New WHO guidance on preventing mother-to-child transmission of hepatitis B

Pregnant women who test positive for hepatitis B infection and have a high level of hepatitis B virus (HBV) in the blood should receive preventive antiviral therapy with tenofovir from the 28th week of pregnancy until birth, the World Health Organization (WHO) recommends in new guidelines on the prevention of mother-to-child hepatitis B transmission released this week.

The new WHO guidance aims to intensify efforts to reduce mother-to-child transmission of hepatitis B. Infant vaccination against hepatitis B has been highly effective in reducing the prevalence of hepatitis B in children. The proportion of children under five years of age chronically infected with hepatitis B dropped to just under 1% in 2019 down from around 5% in the pre-vaccine era (the period between the 1980s and the early 2000s), according to new estimates from WHO.

An additional way to protect children is to provide pregnant women with antiviral treatment to reduce mother-to-child transmission of HBV. WHO already recommends routine testing of all pregnant women for HBV, as well as HIV and syphilis as early as possible in their pregnancy. In view of new evidence on the safety and efficacy of antiviral prophylaxis in pregnant women and their children, WHO recommends:

  • Pregnant women who test positive for hepatitis B infection and have a high level of HBV in the blood (known as HBV viral load) should receive preventive antiviral therapy with tenofovir from the 28th week of pregnancy until birth. The antiviral drug tenofovir is available at low cost in many countries of the world for less than US$3 per month.
  • In settings where HBV viral load testing is not available, WHO recommends the use of an alternative low cost test (HBeAg) to determine whether a woman is eligible for preventive antiviral therapy.

In countries that have already achieved high coverage of hepatitis B immunisation, including timely birth dose, routine testing for HBV infection among pregnant women and antiviral prophylaxis for those in need is an additional opportunity to prevent onward transmission from mother to child. 

Cirrhosis raises the risk of liver injury in COVID-19 patients

People with cirrhosis, especially those with diabetes or obesity, are more likely to suffer significant liver injury after contracting SARS-CoV-2 than others with chronic liver disease, Asian liver specialists report in a multi-centre study published in the journal Hepatology International.

Liver injury caused by severe inflammation, restricted oxygen flow caused by pneumonia or medication used to treat COVID-19 has been reported in up to half of patients in some cohort studies, chiefly in the form of raised liver enzymes.

Although liver injury is transient in most people, it has been unclear if people with underlying liver disease are at greater risk of more severe liver injury after developing COVID-19.

Investigators in 13 countries in the Asia-Pacific region collected data on COVID-19 outcomes in people with chronic liver disease, including predictors of mortality.

The APASL COVID-19 Liver Injury Spectrum study (APCOLIS) accumulated data on 185 people with chronic liver disease without cirrhosis and 43 people with cirrhosis.

People with cirrhosis were significantly more likely to have new acute liver injury at admission (32% vs 20%) and during hospitalisation (39% vs 7%) (P < 0.001). Decompensation after admission was significantly more common in the cirrhosis group (7% vs 0%). They were also more likely to develop more severe liver-related complications (32% vs 14%, p = 0.007) and more likely to die from liver injury (16% vs 2%, p = 0.002).

People with cirrhosis were also more likely to experience severe COVID-19 complications such as acute kidney injury (18% vs 5%), respiratory failure (23% vs 8%) and low blood pressure (hypotension) (14% vs 3%) (all p < 0.001).

Severity of COVID-19 was associated with severity of cirrhosis. People with decompensated cirrhosis prior to admission (18 out of 43) were five times more likely to present with severe COVID-19 symptoms (severe pneumonia, acute respiratory distress syndrome, acute kidney, heart or circulatory failure) (odds ratio 5.5) and six times more likely to present with acute liver injury at admission (odds ratio 6.2).

How often does COVID-19 cause liver disorders?

Increases in liver enzymes are common in people with COVID-19 and occur more frequently in people with severe COVID-19, a meta-analysis of studies published in Hepatology International shows.

Most liver enzyme elevations were mild-to-moderate and did not result in severe liver injury, the review found. Only one case of liver failure was identified in the 128 studies reviewed.

Liver enzyme abnormalities were more likely to occur in people with chronic liver disease, the meta-analysis found.

The investigators say it is impossible to tell whether liver abnormalities are caused by the virus, by the immune system’s response to the virus or by medications used to treat COVID-19, many of which cause liver enzyme elevations.

Hepatitis C drugs may offer a treatment option for COVID-19

Sofosbuvir and daclatasvir, two antiviral drugs used to treat hepatitis C, were associated with faster recovery, shorter hospitalisation and improved survival among people with moderate or severe COVID-19, researchers reported this month at the COVID-19 Conference that concluded the 23rd International AIDS Conference (AIDS 2020: Virtual).

The trial enrolled 66 people with fever and low oxygen levels who tested PCR positive for SARS-CoV-2 and had diagnostic chest CT scans indicating COVID-19. Just over half were men and the median age was approximately 60 years. Co-morbidities were common, including diabetes, hypertension, chronic pulmonary disease and obesity. Those with poor kidney function or multi-organ failure were excluded.

Sadeghi reported that 88% of people taking sofosbuvir plus daclatasvir experienced clinical recovery – defined as normalisation of fever, respiratory rate and oxygen saturation – compared with 67% of those on standard therapy. This difference fell short of statistical significance, but the time to recovery was significantly shorter in the sofosbuvir plus daclatasvir arm (six versus 11 days, respectively).

A larger randomised, placebo-controlled trial called DISCOVER will compare sofosbuvir plus daclatasvir with lopinavir/ritonavir versus lopinavir/ritonavir alone in 600 people with moderate to severe COVID-19 who have had symptoms for seven days or less.

In addition, a network of five clinical trials has been established to test sofosbuvir plus daclatasvir in over 2000 patients with COVID-19 in Iran, Brazil, Egypt and South Africa, according to a press statement.

"By October, we should know from the trial results if this treatment could be approved for worldwide use," said Prof Shahin Merat of Tehran University of Medical Sciences. "Conducting research amidst a pandemic with overwhelmed hospitals is a challenge and we cannot be sure of success. Sometimes treatments look promising in early trials but then fail later on."

COVID-19 toolkit for patient associations

The European Association for the Study of the Liver (EASL) and the European Reference Network on Rare Liver Disorders (ERN RARE-LIVER) have developed a toolkit on COVID-19 for liver patient associations.

EASL and ERN RARE-LIVER say: “This toolkit has been developed to help liver disease patients during the COVID-19 pandemic. The goal of the toolkit is to help patient associations to support their patients during this time. Three different sections have been made: each section has its own goal.

Section 1 helps patient associations to communicate accurate information about COVID-19 to patients

Section 2 advises on the use of social media and newsletters to make communication to patients easier

Section 3 gives tips about how advocacy can be used to improve the situation and treatment of liver disease patients.”

World Hepatitis Alliance webinar, 31 July 2020 – Ten years to go: prospects of reaching the 2030 elimination targets in the context of COVID-19

On Friday 31 July, the World Hepatitis Alliance will host a webinar to discuss the prospects of achieving hepatitis elimination by 2030 in the context of COVID-19. This webinar will bring together leading experts from across the world to explore how COVID-19 has impacted hepatitis elimination programmes and what needs to be done to accelerate elimination efforts if we are to reach the 2030 goals. 

Hepatitis C doubles the risk of head and neck cancers

Hepatitis C infection doubles the risk of developing cancers of the oral cavity, upper throat and larynx, a meta-analysis of eight studies has shown. The study authors say that people with hepatitis C should be checked regularly for these cancers.

The risk of developing a head or neck cancer is relatively low, although the incidence of these cancers is on the rise. Men are about twice as likely as women to develop one of these cancers. The lifetime chance of developing oral cancer is around one in fifty for men born after 1960 in the United Kingdom, Cancer Research UK has calculated. The risk of other head and neck cancers is lower. Head and neck cancers are more common in Asia. The chief risk factors for head and neck cancers are smoking, high alcohol consumption and human papillomavirus infection.

Doctors treating people with head and neck cancers should consider the possibility of undiagnosed hepatitis C and liver specialists should carry out regular checks for head and neck cancers in their patients with hepatitis C, the authors conclude.  They don’t specify how often people with hepatitis C should be checked.

Hepatitis C cure means many liver failure patients have a better chance at transplantation and recovery

In the era of new antivirals, most liver-transplanted patients can be rapidly cured of hepatitis C infection. This medical progress has also made it possible to expand the donor pool, and transplant hepatitis C-positive organs followed by antiviral treatment.

University of Chicago Department of Medicine reports in the journal Transplantation that the number of hepatitis C-positive livers transplanted to hepatitis C-negative patients rose 35-fold over the past four years in the United States, from eight in 2016 to 280 in 2019. The research also confirms that patients who received the infected livers and were then cured of hepatitis C did as well two years after their operations as patients who received livers that weren't infected.

The study found large variation between regions, suggesting a lack of awareness of recent successful outcomes from hepatitis C-positive organ transplants at larger academic medical centres.

Women suffer less NAFLD but more advanced fibrosis

Medscape reports that women are significantly less likely to develop non-alcoholic fatty liver disease (NAFLD) than men but more likely to develop advanced fibrosis. The findings come from a meta-analysis of 54 studies and more than 62,000 people and are published in the journal Clinical Gastroenterology and Hepatology.

Women had a 19% lower risk of developing NAFLD but a 37% higher risk of advanced fibrosis than men, the meta-analysis showed.

Study author Dr Maya Balakrishnan told Medscape that the course of NAFLD appears to be more aggressive in women.

Although women are less likely to develop NAFLD, the study investigators say that the higher risk of advanced fibrosis in women means that women aged 50 or over who have NAFLD should be monitored regularly for advanced fibrosis and cirrhosis. Dietary modification and weight loss in younger women with NAFLD are important measures to prevent further liver damage, they conclude.

Diabetes doubles the risk of advanced liver disease in NAFLD

A second meta-analysis published this month finds that diabetes doubles the risk of developing advanced fibrosis in non-alcoholic fatty liver disease (NAFLD).

The study pooled data from 18 studies that reported risk factors for the development of advanced liver disease (fibrosis or non-alcoholic steatohepatitis – NASH) in people with metabolic disease (either raised blood pressure, raised lipid levels, diabetes or obesity). The studies followed approximately 20 million people for a median of ten years and compared people with metabolic risk factors to people with no metabolic risk factors. The studies excluded people with viral hepatitis or alcoholic liver disease.

Obesity increased the risk of advanced liver disease by 20%. Raised blood pressure or lipids increased the risk of advanced liver disease to a similar extent.

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