In this issue, a number of important updates in hepatology are highlighted. One of the most remarkable advances in the field in the last decade has been the introduction of direct acting antiviral (DAA) agents for treatment of chronic hepatitis C virus (HCV) infection. These new agents have proved to be so effective and so well tolerated that while initially, their use was triaged largely to patients who had advanced fibrosis, they are now being used in nearly all patients. It is well known that fibrosis may revert, as this has been demonstrated already in patients treated for hepatitis B virus infection, autoimmune hepatitis, alcoholic hepatitis, and others. With the widespread use of DAAs, one of the most important questions, especially in patients with advanced fibrosis is whether patients will gain long-term benefit, particularly as a result of reversion of fibrosis. This topic is addressed by Rockey (pp. 137–144).
Hepatic encephalopathy remains one of the most important complications of cirrhosis and end-stage liver disease (ESLD). This field has evolved extremely rapidly over the last decade, with the development of many novel approaches, largely centered around lowering of ammonia. The introduction of novel potential therapeutic approaches over the last decade has been notable. Alsahhar and Rahimi (pp. 145–154) highlight a number of new studies that shed light on improved management approaches for hepatic encephalopathy.
Patients with ESLD are difficult to manage for many reasons, largely related to the multiple and life-threatening complications as well as the extremely high symptom burden that leads to a poor quality of life. Although liver transplantation can be lifesaving, this is not always possible. Thus, it has become clear that palliative care, a multidisciplinary model of care that focuses on the patient (and is not the same as hospice or end of life care) is a critical element in the care of these patients. This field has rapidly evolved in hepatology, and thus it is fitting that Rakoski and Volk (pp. 155–160) provide a timely update and highlight the latest in this important field.
Despite the conventional wisdom that patients with cirrhosis are ‘auto-anticoagulated’, available data suggests that patients with cirrhosis have a similar (or perhaps even increased) risk for development of deep venous thrombosis and pulmonary embolism; portal vein thrombosis is also an important risk for patients with cirrhosis (and often abnormal portal blood flow). Thus, anticoagulation is often prescribed. In this issue, a review by Sasso and Rockey (pp. 161–167) highlights a variety of important issues on this topic, including the risk of bleeding while on anticoagulation.
Non alcoholic fatty liver disease (NAFLD) has now become the most common cause of chronic liver disease in Western countries, and with the promise of DAAs that will likely eradicate HCV in many patients, it promises to become by far the most prominent cause of liver disease. Current evidence suggests that while the best therapy for NAFLD is lifestyle modification, in particular – weight loss, this is rarely successful because weight loss is often difficult to achieve and/or maintain. Thus, many other approaches have gained great interest and currently there are many ongoing clinical trials to evaluate NAFLD treatments, including a number of novel pharmacologic agents. Vitamin E, pioglitazone, pentoxifylline, and others have been studied, but are largely unsatisfactory. Notwithstanding, Shetty and Syn (pp. 168–176) provide an overview of the newest available therapies (and some others likely to be available soon), as well as an overview of the best practices for NAFLD treatment.
Given that HCV is now more treatable than ever, it has become critically important to identify patients with HCV infection. Since the infection is usually asymptomatic, often until complications of cirrhosis become evident, screening is one of the major methods by which to identify the disease. In 2012, the US Centers for Disease Control and Prevention updated its guidelines by recommending universal HCV screening for the individuals in the 1945–1965 birth cohort. Bian and Schreiner (pp. 177–182) bring to our attention the point that younger birth cohorts have recently been experiencing a higher incidence of HCV infection than those in the birth cohort from 1945 to 1965. Thus, more vigilant screening and monitoring is needed in these individuals. To meet the goal of eliminating HCV infection as a US public health problem in the next decade, significant improvement in screening, detection, and diagnosis will be needed.
Drug-induced liver injury (DILI) remains an important and challenging problem in hepatology. DILI is a clinical diagnosis, based on drug-specific features (such as the timing of the administration of the drug, and the characteristics of the injury pattern) as well as of exclusion of other liver diseases (such as viral and autoimmune hepatitis, etc.). Currently, there are several available causality assessment tools in use, including the Roussel-Uclaf-Causality-Assessment-Method, Digestive-Disease-Week Japan 2004 scale, and Clinical Diagnostic Scale systems. In addition, structured expert opinion has received considerable attention, and appears to be the most reliable current method. In a contribution by Tillmann et al. (pp. 183–190), these various instruments are reviewed, and suggestions for future improvement are highlighted.
Primary biliary cholangitis remains one of the most challenging liver diseases currently faced by clinicians. One of the latest advances in this disease has been the introduction of obeticholic acid (OCA), a synthetically modified bile acid and potent agonist of the farnesoid X nuclear receptor used to treat liver diseases because of its ability to lead to down regulating a variety of activity on enzymes involved in bile acid synthesis [including cytochrome P450 7A1 (CYP7A1) and CYP8B1]. Though OCA appears to significantly lower alkaline phosphatase levels, the Food and Drug Administration warned that OCA is being incorrectly dosed in some patients with moderate-to-severe impairment in liver function, resulting in an increased risk of serious hepatotoxicity. Thus, it is critical to understand the appropriate indications for, and use of this new medication, making the review in this issue by Manne and Kowdley (pp. 191–196) extremely timely.
Financial support and sponsorship
Research funding has been provided to the author's institution (not the author himself) from the following commercial entities for research purposes:
- Connatus Pharmaceuticals
- Cumberland Pharmaceuticals
- Gilead Sciences
- Intercept Pharmaceuticals
- Ironwood Pharmaceuticals
- Mallinckrodt Pharmaceuticals
- Salix Pharmaceuticals
Conflicts of interest
There are no conflicts of interest.