EASL

Berlin, 14 - 18 April 2004

• Cox2 inhibitors.

NSAI drugs frequently induce renal failure in decompensated cirrhosis. Barcelona teams (+ Croatia and USA ) compared the effects of celecoxib or naproxen or placebo on platelet and renal function, and the renal response to furosemide, in 26 patients with cirrhosis and ascites. Celecoxib did not impair platelet and renal function or the response to diuretics in decompensated cirrhosis. However it must be stressed that only 5 doses (every 12 hours) were given, for ethical reasons, and that the follow-up was short, so side effects cannot be excluded and the use of NSAIs, even cox2 selective, cannot be recommended in the clinical practice for patients with decompensated cirrhosis. (1).

The same team examined the role of cox2 in the pathogenesis of liver fibrosis caused by carbon tetrachloride (CCl4) in rats. Administration of a selective cox2inhibitor indeed decreased the liver fibrosis, by mechanisms involving the inactivation of Kupffer cells and by acting as a PPARgamma ligand. (2). So anyway there could be a place (with caution) for selective cox2inhibitors for the treatment of liver inflammation and fibrosis?

• Cannabis

A team from Creteil showed a marked upregulation of cannabinoids receptors CB1 in hepatic myofibroblasts in cirrhosis, and a reduced fibrosis in CB1 knock-out mice, suggesting a profibrogenic role of CB1 receptors. (3).

And indeed the same team found that in patients with hepatitis C, smoking cannabis daily (around 140 cigarettes per month) increased the fibrosis progression rate compared to occasional smokers (around 7 cigarettes per month) or no smokers. (4).

So maybe we should also caution our hepatitis C patients against the (daily) use of cannabis.

But there could be confounding factors (ecstasy for instance?) or a risk a statistical overfitting, and a US team found an antifibrogenic role of CB2 receptors… (5).

• antiHBc in HCV

A large cohort of HCV patients from 8 european centers was studied. AntiHBc positivity was not associated with the treatment outcome (contrary to earlier reports), but well with the occurrence of hepatocarcinoma and liver related death or liver transplantation (with a follow-up of 7 years). HCC was also related to male gender. (6).

In the same cohort, age at infection and HLA were also factors associated with the rate of progression towards liver complications (7).

• HIV-HCV co-infection

The Apricot trial : 868 patients from 19 countries, co-infected with HCV and HIV (with a CD4 count >100 cells/mm3 if HIV-RNA<5000cp/ml, if not >200 cells/mm3, and stable HIV disease, with or without antiretroviral therapy) were randomized to 48 weeks of treatment with either IFN 3 MIU tiw + RBV 800 mg/d, or Pegasys 180 µg/wk + placebo, or Pegasys 180 µg/wk + RBV 800 mg/d. Baseline characteristics of the 3 groups were similar (notably 60% had genotype 1, 15% cirrhosis).

The Sustained Virological Response rates were 40% in patients treated with Pegasys+RBV, 20% in patients treated with Pegasys + placebo, and 12% for IFN + RBV (for genotype 1, 29%, 14% and 7% respectively; for genotypes 2-3, 62%, 36% and 20% respectively). This (40%) is the highest SVR reported in any study of HIV/HVB co-infection. Furthermore, HCV therapy had no negative impact on the control of HIV, and only 15% of patients discontinued for adverse events or lab. abnormalities. (8).

1. J. Claria, J.D. Kent et al. Abstract 3.
2. A. Planaguma, J. Claria et al. Abstract 21.
3. P. Grenard, B. Julien at al. Abstract 20.
4. C. Hezode, F. Roudot-Thoraval et al. Abstract 68.
5. R. Bataller, J. Ros et al. Abstract 308.
6. H.L. Tillmann, P. Pradat et al. Abstract 34.
7. P. Pradat, H.L. Tillmann et al. Abstract 519.
8. F.J. Torriani, J. Rockstroh et al. Abstract 92.