1,721,185 research outputs found
Alcohol addiction: toward a patient-oriented pharmacological treatment
No full textVery few medications (i.e., disulfiram, naltrexone and acamprosate) are approved for the treatment of alcoholism and their effects are suboptimal. The development of new effective and safe pharmacological agents to treat alcoholic patients is crucial, together with the need to identify predictors of outcomes in different subsets of patients
Alcohol-Associated Liver Disease: Integrated Management With Alcohol Use Disorder
No full textAlcohol-associated liver disease (ALD) is the most common cause of cirrhosis and liver-related mortality in many regions worldwide. Around 75% of patients with cirrhosis are unaware of their disease until they are referred to the emergency department. An innovative, noninvasive screening approach is required for an earlier diagnosis of liver fibrosis. In patients with ALD the physician is inevitably dealing with 2 major disorders: the liver disease itself and the alcohol use disorder (AUD). Focus only on the liver disease will inevitably lead to failure because transient improvements in liver function are rapidly overturned if the patient returns to alcohol consumption. For this reason, integrated models of care provided by hepatologists and addiction specialists are an effective approach, which are, however, not widely available. There are multiple pharmacologic and non-pharmacologic therapies for AUD. Progress has recently been made in the management of patients with severe AH who have improved survival through better understanding of the concept of response to medical treatment, improved survival prediction, and the advent of early liver transplantation. The emerging concept is that listing for transplantation a patient with severe ALD could lead to adjusting the duration of abstinence according to the severity and evolution of liver dysfunction and the patient's addictive profile
Pharmacotherapy of acute alcoholic hepatitis in clinical practice
No full textSevere alcoholic hepatitis (AH) is an acute form of alcohol induced liver disease with a poor prognosis that is seen in the patients who consume large quantities of alcohol. The diagnosis of AH is based on the appropriate alcohol intake history and is supported with clinical and histological features, and several scoring systems. Glucocorticoids are the mainstay for treating severe AH with pentoxifylline used as an alternative to steroids in addition to total alcohol abstinence. Liver transplantation is a possible therapeutic option for severe AH. Among the anti-craving medications able to improve abstinence rate, baclofen seems to be effective and safe in the alcoholic patients affected by severe liver damage
Effectiveness and safety of baclofen in the treatment of alcohol dependent patients
No full textBoth preclinical and clinical research studies have shown the GABA(B) receptor agonist baclofen represents a promising treatment for alcohol dependence. Preliminary clinical studies indicate that baclofen is able to suppress withdrawal symptoms in alcohol-dependent patients affected by the alcohol withdrawal syndrome. Moreover, baclofen has shown efficacy and safety in promoting alcohol abstinence in alcohol dependent patients in two placebo-controlled trials including one in alcohol-dependent patients with liver cirrhosis. These trials also demonstrated that baclofen was associated with reductions in withdrawal-related anxiety and alcohol craving. However, more work is needed to clearly demonstrate the efficacy of baclofen and to ascertain whether efficacy is limited to certain subtypes of alcoholic patients. For example, a recent US trial failed to demonstrate a robust effect of baclofen in treating alcohol-dependent patients though the relative moderate severity of alcohol-dependence in that trial has been suggested as one factor that may have contributed to the finding. In the present review, the authors will summarize the published clinical studies on the role of baclofen in alcohol dependence and will also present some unpublished secondary analyses. Finally, the authors will discuss possible future directions to further investigate the role of baclofen in alcohol dependence (e.g., baclofen's biobehavioral mechanisms, different baclofen doses, differences in severity and in alcoholic subtypes, different formulations of baclofen, possible combination of baclofen with other medications)
Treatment of alcohol use disorders in patients with alcoholic liver disease.
Full text linkAlcohol use disorders (AUDs) is one of the leading causes of disease and disability in almost all European countries. Among the alcohol-related diseases, alcoholic liver disease (ALD) is the most common. At present, alcohol is the most frequent cause of liver cirrhosis in the Western world. The cornerstone of treatment for ALD is achieving total alcohol abstinence and preventing relapse; medical and surgical treatments for ALD are limited when drinking continues. This narrative review summarizes current treatments for AUDs with a particular emphasis to the treatment of AUDs in patients with ALD. Medical management, psychosocial and pharmacological interventions are analyzed, underlying limits and options in AUD patients. Finally, this review discusses the most appropriate setting for the management of AUD patients with advanced liver disease as well as the indications for liver transplantation in AUD patients
Safety and compliance of long-term low-dose ondansetron in alcohol use disorder treatment
Full text linkBackground: The increasing prevalence of alcohol use disorder (AUD) and the parallel surge in alcohol-associated liver disease (ALD) emphasize the urgent need for comprehensive alcohol management strategies. Low-dose ondansetron (AD04, a 5-HT3 antagonist) was shown recently to be a promising treatment for AUD with a specific genotypic profile (5-marker). The liver safety of AD04 has never been evaluated in subjects with AUD. The aim of the present study was to assess the liver safety profile of AD04 compared with placebo in subjects with AUD. Methods: Liver biochemical parameters were assessed in subjects with AUD with a 5-marker genetic profile who participated in a Phase 3 randomized controlled trial and received either twice-daily, low-dose AD04 (ondansetron 0.33 mg twice daily) or matching placebo, combined with brief psychosocial counseling. ALT, AST, GGT, Serum Bilirubin, MCV, and Prothrombin were evaluated at weeks 0, 12, and 24. Adverse cardiac events, general well-being, and study completion were also assessed. Results: Low-dose AD04 did not significantly change biochemical markers of liver injury, such as ALT, AST, and Serum Bilirubin. While patients with AUD displayed elevated GGT levels, typically associated with increased alcohol consumption, this parameter remained unaffected by low-dose AD04. Notably, no significant adverse effects were observed due to oral low-dose AD04 treatment. Conclusions: Low-dose AD04 has the potential to be a safe treatment option for subjects with AUD and ALD, indicating the need for an RCT for this specific cohort. Such a trial would pave the way for the design of a precision treatment for combined AUD with ALD
Reply to "Treatment of alcohol use disorders in patients with liver disease".
No full textRefers To
Alain Braillon
Treatment of alcohol use disorders in patients with liver disease
Journal of Hepatology, Volume 65, Issue 6, December 2016, Page 1270
PDF (169 K)
Giovanni Addolorato, Antonio Mirijello, Pablo Barrio, Antoni Gual
Treatment of alcohol use disorders in patients with alcoholic liver disease
Journal of Hepatology, Volume 65, Issue 3, September 2016, Pages 618-630
PDF (801 K)
To the Editor:
We appreciated the interest by Braillon in our review paper on the treatment of alcohol use disorders (AUDs) in patients with alcoholic liver disease (ALD) [1]; the comments by Braillon focused on nalmefene.
The aim of our review was to provide a comprehensive and balanced update on the treatment of AUDs by discussing behavioral, psychosocial and pharmacological strategies.
In his comments, Braillon reports that the information “nalmefene is effective to reduce heavy drinking in AUDs patients” is a mischaracterisation of the data. We do not agree with this information, since nalmefene was recently approved in Europe on the basis of 3 RCT in which 1997 AUD patients were randomized (ESENSE 1, 604 patients; ESENSE 2, 718 patients, SENSE, 675 patients) [2], [3] and [4]. With respect to placebo, the drug was effective in reducing the number of heavy drinking days and the total alcohol consumption [2], [3] and [4]. For these reason this drug was approved to reduce alcohol consumption in adults with alcohol dependence in the European Union by the European Medical Agency in 2013 with a reimbursement policy variable in the different countries.
In our review [1] a particular emphasis has been given to those treatments available for patients with comorbid ALD. Under these circumstances, differences in terms of medical management, psychosocial and pharmacological interventions (both for alcohol withdrawal syndrome and alcohol relapse prevention) have been highlighted. In this case we totally agree with Braillon on the absence of data on the efficacy and safety of nalmefene in patients with liver disease; for this reason, we did not include this drug among the medications effective and safe in this subset of patients. In particular, the need for total alcohol abstinence in AUD patients, especially for those with comorbid ALD, as underlined in our paper [1], prevents the use of a drug approved for reduction of alcohol intake and not for alcohol abstinence.
As correctly commented by Dr. Braillon, the choice of the most appropriate treatment remains a decision of the physician who manages the patients and knows his clinical status and comorbidities. However, it should be emphasised that one of the main problems in the field is that few medications are available for the treatment of AUD and that the approved ones are prescribed to a minority of patients [5] and [6]
Alcoholic Hepatitis and Liver Transplantation: The Good News and What to Do about It
Full text linkNo abstract availabl
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