Pharmacological And Behavioral Management Of Alcohol Use Disorder In Patients With Alcoholic Liver Disease (Research Paper Sample)

Pharmacological and behavioral management of alcohol
use disorder in patients with alcoholic liver disease
Giovanni Addolorato1, Gabriele Angelo Vassallo1, Antonio Mirijello2, Antonio Gasbarrini1
1 Department of Internal Medicine, Gastroenterology and Hepatology, Catholic University of Rome, Italy
2 …………………Antonio……………………………….
Please send any correspondence to:
Giovanni Addolorato, M.D.
Department of Department of Internal Medicine, Gastroenterology and Hepatology
Catholic University of Rome, Gemelli Hospital
Largo Gemelli 8, 00168 Rome, Italy
Phone: +39-06-30154334; Fax: +39-06-35502775
e-mail: g.addolorato@rm.unicatt.it
Abstract
Alcohol use disorder (AUD) is considered as the most common cause of liver disease in the Western world. Alcohol abstinence is the gold standard treatment of alcoholic liver disease, because the medical and surgical interventions have limited rate of success in case when the alcohol consumption continues. Motivational advice, brief intervention and psychosocial support are essential components for the treatment of AUD patients. The addition of effective pharmacological therapy could be useful in these patients. However, medical recommendations and psychosocial interventions may not be sufficient to achieve and maintain alcohol abstinence. At present baclofen is the only drug tested AUD patients affected by liver cirrhosis, showing both efficacy and safety in these patients. When total alcohol abstinence does not result in a significant improvement of liver function, liver transplantation represents the gold standard treatment for end-stage alcoholic liver disease.
Key words: alcohol use disorder, alcoholic liver disease, alcoholic hepatitis, alcoholic cirrhosis, alcohol withdrawal syndrome, end stage alcoholic liver disease, baclofen, metadoxine, anti-craving drugs, and liver transplantation.
Abbreviation:
AAU: Alcohol addiction unit
AC: Alcoholic cirrhosis
ALD: Alcoholic liver disease
ALT: alanine aminotransferase
AH: Alcoholic hepatitis
AST: aspartate aminotransferase
AUD: Alcohol use disorders
CDT: Carbohydrate-deficient transferring
CBT: Cognitive-behavioral therapy
DSM-5: Diagnostic and Statistical Manual for mental disorders, 5th revision
EASL: European Association for the Study of the Liver
GHB: Gamma-hydroxybutyric acid
MCV: Mean Corpuscular Volume
NIAAA: National Institute on Alcohol Abuse and Alcoholism
ESALD: End stage alcoholic liver disease
EtG: Ethylglucuronide
GGT: Gamma-glutamyltransferase (GGT)
LD: Liver disease
LT: Liver transplantation
MET: Motivational enhancement therapy
RCT: Randomized controlled trial
TLFB:Time-line follow back
Introduction:
Alcohol use disorder (AUD) is a chronic and relapsing condition characterized by harmful alcohol intake, compulsive drinking, psychological and physical dependence. In US, the prevalence of AUD in 2012 among adults were 7.2 percent, representing approximately 17 million individuals. In European countries, AUD is the third leading risk factor for disease with increased mortality rate after tobacco use and high blood pressure (WHO2009). In these countries, the prevalence of AUD ranges from 0.1% to 6.6% (Wittchen HU, et al 2005), and the deaths related to AUD are 11.0% and 1.8% for men and women, respectively (Anderson HR et al. 2006). AUD is associated with substantial disability, reduced quality of life (Samokhvalov, AV, et al 2010), accidents and violence (Rehm J, et al 2003). AUD is responsible for over 2.5 million deaths every year in the world (WHO, 2011). It represent the most common cause of liver disease in the Western world (Tilg&Day, Nature), which accounts for a large portion of alcohol-related morbidity and mortality. In 2010, alcoholic liver disease (ALD) caused half a million deaths worldwide, accounting for 50% of all liver disease-related mortality. An additional 80,000 deaths resulted from alcohol-related hepatocellular carcinoma (Rehm J et al 2003…….Dugum M et al, 2015). ALD is one of the commonest indications for liver transplantation (LT) in Europe and in North America accounting for 20 to 30% of all transplant indication (Burra et al, 2010……Lucey et al, 2014). Although ALD is associated primarily with heavy drinking, continued alcohol consumption even in low doses, after the onset of ALD increases the risk of severe consequences, including death. Therefore, there is a crucial need to develop effective treatments for AUD in patients with ALD.
Alcohol use disorder and alcoholic liver disease
Alcohol use disorder
AUD is a disease characterized by behavioral-cognitive alterations and multi-organ damage. A strong desire of its intake and difficulties in controlling its consumption, despite of effecting social, working, physical and mental state of patients with Alcohol use disorder (DSM-5).
The diagnosis of AUD is based on the criteria of the Diagnostic and Statistic Manual for mental disorders 5th edition (DSM-5). According to DSM-5 criteria AUD patients can be classified in three sub-groups of a continuum spectrum of disease: mild, moderate, and severe according to the symptoms it presents. Alcohol abuse and dependence are now considered two different stage of the same disease (AUD).
Alcohol craving was added among diagnostic criteria due to its crucial role in the pathogenesis of AUD (Sinha R et al. 1999). The neurobiology of craving is complex, since several pathways are involved and the exact mechanisms were still not completely understood. These pathways include several neurotransmitters, such as gamma-aminobutyric acid, glutamate, opioids, dopamine and serotonin (Addolorato et al, 2005). Patients with AUD can be also classified according to the craving pattern: (a) “reward craving” (characterized by dopaminergic/opioidergic deregulation and characteristic personality trait defined by the search of reward); (b) “relief craving” (characterized by GABAergic/glutamatergic deregulation, significant reactivity to stress, withdrawal symptoms, and reactive drinking); (c) “obsessive craving” characterized by serotoninergic deregulation, personality traits consisting of absence of inhibition, loss of control, compulsive drinking, and alcohol-related damage. (Addolorato et al, 2005).
Screening tools and biological markers to detect alcohol use disorder and monitor alcohol consumption
DSM-5 is the main diagnostic criteria for subjects with AUD, the subjects who fulfill at least 2 of the 11 criteria during last 12 month is diagnosed as AUD, its severity is based on the number of criteria met.
The Alcohol Use Disorders Inventory Test is another screening tool use in subjects with AUD, consists of a total score of more than 8 which indicates chronic and harmful drinking behavior (Saunders JB et al. 1993).
CAGE (Cutting down, Annoyance by criticism, Guilty feeling, and Eye-openers) questionnaire is also used for AUD screening based on four clinical interview questions in which two positive responses indicate the possible presence of AUD (Ewing JA 1984).
Alcohol time-line follow back (TLFB) subjective method of daily assessment of alcohol consumption. It gives information about the pattern, intensity and frequency of alcohol drinking. (Sobell LC et al. 1979).
Some biological markers can also be used for screening of alcohol consumption in our clinical settings that includes; gamma-glutamyl transferase (GGT), mean cellular volume (MCV), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and AST/ALT ratio (DeRitis ratio). These biological markers are likely to lose their utility in patients affected by advanced LD.
Carbohydrate-deficient transferring (CDT) is another tool used more specifically for heavy alcohol consumption (about 4-5 drinks per days) and it remains elevated for two weeks after consumption. Its disadvantage is that it gives false positive results in patients with LD (Allen JP et al. 2013) (Morin L. et al. 2011). A combination of CDT, GGT, and MCV is better for diagnostic purpose (Golka K. et al. 2004).
Ethylglucuronide (EtG) a metabolite of alcohol, has emerged its role in detection of alcohol consumption. It can be measurable in tissue, blood, hair and urine of the subjects in a specific period of time ranging from 4 to 5 days of alcohol consumption. (Allen JP et al. 2013).
Alcoholic liver disease
ALD represents the main alcohol-related medical complication [5, 7]. ALD includes a spectrum of alcohol induced liver pathology, ranging from steatosis and alcoholic steatohepatitis leading to progressive fibrosis, cirrhosis and hepatocellular carcinoma [7]. Quantity, duration and pattern of drinking behavior play a causal role on the entity of liver damage. A linear correlation between alcohol and liver damage seems to exist, but it remains controversial what amount of daily alcohol consumption may be considered safe. Corrao and colleagues suggested that a daily alcohol consumption ≥ 25g is associated to increased risk of liver cirrhosis [22]. In a large population study, Bellentani and colleagues observed a significantly higher prevalence of liver cirrhosis in those subject consuming ≥30g/day of alcohol compared to those consuming <30g/day [23]. According to the WHO, in healthy subjects, a consumption of 2 alcohol units/day (1 unit of alco...