Aliment Pharmacol Ther 2011; 34: 353–362Summary: Background  Transient elastography has gained popularity to stage liver fibrosis in chronic viral hepatitis, however, diagnostic cut‐offs for severe fibrosis in chronic hepatitis B are poorly defined.Aim  To evaluate an algorithm with two distinct cut‐offs for positive and negative prediction of significant fibrosis and cirrhosis in chronic hepatitis B patients.Methods  Two cohorts of treatment‐naïve patients with chronic hepatitis B (125 training and 92 validations) were consecutively and concurrently examined by percutaneous liver biopsy and transient elastography. Fibrosis was staged by Metavir (significant fibrosis = F ≥ 2; cirrhosis = F4) in ≥2 cm long liver tissue cores.Results  A >13.1 kPa positive and a ≤9.4 kPa negative cut‐off for cirrhosis had a >90% sensitivity and specificity, with an accuracy of 94%. The corresponding cut‐offs for F ≥ 2 were >9.4 and ≤6.2 kPa, thus classifying 56% of patients with an overall accuracy of 90%. In the validation cohort, F4 and F ≥ 2 were predicted by the above transient elastography cut‐offs with an overall accuracy >90%. In 165 patients with higher than upper limit of normal transaminase activity the dual cut‐off algorithm of transient elastography was as accurate as in the 52 patients with normal alanine aminotransferase values in the prediction and exclusion of cirrhosis, only.Conclusions  A dual cut‐off algorithm allowed for correctly classifying both significant fibrosis and cirrhosis in the majority of the patients with chronic hepatitis B, independent of alanine aminotransferase values, thus reducing the need for liver biopsy investigations.

Despite progress in our understanding of the biology of hepatocellular carcinoma (HCC), this tumour remains difficult-to-cure for several reasons, starting from the particular disease environment where it arises—advanced chronic liver disease—to its heterogeneous clinical and biological behaviour. The advent, and good results, of immunotherapy for cancer called for the evaluation of its potential application also in HCC, where there is evidence of intra-hepatic immune response activation. Several studies advanced our knowledge of immune checkpoints expression in HCC, thus suggesting that immune checkpoint blockade may have a strong rationale even in the treatment of HCC. According to this background, initial studies with tremelimumab, a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor, and nivolumab, a programmed cell death protein 1 (PD-1) antibody, showed promising results, and further studies exploring the effects of other immune checkpoint inhibitors, alone or with other drugs, are currently underway. However, we are still far from the identification of the correct setting, and sequence, where these drugs might be used in clinical practice, and their actual applicability in real-life is unknown. This review focuses on HCC immunobiology and on the potential of immune checkpoint blockade therapy for this tumour, with a critical evaluation of the available trials on immune checkpoint blocking antibodies treatment for HCC. Moreover, it assesses the potential applicability of immune checkpoint inhibitors in the real-life setting, by analysing a large, multicentre cohort of Italian patients with HCC.

Prevention of infections is crucial in solid organ transplant (SOT) candidates and recipients. These patients are exposed to an increased infectious risk due to previous organ insufficiency and to pharmacologic immunosuppression. Besides infectious-related morbidity and mortality, this vulnerable group of patients is also exposed to the risk of acute decompensation and organ rejection or failure in the pre- and post-transplant period, respectively, since antimicrobial treatments are less effective than in the immunocompetent patients. Vaccination represents a major preventive measure against specific infectious risks in this population but as responses to vaccines are reduced, especially in the early post-transplant period or after treatment for rejection, an optimal vaccination status should be obtained prior to transplantation whenever possible. This review reports the currently available data on the indications and protocols of vaccination in SOT adult candidates and recipients.

Background and aims The diagnostic accuracy of transient elastography (TE) for assessment of hepatic fibrosis is hampered by several factors, including acute parenchymal injury. Evaluation of liver stiffness (LS) using TE during acute hepatitis B may help to assess chronic hepatitis B patients with flares. Patients and methods Twelve patients consecutively referred for acute hepatitis B, underwent sequential examinations with TE and laboratory examinations for 24 weeks. Results On admission, aminotransferase ranged from 487 to 6067 IU/l (median=2590 IU/l) and LS ranged from 7.1 to 57 kPa (median=15.6 kPa) with nine (75%) patients showing LS greater than 11.9 kPa, that is, the predictive cutoff for cirrhosis. LS levels correlated significantly with bilirubin, only (r=0.58, P<0.05). During follow-up, LS declined from 15.6 to 5.2 kPa at week 24, with a significant reduction being observed at week 2 for aminotransferase (from 2590 to 452 IU/l, P<0.0001) and at week 6 for both LS (from 15.6 to 6.0 kPa, P=0.008) and bilirubin (from 10.7 to 0.95 mg/dl, P<0.01). Median decline of LS significantly correlated with bilirubin decline (r_s=0.70, P<0.05). At week 24, 10 (83%) patients showed LS of less than 7.9 kPa and two (17%) patients had LS values between 7.9 and 11.9 kPa, including the only patient who developed chronic hepatitis B. Conclusion In patients with acute hepatitis B, the initial high values of LS mimicking LS cutoff of cirrhosis, likely reflect the liver cell inflammation, oedema and swelling as they progressively taper down during hepatitis resolution.