Optimized Remission in Alcohol-related Liver Cirrhosis

The incidence of liver cirrhosis is increased fivefold for men and tripled for women in the last forty years. The clinical course of liver cirrhosis includes complications of ascites, hepatic encephalopathy, variceal bleeding, kidney dysfunction, and infections that markedly worsen prognosis. These complications are driven by the development of portal hypertension in the liver. This progression to the 'decompensated' stage is considered a hallmark in the disease course, as the decompensation is associated with a markedly increased risk of further complications and death. Increasing evidence indicate that active measures of treatment of the underlying cause of liver disease and removal of the toxic agents causing cirrhosis may slow disease progression or even induce regression of cirrhosis. This concept is described as hepatic recompensation. There is a need for clinical studies investigating novel biomarkers with the capability to predict and monitor improvement in alcohol related liver cirrhosis, Between 75% and 80% of patients with liver cirrhosis in Denmark have or have had a harmful use of alcohol. Alcohol related liver disease (ArLD) has a major impact on patients' health and lives, and there is an unmet need to investigate treatment options that not only relieves complications, but also address the underlying pathways of alcohol related liver disease, also in severe stages of alcohol related cirrhosis (ALC). Factors such as BMI, female gender and mild portal hypertension are known to be associated with an increased likelihood of recompensation. Additional factors of genetic activation and molecular biomarkers from the proteome and lipidome have only attracted minor attention, and the impact of treating the drivers of decompensation, portal hypertension and alcohol use, and their impact on the natural cause of disease, have not been addressed. The molecular pathophysiology of ArLD is incompletely understood. Characterization of the proteome dynamics across the spectrum of ALD could provide new insights into disease mechanisms of both progression and remission of disease. Several markers of inflammation and cytokines are involved in driving decompensation and has the potential to predict the risk of early death. It is unknown whether such markers can predict remission and recompensation in ALC and AH. Prospective studies investigating the associations between biomarkers of metabolism and prognosis, monitoring and efficacy og treatment in ALC are missing. The overall objective of the present study is to investigate the molecular profile and pathways in persons with ALD to support personalized monitoring and follow-up in liver cirrhosis. The study is an incidence cohort in which patients will be followed from diagnosis to death or withdrawal from the cohort. We will seek to include patients consecutively within three months of diagnosis. All patients with a debut of alcohol related liver cirrhosis during admission regardless of the reason for admission, are eligible for inclusion. All participants in this study will be offered the standard of care treatment. Alcohol cessation intervention including medical treatment of withdrawal symptoms and craving, referral to municipal offers of alcohol treatment, and motivational interviews is part of the treatment. The study will contribute to a better characterization of advanced liver disease related to alcohol and contribute to an improved future organization of treatment- and rehabilitation offers to patients with liver disease. thorough characterization and consecutive inclusion will enhance our understanding on the incidence, prevalence and impact of ALC in the population, as well as the utilization of health care resources allocated to its treatment. A deeper insight into the molecular mechanisms of liver progression and remission will, in combination with clinical data, support our ability to predict outcomes in cirrhosis, facilitate personalized monitoring aiming at providing the right treatment for the right patient at the right time.