Antibiotic prophylaxis reduces the risk of short-term death in people with decompensated cirrhosis

Keith Alcorn
Published:
20 April 2017
Richard Moreau at the International Liver Congress 2017. Photo by Liz Highleyman, hivandhepatitis.com

Long-term prophylaxis with the antibiotic norfloxacin significantly reduced the incidence of deaths in people with decompensated cirrhosis over a six-month follow-up period, a French randomised trial reported today at the International Liver Congress in Amsterdam.

Norfloxacin is a fluoroquinolone antibiotic. Its use has been proposed as a means of preventing bacterial infections in people with very advanced, or decompensated cirrhosis. When liver function is severely reduced in late-stage cirrhosis, bacteria from the gut can leak into the liver, causing infections and promoting inflammation, so leading to worsening cirrhosis.

Some liver specialists are concerned that prolonged use of fluoroquinolone antibiotics can lead to the development of antibiotic resistance, encouraging the development of hard-to-treat gram-negative bacterial infections in people already at high risk of bacterial infection.

Glossary

ascites

An accumulation of fluid in the abdomen; may be caused by liver damage, especially cirrhosis. 

decompensated cirrhosis

The later stage of cirrhosis, during which the liver cannot perform some vital functions and complications occur. See also ‘cirrhosis’ and ‘compensated cirrhosis’.

encephalopathy

A disease or infection affecting the brain.

intent to treat analysis

All participants in a clinical trial are included in the final analysis, in the groups they were originally assigned to, whether or not they actually completed their course of treatment. Provides a better estimate of the real world effect of a treatment than an ‘on treatment analysis’.

The French study was designed to test the effect of a six-month course of daily norfloxacin (400mg) on mortality and the incidence of severe liver complications or liver transplantation in people with decompensated cirrhosis.

People were eligible to join the study if they had Child-Pugh C cirrhosis, but the study excluded people with HIV co-infection and people with hepatocellular carcinoma.

The study recruited 291 patients at 18 hospitals in France. Participants were randomised in a double-blinded manner to receive either norfloxacin (n = 144) or placebo (n = 147) and attended the clinic once a month for follow-up visits.

The study population was largely composed of people with alcoholic cirrhosis (80% in the norfloxacin arm and 74% in the placebo arm), 65% of the norfloxacin arm and 74% of the placebo arm were male, and the average age of participants was 55.

Participants had a median MELD score of 21, and a Child-Pugh score of 11. Eighty-eight per cent of the norfloxacin group had ascites, and 44% of the norfloxacin group and 47% of the placebo group were receiving beta-blocker treatment to manage portal hypertension and ascites, as a consequence of cirrhosis.

After six months of study treatment, a high proportion of participants (46%) had discontinued study treatment, 12% by their own wish, 15% due to death, 9% due to liver transplant and 9% due to spontaneous bacterial peritonitis (SBP).

By intent to treat analysis, the incidence of death was 43% lower in the norfloxacin group (adjusted hazard ratio 0. 57, 95% CI 0.33-0.97, p = 0.041), a significant reduction in risk. People in the norfloxacin group were significantly less likely to develop an infection during the first six months too (23.9% vs 32.3%), especially gram-negative bacterial infections.

There was no significant difference in the other secondary outcomes of liver transplantation, hepatic encephalopathy, variceal haemorrhage or kidney dysfunction.

Reference

Moreau R et al. A randomized trial of 6-month norfloxacin therapy in patients with Child-Pugh class C cirrhosis. International Liver Congress, Amsterdam, abstract GS-001, 2017.