed to give a clearer idea of its prevalence.
  • People with features of metabolic syndrome should be thoroughly investigated for NAFLD.
  • Lifestyle changes are the mainstay of treatment for NAFLD, but few people manage to achieve the changes needed to remedy the disorder. People with HIV should, therefore, be allowed to participate in clinical studies investigating experimental drug therapies for the condition.

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