Liver at risk: How alcohol abuse causes lasting damage

Around 7% of the world population greater than 15 years lives with alcohol use disorder and 3.7% with alcohol dependance and33% of adults have consumed alcohol. Alcohol is widely available as beers, wines and spirits with alcohol content varying from 3-50%. Alcohol is measured in the grams of alcohol per 100 mL of the drink consumed. Alcohol consumption plays a causal role in more than 200 diseases, injuries and other health conditions. Younger people are disproportionately negatively affected by alcohol.

There is an increased risk of liver disease, heart disease, cardiovascular disease, stroke, cancers and mental health disorders in those who consume alcohol. Smoking damages the smoker, but alcohol destroys the families of the alcoholics andcauses significant harm to others also (drunken driving). It is important to note that no form of alcohol is risk free. Even low levels of consumption carry some risk and can cause harm. Factors affecting risk of alcoholic liver disease are alcohol consumption above threshold (1 drink/day for women and 2 drink/day for men), daily drinking, duration of drinking (5 years for women and 8-10 years for men), binge drinking, drinking while fasting, obesity, concomitant smoking, genetic factors (family history of alcoholism) and underlying liver disease (hepatitis C virus, metabolic syndrome). Data is equivocal on the type of alcohol consumed.

Alcohol is primarily metabolized in the liver
The enzyme called alcohol dehydrogenase (ADH) converts alcohol to acetaldehyde which is then converted to carbon di oxide and water. There are various genetic polymorphism as regards the ADH enzymes with some slow metabolizers and others rapid metabolizers. This will throw some insight into the question why some people, who drink daily continue to lead a “healthy, happy long life”. If the rate at which alcohol consumption exceeds the rate of metabolism, then the individual becomes intoxicated and can lead to liver damage.

There are various oxidants released during the metabolism of alcohol which are harmful to the liver. This sets in motion a cascade of inflammatory mediators (cytokines) which can cause damage to the hepatocytes. There is a wide spectrum of alcohol associated liver diseases ranging from fat accumulation to inflammation to fibrosis to irreversible injury and finally development of cancer.

Alcohol use leads to activation of pathways involved in fatty acid synthesis and suppression of pathways of oxidation (which can clear the reactive oxygen species -ROS). This leads to accumulation of fat in the liver – in the hepatocytes- condition called as macro vesicular steatosis (large droplets of fat within the liver cells). The percentage of fat accumulation can vary from 10% to greater than 50%. Majority of these patients are asymptomatic. Their liver function tests (LFTs) are normal and hence continue to consume alcohol and progress to the next stage. Ultrasound imaging, fibroscan and MRI scan can help in early identification.

With continued alcohol consumption, people progress to the second stage which is alcoholic hepatitis, which can range from mild to severe and occasionally can present as fulminant hepatic failure. There is an increase in the gut permeability which leads to endotoxins entering the liver. This sets up the cascade of liver inflammation. The immune response and the liver cell inflammation leads to injury, apoptosis and necrosis (cell death). All this causes the process of fibrosis, which makes the liver ‘stiff’. There is an increased resistance to the flow of blood through the sinusoids which leads to a condition called portal hypertension. Slowly the complications of portal hypertension set in.

With continued insult to the injury, alcoholic hepatitis progresses from alcoholic hepatitis to cirrhosis (irreversible liver damage). With continue alcohol abuse, complications of cirrhosis (decompensation) begin with appear. Portal hypertension with upper gastrointestinal bleeding (variceal bleed), ascites (accumulation of fluid in the abdomen), spontaneous bacterial peritonitis – SBP (infection of ascitic fluid), acute kidney injury starts to develop. With development of end stage liver disease, there is development of various grades of hepatic encephalopathy (precoma progressing to coma). The picture can get complicated by development of cancer in the liver ( hepatocellular carcinoma HCC).

Treatment would be the treatment the complications of liver cell failure and portal hypertension. Patients would need diuretics (for control of ascites), betablockers (for portal hypertension) drugs like rifaximin and lactulose (for hepatic encephalopathy). Endoscopic procedure like band ligation of varices in case of gastrointestinal bleed are needed. In those with signs of liver cells failure with ascites, jaundice, patients are advised salt restriction (2-4 gm/ day), fluid restriction (1.2 – 1.5L/day) and high protein (recommend 2 egg whites/ day) and high caloric diet.

Continued alcohol abuse increases rates of development of variceal bleed, ascites, acute kidney injury, hepatic encephalopathy and hepatocellular carcinoma. The only treatment of proven benefit is strict abstinence of alcohol. Most patients find this very challenging and will need strong support from the family and help from psychiatrists and psychologists. There is high prevalence of malnutrition in this subset of patients and enteral nutritional supplements with micronutrients (beta-carotene, vitamin A, C, E, zinc and selenium) is needed in the diet. Drugs like steroids, pentoxyphylline, UDCA, SAME play a role in a limited subset of patients. Alcoholic liver disease is one of the leading indications of liver transplantation. The challenge is to have strict abstinence for 3-6 months as there is a high risk (up to 30%) of recidivism post transplant. Hence the timing of referral, selection of candidates is crucial. Most centers have multidisciplinary teams involved in this decision process.

WHO Global alcohol action plan 2022-2030 for prevention and treatment of harmful use of alcohol is a part of sustainable development goal SDG 3.5 There is no level of alcohol that is safe for our health. WHO has stated that “the risk to the drinker’s health starts from the first drop of any alcoholic beverage”. Hence let us choose our drink wisely.

Dr. Sandeep M S, Senior Consultant Gastroenterology, Apollo Hospitals Sheshadripuram, Bengaluru