Current Hepatology Reports

This paper aims to summarize the data of recently completed and key ongoing clinical trials of systemic agents for advanced hepatocellular carcinoma (aHCC). In particular, the review focuses on ongoing checkpoint inhibitor combination trials and promising studies combining tyrosine kinase inhibitors with checkpoint inhibitors. The recently approved combination of atezolizumab and bevacizumab based on the IMbrave150 trial has shown the most potential with the highest overall survival of any systemic agent in HCC to date, surpassing sorafenib. Despite COVID-19 delays, other promising trials that involve combining VEGF-directed therapy and checkpoint inhibition, cancer vaccines, phosphatidylserine, YIV-906, and oncolytic and immunotherapeutic vaccinia virus are actively recruiting patients. After almost a 10-year dormancy, the list of potential systemic treatment options for aHCC is growing rapidly. Given the promising data from the IMbrave150 trial, the combination of atezolizumab and bevacizumab is now the new first-line therapy. We discuss the change in landscape, the new second- and third-line systemic treatments in aHCC, and the ongoing clinical trials for newer agents including combination therapies.

The growing epidemic of obesity has led to an increase in the number of patients developing end-stage liver disease related to nonalcoholic steatohepatitis (NASH). In fact, NASH is now the second-leading etiology for liver transplantation in the USA. In this context, interest is growing in understanding the outcomes of liver transplantation in patients with NASH. Current data suggest that the short- and medium-term outcomes for NASH patients post-transplantation are not different from those for other recipients. Nevertheless, patients with NASH and diabetes may have higher risk post-transplantation for de novo diabetes. Caregivers must be vigilant post-transplant for the development of de novo diabetes regardless of their pre-transplant status. NASH patients also seem to have a lower functional status post-transplant. There are conflicting data regarding the outcome of morbidly obese patients with NASH who undergo liver transplantation. The pre-transplant management of these patients with surgical weight loss is reported, but caution must be exercised in considering them for transplant.

Direct-acting antiviral regimens for chronic hepatitis C virus (HCV) infection became available in 2014, and these highly curative therapies have the potential to reduce HCV-associated morbidity and mortality, decrease HCV transmission, and eliminate HCV infection as a public health problem. This review summarizes the recommendations by the National Academies of Sciences, Engineering, and Medicine for a US strategy for HCV elimination. To achieve proposed targets of reducing HCV incidence by 90% and decreasing HCV-related mortality by 60% by 2030, there is a critical need to improve HCV diagnosis and linkage to care, reduce HCV-related disease by antiviral treatment scale-up, reduce HCV incidence, and strengthen HCV surveillance to determine achievement of HCV elimination targets over time. While HCV elimination is feasible, success of this national effort will require ongoing collaboration and critical resource investment by key stakeholders, including medical and public health communities, legislators, community organizers, and patient advocates.

Trong bài tổng quan này, chúng tôi trình bày những bằng chứng cho thấy phần lớn bệnh nhân viêm gan B mãn tính HBeAg âm tính, người đã từng được điều trị bằng lamivudine và sau đó là adefovir và entecavir, sẽ gặp phải tái phát vi sinh cũng như lâm sàng nếu các liệu pháp này bị ngừng. Do đó, các hướng dẫn điều trị hiện tại của AASLD và EASL khuyến nghị thời gian điều trị bằng thuốc kháng vi-rút (NA) là không có giới hạn cho những bệnh nhân này. Tuy nhiên, khuyến nghị của APASL lại khác, khuyên nên ngừng điều trị NA nếu HBV-DNA âm tính trong ba lần xét nghiệm liên tiếp ít nhất cách nhau 6 tháng. Rõ ràng rằng thời gian remiss kéo dài sau điều trị là biến đổi và kết quả cuối cùng là không thể dự đoán. Tuy nhiên, sự dao động của mức độ HBV-DNA sau điều trị không phải là hiếm và bệnh nhân viêm gan B mãn tính HBeAg âm tính có thể trải qua những khoảng thời gian dài không phát hiện được HBV-DNA tạm thời. Dữ liệu về tần suất mất HBsAg sau điều trị là đầy hứa hẹn nhưng vẫn còn hạn chế. Cần nhấn mạnh rằng cần phải có các nghiên cứu đa trung tâm, đa quốc gia, tiềm năng.

Venous thromboembolism (deep vein thrombosis and pulmonary embolism) and portal vein thrombosis (PVT) occur in up to 6.3 % and 15.9 % of patients with cirrhosis, respectively. There is recent evidence that a procoagulable prothrombotic state is related to cirrhosis despite the reduced levels of many coagulation factors, and decreased platelet counts. Indeed, (i) the combination of high levels of factor VIII, with low levels of protein C and antithrombin induces a procoagulant state in vitro; while (ii) increased levels of von Willebrand factor and decreased ADAMTS 13 activity can compensate for decreased platelet counts. PVT is partial in a majority of patients in whom it develops and may spontaneously resolve in some of them. Although PVT is associated with features of more severe liver disease, it is uncertain whether it plays a causal role in the decompensation of cirrhosis. In patients listed for liver transplantation, PVT may make the procedure difficult or impossible. Pre-transplant PVT is associated with increased post-transplant mortality rates. Studies evaluating clinical outcome of anticoagulation therapy for splanchnic or extrasplanchnic venous thrombosis are scarce. Anticoagulation therapy, given to patients with cirrhosis of intermediate severity before PVT occurrence, in prophylactic doses, appears to decrease decompensation and mortality rate. Interestingly, this improvement is out of proportion of the prophylaxis of extrahepatic portal vein thrombosis. The risk of bleeding does not seem to be increased in patients with cirrhosis receiving anticoagulation therapy, once prophylaxis for bleeding related to portal hypertension has been implemented. Overall, the room for anticoagulation therapy is probably larger than previously recognized, and may be of particular benefit in patients without portal vein thrombosis. However, clinical trials remain to be done before the benefit risk ratio of anticoagulation therapy is properly evaluated.

The purpose of this review was to analyze the current evidence regarding the incidence, mechanisms, and outcomes of drug-induced liver injury (DILI) and hepatotoxicity in patients with metabolic syndrome and nonalcoholic fatty liver disease. DILI is a complex clinical entity. Although uncommon, its incidence and diagnosis have been rising in recent years as basic research and clinical databases provide information about its etiology, clinical course, and prognosis. The prevalence of metabolic syndrome and non-alcoholic fatty liver disease is on the rise in western countries. Recently, features of the metabolic syndrome have been identified as factors affecting the phenotype and evolution of DILI, both in pre-clinical and clinical research. In the present review, we summarize current evidence regarding the influence of features of metabolic syndrome in the presentation, clinical course, and prognosis of DILI.

Nonalcoholic fatty liver disease (NAFLD) has emerged as the most common cause of chronic liver disease in Western countries. NAFLD can progress to cirrhosis and its related complications, including hepatocellular carcinoma (HCC). Review of available evidence suggests an increased risk of HCC among patients with NAFLD-related cirrhosis, although this risk is smaller than risk of HCC among patients with viral hepatitis-related cirrhosis. Preliminary evidence suggests that a proportion of NAFLD-related HCC could develop in the absence of advanced liver disease or cirrhosis. NAFLD-related HCC is expected to increase, given the increasing prevalence of NAFLD; but this increase is not yet evident. Risk factors for HCC in NAFLD include older age, coexisting obesity or diabetes, high hepatic iron, and the presence of cirrhosis.

Hepatitis B virus (HBV) is a leading cause of hepatocellular carcinoma (HCC). Patients in the early phase of chronic HBV infection are designated “immune-tolerant” due to highly active viral replication without significant liver damage. Although these individuals are believed to have a low HCC risk, recent data showed conflicting results, which are summarized in this review. Clonally expanded hepatocytes with HBV integration have been detected in immune-tolerant patients, implying a theoretical HCC risk. Different cohort studies have shown conflicting HCC risk due to the heterogeneity of the patient population defined by fluctuating variables such as HBV DNA and alanine aminotransferase levels. As antiviral treatment response is poor, initiating prolonged therapy in immune-tolerant patients poses a challenge. The absence of a clear definition for “genuine” immune-tolerant patients underscores the necessity for novel and stable biomarkers to guide when to start antiviral treatment.