DAA treatment reduces the risk of death and liver cancer in France

Direct-acting antiviral (DAA) treatment for hepatitis C was introduced in France from 2012, and the most effective regimens deliver almost universal cure rates. Many countries are now moving to implement testing and treatment programmes designed to eliminate hepatitis C as a significant cause of illness and death by 2030, by seeking to diagnose and treat everyone with the infection.

However, a systematic review by the Cochrane Collaboration concluded that trials of DAAs did not provide enough evidence to conclude that curing hepatitis C reduced risks of death or clinical illness. The review was strongly criticised by liver experts, including the American Association for the Study of Liver Diseases, for the short follow-up period of the studies selected and the lack of statistical power to detect differences in death rates in relatively small studies.

Now, a study carried out by French researchers in a large national cohort followed over several years, shows that DAA treatment is associated with a 61% reduction in the risk of liver-related death, a 52% reduction in the risk of death from any cause and a 34% reduction in the risk of hepatocellular carcinoma.

In an accompanying Comment article, Jacinta Holmes, Stephanie Rutledge and Raymond Chung say “these findings firmly counter those of a Cochrane review of direct-acting antiviral treatment trials that could neither confirm nor reject if direct-acting antivirals had an effect on long-term HCV-related morbidity and mortality. They also provide the best evidence to date to support guidance documents that recommend direct-acting antiviral treatment for all patients with chronic HCV infection.”

Experimental therapy improves liver health in people with fatty liver disease

Efforts to bring to market a treatment for non-alcoholic steatohepatitis (NASH) saw one success and one setback in February. NASH is the result of fat accumulation in the liver. A minority of people with non-alcoholic fatty liver disease (NAFLD) eventually develop liver damage, or fibrosis, and may eventually develop cirrhosis.

The global burden of severe liver disease due to NASH is projected to double by 2030 and one model suggests that 376,000 people in the United States will develop decompensated cirrhosis in 2030 alone as a result of NASH. Finding effective treatments to reverse the condition is a major challenge; pharmaceutical companies also see it as a lucrative market.

Intercept Pharmaceuticals reported a successful outcome in a phase 3 study of its treatment obeticholic acid (OCA). More people receiving OCA (23%) experienced an improvement in liver fibrosis compared to those who received a placebo (12%) in a 993-person study. However, just over half of participants experienced itchy skin and 5% experienced severe itching. Intercept will now file for registration of OCA as a treatment for NASH in the United States.

Gilead Sciences reported disappointing results from its phase 3 study of selonsertib. The highest dose of the drug was no more effective than a placebo in reversing liver fibrosis in people with NASH.

Immunotherapy combinations show promise for liver cancer

Checkpoint inhibitor immunotherapy combinations may slow disease progression in people with hepatocellular carcinoma, according to two small studies presented at the 2019 Gastrointestinal Cancers Symposium in San Francisco in January. However, response rates remain low for this difficult-to-treat cancer.

One study showed that a combination of durvalumab and tremelimumab resulted in control of cancer progression in 70% of people treated, although the median survival time in this group of patients with advanced liver cancer was 15.9 months.

Another small study showed that the use of nivolumab alone or in combination with ipilimumab alongside surgery to remove liver tissue affected by cancer in patients with less advanced cancer was associated with no tumour recurrence in three out of eight people.

A larger phase 3 study of a checkpoint inhibitor as treatment for liver cancer produced less promising results. The study of Keytruda (pembrolizumab) found that people who received the drug did not live longer and experienced progression of liver cancer just as quickly as people who received a placebo. Participants in this study had advanced hepatocellular carcinoma.

Generic treatment and hepatitis C elimination in Egypt

Egypt has the highest prevalence of hepatitis C in the world and the Egyptian government has mounted a large-scale national campaign to diagnose and treat hepatitis C, using generic versions of direct-acting antivirals (DAAs). Approximately 10% of the Egyptian population has chronic hepatitis C virus (HCV) infection and 95% of these individuals carry HCV genotype 4.

Egyptian researchers reported on the use of generic versions of the DAAs sofosbuvir (SOF), ledipasvir (LDV) and daclatasvir (DAC) in the journal Liver International. The retrospective study found that 98% of people treated with generic DAAs were cured. Average treatment costs of SOF/DAC and SOF/LDV were $85 and $141, respectively. The authors note that a single course of therapy with branded medications, even with a substantial drug company discount, would cost in the region of $1500.

In an interview with IS Global, Dr Ammal Metwally, research professor of public health and preventative and community medicine at the Egyptian National Research Centre, described how her group is working with the Egyptian government and community groups on village-level elimination plans for hepatitis C. The scheme offered free screening for nearly half a million people and free treatment and care for all diagnosed cases. Sixty-three villages were declared free from viral hepatitis in 2018.

Hepatitis C cure does not improve long-term glucose control

A successful response to hepatitis C virus (HCV) therapy does not result in long-term improvements in glucose metabolism for people with type 2 diabetes, according to US research published in Liver International.

Type 2 diabetes is common in people with hepatitis C. A recently published meta-analysis found that prevalence ranged from 15% in European patients to 20% in Asian patients.

The study looked at 384 people in the US Chronic Hepatitis Cohort Study who had chronic hepatitis C and type 2 diabetes and followed them for a median of 30 months.

A sustained virological response (SVR) was associated with a short-term improvement in a key marker of glucose control, but these improvements were not sustained in the longer-term and within three years glucose control was comparable between people with an SVR and individuals who did not receive any HCV therapy or who had an unsuccessful treatment response.

Tackling HIV and hepatitis C in Europe: towards minimum standards

Efforts to eliminate hepatitis C in Europe are being held back by lack of harm reduction services and the lack of plans to diagnose the infection, a European meeting on standards of care in hepatitis and HIV heard in January.

In Eastern Europe and Central Asia modelling shows that direct-acting antiviral (DAA) availability will not have a large impact on hepatitis C transmission. In contrast simply providing needle and syringe exchange would reduce infections by 10 to 25% and adding opioid substitution therapy (OST) to that would reduce infections by 45 to 55%. Adding in DAAs to that would further reduce new infections, but not by all that much: about 5% more. Finally, if targeted screening programmes were also added, reductions could range from 55% in Tajikistan to 70% in Moldova.

Dr Michel Kazatchkine, UN Special Envoy on HIV in central and eastern Europe, said: “We’re in a region where 1.9 million people who inject drugs have hepatitis C and 750,000 of those have HIV. One per cent of them are accessing OST, and the average annual allocation of clean syringes is 15 each. This is a health emergency.

“Physicians have to be more vocal about this. Where there is a conflict between legislation and public health, it is legislation that should be changed.”

Improving the uptake of hepatitis C care in people who inject drugs

People attending specialist addiction centres in England where a facilitator enabled access to hepatitis C care services were ten times more likely to be referred to hepatology services and to start treatment for hepatitis C virus (HCV), a pilot study found. The study findings are published in advance online in the journal Addiction.

The prevalence of hepatitis C is high among people who inject drugs but rates of diagnosis, engagement in care and treatment tend to be low unless special efforts are made to overcome barriers in engagement in health care and treatment.

The Hepatitis C – Awareness Through to Treatment (HepCATT) study was designed to test the effect of placing a facilitator in specialist addiction clinics on engagement in care and treatment. The facilitator was expected to carry out a range of actions that might improve engagement, but the precise mix of activities was not specified in advance for each clinic.

The facilitators undertook a range of activities designed to improve the offer of testing and engagement with care. These included:

  • Conducting training on hepatitis C natural history and treatment for all clinic staff in direct contact with people who inject drugs.
  • Training on how to engage clinic clients in pre- and post-test discussions.
  • Direct engagement with clients to talk about HCV testing, treatment and care.
  • Scheduling of hepatology clinic appointments to align with addiction clinic appointments, especially for those receiving opioid substitution therapy.
  • Active follow-up of all clients who had not been tested for hepatitis C.
  • Active reminder system for appointments and re-booking of appointments when the client missed one (this was thought to be the most effective intervention at two out of three centres).
  • Establishment of peer support system to help attendance at appointments.
  • Introduction of dried blood spot sampling for HCV testing.

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