Alcohol consumption remains a major risk factor for liver cirrhosis, with risk increasing exponentially, while genetic factors like alpha-1 antitrypsin deficiency (AATD) can also present with liver disease in a small percentage of affected adults and children according to public health and clinical research data.
Alcohol Consumption and the Exponential Risk of Liver Cirrhosis
Alcohol is a primary driver of liver disease, and research shows that about half of the overall liver cirrhosis burden of morbidity and mortality would disappear in a world without alcohol. Mortality from liver cirrhosis has been on the rise in the US and Europe, more so in women than in men.
A systematic review and meta-analysis searched Medline and Embase up to March 6th, 2019, identifying seven cohort studies and two case-control studies that met inclusion criteria. This provided data from 2,629,272 participants with 5,505 cases of liver cirrhosis. The analysis found no increased risk for occasional drinkers. However, consumption of 1 drink per day in comparison to long-term abstainers showed an increased risk for liver cirrhosis in women, but not in men. The risk for women was consistently higher compared to men.
When drinking reached higher thresholds, the risk increased substantially in both sexes. Drinking ≥5 drinks per day was associated with a substantially increased risk in both women (RR = 12.44, 95% CI: 6.65 – 23.27 for 5–6 drinks, and RR = 24.58, 95% CI: 14.77 – 40.90 for ≥7 drinks) and men (RR = 3.80, 95% CI: 0.85 – 17.02, and RR = 6.93, 95% CI: 1.07 – 44.99, respectively). Heterogeneity across studies indicated the additional impact of other risk factors.
Genetic Contributions: Alpha-1 Antitrypsin Deficiency and Liver Disease
Liver disease is increasingly recognized as a multifactorial disease process, where genetics and metabolic conditions intersect with alcohol use. Alpha-1 antitrypsin deficiency (AATD) can present as lung disease in adults and can be associated with liver disease in a small portion of affected children. In affected adults, the first symptoms of AATD are shortness of breath with mild activity, reduced ability to exercise and wheezing. These symptoms usually appear between the ages of 20 and 40. Other signs and symptoms can include repeated respiratory infections, fatigue, rapid heartbeat upon standing, vision problems and unintentional weight loss.
Some individuals with AATD have advanced lung disease and have emphysema, in which the small air sacs (alveoli) in the lungs are damaged. Symptoms of emphysema include difficulty breathing, a hacking cough and a barrel-shaped chest. Smoking or exposure to tobacco smoke increases the appearance of symptoms and damage to the lungs. Other common diagnoses include COPD (chronic obstructive pulmonary disease), asthma, chronic bronchitis and bronchiectasis – a chronic inflammatory or degenerative condition of one or more bronchi or bronchioles.
Liver disease, called cirrhosis of the liver, is another symptom of AATD. It can be present in some affected children, about 10 percent, and has also been reported in 15 percent of adults with AATD. In its late stages signs and symptoms of liver disease can include a swollen abdomen, coughing up blood, swollen feet or legs, and yellowing of the skin and the whites of the eyes (jaundice). Rarely, AATD can cause a skin condition known as panniculitis, which is characterized by hardened skin with painful lumps or patches. Panniculitis varies in severity and can occur at any age.
Understanding the dual impact of lifestyle factors and genetic conditions requires examining how liver pathology progresses. The International Classification of Diseases (ICD-10) recognizes several forms of alcoholic liver disease (ICD-10, K70), sometimes considered stages that range from relatively mild and reversible alcoholic hepatic steatosis (fatty liver) (K70.0) and alcoholic hepatitis (K70.1), to alcoholic fibrosis and sclerosis of the liver (K70.2), and further to severe and irreversible stages such as alcoholic liver cirrhosis (K70.3) and alcoholic hepatic failure (K70.4). Alcohol consumption, in particular heavy use over time, has been found crucial in the etiology and progression of these diseases. At the same time, liver diseases are multifactorial, and alcohol use may play a role in the progression of all types of cirrhosis, while more high-quality research is necessary to elucidate the role of other risk factors, such as genetic vulnerability, body weight, metabolic risk factors, and drinking patterns over the life course.
Public health recommendations emphasize that high alcohol consumption should be avoided, and people drinking at high levels should receive interventions to reduce their intake.
