Classification and Epidemiologic Aspects of Acute-on-Chronic Liver Failure.

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.

Efficacy and safety of anti-hepatic fibrosis drugs.

Recent progress in our understanding of the pathways linked to progression from hepatic insult to cirrhosis has led to numerous novel therapies being investigated as potential cures and inhibitors of hepatic fibrogenesis. Liver cirrhosis is the final result of prolonged fibrosis, which is an intimate balance between fibrogenesis and fibrinolysis. A number of these complex mechanisms are shared across the various etiologies of liver disease. Thankfully, investigation has yielded some promising results in regard to reversal of fibrosis, particularly the indirect benefits associated with antiviral therapy for the treatment of hepatitis B and C and the farnesoid receptor agonist for the treatment of primary biliary cholangitis and metabolic associated fatty liver disease. A majority of current clinical research is focused on targeting metabolic associated fatty liver disease and its progression to metabolic steatohepatitis and ultimately cirrhosis, with some hope of potential standardized therapeutics in the near future. With our ever-evolving understanding of the underlying pathophysiology, these therapeutics focus on either controlling the primary disease (the initial trigger of fibrogenesis), interrupting receptor ligand interactions and other intracellular communications, inhibiting fibrogenesis, or even promoting resolution of fibrosis. It is imperative to thoroughly test these potential therapies with the rigorous standards of clinical therapeutic trials in order to ensure the highest standards of patient safety. In this article we will briefly review the key pathophysiological pathways that lead to liver fibrosis and present current clinical and experimental evidence that has shown reversibility of liver fibrosis and cirrhosis, while commenting on therapeutic safety.

Severe Hepatotoxicity due to Ibrutinib with a Review of Published Cases.

Ibrutinib, an irreversible Bruton's tyrosine kinase inhibitor, is an effective treatment for Waldenström's macroglobulinemia, chronic lymphocytic leukemia, and several other types of lymphoma. Studies prior to FDA approval in 2015 failed to demonstrate any hepatotoxicity. However, since then, there have been 2 reports in the literature of severe hepatic injury. We present a third case of a 77-year-old woman presenting with nausea and jaundice after recent discontinuation of ibrutinib and compare the presentation as well as course of all 3 known cases. The sudden onset of acute hepatotoxicity is idiosyncratic, occurring weeks after starting ibrutinib treatment. Liver biopsies in all cases revealed mixed hepatocellular and cholestatic features. Improvement progressed slowly upon discontinuation of ibrutinib. Awareness of ibrutinib hepatotoxicity, periodic surveillance of liver function tests, early recognition of any abnormalities, and prompt discontinuation of the medication are recommended.

Role of inflammatory markers as hepatocellular cancer selection tool in the setting of liver transplantation.

Since the advent of the Milan criteria in 1996 and its widespread adoption for selection of patients with hepatocellular carcinoma (HCC) who would benefit from transplant, there has been an extensive hunt for the ideal clinical biomarker to predict HCC recurrence. This is because Milan lack does not include tumor biology indices and recurrence rates remain in the 15-20% range worldwide. While a 'silver-bullet' biomarker has not been found, several useful inflammatory markers have been identified and used in scoring systems that supersede Milan in their ability to predict HCC recurrence post liver transplantation (LT). In this review, we aim to summarize the role of inflammatory markers paly in the selection of HCC patients awaiting LT.

Managing nonalcoholic fatty liver disease in patients living with HIV.

PURPOSE OF REVIEW: Nonalcoholic fatty liver disease (NAFLD) is common among patients living with HIV and may lead to liver-related morbidity and mortality. RECENT FINDINGS: The prevalence of NAFLD among patients with HIV is increasingly well described due to new noninvasive techniques to quantify hepatic steatosis and fibrosis. Patients with HIV may be at increased risk of disease progression, though high-quality natural history studies are not available. The high rates of metabolic syndrome, dyslipidemia and insulin resistance may partially account for this excess risk, though the impact of HIV itself, antiretroviral medications and dysregulation of the gut-liver axis likely play important roles. Treatment of NAFLD in patients with HIV is poorly studied. Current recommendations include diet and lifestyle modifications, HIV viral suppression and limitation of hepatotoxic medications as possible. In addition, there are a large number of novel medications now in clinical trials designed to target the accumulation of hepatic fat, oxidative stress, inflammation and/or fibrosis, which will revolutionize this field. SUMMARY: Although additional work is needed to understand the natural history of NAFLD in patients with HIV and identify those at highest risk, novel treatment approaches are now being tested in this population. We may soon have effective treatments to combat this epidemic.