Álvaro Díaz-González

Treatment of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) represents the most frequent primary liver cancer. This disease usually arises as a result of a chronic liver disease, but may appear without any underlying disease. In most units, the staging and treatment decision in patients with HCC follows the Barcelona Clínic Liver Cancer (BCLC) strategy. Following this approach, patients diagnosed with HCC are classified according to tumour burden, liver function and ECOG-Performance Status (PS). This stratifies patients according to prognosis and links each stage with the evidence-based treatment approach to be first considered. Patients correspond to BCLC stage 0 (very early) when the tumour burden accounts for just one nodule and it measures 2 cm or less. BCLC stage A includes patients with just one nodule or 3 nodules under 3 cm. Both stages 0 and A gather patients with preserved liver function according to Child-Pugh score, being Child-Pugh A. Patients in BCLC B stage (intermediate stage) are patients with multinodular liver cancer confined to the liver, without extrahepatic disease, ECOG-PS 0 and preserved liver function (Child-Pugh A or B). Patients with portal venous invasion, extrahepatic disease or cancer-related symptoms measured by PS (1-2) and still with preserved liver function correspond to BCLC C (advanced) stage. Finally, patients classified in BCLC stage D are those with a severe alteration of liver function (Child-Pugh C) or severe cancer-related symptoms with PS above 2. In very early and early stages (BCLC 0 and A), treatment options include surgical treatment, ablation and liver transplantation. Intermediate stage (BCLC B) patients should be considered for transarterial chemoembolization. At advanced stage (BCLC C), the recommended treatment is sorafenib. Finally, at the end stage (BCLC D), symptomatic treatment is the suggested option. The treatment stage migration concept refers to patients who at first glance would be treated with the option that corresponds to their BCLC stage but, because of any coexisting comorbidity, technical issue or even treatment failure/progression but still within the original stage cannot be treated by the initial suggested treatment. These patients then move to the treatment that would correspond to the next stage/s.

Endoscopic retrograde cholangiography for biliary anastomotic strictures after liver transplantation.

Biliary complications after liver transplantation (LT) are an important cause of morbidity and mortality. In most cases, an anastomosis of the bile duct is performed as a duct-to-duct reconstruction, which makes endoscopic therapy with endoscopic retrograde cholangiography (ERC) feasible. Biliary anastomotic strictures (AS) are the most common cause of biliary complications. The early detection of an AS, which can sometimes be challenging given that its clinical presentation is often subtle, is of key importance to obtain high treatment success. In this review, we focus on the management of AS after LT with a special emphasis on ERC.

Complete response under sorafenib in patients with hepatocellular carcinoma: Relationship with dermatologic adverse events

The clinical benefit of sorafenib in patients with hepatocellular carcinoma (HCC) has been undervalued due to the absence of complete responses, even though patients who develop early dermatologic reactions have shown to have a positive outcome. In addition, sorafenib is described as an antiangiogenic drug, but it also acts on immunological cells. Thus, the goal of this study was to assess the complete response rate in a retrospective cohort of HCC patients treated with sorafenib and to describe the profile of the patients who achieve complete response for identifying factors related to this event and their connection with the immunological profile of sorafenib. Ten Spanish centers submitted cases of complete response under sorafenib. The baseline characteristics, development of early dermatologic reactions, and cause of treatment discontinuation were annotated. Radiological images taken before starting sorafenib, at first control, after starting sorafenib, at the time of complete response, and at least 1 month after treatment were centrally reviewed. Of the 1119 patients studied, 20 had been classified as complete responders by the centers, but eight of these patients were excluded after central review. Ten patients had complete disappearance of all tumor sites, and two had just a small residual fibrotic scar. Thus, 12 patients were classified as complete responders (58% HCV, median age 59.7 years, 83.4% Child‐Pugh class A, Eastern Cooperative Oncology Group performance status 0 91.7%, and Barcelona Clinic Liver Cancer stage C 83.3%). The median overall survival and treatment duration were 85.8 and 40.1 months, respectively. All but one patient developed early dermatologic reactions, and seven patients discontinued sorafenib after achieving complete response due to adverse events, patient decision, or liver decompensation. Conclusion: Complete response affects 1% of patients with HCC who are treated with sorafenib. The association of complete response with early dermatologic reactions supports the role of a specific immune/inflammatory patient profile in the improved response to sorafenib. (Hepatology 2018;67:612‐622).

Surveillance for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) appears mainly in patients with underlying liver disease and it is recognized as one of the most important causes of death in this population. Early detection by surveillance has been suggested as an effective tool for reducing cancer-specific mortality and the most accepted strategy is semiannual abdominal ultrasound in those patients at risk of HCC development. The benefit of HCC surveillance is proven by a randomized-controlled study, several prospective or retrospective analyses, and multiple modeling studies and according to the current scientific evidence, surveillance of HCC should be recommended and widely implemented. Major efforts should be done for improving the diagnostic accuracy of the screening tools and for better identifying those patients at risk of HCC development in whom a surveillance program would be cost-effective.

Prognosis prediction and staging

Staging and prognosis assessment are critical steps in the management of patients with hepatocellular carcinoma. This cancer is a complex disease usually associated with chronic liver disease, and any attempt to assess the prognosis should consider tumour burden, degree of liver function impairment and evaluation of cancer-related symptoms. In addition, for any staging system to be meaningful it has to link staging with treatment indication and this should be based on robust scientific data. Currently, the only proposal that serves both aims is the Barcelona Clinic Liver Cancer (BCLC) staging system. It divides patients into very early/early, intermediate, advanced and end-stage. Very early/early stage HCC patients should be considered for potentially curative options such as resection, transplantation and ablation. Patients at intermediate stage benefit from chemoembolization, while patients at an advanced stage or who cannot benefit of options of higher priority have sorafenib as standard of care. Finally, patients at end-stage should receive best supportive care.

Liver Metastases From Gastric Adenocarcinoma Mimicking Multinodular Hepatocellular Carcinoma: Clinical Observations in Hepatology

Hepatoid Adenocarcinoma of the Stomach (HAS) is a very infrequent condition. It represents <1% of all gastric tumors(1), and includes those with adenocarcinomatous and hepatocellular differentiation. Diagnosing metastatic HAS involving the liver may be challenging due to its hepatoid appearance at pathology. This is more relevant in Asia, where HAS is more prevalent and overlaps with a high prevalence of hepatocellular carcinoma (HCC). This article is protected by copyright. All rights reserved.

New Systemic Treatments in Advanced Hepatocellular Carcinoma

The principal advancements in the treatment of hepatocellular carcinoma (HCC) are the use of new systemic treatments, such as lenvatinib in first‐line treatment and regorafenib, cabozantinib, and ramucirumab in second‐line treatment, because of their benefits in terms of overall survival. In addition, nivolumab as a second‐line agent was approved by the US Food and Drug Administration in 2017 based on improved radiological response data. Physicians and patients alike will greatly benefit from this expanded arsenal of treatments once all these new drugs for the treatment of HCC finally become available. Unfortunately, in our review of the available data, we found a conspicuous lack of approved systemic treatments for HCC in the distinct setting of after liver transplantation (LT). Careful evaluation of the clinical trials for approved systemic treatments of HCC is crucial when considering the best options for those with HCC recurrence after LT. Although several first‐line or second‐line treatments have been shown to be effective for HCC, each of these trials was composed of its own specific populations, and those with HCC recurrence after LT were excluded. We have also summarized from a critical and clinical point of view the issues involved in the management of patients who are candidates for systemic treatment in this era of multiple drugs for the same indication.

Sorafenib and Clinical Patterns of Resistance in Hepatocellular Carcinoma

Sorafenib is the first-line systemic treatment in hepatocellular carcinoma (HCC). The benefits of sorafenib in HCC show an improvement in overall survival and delay of radiologic tumor progression. These benefits were demonstrated in the absence of a high rate of overall response and the magnitude of this improvement varies considerably from patient to patient. Several hypotheses have tried to address the reason for this variability, giving birth to the emerging field of sorafenib resistance. The aim of this chapter is to discuss the clinical evolutionary events such as early dermatologic adverse events, pattern of progression or serum biomarkers modification that have an impact both on the patient’s outcome as well as in the patient’s management. The pattern of progression classifies patients in four different groups: (1) intra-hepatic (2) extra-hepatic increase in tumor size (3) new intra-hepatic lesion and (4) new extra-hepatic lesion and it is correlated with the post-progression overall survival. Hence, careful evaluation of patients characteristics and their evolutionary events during sorafenib treatment are key to identify the best candidates to continue on sorafenib, those who should receive regorafenib as second-line treatment, second-line trials or best supportive care. In addition, the design of second- and third-line clinical trials should consider all the components discussed in this chapter.