Fifty-two per cent of surveyed European (25) and Mediterranean Basin (2) countries lack national strategies to address viral hepatitis B or C despite the World Health Organization World Health Assembly resolution calling on all countries to have one. Only three of these countries have access to the new, highly effective medicines (direct-acting antivirals) for hepatitis C without restrictions.

These are just two sobering results from The 2016 Hep-CORE Report on the state of viral hepatitis policy and practice in Europe, released by the European Liver Patients Association (ELPA) in December 2016.

The research also found that patient groups from ten countries (37%) reported that there are no hepatitis C virus (HCV) testing or screening sites outside of hospitals for the general population in their countries. Even more alarming, patient groups from 12 of the countries (44%) reported that there are no such sites outside of hospitals that provide testing or screening services for high-risk populations.

In its design of the report, ELPA has taken a unique approach. The data were collected from local specialists in each country. The research team asked one patient group in each of ELPA’s 27 member-countries to complete a 39-item survey about various aspects relating to hepatitis B virus and HCV: overall national response, public awareness and engagement, disease monitoring and data collection, prevention, testing and diagnosis, clinical assessment, and treatment.

Direct-acting antiviral treatment and kidney disease

Edward Gane, presenting at AASLD 2016. Photo by Liz Highleyman, hivandhepatitis.com

People who achieved sustained virological response (SVR) to interferon-based hepatitis C treatment experienced significantly less decline in kidney function, especially if they had liver cirrhosis, according to study findings presented at the 2016 AASLD Liver Meeting last November in Boston.

People with chronic hepatitis C have an increased risk of chronic kidney disease and experience more rapid kidney disease progression, though the reasons for this effect are not well understood.

A study of kidney function in 3258 people treated for hepatitis C between 2004 and 2014 in Kaiser Permanente Southern California and Mid-Atlantic clinics found that people cured of hepatitis C had significantly smaller reductions in kidney function during an average follow-up period of four years when compared to people who were not cured. The effect of successful treatment was most pronounced in people with cirrhosis.

"SVR reduced the average annual rate of renal decline by half and the risk of ESRD [end-stage renal disease] by almost 87%," Dr Carla Rodriguez of Kaiser Permanente told the conference.

For people who already have advanced kidney disease, hepatitis C treatment options are somewhat limited by the need to avoid sofosbuvir. The drug is excreted through the kidneys and impaired kidney function can lead to high blood levels of sofosbuvir. Alternative regimens are recommended for people with advanced kidney disease.

A two-drug pangenotypic regimen combining AbbVie's glecaprevir and pibrentasvir demonstrated a high sustained response rate for people with chronic hepatitis C who have severe kidney impairment, according to results from the EXPEDITION-4 study presented at the 2016 AASLD Liver Meeting last November in Boston. The combination cured 98% of people enrolled in the study. The results from EXPEDITION-4 show that glecaprevir/pibrentasvir, when approved, could be a good pangenotypic option for this population.

The RUBY-I study, also presented at The Liver Meeting, showed that the 3D regimen of paritaprevir/ritonavir/ombitasvir plus dasabuvir (Viekirax + Exviera) taken for 12 weeks cured 100% of people with genotype 1b with severe kidney impairment or end-stage renal disease. In the RUBY-II study, the 3D regimen for 12 weeks without ribavirin demonstrated a 100% SVR12 rate for people with severe kidney disease with genotype 1a.

Liver transplant demand

People successfully treated for hepatitis are less likely to need liver transplants and less likely to die while on a transplant waiting list, according to studies presented at the 2016 AASLD Liver Meeting.

A study of people waiting for liver transplants in the United States found a 22% reduction in the risk of death among people with the hepatitis C virus (HCV) waiting for a liver transplant since 2014 when compared to people listed for a transplant between 2009 and 2014. In comparison the risk of death fell by only 3% in people without HCV. The decline in the risk of death was greater in people with HCV who had the highest MELD scores (indicating severe decompensation).

A second study of people waiting for a transplant in the United States found that the number of people put on a waiting list for a liver transplant due to decompensated cirrhosis fell by 32% in 2014 to 2015 compared to the period 2003 to 2010.

The authors of both studies say that the availability of direct-acting antivirals for hepatitis C treatment explains the declining need for liver transplants among people with HCV. However, the statistics may not tell the full story. A debate continues among liver specialists regarding the best time to treat hepatitis C in people on the transplant waiting list. On the one hand, treatment may improve liver function (as measured by MELD score) sufficiently that a person no longer qualifies for a transplant. Nevertheless, people with advanced cirrhosis who experience improvement will remain at high risk for liver cancer and other complications of cirrhosis – which may ultimately require liver transplantation. On the other side of the debate, some argue that it is better to treat hepatitis C after transplantation due to these risks. Of course, it is also possible that treatment may improve liver function sufficiently that people live long enough to benefit from a liver transplant.

Liver cancer treatment

Bruno Sangro, presenting at AASLD 2016. Photo by Liz Highleyman, hivandhepatitis.com

Nivolumab (Opdivo), an antibody that blocks the PD-1 receptor and restores T-cell anti-tumour activity, appeared safe and was associated with disease control and stabilisation in a phase 1/2 study of people with hepatocellular carcinoma, according to late-breaking results from the CheckMate 040 study presented at the 2016 AASLD Liver Meeting.

Hepatocellular carcinoma (HCC) is often diagnosed late when it is difficult to treat, and it is a leading cause of cancer death worldwide. Sorafenib (Nexavar), a multikinase inhibitor, is the standard of care for HCC that cannot be surgically removed or resected, but it typically extends survival by only a few months and more effective therapies are urgently needed.

Nivolumab is a human IgG4 monoclonal antibody that blocks PD-1 (programmed death protein 1). By blocking the PD-1 receptor or its ligand (binding partner) PD-L1, checkpoint inhibitors like nivolumab can re-enable immune responses against tumour cells.

In the phase I/II studies around two-thirds of people experienced reversal or stabilisation of liver cancer. Median survival time among those treated in the first phase of the study was 14 months.

Investigator Bruno Sangro said that the study "challenges the assumption that immune therapy cannot be effective for patients with a high tumour burden.”

A randomised phase 3 study, CheckMate 459, comparing nivolumab to sorafenib for first-line treatment of people with advanced HCC is now enrolling.

Vemlidy for hepatitis B approved in European Union

Image: Gilead Sciences

The European Commission has granted marketing authorisation for tenofovir alafenamide, to be sold under the brand name Vemlidy, for the treatment of chronic hepatitis B virus (HBV) infection.

Tenofovir alafenamide or TAF is a new pro-drug formulation that produces high levels of the active drug in liver cells with smaller doses than tenofovir DF (Viread), the earlier formulation. This means lower tenofovir concentrations in the blood and less drug exposure for the kidneys, bones, and other organs and tissues. While nucleoside/nucleotide analogues like tenofovir suppress HBV replication during treatment, they usually do not lead to a cure and long-term therapy is generally required. This is also the case with TAF, which is a nucleotide analogue. Research presented at the 2016 AASLD Liver Meeting showed that people with hepatitis B treated with TAF experienced less decline in bone mineral density than people treated with TDF.

Counterfeit Harvoni found in Japan

Japan’s Ministry of Health has warned that fake versions of the hepatitis C drug combination Harvoni are circulating in Japan, following the discovery of fake pills earlier this month. Investigations show that fake pills have been supplied in genuine Harvoni pill bottles. Genuine Harvoni tablets are diamond-shaped, orange, and marked "GSI" or "7985." Fakes discovered so far are either oval or round, and either light yellow or light purple.

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