Summary Pruritus is often the most troublesome symptom in patients with chronic liver disease, particularly when cholestasis is a prominent feature. The exact pathogenesis is unknown, but empirical treatment, such as cholestyramine, based on a liver‐based origin of pruritus, has been used for many years. Recently, evidence for a central mechanism for pruritus has been obtained and opioid antagonists have been tried clinically with some benefit, but their use is not widespread. In addition, the pruritus associated with intrahepatic cholestasis of pregnancy can now be alleviated in many cases by ursodeoxycholic acid. As it also improves foetal outcome, this should become first‐line therapy. We review the pathogenesis and therapy of pruritus, highlighting practical aspects to help with patients with seemingly intractable pruritus.

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Progression of fibrosis following recurrent hepatitis C virus (HCV) infection is frequent after liver transplantation (LT).Histology remains the gold standard to assess fibrosis, but the value of hepatic venous pressure gradient (HVPG) is being explored. We evaluated patients with recurrent HCV infection after LT to assess whether HVPG correlates with liver histology, particularly fibrosis. A total of 90 consecutive patients underwent 170 HVPG measurements concomitant with transjugular liver biopsy (TJB), with 31.5 (range, 6-156) months of follow up. Median biopsy length was 22 mm and total portal tract count was 12 (complete 6, partial 6). Median HVPG was 4 mmHg: 38% of patients Ն6 mmHg (portal hypertension, PHT), 13% Ն10 mmHg. HVPG correlated with Ishak stage (r ϭ 0.73, P Ͻ 0.001) for mild (0-3) and severe fibrosis (4-6), and grade score (r ϭ 0.47, P Ͻ 0.001), but neither correlated with interval from LT nor biopsy length. HVPG was Ն10 mmHg in 15 patients: 12 had stage 5 or 6, and 3 severe portal expansion. HVPG was repeated in 49, between 7 and 60 months with weak correlation to fibrosis score (r ϭ 0.30, P ϭ 0.045). A total of 12 patients with HVPG Ն6 mmHg had fibrosis score Յ3, while 8 patients had normal HVPG but fibrosis stage Ն4. These discrepancies were mostly associated with specific histological features such as perisinusoidal fibrosis rather than errors in measuring HVPG. In 29 with HVPG Ͻ6 mmHg at 1 yr, none decompensated compared to 4 of 13 (31%) with PHT. In conclusion, HVPG correlates with fibrosis and its progression, due to recurrent HCV infection, assessed in TJB. Liver Transpl 13:1305Transpl 13: -1311Transpl 13: , 2007 The severity of portal hypertension (PHT) correlates with the severity of liver disease and cirrhosis, both functionally and histologically 1 and also with the Model for End-Stage Liver Disease, 2 such that it has independent prognostic value separate from clinical and laboratory assessment. 2,3 Hepatic vein catheterisation 4 was modified by Groszmann et al. 5 using a balloon catheter. The measurement of hepatic venous pressure gradient (HVPG) (the difference between wedge hepatic venous pressure [WHVP] Ϫ free hepatic venous pressure) is reproducible 6 and is the preferred technique for evaluating PHT, correlating 1:1 with the direct measurement of portal vein pressure in patients with sinusoidal and postsinusoidal causes of cirrhosis, 7,8 particularly alcoholic and viral-related cirrhosis. Normally HVPG ranges from 1 to 5 mmHg; pressures Ն6 mmHg indicate PHT. 6 WHVP increases with progression of chronic hepatitis and PHT, before histologically detectable cirrhosis. 9 A gradient Ͼ5 mmHg was always associated with significant changes in liver biopsy in 1 study, although a normal gradient did not completely rule out cirrhosis, 10 suggesting that WHVP could provide supplementary information to liver biopsy, with a higher predictive value for assessing stage and activity of chronic liver disease, than routine biochemical tests. 10 Other studies have correlated HVPG both with severit...

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Hepatocellular carcinoma (HCC) may still develop in chronic hepatitis B (CHB) patients treated with lamivudine. Whether HCC rates are comparable in patients treated with the current first-line antivirals remains uncertain. We estimated the incidence and evaluated predictors of HCC in a large nationwide prospective cohort (HepNet.Greece) of HBeAg-negative CHB patients treated with entecavir. HBeAg-negative CHB patients from the same cohort who were initially treated with lamivudine were used as controls. We included 321 patients treated with entecavir for a median of 40 months and 818 patients treated initially with lamivudine for a median of 60 months. In the entecavir group, HCC developed in 4 of 321 (1.2%) patients at a median of 1.5 (range: 1.0-4.5) years, while the cumulative HCC incidence was significantly higher in cirrhotics than noncirrhotics (1, 3, 5 years: 0%, 3%, 9% vs 1%, 1%, 1%; P = 0.024) and in older patients (P = 0.026). Entecavir compared with lamivudine group patients had lower HCC incidence (1, 3, 5 years: 0.3%, 1.2%, 2.8% vs 0.7%, 3.8%, 5.6%; P = 0.024). However, in multivariable Cox regression analysis, the HCC risk was independently associated with older age (P < 0.001), male gender (P = 0.011) and cirrhosis (P = 0.025), but not with the initial agent. In conclusion, our large nationwide study indicates that the HCC risk remains increased in entecavir-treated HBeAg-negative CHB patients with cirrhosis, particularly of older age, at least for the first 5 years. The HCC risk does not seem to be significantly reduced with entecavir compared with antiviral therapy starting with lamivudine.