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.