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EASL releases guide for management of alcoholic liver disease

AMSTERDAM — EASL presented its new Clinical Practice Guideline addressing the management of alcoholic liver disease at the International Liver Congress.

“ALD is a complex disease, the successful management of which hinges on the integration of all the competences in public health, epidemiology, addiction behavior and alcohol-induced organ injury,” the researchers wrote. “Both primary intervention to reduce alcohol-associated morbidity and mortality rely on the coordinated action of multidisciplinary teams established at local, national and international levels.”

ALD diagnosis

Most patients with moderate forms of ALD are asymptomatic and will require initial screening. Noninvasive tests to estimate liver fibrosis include serum markers, transient elastography and hepatic imaging techniques. As liver biopsy is an invasive procedure with significant morbidity, it is not recommended for all patients with suspected ALD. However, it is indicated in patients with aggressive forms of ALD, such as severe steatohepatitis, and is required for confirmation.

The morphological spectrum of ALD consists of one or a combination of the following: steatosis with a predominant future of macro-vesicles, associated or not with a variable blend of macro- and micro-vesicles; hepatocyte damage often described as ballooning; an inflammatory infiltrate that predominates in the lobules; and a variable degree of fibrosis and lobular distortion that may progress to cirrhosis.

Macrovesicular steatosis is considered to present earliest and most frequently in alcohol-induced liver injury. Additionally, fibrosis is a key event in ALD as it is a prerequisite for progression to cirrhosis.

Risk factors, disease progression

Environmental risk factors for disease progression in ALD include the amount and type of alcoholic beverages consumed and the duration of abuse and patterns of drinking. Genetic or host factors include sex, ethnicity, coexisting conditions such as metabolic syndrome, iron overload and infection with chronic hepatitis viruses.

Women are more susceptible toward the hepatotoxic effects of alcohol and develop ALD more quickly compared with men who consume the same amount of alcohol. Regarding ethnicity, mortality rates for men are highest among white Hispanic men, followed by black non-Hispanics, white non-Hispanics and black Hispanics; and highest for women among black non-Hispanics, followed by white Hispanics, white non-Hispanics and black Hispanics. Obesity appears to be the most significant, diet-related risk factor related to the progression to fibrosis and risk for cirrhosis in patients who consume large amounts of alcohol.

Data that are still lacking include whether drinking patterns affect the likelihood of ALD evolution, the pathophysiology related to women’s higher susceptibility toward hepatotoxic effects of alcohol, and the relation of ethnicity to higher mortality rates in patients with ALD.

Burden, management of ALD

“Drinking habits of patients need to be routinely screened in patients with liver diseases, and this must be done with tools that have proven its reliability,” the researchers wrote. “There is a common trend to measure alcohol intake in grams per day or grams per week. Calculations are usually made counting standard drink units. The content of a standard drink may differ from country to country, but in Europe most of the countries have fixed their standard drink unit to an ethanol content of 8 to 10g. Even though measurements in standard drinks may lose accuracy, they are reliable, save time and are particularly useful in busy clinical settings.”

The guideline recommends that in addition to standard quantity-frequency questionnaires and retrospective diaries to calculate patients’ drinking habits, the Alcohol Use Disorders Inventory Test (AUDIT) is considered the “gold standard” to assess patients with risky drinking habits and alcohol dependence. Additionally, patients should be screened for psychiatric disorders, as many alcoholics often exhibit anxiety disorders, affective disorders and schizophrenia.

Recommendations for patients with alcohol withdrawal syndrome include the use of benzodiazepines for treatment. The most effective recommendation for patients with ALD is total alcohol abstinence. Brief motivational interventions should be routinely used to manage alcohol disorders. Disulfiram, naltrexone and acamprosate, combined with counseling, can be used to reduce alcohol consumption and prevent relapse in patients without advanced ALD, while patients with advanced ALD should avoid these drugs. Baclofen, however, is safe and effective for advanced ALD.

Future studies

The guideline recommends several necessary areas for which additional studies and data could benefit the diagnosis and management of alcohol-related liver disease and injury.

Regarding alcoholic steatohepatitis, further progression is needed toward noninvasive tools for diagnosis, data on patients with alcoholic steatohepatitis of intermediate severity, data on molecular patterns such as liver inflammation and regeneration signaling associated with different outcomes, and the identification of primary end points other than short-term mortality to facilitate testing of new therapies.

Further evaluation is also needed in the role of s-adenosyl methionine in alcoholic cirrhosis and studies evaluating the effects of new immunosuppressive regimens on the risk for cardiovascular disease and de novo neoplasms are warranted.

Conclusion

“Even though there remain uncertainties about the precise burden of and trends in ALD in Europe, there is no doubt that in many countries it is very substantial and or increasing,” the researchers wrote. “While improvements in treatment are essential, developing population-based policies to reduce levels of harmful and hazardous consumption are a priority. More broadly, there is increasing recognition of the heavy social, health, and economic burdens imposed by heavy alcohol drinking and the policies to reduce harm caused by alcohol, need to be urgently implemented.” – by Talitha Bennett

References:

European Association for the Study of the Liver. J Hepatol. 2017;doi:10.1016/j.jhep.2012.04.004

Disclosure: Please see the full guideline for the researchers’ relevant financial disclosures.

AMSTERDAM — EASL presented its new Clinical Practice Guideline addressing the management of alcoholic liver disease at the International Liver Congress.

“ALD is a complex disease, the successful management of which hinges on the integration of all the competences in public health, epidemiology, addiction behavior and alcohol-induced organ injury,” the researchers wrote. “Both primary intervention to reduce alcohol-associated morbidity and mortality rely on the coordinated action of multidisciplinary teams established at local, national and international levels.”

ALD diagnosis

Most patients with moderate forms of ALD are asymptomatic and will require initial screening. Noninvasive tests to estimate liver fibrosis include serum markers, transient elastography and hepatic imaging techniques. As liver biopsy is an invasive procedure with significant morbidity, it is not recommended for all patients with suspected ALD. However, it is indicated in patients with aggressive forms of ALD, such as severe steatohepatitis, and is required for confirmation.

The morphological spectrum of ALD consists of one or a combination of the following: steatosis with a predominant future of macro-vesicles, associated or not with a variable blend of macro- and micro-vesicles; hepatocyte damage often described as ballooning; an inflammatory infiltrate that predominates in the lobules; and a variable degree of fibrosis and lobular distortion that may progress to cirrhosis.

Macrovesicular steatosis is considered to present earliest and most frequently in alcohol-induced liver injury. Additionally, fibrosis is a key event in ALD as it is a prerequisite for progression to cirrhosis.

Risk factors, disease progression

Environmental risk factors for disease progression in ALD include the amount and type of alcoholic beverages consumed and the duration of abuse and patterns of drinking. Genetic or host factors include sex, ethnicity, coexisting conditions such as metabolic syndrome, iron overload and infection with chronic hepatitis viruses.

Women are more susceptible toward the hepatotoxic effects of alcohol and develop ALD more quickly compared with men who consume the same amount of alcohol. Regarding ethnicity, mortality rates for men are highest among white Hispanic men, followed by black non-Hispanics, white non-Hispanics and black Hispanics; and highest for women among black non-Hispanics, followed by white Hispanics, white non-Hispanics and black Hispanics. Obesity appears to be the most significant, diet-related risk factor related to the progression to fibrosis and risk for cirrhosis in patients who consume large amounts of alcohol.

Data that are still lacking include whether drinking patterns affect the likelihood of ALD evolution, the pathophysiology related to women’s higher susceptibility toward hepatotoxic effects of alcohol, and the relation of ethnicity to higher mortality rates in patients with ALD.

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Burden, management of ALD

“Drinking habits of patients need to be routinely screened in patients with liver diseases, and this must be done with tools that have proven its reliability,” the researchers wrote. “There is a common trend to measure alcohol intake in grams per day or grams per week. Calculations are usually made counting standard drink units. The content of a standard drink may differ from country to country, but in Europe most of the countries have fixed their standard drink unit to an ethanol content of 8 to 10g. Even though measurements in standard drinks may lose accuracy, they are reliable, save time and are particularly useful in busy clinical settings.”

The guideline recommends that in addition to standard quantity-frequency questionnaires and retrospective diaries to calculate patients’ drinking habits, the Alcohol Use Disorders Inventory Test (AUDIT) is considered the “gold standard” to assess patients with risky drinking habits and alcohol dependence. Additionally, patients should be screened for psychiatric disorders, as many alcoholics often exhibit anxiety disorders, affective disorders and schizophrenia.

Recommendations for patients with alcohol withdrawal syndrome include the use of benzodiazepines for treatment. The most effective recommendation for patients with ALD is total alcohol abstinence. Brief motivational interventions should be routinely used to manage alcohol disorders. Disulfiram, naltrexone and acamprosate, combined with counseling, can be used to reduce alcohol consumption and prevent relapse in patients without advanced ALD, while patients with advanced ALD should avoid these drugs. Baclofen, however, is safe and effective for advanced ALD.

Future studies

The guideline recommends several necessary areas for which additional studies and data could benefit the diagnosis and management of alcohol-related liver disease and injury.

Regarding alcoholic steatohepatitis, further progression is needed toward noninvasive tools for diagnosis, data on patients with alcoholic steatohepatitis of intermediate severity, data on molecular patterns such as liver inflammation and regeneration signaling associated with different outcomes, and the identification of primary end points other than short-term mortality to facilitate testing of new therapies.

Further evaluation is also needed in the role of s-adenosyl methionine in alcoholic cirrhosis and studies evaluating the effects of new immunosuppressive regimens on the risk for cardiovascular disease and de novo neoplasms are warranted.

Conclusion

“Even though there remain uncertainties about the precise burden of and trends in ALD in Europe, there is no doubt that in many countries it is very substantial and or increasing,” the researchers wrote. “While improvements in treatment are essential, developing population-based policies to reduce levels of harmful and hazardous consumption are a priority. More broadly, there is increasing recognition of the heavy social, health, and economic burdens imposed by heavy alcohol drinking and the policies to reduce harm caused by alcohol, need to be urgently implemented.” – by Talitha Bennett

References:

European Association for the Study of the Liver. J Hepatol. 2017;doi:10.1016/j.jhep.2012.04.004

Disclosure: Please see the full guideline for the researchers’ relevant financial disclosures.

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