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The multikinase inhibitor sorafenib was the only approved systemic therapy in advanced hepatocellular carcinoma (hcc) for about a decade. In recent years, the number of approved agents has increased significantly as a result of a number of positive phase iii clinical trials. Lenvatinib as a first-line treatment, and regorafenib, cabozantinib, and ramucirumab in the second-line setting are now approved by the U.S. Food and Drug Administration (fda) and the European Medicines Agency. In phase ii studies, immunotherapy with nivolumab and monotherapy using pembrolizumab yielded impressive results for overall survival in therapy-naïve and pretreated patients, leading to the accelerated approval by the fda of nivolumab and pembrolizumab for second-line treatment. However, phase iii trials of nivolumab in the first line and pembrolizumab in the second line as single agents failed to reach statistical significance, although clinical benefit for a subset of patients with long durations of response could be demonstrated. Despite that setback, immunotherapy for hcc is a promising therapeutic approach, and the combination of immunotherapy with other treatment modalities such as monoclonal antibodies, tyrosine kinase inhibitors, or local therapies has the potential to increase the overall response rate and survival. Recently, the results of a phase iii trial of combination atezolizumab-bevacizumab compared with sorafenib showed a highly significant survival benefit and median overall survival that was not reached in the immunotherapy arm, making the combination the preferred standard of care in first-line therapy. Despite the impressive results and generally good toxicity profile of immunotherapy, patients who respond to therapy constitute only a subset of the overall population, and response rates are still limited. This review focuses on the currently reported results and ongoing clinical trials of checkpoint inhibitor-based immunotherapy in hcc., Competing Interests: CONFLICT OF INTEREST DISCLOSURES We have read and understood Current Oncology’s policy on disclosing conflicts of interest, and we declare the following interests: AW has received lecture fees from Bayer, Leo Pharma, and Eisai, and has received advisory board fees and travel support from Bayer, Bristol Myers Squib, and Wako Diagnostics. PRG has received consulting fees from AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, Eli Lilly, Hoffmann–La Roche, Ipsen Biopharmaceuticals, Merck Sharp and Dohme, and Sirtex Medical., (2020 Multimed Inc.)

Background: External validation of prognostic risk models is essential before they are implemented in clinical practice. This study evaluated the recently developed MEGNA score for survival prediction after resection of intrahepatic cholangiocarcinoma (ICC), with a focus on the direct comparison of its prognostic value to that of the current International Union Against Cancer (UICC)/American Joint Committee on Cancer (AJCC) Cancer staging system., Material and Methods: Between 1997 and 2018, 417 consecutive patients with ICC were referred to our tertiary care centre and were retrospectively identified out of a dedicated clinical database. Of this group, 203 patients underwent surgical resection and met the inclusion criteria. Multivariate analysis was performed to assess the predictors of the recently proposed MEGNA score regarding overall survival (OS). Concordance indices (C-indices) and integrated Brier scores (IBS) were calculated to assess the ability of both the MEGNA score and the current (8th) edition of the UICC/AJCC Cancer staging system to predict individual patient outcome., Results: Stratification according to the MEGNA score resulted in a median OS of 34.5 months, 26.1 months, 21.5 months, and 16.6 months for MEGNA scores 0, 1, 2, and ≥3, respectively (log rank p < 0.001). However, of the five factors that contribute to the MEGNA score, age > 60 years was not a predictor for poor OS in our cohort. The C-index for the MEGNA score was 0.58, the IBS was 0.193. The 8th edition of the UICC/AJCC system performed slightly better, with a C-index of 0.61 and an IBS of 0.186., Conclusion: The ability of the MEGNA score to predict individual patient outcome was only moderate in this external validation. Its prognostic value did not reach that of the more widely known and used UICC/AJCC system. However, neither scoring system performed well enough to support clear-cut clinical decisions., Competing Interests: The authors have declared that no competing interests exist.

Background: Antibodies to soluble liver antigen/liver pancreas (SLA/LP) are specific markers of autoimmune hepatitis. Their target antigen has recently been cloned., Aims: To establish standardised immunoassays using the recombinant antigen, and to assess the frequency and significance of seropositivity in patients from different countries., Methods: An enzyme linked immunoassay was developed using purified recombinant antigen and validated by testing sera from 200 healthy blood donors and 1026 patients with various liver and non-liver diseases. The assay was then applied to 454 sera from 419 patients with autoimmune hepatitis from different countries. All sera were also tested by inhibition immunoassay and western blot., Results: Antibodies were reliably detected by the recombinant immunoassay and occurred exclusively in patients with autoimmune liver disease. Twenty three of 149 patients from the USA (15%), 23/132 from Brazil (17%), 21/108 from Germany (19%), and 2/30 from Japan (7%) were seropositive. Clinical features at presentation were similar between seropositive and seronegative patients. However, relapse after corticosteroid withdrawal or during maintenance therapy occurred more commonly in seropositive patients., Conclusions: Antibodies to SLA/LP can be reliably detected by these standardised immunoassays based on recombinant antigen. Antibodies to SLA/LP occur with similar frequencies in different geographical regions, races, and age groups, and are of exquisite diagnostic specificity. Whether SLA/LP positive patients represent a clinically distinct subgroup remains to be determined; relapse during treatment reduction appeared to be more common in the SLA/LP group.