The main aim of antiviral therapy in patients with chronic hepatitis B (CHB) is to prevent disease progression and reduce the risk of hepatocellular carcinoma (HCC). In general, treatment is recommended for select patien...The main aim of antiviral therapy in patients with chronic hepatitis B (CHB) is to prevent disease progression and reduce the risk of hepatocellular carcinoma (HCC). In general, treatment is recommended for select patient groups viewed as being at higher risk of developing adverse outcomes from CHB. However, patients who do not meet treatment criteria under current international guidelines may still benefit from antiviral therapy to reduce CHB-related complications. Moreover, well-tolerated antiviral drugs that are highly effective at suppressing viral replication are now widely available, and withholding therapy from patients with viremia is increasingly controversial. In this article, we review traditional treatment paradigms and argue the merits of expanding treatment eligibility to patients with CHB who do not meet current treatment criteria.
Acute-on-chronic liver failure (ACLF) results from an acute decompensation of cirrhosis due to exogenous insult. The condition is characterized by a severe systemic inflammatory response, inappropriate compensatory anti-...Acute-on-chronic liver failure (ACLF) results from an acute decompensation of cirrhosis due to exogenous insult. The condition is characterized by a severe systemic inflammatory response, inappropriate compensatory anti-inflammatory response, multisystem extrahepatic organ failure, and high short-term mortality. Here, the authors evaluate the current status of potential treatments for ACLF and assess their efficacy and therapeutic potential.
Owing to inherent limitations of static cold storage, marginal liver grafts from donors after circulatory death and extended criteria donors after brain death are prone to be discarded secondary to the increased risk of...Owing to inherent limitations of static cold storage, marginal liver grafts from donors after circulatory death and extended criteria donors after brain death are prone to be discarded secondary to the increased risk of severe early allograft dysfunction and ischemic cholangiopathy. Marginal liver grafts resuscitated with hypothermic machine perfusion and normothermic machine perfusion demonstrate lower degree of ischemia-reperfusion injury and have decreased risk of severe early allograft dysfunction and ischemic cholangiopathy. Marginal grafts preserved by ex vivo machine perfusion technology can be used to rescue patients with acute-on-chronic liver failure who are underserved by the current deceased donor liver allocation system.
In recent years there has been a significant increase in the incidence of acute-on-chronic liver failure (ACLF). This syndrome is characterized by infections, organ failures, and high short-term mortality. Although progr...In recent years there has been a significant increase in the incidence of acute-on-chronic liver failure (ACLF). This syndrome is characterized by infections, organ failures, and high short-term mortality. Although progress in the management of these sick patients has been evident, liver transplantation (LT) remains the best treatment modality to date. Several studies have reported LT as a feasible option, despite organ failures. The outcomes following LT are inversely related to the grade of ACLF. This review discusses the current literature on the feasibility, futility, timing, and outcomes of LT in patients with ACLF.
Portal hypertension is central to the pathogenesis of complications of cirrhosis, including acute-on-chronic liver failure (ACLF). Both nonselective beta-blockers and preemptive transjugular portal-systemic stent shunt c...Portal hypertension is central to the pathogenesis of complications of cirrhosis, including acute-on-chronic liver failure (ACLF). Both nonselective beta-blockers and preemptive transjugular portal-systemic stent shunt can lower portal pressure, reducing the risk of variceal bleeding, a known trigger for ACLF. However, in patients with advanced cirrhosis, both could potentially induce ACLF by causing hemodynamic instability and hepatic ischemia, respectively, and therefore must be used with caution. Lowering portal pressure with vasoconstrictor such as terlipressin can reverse the kidney failure but careful patient selection is key for success, with careful monitoring for complications.
Bacterial infections (BIs) are the most common precipitating event of acute-on-chronic liver failure (ACLF) and a frequent complication of ACLF. BIs aggravate the course of the syndrome and are associated with higher mor...Bacterial infections (BIs) are the most common precipitating event of acute-on-chronic liver failure (ACLF) and a frequent complication of ACLF. BIs aggravate the course of the syndrome and are associated with higher mortality rates. For this reason, BIs should be promptly diagnosed and treated in all patients with ACLF. The administration of an appropriate empirical antibiotic therapy improves survival in patients with BIs and ACLF and is the cornerstone of treatment. Due to the spread of antibiotic resistance worldwide, the empirical treatment should cover multi-drug-resistant organisms. Herein we reviewed the current evidence about the management of BIs in ACLF.
Acute-on-chronic liver failure (ACLF) is characterized by the presence of chronic liver disease and extrahepatic organ failure and is associated with a high rate of short-term mortality. International societies have soug...Acute-on-chronic liver failure (ACLF) is characterized by the presence of chronic liver disease and extrahepatic organ failure and is associated with a high rate of short-term mortality. International societies have sought to define the criteria for ACLF and differ on definitions. Encephalopathy is an important organ failure in ACLF cases and is included as a marker of ACLF across society definitions. Both brain failure and ACLF commonly occur in the presence of a triggering event and in the setting of the large amount of inflammation that ensues. The presence of encephalopathy as a part of ACLF not only increases the chances of mortality but also provides unique challenges in that the patient will be limited in conversations around major decisions such as need for advanced level of care, liver transplant, or even end-of-life decisions. Many decisions need to be made quickly and occur in parallel in the care of patients with encephalopathy and ACLF and include stabilizing the patient, identifying precipitants or alternative diagnoses, and medical management. Infections has emerged as a major trigger for both ACLF and encephalopathy, and special attention should be given to identifying and treating infections as they occur.
Acute-on-chronic liver failure (ACLF) is a clinical syndrome characterized by severe hepatic dysfunction leading to multiorgan failure in patients with end-stage liver disease. ACLF is a challenging clinical syndrome wit...Acute-on-chronic liver failure (ACLF) is a clinical syndrome characterized by severe hepatic dysfunction leading to multiorgan failure in patients with end-stage liver disease. ACLF is a challenging clinical syndrome with a rapid clinical course and high short-term mortality. There is no single uniform definition of ACLF or consensus in predicting ACLF-related outcomes, which makes comparing studies difficult and standardizing management protocols challenging. This review aims to provide insights into the common prognostic models that define and grade ACLF.
Acute-on-chronic liver failure (ACLF) is characterized by abrupt decompensation in a patient with chronic liver disease with extrahepatic organ dysfunction and is implicated in an increased risk of mortality. ACLF may be...Acute-on-chronic liver failure (ACLF) is characterized by abrupt decompensation in a patient with chronic liver disease with extrahepatic organ dysfunction and is implicated in an increased risk of mortality. ACLF may be present in approximately 20% to 40% of hospitalized cirrhosis. There are several diagnostic scoring systems for ACLF; one defined by the North American Consortium for Study of End-stage Liver Disease is the presence of acutely decompensated cirrhosis complicated by failure of two or more organ systems: circulatory, renal, neurological, coagulopathy, and/or pulmonary.
Acute on chronic liver failure (ACLF) is a unique disease process associated with significant short-term mortality wherein patients with either chronic liver disease or cirrhosis suffer rapid decompensation in hepatic fu...Acute on chronic liver failure (ACLF) is a unique disease process associated with significant short-term mortality wherein patients with either chronic liver disease or cirrhosis suffer rapid decompensation in hepatic function accompanied by extrahepatic organ failures. Alcohol-associated hepatitis (AH) is a common precipitant of ACLF and has been shown to uniquely affect the pathophysiology of systemic and hepatic immune responses in patients with ACLF. Treatment of AH-associated ACLF includes supportive measures as well as treatment directed at AH; however, AH-directed therapies unfortunately remain limited and are of suboptimal efficacy.
Vascular, autoimmune hepatitis, and malignant causes of acute-on-chronic liver failure are rare but important to consider and investigate in patients with underlying liver disease who present with acute deterioration and...Vascular, autoimmune hepatitis, and malignant causes of acute-on-chronic liver failure are rare but important to consider and investigate in patients with underlying liver disease who present with acute deterioration and other more common etiologies have been excluded. Vascular processes including Budd-Chiari syndrome and portal vein thrombosis require imaging for diagnosis and anticoagulation is the mainstay of therapy. Patients may require advanced interventional therapy including transjugular intrahepatic portosystemic shunt or consideration of liver transplantation. Autoimmune hepatitis is a complex disease entity that requires a high degree of clinical suspicion and can present heterogeneously.
Drug-induced liver injury (DILI) is a global problem related to prescription and over-the-counter medications as well as herbal and dietary supplements. It can lead to liver failure with the risk of death and need for li...Drug-induced liver injury (DILI) is a global problem related to prescription and over-the-counter medications as well as herbal and dietary supplements. It can lead to liver failure with the risk of death and need for liver transplantation. Acute-on-chronic liver failure (ACLF) may be precipitated by DILI and is associated with a high risk of mortality. This review addresses the challenges in defining the diagnostic criteria of drug-induced ACLF (DI-ACLF). The studies characterizing DI-ACLF and its outcomes are summarized, highlighting geographic differences in underlying liver disease and implicated agents, as are future directions in the field.
Acute-on-chronic liver failure (ACLF) is a potentially reversible syndrome that develops in patients with cirrhosis or with underlying chronic liver disease (CLD) and is characterized by acute decompensation, organ failu...Acute-on-chronic liver failure (ACLF) is a potentially reversible syndrome that develops in patients with cirrhosis or with underlying chronic liver disease (CLD) and is characterized by acute decompensation, organ failure, and high short-term mortality. Hepatitis A and hepatitis E are major causes of ACLF. Hepatitis B may also cause ACLF through a flare of hepatitis B, acute infection, or reactivation. Besides supportive care, nucleoside/nucleotide analog therapy should also be initiated in this setting. Nonhepatotropic viruses may rarely also cause ACLF with the severe acute respiratory syndrome coronavirus 2 virus recently being identified with poorer outcomes in those with underlying CLD.
Liver regeneration is a multifaceted process by which the organ regains its original size and histologic organization. In recent decades, substantial advances have been made in our understanding of the mechanisms underly...Liver regeneration is a multifaceted process by which the organ regains its original size and histologic organization. In recent decades, substantial advances have been made in our understanding of the mechanisms underlying regeneration following loss of hepatic mass. Liver regeneration in acute liver failure possesses several classic pathways, while also exhibiting unique differences in key processes such as the roles of differentiated cells and stem cell analogs. Here we summarize these unique differences and new molecular mechanisms involving the gut-liver axis, immunomodulation, and microRNAs with an emphasis on applications to the patient population through stem cell therapies and prognostication.
Liver failure can develop as either acute liver failure in the absence of preexisting liver disease, or as acute-on-chronic liver failure in a patient with underlying chronic liver disease or cirrhosis. A timely liver bi...Liver failure can develop as either acute liver failure in the absence of preexisting liver disease, or as acute-on-chronic liver failure in a patient with underlying chronic liver disease or cirrhosis. A timely liver biopsy is helpful to distinguish acute and chronic liver disease, identify precipitating factors, provide prognostic information based on pathologic changes, and aid in making appropriate decisions for patient management. This article will discuss the pathologic features of acute and acute-on-chronic liver failure. Developing an appreciation for the histopathologic patterns of injury observed in these entities is essential for a practical understanding of the diagnostic process.
The three most common definitions of acute-on-chronic liver failure (ACLF) are derived from data from North America, Europe, and the Asian-Pacific Region. All three definitions identify patients with underlying liver dis...The three most common definitions of acute-on-chronic liver failure (ACLF) are derived from data from North America, Europe, and the Asian-Pacific Region. All three definitions identify patients with underlying liver disease who are at increased risk for mortality who develop a syndrome often characterized by associated organ failures. The epidemiology of ACLF differs throughout various regions globally and is driven by the cause of the underlying chronic liver disease and the triggers of ACLF.
NAFLD is a multisystem condition and the leading cause of chronic liver disease globally. There are no approved NAFLD-specific dugs. To advance in the prevention and treatment of NAFLD, there is a clear need to better un...NAFLD is a multisystem condition and the leading cause of chronic liver disease globally. There are no approved NAFLD-specific dugs. To advance in the prevention and treatment of NAFLD, there is a clear need to better understand the pathophysiology and genetic and environmental risk factors, identify subphenotypes, and develop personalized and precision medicine. In this review, we discuss the main NAFLD research priorities, with a particular focus on socioeconomic factors, interindividual variations, limitations of current NAFLD clinical trials, multidisciplinary models of care, and novel approaches in the management of patients with NAFLD.
Globally, the use of digital health interventions (DHIs) is expanding, along with growing scientific evidence of their effectiveness. Given the high and increasing prevalence of noncommunicable liver disease, we surveyed...Globally, the use of digital health interventions (DHIs) is expanding, along with growing scientific evidence of their effectiveness. Given the high and increasing prevalence of noncommunicable liver disease, we surveyed 295 physicians across Spain about their knowledge, beliefs, attitudes, practices, and access with regard to DHIs for patient care and in particular for liver diseases, including nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Physicians reported high familiarity with DHIs, although most had not recommended them in patient care. Addressing concerns, including limited available time, evidence of effectiveness, education, training, and access may contribute to an increased uptake of these technologies.
In addition to adverse clinical outcomes such as liver-related morbidity and mortality, nonalcoholic fatty liver disease (NAFLD) is associated with a substantial public health and economic burden and could also potential...In addition to adverse clinical outcomes such as liver-related morbidity and mortality, nonalcoholic fatty liver disease (NAFLD) is associated with a substantial public health and economic burden and could also potentially impair health-related quality of life and other patient-reported outcomes. The disease also affects multiple aspects of patients' quality of life which are the most pronounced in physical health-related and fatigue domains as well as work productivity, and get more severe in patients with advanced liver disease or with non-hepatic comorbidities. The economic burden of NAFLD is substantial and is increasing, with the highest costs in those with advanced disease.