Of these 12, there were only five with possible cirrhosis on biopsy. The other seven had varying degrees of fibrosis (F3 in four patients, F2 in one patient, F1 in one patient, and F0 in one patient) and therefore represent NCPH. Four of these seven

were scored on liver explants and therefore sampling error certainly did not play a role. In two of these patients, we were able to perform hemodynamic measurements that revealed a hepatic venous pressure gradient of 5 and 9 mm Hg, respectively, Everolimus solubility dmso despite the presence of esophageal varices. This is clear proof of an important presinusoidal component in the portal hypertension consistent with NCPH.2 Using this technique, there is also no sampling error. Portal hypertension out of proportion with the fibrosis

suggests NCPH and therefore an important vascular component. Analysis of our biopsies revealed portal branch venopathy in all the patients with NCPH (most notably, Pirfenidone cell line absence of portal veins in more than 40% of portal tracts3) (Fig. 1). These findings were clearly more prevalent in our patients with NCPH than in a reanalyzed control group4 of 20 patients with CFLD without portal hypertension (P = 0.008) adding to the evidence of a presinusoidal vascular component. The development of this portal branch venopathy remains obscure. It could be due to spillover of the inflammatory infiltrate of the bile ducts (as suggested in other biliary diseases with presinusoidal portal hypertension5), due to microthrombosis (platelets are hyperactive in CF6), or due to primary endothelialitis (CF is associated with

a rise in markers of vasculitis7). Although the findings of Lewindon et al. and our findings demonstrate the importance of liver biopsies in CF, extreme care must be taken not to underestimate the degree of portal hypertension medchemexpress based on these biopsies. In view of the good hepatic synthetic function, management of patients with CF who have NCPH should probably seek the alleviation of this portal hypertension by shunting procedures (that is, transjugular intrahepatic portosystemic shunt) rather than referring these patients for liver transplantation. Also in that respect, performing liver biopsies and hemodynamic measurements seems indicated. Peter Witters M.D., Ph.D.* **, Louis Libbrecht M.D., Ph.D.** ††, Tania Roskams M.D., Ph.D.†, Kris De Boeck* ‡‡, Lieven Dupont§§, Marijke Proesmans M.D., Ph.D.* ‡‡, François Vermeulen M.D.* ‡‡, Birgitta Strandvik¶¶, Anders Lindblad M.D.11, Xavier Stéphenne12, Etienne Sokal M.D., Ph.D.12, Serge Gosseye M.D.13, Sam Heye‡, Geert Maleux‡, Raymond Aerts Ph.D.§, Diethard Monbaliu M.D.§, Jacques Pirenne M.D., Ph.D.§, Ilse Hoffman*, Frederik Nevens M.D.¶ **, David Cassiman M.D., Ph.