This began to change first with the demonstration of associated protective HLA variants by means of large-scale candidate-gene association studies. However, the major role of the HLA region in the genetic architecture of PBC susceptibility became definitively clear after the first GWAS in PBC. On the basis of these data, it will be challenging to perform a deep, high-throughput analysis of this genetic region, although these efforts must consider that the extensive linkage disequilibrium and variability across
the HLA region makes a further resolution of these associations difficult. Moreover, because the HLA molecules are tightly linked with the maintaining (or breaking) of the immune system homeostasis, functional studies on new candidate HLA variants have to be carried out with the final goal of understanding PBC etiopathogenesis find more and developing novel disease-specific therapies. “
“With great interest ubiquitin-Proteasome pathway we appreciated the recent article in HEPATOLOGY by Iavarone et al.,1 who provided
indirect evidence for the efficacy of sorafenib in a multicenter field-practice study in Italy finding a median overall survival (OS) of 10.5 months compared with 10.7 months in the SHARP trial.2 In addition, the authors set out to determine the differences in OS concerning Barcelona Clinic Liver Cancer (BCLC) stage, observing a significantly higher survival rate in patients with BCLC-B compared with BCLC-C (26.0 versus 8.4 months, P < 0.001). They reproduced the data from the SHARP trial in terms of OS and adverse events. The most common adverse events in their study were fatigue, weight loss, hand-foot syndrome, and diarrhea. Interestingly, recent studies have indicated that adverse events
may be of prognostic and predictive importance in patients treated with sorafenib.3 Vincenzi et al.4 reported Paclitaxel nmr that early hand-foot reaction may be a positive predictive factor for response to sorafenib showing a prolongation of the time to progression (TTP) in patients with confirmed hand-foot syndrome. We retrospectively analyzed 112 patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib with respect to OS, TTP, and prognostic importance of the most common adverse events. We found a median OS of 9.6 months and a median TTP of 3.9 months. The median duration of sorafenib treatment was 3 months and 75 patients (66.4%) reported adverse events. The most common ones were diarrhea in 36/112 patients (32.1%), hand-foot syndrome (15.2%), fatigue (13.4%), and loss of appetite (7.2%). Multivariate Cox regression models revealed BCLC stage as a negative independent prognostic factor (hazard ratio [HR]: 3.08; P = 0.001), while diarrhea was a positive independent prognostic factor (HR: 0.41; P = 0.001). Patients with diarrhea had a significantly longer median OS of 14.1 months as compared with 7.1 months in patients without diarrhea (P = 0.011; Fig. 1), while hand-foot syndrome was not associated with OS or TTP (P = 0.