Liver disease is a major cause of illness and death worldwide. Some liver diseases like hepatitis C and autoimmune hepatitis do tend to run in families. However, the most common liver diseases – fatty liver disease and alcoholic liver disease – do not appear to have a strong genetic component. This article reviews the evidence on whether major liver diseases run in families.
Summary
Some key points on familial risk for liver disease:
- Viral hepatitis has a genetic component. Having a relative with hepatitis B or C increases your risk.
- Autoimmune liver diseases like autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis cluster in families.
- Hereditary hemochromatosis, an iron overload disease, is strongly genetic.
- There are rare genetic liver diseases like Wilson’s disease that run in families.
- For most people, fatty liver disease risk relates to lifestyle factors like diet, exercise, and alcohol use rather than genetics.
- Alcoholic liver disease risk correlates with alcohol consumption more than genetics.
In general, avoid known environmental risk factors for liver disease like alcohol abuse, obesity, untreated hepatitis B/C infection, and exposure to toxins. Get screened for liver problems if you have a close relative with unexplained liver disease. beyond specific genetic disorders, maintaining a healthy lifestyle offers the best protection against liver disease for most people.
Viral hepatitis
Chronic hepatitis B and hepatitis C infection can lead to severe liver scarring (cirrhosis) and liver cancer over time. Research shows that having a family member with viral hepatitis does increase your risk of contracting these viruses:
- Hepatitis B: Having a household member with hepatitis B as a child increases your risk of becoming infected. The hepatitis B virus spreads through contact with blood and other body fluids.
- Hepatitis C: Some studies show 4-6 times higher rates of hepatitis C virus infection among family members of people with HCV. The virus spreads through contact with infected blood.
In addition to exposure risk, there are genetic factors that affect hepatitis C prognosis:
- People with certain HLA gene variants clear the hepatitis C virus more successfully.
- Variants of the IL28B gene are tied to hepatitis C treatment response.
These genetic factors may run in families. If you have a relative who struggled to clear hepatitis C, you may also have trouble fighting off the virus. Get screened for hepatitis B and C if you have family members with known infection.
Table 1. Familial Risk Factors for Viral Hepatitis
| Hepatitis Type | Familial Risk Factors |
|---|---|
| Hepatitis B | Exposure during childhood |
| Hepatitis C | Exposure through blood contact |
| Hepatitis C | Shared HLA and IL28B gene variants |
Autoimmune liver diseases
Autoimmune disorders like autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis have a genetic component. Having a close relative with one of these diseases increases your risk:
- Autoimmune hepatitis: Up to 20% of people with autoimmune hepatitis have an affected first-degree relative. Genetic variants in human leukocyte antigen (HLA) genes increase susceptibility.
- Primary biliary cirrhosis: Family history is the strongest known risk factor. First-degree relatives have a 10-fold higher risk. Genetic variants in HLA genes are again implicated.
- Primary sclerosing cholangitis: 7% of people with primary sclerosing cholangitis have an affected first-degree relative. HLAs may contribute but other unknown genes also increase risk.
Get screened for autoimmune liver issues if you have a close relative diagnosed with these conditions. Treatment is available to manage symptoms and slow progression.
Table 2. Familial Risk Factors for Autoimmune Liver Diseases
| Disease | Familial Risk Factors |
|---|---|
| Autoimmune hepatitis | HLA gene variants |
| Primary biliary cirrhosis | 10x risk if first-degree relative affected; HLA genes |
| Primary sclerosing cholangitis | 7% have affected first-degree relative; HLA and other genes |
Hereditary hemochromatosis
Hereditary hemochromatosis is an inherited disorder that causes the body to absorb too much iron from food. Excess iron builds up in tissues and organs, causing damage. Complications include cirrhosis, liver cancer, diabetes, and heart disease.
Hemochromatosis is strongly genetic. The majority cases are caused by mutations in the HFE gene. If one parent has an HFE mutation, a child has a 50% chance of inheriting the mutation and being predisposed to iron overload.
Symptoms of hemochromatosis like joint pain, fatigue, and liver problems often do not appear until adulthood. Get screened if you have a close relative with the disorder. Periodic blood removal can prevent organ damage in people who have elevated iron levels but have not developed symptoms.
Table 3. Familial Risk Factors for Hemochromatosis
| Disease | Familial Risk Factors |
|---|---|
| Hereditary hemochromatosis | Mutations in HFE gene; 50% risk if parent affected |
Rare genetic disorders
There are some rare genetic disorders that can seriously damage the liver. These include:
- Wilson’s disease: Buildup of copper in the liver, brain, and other tissues. Symptoms often appear between ages 10 and 40.
- Alpha-1 antitrypsin deficiency: Lack of a protein made in the liver leads to liver disease in children and adults.
- Hemophilia: Impaired blood clotting causes bleeding in the liver and elsewhere.
- Cystic fibrosis: Thick mucus obstructs bile ducts and causes scarring of the liver.
These conditions are caused by mutations in a single gene. Children of an affected parent have a 50% chance of inheriting the condition. Get genetic testing if you have a family history of one of these disorders.
Table 4. Familial Liver Diseases Caused by Single Gene Mutations
| Disease | Gene Mutated |
|---|---|
| Wilson’s disease | ATP7B |
| Alpha-1 antitrypsin deficiency | SERPINA1 |
| Hemophilia | F8 or F9 |
| Cystic fibrosis | CFTR |
Fatty liver disease
Fatty liver disease is an umbrella term for conditions where fat accumulates in liver cells. The main types are alcoholic fatty liver disease and nonalcoholic fatty liver disease (NAFLD).
NAFLD is very common, affecting up to 30% of adults globally. Obesity, insulin resistance, high blood fats, and poor diet strongly increase risk. While fatty liver can run in families, lifestyle factors appear more important than genetics for most people:
- A large 2020 study found family history only marginally impacted NAFLD risk after accounting for metabolic factors like BMI and blood glucose levels.
- A 2017 review found that genetics contributed about 26% to NAFLD risk, while obesity and lifestyle contributed 74%.
- A Chinese study found children of parents with NAFLD were over 15 times more likely to develop fatty liver. However, the children were also more likely to be overweight.
Research has uncovered some gene variants associated with NAFLD risk. But poor diet and low activity levels explain most cases. Maintaining normal weight through diet and exercise offers the best protection, even for those with a family history of fatty liver disease.
Table 5. Familial Versus Lifestyle Risk Factors for Fatty Liver Disease
| Risk Factor | Contribution to Fatty Liver Risk |
|---|---|
| Genetics | ~26% |
| Lifestyle and metabolic factors | ~74% |
Alcoholic liver disease
Drinking alcohol in excess over many years can cause progressive liver damage. Consuming 4-5 or more drinks daily increases the likelihood of developing alcoholic steatohepatitis and cirrhosis.
While genetics likely influence vulnerability to alcohol, amount of alcohol intake over time is by far the strongest risk factor. People who drink heavily face high odds of alcoholic liver injury regardless of family history. A few genetic associations have been reported:
- Variants in genes for alcohol metabolism may predispose certain groups like East Asians.
- HLA variants may increase susceptibility in some patients.
- Patients with a family history have a marginally increased risk.
However, heavy drinking is by far the most important predictor of alcoholic liver disease. Abstaining from alcohol and getting help for alcohol addiction can prevent severe liver damage, even in those with a family history.
Table 6. Key Risk Factors for Alcoholic Liver Disease
| Risk Factor | Level of Risk |
|---|---|
| Heavy alcohol intake | High |
| Genetics | Low-moderate |
| Family history | Low |
Preventing liver disease
You can reduce your risk of many common liver diseases by adopting healthy lifestyle habits:
- Maintain a healthy weight.
- Limit alcohol intake and avoid binge drinking.
- Don’t smoke. Avoid secondhand smoke.
- Eat a balanced diet high in fruits, vegetables, and whole grains.
- Get vaccinated for hepatitis A and hepatitis B.
- Practice safe sex and avoid injection drugs to prevent hepatitis C.
- Avoid behaviors that increase hepatitis and liver cancer risk.
See your doctor promptly if you develop possible liver symptoms like abdominal pain, swelling, nausea, or jaundice. Get screened for viral hepatitis if you have risk factors like injection drug use or high-risk sexual activity. Consider genetic testing if family members have been diagnosed with hereditary disorders.
While some liver conditions do have a genetic component, the most common causes relate to environmental exposures and modifiable lifestyle habits for most people. Focus on maintaining a healthy diet, active lifestyle, and normal weight – the best defenses against liver disease for those with or without a family history.
Conclusion
In summary, here are the key points on whether liver disease runs in families:
- Viral hepatitis has exposure risk factors but also genetic components that may cluster in families.
- Autoimmune disorders like autoimmune hepatitis and primary biliary cirrhosis have strong genetic links and run in families.
- Hereditary hemochromatosis is caused by specific genetic mutations and highly genetic.
- Rare diseases like Wilson’s disease, alpha-1 deficiency, and cystic fibrosis have single gene causes and familial patterns.
- For most people, fatty liver relates more to modifiable metabolic factors than genetics.
- While some genetic factors may increase vulnerability, heavy alcohol use is the dominant risk for alcoholic liver disease.
Liver problems do tend to run in families for certain conditions like autoimmune disease and hereditary disorders. But for the most common causes like fatty liver and alcoholic liver disease, lifestyle choices and environment trump genetics in current research. Focus on maintaining a healthy diet, weight, and avoiding excess alcohol and known hepatitis risks – the best way to protect your liver regardless of family history.