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A new international study has found high mortality rates from COVID-19 among people with chronic liver disease and cirrhosis.

The researchers, led by teams at Oxford University Hospitals NHS Foundation Trust and the University of North Carolina, set up an international registry to collect clinical details of patients with chronic liver disease and cirrhosis who develop COVID-19.

Between 25 March 2020 and 20 April 2020, 152 cases were submitted to the registry, over 95 percent of which were hospitalised. Patients with cirrhosis had poor outcomes with an overall death rate of 40 percent. Those with advanced disease called ‘decompensated cirrhosis’ had the highest rate of death (between 43 and 63 percent), compared with 12 percent for patients with liver disease but without cirrhosis.

The paper has been published online by the Journal of Hepatology.

Dr Thomas Marjot, who leads the project alongside Dr Gwilym Webb and Professor Ellie Barnes at the Translational Gastroenterology Unit at Oxford’s John Radcliffe Hospital, said: “Until now, very little was known about the impact of COVID-19 on patients with pre-existing liver disease.

“Our data, which were gathered from 21 countries, show that people with liver disease, and especially those with decompensated cirrhosis, have particularly poor outcomes once they develop COVID-19.

“Even when other risk factors for poor outcomes - such as age, obesity, diabetes and high blood pressure - were taken into account, the severity of baseline liver disease was still associated with increased mortality,” he explained.

The study also showed that many patients with cirrhosis and COVID-19 developed features of worsening liver function (encephalopathy, ascites, bleeding), and in 24 percent of cases this occurred even without any chest symptoms or breathing difficulties.

However, Dr Marjot explained, these preliminary findings should be interpreted with caution: “our study is limited by selection bias; this is when doctors tend to report more severe cases with the worst outcomes. Many patients with cirrhosis and COVID-19 who have good outcomes will therefore not be included in the registry.”

“Nonetheless, these findings do suggest high death rates with COVID-19 in patients with cirrhosis and that contracting the virus may lead to a deterioration in liver function. Therefore, anyone coming into hospital with worsening symptoms of liver disease should be considered for coronavirus testing”.

Pamela Healy, Chief Executive of the British Liver Trust said: “This important study demonstrates the devastating impact of coronavirus on liver patients. We are asking the Government to quickly review the shielding guidance and ensure that those with the most severe forms of liver disease have clear advice and support. Whilst lockdown may be easing for many of us, these patients often have multiple complex problems and urgently need clarity and to remain protected.”

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Two new hepatology trials have been discussed and intellectually supported by the BSG-BASL Liver Research Development Group. These are supported from the NIHR HTA funding stream.

Beta Blockers Or Placebo for Primary Prophylaxis of oesophageal varices (BOPPP) is a UK wide multi-centre liver study. It will address whether primary prophylaxis against future variceal haemorrhage with non-selective beta blockers  is clinically and economically effective in patients with cirrhosis and small varices. £2.3 million will be provided to consent, treat and follow up 1,200 patients at 25 different hospitals across the UK. The trial is led by the Institute of Liver Sciences, King’s College Hospital and King’s College London Clinical Trials Unit. For more information: Download Press release BOPPP_FINAL_19.09.2018.pdf.

Antibiotic SpontanEous PeritoniTIs Cirrhosis (ASEPTIC) is a double blind placebo controlled trial to determine whether primary antibiotic prophylaxis with Cotrimoxazol substantially reduces the incidence of spontaneous bacterial peritonitis (SBP) in people with advanced liver disease. This will be the largest study of SBP prophylaxis ever, involving patients at 30 sites. The trial is led by Unveristy College London. For more information:  Download ASEPTIC trial information for BSG and BASL.pdf.

A large observational study in the USA confirmed haemophilia per se does not have a specific influence on transplant outcomes in HCV patients, but that HIV infection increases the risk of mortality in both haemophilic (H) and non-haemophilic (NH) patients.

Researchers identified 2,502 HCV-positive liver transplant candidates from eight US university-based transplant centres between 2004 and 2010, including 144 HIV-positive and 2,358 HIV-negative; 36 H and 2,466 NH; 1,213 transplanted and 1,289 not transplanted patients.

In univariate analysis, 90-day pre-transplant mortality was associated with higher baseline MELD (hazard ratio 1.15), lower baseline platelet count (hazard ratio 1.11 per 25k/µL), and having HIV/HCV-positive haemophilia.

In multivariate analysis, pre-transplant mortality was associated with higher MELD and was significantly greater in HIV-positive than HIV- groups, but did not differ between HIV-positive H and NH (hazard ratio 1.7). Among HIV/HCV-positive, post-transplant mortality was similar between H and NH, despite lower CD4 in H.

Reference

Haemophilia liver transplantation observational study (HOTS). Ragni MV, Humar A, Stock PG et al. Liver Transpl. 2016 Dec 9 [Epub ahead of print]

Some patients with non-alcoholic steatohepatitis (NASH) show recurrence of fibrosis as early as six to 12 months following their transplant.

This emerged in a study at the Medical University of Vienna which compared the recurrence of liver fibrosis in 15 patients transplanted for NASH with 12 to cryptogenic cirrhosis (CC) patients after orthotopic liver transplantation (OLT) between 2004 and 2015.

The case load for OLT because of NASH was constantly increasing (two in 2004-2007 compared with nine in 2012-2015) whilst decreasing for CC (six in 2004-2007 compared with two in 2012-2015). Patient characteristics at OLT were similar, except for an older age and a higher BMI in the NASH patients.

Although post-OLT plasma lipid levels and the incidence of de-novo hypertension, diabetes, and hyperlipidemia were similar between groups, the post-transplant NAFLD fibrosis score (NFS) re-increased in the NASH group but not in the CC group (-0.1317 versus -1.3645 at 12 months post-OLT.

Reference

The post-transplant course of patients undergoing liver transplantation for nonalcoholic steatohepatitis versus cryptogenic cirrhosis: a retrospective case-control study. Unger LW, Herac M, Staufer K et al. Eur J Gastroenterol Hepatol. 2016 Dec 2 [Epub ahead of print]

Although tenofovir (TDF) was more effective at three months, there was no significant difference between TDF and entecavir (ETV) in the long-term treatment of HBV related liver cirrhosis, a new meta-analysis of studies found.

A literature search, conducted by reviewers from Beijing You'an Hospital, found significant difference of ALT norm level at three months (RR 1.43) and six months (RR 0.89), and significant difference of undetectable HBV-DNA only at three months follow-up period (RR 1.59) between TDF and ETV, but no significant difference in the long-term period. There was a significant difference between TDF and ETV in eGFR level (RR 1.601) and hypophosphatemia incidence (RR 4.008).

Reference

The efficacy and safety comparison between tenofovir and entecavir in treatment of chronic hepatitis B and HBV related cirrhosis: a systematic review and meta-analysis. Han Y, Zeng A, Liao H et al. Int Immunopharmacol. 2016 Dec 1;42: 168-175 [Epub ahead of print]