FDA warns of rare cases of serious liver injury with newer hepatitis C drugs

The US Food and Drug Administration (FDA) has issued a warning about the risk of serious liver injury in people with hepatitis C after starting recently approved direct-acting antiviral regimens that contain a hepatitis C virus protease inhibitor. The drug regimens are Zepatier (grazoprevir/elbasvir), Mavyret (glecaprevir/pibrentasvir) and Vosevi (sofosbuvir, velpatasvir and voxilaprevir).

FDA has received 63 reports of cases in which people with hepatitis C suffered worsening liver function or liver failure.

In many of the reported cases, liver failure occurred in people who had signs and symptoms of moderate to severe liver impairment (Child-Pugh B or C) or other serious liver problems and should not have been treated with these medicines.

In some cases, people were reported to have no cirrhosis or compensated cirrhosis with mild liver impairment (Child-Pugh A) despite having evidence of decreased platelets at baseline or an increase in the pressure within the portal vein that carries blood from the digestive organs to the liver.

In addition, some cases had other significant pre-existing risk factors such as liver cancer, alcohol abuse, or serious medical illnesses associated with serious liver problems.

These factors may have contributed to clinical worsening of liver function or liver failure during treatment with these hepatitis C medicines. In most cases, liver failure or decompensation typically occurred within the first four weeks of starting treatment.

FDA says that doctors can continue prescribing the drugs to people with mild cirrhosis (Child-Pugh A) but should monitor patients closely, especially if they are abusing alcohol or have liver cancer (hepatocellular carcinoma).

The agency emphasises that these medicines have been widely used and are safe and effective in people with no or mild liver impairment.

To put the number of cases of liver injury in context, FDA reports that 83,000 people in the United States underwent treatment for hepatitis C with one of the medications in 2018.

Voluntary licensing of hepatitis C drugs has led to more people on treatment

Late diagnosis of hepatitis C

Late diagnosis of hepatitis C, after the development of liver cirrhosis, is a major contributor to liver-related illness and deaths from end-stage liver disease.

A study conducted in the United States, published recently in The American Journal of Managed Care, highlights the extent of late diagnosis and its consequences.

The study found that doctors are failing to test for hepatitis C in up to one in five people who have advanced liver disease despite many years of medical care, and these people are more likely to have hospital stays after hepatitis C diagnosis.

Late diagnosis was even more common among people born between 1945 and 1965, all of whom should have been screened for hepatitis C under US Centers for Disease Control and Prevention guidelines. One in four were diagnosed late despite often having raised liver enzymes on previous laboratory tests. In some cases, patients had evidence suggesting cirrhosis on laboratory tests five years prior to hepatitis C diagnosis.

“Patients with undiagnosed cirrhosis are being followed in health systems for years prior to receiving a diagnosis of HCV [hepatitis C virus], but waiting until it is clear that liver disease is present is a failed strategy for reducing morbidity and health costs,” the study authors conclude.

“These patients are losing the opportunity to access the healthcare appropriate for those with cirrhosis, such as vaccinations, screening for liver cancer and oesophageal varices, and counselling about the risks of common medications or foods in those with cirrhosis.”

Hepatitis B raises the risk of some cancers

Chinese people with chronic hepatitis B infection had an increased risk of several digestive system cancers, especially stomach cancer, researchers report in JAMA Network Open.

Around 250 million people are living with hepatitis B worldwide, but only 10% have been diagnosed. Approximately one in three people with hepatitis B live in China.

Hepatitis B virus is estimated to cause around 80% of all liver cancers (hepatocellular carcinoma) as a result of persistent infection of liver tissue by the virus. Some cohort studies have found an increased risk of several other cancers in people with chronic hepatitis B infection, notably lymphoma and pancreatic cancer.

The study of cancers in Chinese people looked at several large cohorts that included approximately 567,000 people. Researchers found that, in addition to hepatocellular carcinoma, people with hepatitis B were also at higher risk of developing several other cancers. The cohorts were analysed separately. Results from the largest cohort showed that hepatitis B infection was associated with a higher risk of stomach cancer, colorectal cancer, pancreatic cancer, oral cavity cancer and lymphoma. In the smaller cohort, the only cancer to show a significant relationship to hepatitis B apart from liver cancer was stomach cancer, owing to the low incidence of other cancers.

Researchers found that samples of stomach cancer tumours showed evidence of hepatitis B infection, but not of virus replication. Viral proteins were not present in surrounding tissue also included in the samples. They say that more work is needed to establish how hepatitis B might cause cancers outside liver tissue.

The researchers say that people infected with hepatitis B ought to receive screening for digestive system cancers. Screening for some digestive system cancers is already standard practice in most countries. For example, screening for colorectal cancer in people aged 50 and over is now recommended in many higher income countries. However, cancer screening practices vary in lower-income and middle-income countries, and routine screening for stomach cancer is not recommended except in some Asian countries.

Young adults with vertical HIV and hepatitis C co-infection have a high hepatitis C cure rate

Between 3.5 and 5 million young people under 15 years old have chronic hepatitis C infection, mainly acquired through vertical transmission (mother to child) during gestation or delivery.

Some research suggests that cirrhosis develops more rapidly in children with hepatitis C virus (HCV). Co-infection with HIV is associated with more aggressive liver disease progression.

At the 10th International AIDS Society Conference on HIV Science (IAS 2019), held in Mexico City last month, Spanish researchers reported on direct-acting antiviral (DAA) treatment in 27 young adults who acquired hepatitis C through vertical infection. Twenty-six per cent had advanced fibrosis (stage F3) and 4% had cirrhosis (stage F4).

All the young adults achieved sustained virological response (SVR), or undetectable HCV at 12 weeks after completing treatment, which is considered a cure. However, despite successful treatment, just 29% saw improvement in their liver disease stage after treatment, while 57% stayed the same and 14% had worsening fibrosis.

These study findings indicate that it is important to treat children with hepatitis C early, before they develop advanced liver disease. "To speed up access to new DAA treatments for paediatric populations is an urgent need," the researchers concluded.

Sofosbuvir/ledipasvir is approved in Europe and the United States for people aged 12 and over with HCV genotypes 1, 4, 5 or 6, while sofosbuvir (Sovaldi) plus ribavirin is indicated for those with genotypes 2 or 3. Studies have shown that sofosbuvir/ledipasvir is also effective for children aged 6 to 11 years and those aged 3 to 5 years. Glecaprevir/pibrentasvir (Maviret), a pangenotypic regimen that works against all HCV genotypes, is also approved for those aged 12 and over. However, no DAAs are currently approved for children under 12.

13% of HIV-positive Europeans who are cured of hepatitis C are reinfected

Sarah Amele at IAS 2019. Photo by Liz Highleyman.

More than one in ten HIV-positive people in the large EuroSIDA cohort who were cured of hepatitis C were reinfected within two years, according to a report last month at IAS 2019 in Mexico City.

These findings underscore the need for education and harm reduction services to reach the goal of eliminating hepatitis C virus (HCV) as a public health threat, according to presenter Sarah Amele of the University College London Centre for Global Health.

The analysis included 585 people living with HIV who had achieved sustained virologic response or continued undetectable HCV RNA after completing hepatitis C treatment using either direct-acting antivirals (18.8%) or the older interferon-based therapy (81.2%).

Overall, 78 people, or 13.3%, were reinfected.

"Active surveillance to detect early HCV reinfection (with an offer of early treatment) is essential," they concluded. "Reducing the rate of HCV reinfection is urgently needed to reach the goal of elimination by 2030, especially among marginalised groups."

Statins linked to lower risk of liver cancer in people with hepatitis B or C

People with hepatitis B or C treated with lipophilic statins – atorvastatin, lovastatin, and simvastatin – were significantly less likely to develop hepatocellular carcinoma (liver cancer) than people not treated with statins, a Swedish study has found.

However, people who received hydrophilic statins – rosuvastatin, pravastatin or fluvastatin – did not show any reduced risk of liver cancer compared to untreated people.

The Swedish study, published in Annals of Internal Medicine, was a prospective cohort study of 16,648 people with hepatitis B or C. The study matched people prescribed statins with people who did not receive a statin prescription. Study participants were followed for a median of eight years.

People prescribed a lipophilic statin had a 44% lower risk of hepatocellular carcinoma and a 38% lower risk of death.

It is unlikely that this result could be influenced by a prescriber preference to give lipophilic statins to people with viral hepatitis, as the various statins have many different characteristics each influencing prescriber decision making.

San Francisco sees new success in treating homeless people with hepatitis C

San Francisco Weekly reports on the use of a mobile outreach and screening van – the DeLiver van – to reach homeless people in the city and offer hepatitis C testing and treatment. The vans provide 20-minute rapid testing for hepatitis C and Fibroscan screening for liver damage. People diagnosed with hepatitis C are linked with primary care providers in the community.

Since January, the outreach team has done more than 420 screenings on people through the DeLiver van, and 140 Fibroscans. Twenty-seven people have been treated for hepatitis C.

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