Alcoholic liver disease (ALD) comprises a clinical-histologic spectrum including fatty liver, alcoholic hepatitis (AH), and cirrhosis with its complications. Most patients are diagnosed at advanced stages and data on the prevalence and profile of patients with early disease are limited. Diagnosis of ALD requires documentation of chronic heavy alcohol use and exclusion of other causes of liver disease. Prolonged abstinence is the most effective strategy to prevent disease progression. AH presents with rapid onset or worsening of jaundice, and in severe cases may transition to acute on chronic liver failure when the risk for mortality, depending on the number of extra-hepatic organ failures, may be as high as 20-50% at 1 month. Corticosteroids provide short-term survival benefit in about half of treated patients with severe AH and long-term mortality is related to severity of underlying liver disease and is dependent on abstinence from alcohol. General measures in patients hospitalized with ALD include inpatient management of liver disease complications, management of alcohol withdrawal syndrome, surveillance for infections and early effective antibiotic therapy, nutritional supplementation, and treatment of the underlying alcohol-use disorder. Liver transplantation, a definitive treatment option in patients with advanced alcoholic cirrhosis, may also be considered in selected patients with AH cases, who do not respond to medical therapy. There is a clinical unmet need to develop more effective and safer therapies for patients with ALD.
Bioenergetics has become central to our understanding of pathological mechanisms, the
development of new therapeutic strategies and as a biomarker for disease progression
in neurodegeneration, diabetes, cancer and cardiovascular disease. A key concept is
that the mitochondrion can act as the ‘canary in the coal mine’ by
serving as an early warning of bioenergetic crisis in patient populations. We propose
that new clinical tests to monitor changes in bioenergetics in patient populations
are needed to take advantage of the early and sensitive ability of bioenergetics to
determine severity and progression in complex and multifactorial diseases. With the
recent development of high-throughput assays to measure cellular energetic function
in the small number of cells that can be isolated from human blood these clinical
tests are now feasible. We have shown that the sequential addition of
well-characterized inhibitors of oxidative phosphorylation allows a bioenergetic
profile to be measured in cells isolated from normal or pathological samples. From
these data we propose that a single value–the Bioenergetic Health Index
(BHI)–can be calculated to represent the patient's composite mitochondrial
profile for a selected cell type. In the present Hypothesis paper, we discuss how BHI
could serve as a dynamic index of bioenergetic health and how it can be measured in
platelets and leucocytes. We propose that, ultimately, BHI has the potential to be a
new biomarker for assessing patient health with both prognostic and diagnostic
value.
LT performed for NASH and HCC are increasing. Potent treatment options resulted in a decrease in number of transplants for HBV, HCV, and PBC. Better treatment modalities for HCV are expected to further reduce the number of LT for HCV. Excellent posttransplantation outcomes for NASH and AC are encouraging, resulting in wider acceptance of transplants for these etiologies.
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