Reviews
Intercellular crosstalk of liver sinusoidal endothelial cells in liver fibrosis, cirrhosis and hepatocellular carcinoma
Intercellular crosstalk among various liver cells plays an important role in liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Capillarization of liver sinusoidal endothelial cells (LSECs) precedes fibrosis and accumulating evidence suggests that the crosstalk between LSECs and other liver cells is critical in the development and progression of liver fibrosis. LSECs dysfunction, a key event in the progression from fibrosis to cirrhosis, and subsequently obstruction of hepatic sinuses and increased intrahepatic vascular resistance (IHVR) contribute to development of portal hypertension (PHT) and cirrhosis.Distinctive features of hepatocellular carcinoma in non-alcoholic fatty liver disease
Hepatocellular carcinoma (HCC) is on the rise globally, causing more than 800 thousand deaths annually, with an estimated annual percent change of 0.51 for causes other than viral hepatitis, including nonalcoholic fatty liver disease (NAFLD). The incidence of NAFLD-related HCC is peaking in several Far East regions (6–12% vs. 2–3% in Western Europe and USA), HCC risk being mainly driven by the epidemic of obesity and diabetes, both favored by an unhealthy diet and sedentary lifestyle. Under inherited susceptibility outlined by such genetic markers as variants in PNPLA3, TM6SF2 and MBOAT7, neoplastic transformation of NAFLD is driven by sublethal lipotoxicity consequent to hepatocyte lipid overload, whereas a myriad of factors spanning from subverted circadian homeostasis and gut dysbiosis to alcohol abuse and tobacco may interact as risk modifiers.Pathogenesis of hypothyroidism-induced NAFLD: Evidence for a distinct disease entity?
Nonalcoholic fatty liver disease (NAFLD), the most common liver disease worldwide, may be associated with primary hypothyroidism. However, the pathogenesis underlying such an association is complex and not completely understood. Here, we specifically discuss the pathogenic mechanisms potentially involved in hypothyroidism-induced NAFLD. To this end, we summarize the general pathophysiology of thyroid hormones (TH). Next, we analyze the published data from rodent studies by discussing whether hypothyroid rats may develop NAFLD via hyperphagia; whether mitochondria become energetically more efficient; what the overall energy balance is and if diversion of fatty substrates occurs; and the latest advancements in molecular pathogenesis brought about by metabolomics, cell imaging, lipophagy, autophagy and genetically engineered mouse models.Recurrence of hepatocellular carcinoma after direct acting antiviral treatment for hepatitis C virus infection: Literature review and risk analysis
Although studies suggest decreased incident hepatocellular carcinoma (HCC) after treatment with direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection, data are conflicting regarding risk and aggressiveness of recurrence in patients who have a history of treated HCC. This review analyses data available in literature in order to elucidate the impact of DAAs on the risk of HCC recurrence after successful treatment of the tumor. Overall 24 papers were identified. The available data cannot be considered definitive, but the initial alarmist data indicating an increased risk of recurrence have not been confirmed by most subsequent studies.Drug-eluting beads versus conventional chemoembolization for the treatment of unresectable hepatocellular carcinoma: A meta-analysis
Despite the promising results of earlier studies, a clear superiority of drug-eluting beads transarterial chemoembolization over conventional chemoembolization in unresectable hepatocellular carcinoma patients has not been established yet.Liver carcinogenesis: Rodent models of hepatocarcinoma and cholangiocarcinoma
Hepatocellular carcinoma and cholangiocarcinoma are primary liver cancers, both represent a growing challenge for clinicians due to their increasing morbidity and mortality. In the last few years a number of in vivo models of hepatocellular carcinoma and cholangiocarcinoma have been developed. The study of these models is providing a significant contribution in unveiling the pathophysiology of primary liver malignancies. They are also fundamental tools to evaluate newly designed molecules to be tested as new potential therapeutic agents in a pre-clinical set.Transient Hepatic Parenchymal Enhancement detected at dynamic imaging: A short instruction manual for the clinician
Basic knowledge in the interpretation of hepatic imaging is essential for the clinical hepatologist. In recent years, the availability of dynamic imaging studies of the liver using computed tomography or magnetic resonance has led to appreciate the importance of early changes in arterial perfusion for the interpretation of hepatic lesions. Transient Hepatic Parenchymal Enhancement (THPE) is defined as a normal area of liver parenchyma that enhances after injection of contrast agent during the arterial phase of perfusion.Bleeding and thrombosis in cirrhotic patients: What really matters?
Bleeding complications, particularly in the gastro-intestinal tract, may complicate the clinical course of liver cirrhosis. Coexistence of abnormal global tests exploring the platelet and clotting systems generated the hypothesis that cirrhotic patients have “coagulopathy” predisposing to bleeding complications. Using more sophisticated laboratory methods this hypothesis has been partly confuted as cirrhotic patients actually disclose an ongoing prothrombotic state in the portal and systemic circulation that could predispose to thrombosis.New frontiers in biomarkers for hepatocellular carcinoma
Hepatocellular carcinoma represents the fifth most frequent cancer in the world; it commonly occurs on cirrhotic liver. Prognosis and survival are still poor, mainly because of diagnosis at a late stage and/or recurrence of the disease. For this reason, surveillance strategies are widely used to screen for early occurrence of cancer in populations at risk. Alpha-foetoprotein is so far the only serological marker available, but its diagnostic accuracy is unsatisfactory because of low sensitivity despite reliable specificity.Is there a role for immunotherapy in hepatocellular carcinoma?
Incidence of hepatocellular carcinoma has been rising in the last two decades because of the wide exposure to hepatitis C virus during 1960s and 1970s. Improvement in treatment has been achieved by local ablative therapies, however because of early recurrence and lack of effective chemotherapies, alternative treatments based on stimulation of the anti-tumour immune response could represent new strategies to control hepatocellular carcinoma spread and recurrence. Proof of principle of an effective immunotherapy has been achieved for other solid tumours such as melanoma and several results could be transferred to the immunotherapy of hepatocellular carcinoma.
