A survey of physicians in France, Germany, Italy, Spain and the United Kingdom by Decision Resources Group has found substantial differences in access to new direct-acting antivirals, especially among people with hepatitis C virus (HCV) with less advanced liver disease. Physicians surveyed said that “two-thirds of their genotype-1 and -2/3 HCV patients are non-cirrhotic and thus are not prioritized for treatment.” The survey found that 45% of people with genotype 1 HCV who did not have cirrhosis (‘non-cirrhotic’) and had not taken treatment before (‘treatment-naive’), who were in the care of UK physicians who responded to the survey were being treated with interferon dual therapy or first-generation protease inhibitor triple therapy.

Cost of treatment remains a major barrier. In the United Kingdom, the National Institute for Health and Care Excellence (NICE) confirmed last month that sofosbuvir/ledipasvir (Harvoni), daclatasvir (Daklinza) and Viekirax & Exviera will be made available for treatment of people with HCV genotype 1 and 4 who do not have cirrhosis, in addition to existing recommendations regarding people who have cirrhosis. Sovaldi and Daklinza will be available only to people with genotype 3  who have advanced liver disease. However, NICE said that clinical teams will still be expected to prioritise which patients should receive treatment first, which means that the number of people who can be treated each year will be determined by the prices for drugs negotiated by NHS England.

Further controversy over the cost of hepatitis C treatment in the United States has been stirred by a US Senate Finance Committee report which condemns Gilead’s pricing strategy for sofosbuvir (Sovaldi) and sofosbuvir/ledipasvir (Harvoni).

Introducing the report, Senator Ron Wyden told journalists, “Gilead pursued a calculated scheme for pricing and marketing its Hepatitis C drug based on one primary goal, maximizing revenue, regardless of the human consequences. There was no concrete evidence in emails, meeting minutes or presentations that basic financial matters such as R&D [research and development] costs or the multi-billion dollar acquisition of Pharmasset, the drug’s first developer, factored into how Gilead set the price. Gilead knew these prices would put treatment out of the reach of millions and cause extraordinary problems for Medicare and Medicaid, but still the company went ahead.”

Their central criticism is that Gilead’s pricing strategy has created enormous financial pressures for America’s two publicly funded insurance systems, Medicaid and Medicare. Much of the cost of hepatitis C treatment in the United States is likely to occur during the next five years, according to research presented at The Liver Meeting last month (the annual meeting of the American Association for the Study of Liver Diseases). The cost of treating hepatitis C is likely to decline dramatically over the next decade in the United States, not because of cuts in drug prices but because the population in need of treatment will shrink by 2020 as a majority of patients will already have been treated, according to research by Jagpreet Chhatwal of Massachusetts General Hospital.

HCV spending peaked in the United States in 2015 at $21 billion and will decline to around $4 billion per year in 2020, Chhatwal estimates. Approximately 80% of spending ($17 billion) in 2015 went toward direct-acting antivirals, mainly sofosbuvir (Sovaldi) and sofosbuvir/ledipasvir (Harvoni). By 2020, the cost of direct-acting antiviral treatment will fall to $2 billion due to the declining number of people in need of treatment.

Another model published in the online edition of Clinical Infectious Diseases in December found that a four-fold increase in treatment rates could prevent over a quarter of a million HCV-related deaths by 2040. It found that prevalence could be reduced by 90% with the scaling up of screening efforts, especially the targeting of people who inject drugs. But the investigators caution that elimination of the epidemic with direct-acting antivirals would require near-universal testing and a 20% annual treatment rate. The model did not look at how much it would cost to eliminate hepatitis C.

Month-by-month tracking of the prices paid in India for the chemicals used to make hepatitis C direct-acting antivirals shows that it is now possible to make and sell a combination of drugs to cure hepatitis C for less than $200, Dr Andrew Hill of Liverpool University told the Second European HIV Hepatitis Co-infection Conference in London last week.

If those drugs were bought at list price in the United States they would cost approximately $147,000 for a 12-week course of treatment – $84,000 for sofosbuvir (Sovaldi), manufactured by Gilead Sciences, and $63,000 for daclatasvir (Daklinza), manufactured by Bristol-Myers Squibb.

Tracking of shipments of active pharmaceutical ingredients (APIs) by indiainfodrive.com, a reporting mechanism for importers and exporters, shows that the value of shipments of the APIs that are used to make sofosbuvir, the world’s most frequently prescribed hepatitis C direct-acting antiviral, had fallen from around $8000 per kilogram in January 2015 to around $2000 per kg by September 2015.

Generic versions of hepatitis C drugs are already available in India at prices of $200 to $400. These findings suggest that prices could fall further if the number of people treated increases, and also show how cheaply these drugs can be produced.

The availability of generic hepatitis C drugs in India has led Australians with hepatitis C to begin importing these products, due to lack of access in Australia. The FixHepC buyers club is able to provide detailed information on how to import these drugs legally into Australia, New Zealand, United Kingdom and United States, where laws permit the import of small amounts of medication for personal use. Laws differ in other countries.

The FixHepC buyers club also warns people of the risks of importing products bought on the internet, and the advisability of carrying out some form of testing to ensure that the ingredients in the tablets correspond to the chemical ‘signatures’ of the drugs already established by independent laboratories in Australia.

Drinking coffee was associated with lower liver stiffness – a non-invasive measure used to estimate liver fibrosis – in people with hepatitis B, hepatitis C and non-alcoholic fatty liver disease (NAFLD), research presented at the Liver Meeting showed.

In prior studies, coffee consumption has been linked to a wide range of health benefits including reduced risk of type 2 diabetes, metabolic syndrome and several types of cancer, the researchers noted as background. It may have a particularly beneficial effect on the liver, being associated with lower liver enzyme levels and reduced cirrhosis and liver cancer. It is not yet known whether these benefits are related to caffeine or other components of coffee such as antioxidants or other phytochemicals. Some studies suggest caffeine and other chemicals in coffee may dampen inflammation and reduce collagen production.

In this study, people with hepatitis C who drank two or more cups of coffee daily had a 13% reduction in liver stiffness after taking into account confounding factors including age, sex, weight, alcohol consumption and smoking – a significant association. People with hepatitis B who drank four or more cups of coffee had a significant 18% reduction in liver stiffness in an adjusted analysis including ALT (alanine transaminase). There were no significant associations between coffee consumption and CAP (controlled attenuation parameter) scores among people with hepatitis B or C.

Among people with NAFLD, those who drank four or more cups of coffee daily had a 24% decrease in liver stiffness.

The number of hepatitis C virus (HCV)-related referrals for liver transplant has declined significantly since the introduction of HCV direct-acting antivirals, according to two US studies presented to The Liver Meeting. The approval of the second generation of direct-acting antivirals was accompanied by a 23% reduction in the proportion of liver transplant referrals that were HCV related.

There was a significant 33% reduction in the proportion of referrals related to HCV that had not yet progressed to non-hepatocellular carcinoma (HCC). The investigators suggest their findings are early evidence of the clinical impact of direct-acting antivirals.

However, a study of the impact of direct-acting antiviral treatment on liver transplant waiting list numbers in France found that despite improvements in liver function as a result of treatment, and a high cure rate, only 16% of candidates with decompensated cirrhosis due to hepatitis C were taken off the list as a result of treatment.

Response-guided therapy using an all-oral regimen of three direct-acting antivirals cured a majority of people with easier-to-treat genotype 1b hepatitis C in just 3 weeks, according to results from the small SODAPI pilot study, presented in a late-breaking poster at The Liver Meeting. Further research will be needed to see if these promising results are borne out in larger patient populations.

Participants were randomly assigned to receive three-drug regimens consisting of the NS5B nucleotide polymerase inhibitor sofosbuvir (sold separately as Sovaldi), one of the NS5A replication complex inhibitors ledipasvir (sold in combination with sofosbuvir as Harvoni) or daclatasvir (Daklinza), and one of the HCV NS3/4A protease inhibitors asunaprevir (Sunvepra) or simeprevir (Olysio).

Participants with rapid virological response (RVR), defined as HCV RNA < 500 IU/ml by day 2, stopped treatment after 3 weeks, while the remainder continued for 8 to 12 weeks.

Overall, 18 participants (67%) – six in each treatment arm – experienced RVR at day 2 of therapy. By week 3, all participants in all treatment arms had HCV RNA below the limit of quantification. All 18 people who had RVR at day 2 and completed treatment at 3 weeks achieved SVR12 (sustained virological response twelve weeks after the end of treatment).

People who achieved RVR had lower baseline viral load on average than those without RVR (about 6 vs 7 log IU/m), and were less likely to have high baseline viral load (55% vs 100%, respectively) – these were the only significant predictors.

Compared to standard treatment using sofosbuvir/ledipasvir for 8 weeks or sofosbuvir plus daclatasvir for 12 weeks, the researchers calculated that the 3-week regimen could save between $37,454 and $107,045 per patient.

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