COVID-19 in chronic liver disease: advanced cirrhosis greatly raises risk of death

People with chronic liver disease admitted to hospital with COVID-19 are dying at a much higher rate than the rest of the population, figures collated by liver specialists in Europe, Asia and North America show. Advanced cirrhosis greatly increased the risk of death, the study found.

People with severe cirrhosis were almost 30 times more likely to die after a COVID-19 diagnosis than people with chronic liver disease without cirrhosis, the figures show. The overall death rate in people with chronic liver disease was 39% among reported cases.

Two international registries were established in March 2020 to track the outcomes of people with chronic liver disease and cirrhosis after diagnosis with COVID-19. Investigators from 14 specialist liver clinics in the United States, Spain and the United Kingdom have now reported on the first 152 cases submitted to the registries, in a publication in the Journal of Hepatology.

The registry and registry accumulated 152 consecutive physician reports of laboratory-confirmed cases of COVID-19 between 25 March and 20 April 2020, of cases with definite outcomes (either death or discharge from hospital). The registry is an uncontrolled study of cases voluntarily reported by doctors and the findings highlight trends rather than prospective analysis of all patients treated at a range of clinical centres.

One hundred and three were cases of cirrhosis. 22.3% of reported cases occurred in people with viral hepatitis, 22.4% in people with non-alcoholic fatty liver disease and 19.7% in alcoholic liver disease. The remainder had other causes or a combination of causes.

Ninety-five per cent of the reported cases were admitted to hospital, and 23% were admitted to an intensive care unit. Forty-seven of the 152 people died (39.8%).

Multivariable analysis showed that severe cirrhosis (Child-Pugh C stage) was strongly associated with an increased risk of death from COVID-19. People in Child-Pugh stage C, who comprised 17.8% of all reported cases, were 28 times more likely to die than people without cirrhosis (32.2% of cases) (odds ratio 28.07, 95% CI 4.42-178.46, p < 0.001). Sixty-three per cent of people with Child-Pugh stage C cirrhosis died compared to 12.2% of those without cirrhosis.

Decompensation events occurred frequently in the reported cases; around half of people with Child-Pugh B or C cirrhosis suffered at least one new or worsening event after diagnosis with COVID-19 and these events often occurred in people without respiratory symptoms of COVID-19.

The investigators say that the findings regarding decompensation events, especially in the absence of respiratory symptoms, underline the importance of testing for SARS-CoV-2 in any patient with chronic liver disease who experiences a decompensation event.

Controversy: Does non-alcoholic fatty liver disease raise the risk of COVID-19?

Many patients with non-alcoholic fatty liver disease (NAFLD) are older or have co-morbidities such as obesity, diabetes or hypertension, which are known to raise the risk of severe COVID-19.

Chinese findings suggest that people with NAFLD, also known as metabolic-associated fatty liver disease, were at higher risk of severe COVID-19. A separate study in China also found a higher risk of severe COVID-19 illness in people under 60 years old who had metabolic-associated fatty liver disease. The authors suggested that liver steatosis in NAFLD could be an independent risk factor for severe COVID-19.

New data from UK however call this into question. People with a genetic profile that strongly predicts non-alcoholic or metabolic-associated fatty liver disease were not at higher risk of being hospitalised with COVID-19 in the United Kingdom, an analysis of the UK Biobank has found.

Researchers in Italy and Sweden analysed data on 1460 white British cohort members who had been tested for SARS-CoV-2 infection (526 positive and 934 negative). Fifty-seven per cent of the entire sample were hospitalised and the researchers used hospitalisation in the positive cases as a surrogate for a severe COVID-19 outcome.

They looked for people with a high genetic risk score for NAFLD, looking for genes previously validated as predictive for the accumulation of fat in the liver and concomitant liver damage. In the absence of systematic testing for NAFLD, genetic markers that are highly predictive of liver fat accumulation in the age group studied are a surrogate for a diagnosis of NAFLD using laboratory and biopsy measures.

The researchers found no association between a high genetic risk score for NAFLD and higher risk of severe COVID-19 outcome. They say that much larger studies are needed to examine the impact of obesity, metabolic disorders and cardiovascular disease on the risk of severe COVID-19 outcomes.

Weight gain after hepatitis C cure is common

Substantial weight gain is common after hepatitis C cure, an analysis of a large cohort shows, and around one in five people with normal body weight became overweight within two years, US Veterans Affairs researchers report in the Journal of General Internal Medicine.

Being overweight or obese is associated with an increased risk of raised blood pressure (hypertension), cardiovascular disease, type 2 diabetes and some types of cancer. Obesity (a body mass index above 30) is associated with a higher risk of all these conditions compared to being overweight (BMI 25-29.9) but being moderately overweight is nevertheless associated with an increased risk of serious health conditions.

Reasons for weight gain are unclear. Although curing hepatitis C may improve liver function in ways that lead to increased muscle mass, muscle tends to be replaced by fat in older people. Dietary and lifestyle factors are more likely to influence weight gain.

Short-course treatment for recent hepatitis C: some courses may be too short

An eight-week course of grazoprevir/elbasvir (Zepatier) achieved a high cure rate in people recently infected with hepatitis C, but a six-week course of sofosbuvir/velpatasvir (Epclusa) resulted in an inferior cure rate compared to standard treatment, two recent studies show.

Both studies tested shorter durations of treatment predominantly in people co-infected with HIV and hepatitis, as the incidence of new hepatitis C infections and reinfections in HIV-positive gay and bisexual men makes treatment of acute infection a priority for hepatitis C control in this population.

Short-course treatment for acute hepatitis C infection remains experimental. The AASLD hepatitis C treatment guidelines say that as of November 2019, there isn’t enough evidence to recommend any short-course regimen and that acute infection should be treated in the same way as chronic infection. The only eight-week pangenotypic regimen approved for chronic hepatitis C treatment is glecaprevir/pibrentasvir (Maviret).

The French SAHIV study evaluated an eight-week course of treatment with grazoprevir/elbasvir in 30 recently infected gay and bisexual men. Twenty-eight out of 30 who completed treatment achieved a sustained virologic response (91%).

A second study of treatment in acute or recent infection found that six weeks of treatment with sofosbuvir/velpatasvir (Epclusa) resulted in an inferior cure rate in people recently infected with hepatitis C when compared to a 12-week treatment course.

Ninety-three people were randomised to the short-course arm and 99 to the 12-week arm. The Data and Safety Monitoring Board stopped the study at the second scheduled review of the data in May 2019 due to an unacceptably high rate of virological relapse in the short-course arm. Eighty-two per cent in the short-course arm achieved a sustained virologic response compared to 91% in the 12-week arm.

The reason for the higher rate of virological rebound in the short-course arm is unclear. Only one person who experienced rebound had sub-optimal adherence. It is possible that the combination of a nucleotide analogue (sofosbuvir) and NS5A inhibitor (velpatasvir) may not induce sufficiently rapid viral load reduction to permit a six-week treatment course.

Non-alcoholic fatty liver disease affects a quarter of lean people living with HIV

A quarter of people living with HIV with normal body weight have non-alcoholic-fatty liver disease (NAFLD), Italian and Canadian investigators report in Clinical Infectious Diseases. Risk factors were older age, high blood lipids and disturbed liver function. Significant liver fibrosis was observed in 16% with NAFLD, and this progressed in a significant proportion of individuals at a rate comparable to that seen in overweight or obese study participants.

NAFLD is normally associated with excess weight and obesity. This study shows that it is also a concern for lean people living with HIV. The authors recommend that older patients should be screened for NAFLD, especially if they have elevated blood lipids and abnormal liver function.

New estimates highlight need to step up the response to hepatitis D

In a study published in the Journal of Hepatology, Professor Anna Maria Geretti and Dr Alexander Stockdale from the University of Liverpool, UK, in collaboration with researchers from the World Health Organization (WHO) and the International Agency for Research on Cancer, estimate that worldwide, hepatitis D virus (HDV) affects nearly 5% of people who have chronic infection with hepatitis B virus (HBV) and that HDV co-infection could explain about 1 in 5 cases of liver disease and liver cancer in people with HBV infection.

Professor Geretti urged that more efforts were needed to reduce the global burden of chronic hepatitis B, and to develop affordable medicines that are safe and effective against hepatitis D.

International Liver Congress 2020 to take place online

The International Liver Congress, scheduled to take place in London in late August, will now be held as a Digital International Liver Congress (ILC), with all presentations online, EASL announced last week. This decision was made in the light of the ongoing COVID-19 crisis.

The Digital ILC 2020 will take place from Thursday 27 to Saturday 29 August 2020 and EASL will offer a heavily discounted registration fee. Online conference sessions will be available to registered conference delegates.

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