"Men who are overweight in their late teens have a higher risk of developing liver cancer in later life, new research suggests," reports ITV News. Swedish researchers also found a link to other serious types of liver disease.
The researchers assessed the link between body mass index (BMI) and risk of liver disease in later life in 17-19-year-old Swedish men conscripted into national service, which was compulsory in Sweden until 2010.
More than one million teenage boys were included in the study. Researchers found a higher BMI in late adolescence was associated with an increased risk of severe liver disease, including liver cancer, in later life.
Being diagnosed with type 2 diabetes during follow-up also increased the risk of liver disease, irrespective of weight.
But the main limitation of this study is it isn't able to prove BMI is responsible for the increased risk. Various unmeasured factors could also be having an influence.
Nevertheless, the relationship is in line with current thinking around the risks of excess fat. Fat cells can directly damage the liver in the same way as alcohol (non-alcoholic fatty liver disease).
Obesity can also raise the risk of secondary conditions that can impair the liver, such as diabetes and high blood pressure.
Women shouldn't assume that a similar risk doesn't apply to them. This study only focused on men simply because the Swedish national service system made data on men more easily available for study.
Maintaining a healthy weight will help reduce the risk of a wide range of long-term, often serious, conditions.
Where did the story come from?
The study was carried out by researchers from the Karolinska Institutet and Lund University, both in Sweden.
Funding was provided by grants from the Royal Swedish Academy of Sciences. There were no conflicts of interest declared by the authors.
ITV News' reporting of the study was accurate.
What kind of research was this?
This population-based cohort study aimed to assess whether a high BMI is associated with an increased risk of severe liver disease and liver cancer.
Liver disease is a common illness and cause of death around the world. In the past, many cases of liver disease were related to alcohol misuse or viral infection from hepatitis B or C.
Now, in the developed world, obesity is an increasing underlying cause of severe liver disease and liver cancer.
Previous studies haven't specifically assessed how the risk may differ across BMI categories, and whether there could be an association with type 2 diabetes.
This study design is not able to prove cause and effect – it can only find possible links for further investigation.
What did the research involve?
The researchers used data of 1,220,261 Swedish men who did their military national service between 1969 and 1996, when they were aged 17-19 years.
Baseline data was collected on the following possible confounding factors:
- blood pressure
- cognitive ability
- cardiovascular fitness
- muscular strength
- parental socioeconomic status
- parental and own education
Men were followed up using the personal identification number (PIN) given to all Swedish citizens after birth.
This PIN was used to link the men to three national population-based registers:
- National Patient Register of Hospital Discharges
- Cause of Death Register
- Swedish Cancer Register
Severe liver disease included diagnoses of:
- liver cirrhosis
- liver cancer
- decompensated liver disease – when people develop signs and symptoms their liver isn't working
- liver failure
- cancer of the bile ducts and gallbladder
- high blood pressure in the portal vein, which drains blood from the digestive tract into the liver
- liver transplant
- paracentesis – a procedure to drain fluid from the abdomen
The researchers also looked at whether the association between BMI and severe liver disease was different in those diagnosed with type 2 diabetes during the study period.
What were the basic results?
Men were followed up for an average period of 28.5 years, during which there were 5,281 cases of severe liver disease and 251 cases of liver cancer.
Severe liver disease
All men with a BMI over 22.5 had a significant increased risk of severe liver disease compared with men with a BMI of 18.5-22.5:
- overweight men (BMI 25-30) – 49% increased risk (hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.35 to 1.64)
- obese men – (BMI: ≥30) more than double (217%) increased risk (HR 2.17, 95% CI 1.82 to 2.59)
- healthy weight men (BMI 22.5-24.9) – 17% increased risk (HR 1.17, 95% CI 1.09 to 1.26)
The result for healthy weight men is somewhat surprising. A BMI of between 22.5 and 24.9, even though it's at the top end of the healthy weight range (18-24.9), wasn't previously considered to be a significant risk factor for liver disease.
Risk of severe liver disease on diabetes diagnosis
Type 2 diabetes was diagnosed in 16,451 men during the follow-up period.
Compared with men with type 2 diabetes and a BMI of 18.5 to 22.5, there was an increase in risk of severe liver disease in all BMI categories:
- underweight men (BMI less than 18.5) – more than four times (429%) the risk (HR 4.29, 95% CI 3.17 to 5.81)
- normal weight men (BMI 22.5-24.9) – more than triple (350%) increased risk (HR 3.50, 95% CI 2.85 to 4.30)
- overweight men – more than triple increased (325%) risk (HR 3.25, 95% CI 2.59 to 14.08)
- obese men – more than triple (328%) increased risk (HR 3.28, 95% CI 2.27 to 4.74)
An increased risk of liver cancer was associated with a higher BMI, but this was only for overweight and obese men.
- overweight men (BMI 25-30) – 57% increased risk (HR 1.57 95% CI 1.01 to 2.45)
- obese men (BMI greater than 30) – more than triple (359%) increased risk (HR 3.59, 95% CI 1.85 to 6.99)
How did the researchers interpret the results?
The researchers concluded that, "A high BMI in late adolescent men was associated with an increased risk of future severe liver disease, including liver cancer.
"Development of T2DM [type 2 diabetes] during follow-up was associated with a further increased risk of severe liver disease, independent of baseline BMI."
This cohort study aimed to assess whether a high BMI in late adolescence is associated with an increased risk of severe liver disease and liver cancer in later life.
The researchers generally found a higher BMI was associated with an increased risk of severe liver disease, including liver cancer.
A diagnosis of type 2 diabetes during follow-up was associated with a further increased risk of severe liver disease, regardless of BMI at the start of the study.
This study included a very large population, and has used reliable sources of data for medical diagnoses and cause of death.
But there are limitations to address:
- A study like this isn't able to prove higher BMI in late adolescence is the cause of severe liver disease – it can only suggest this as a possible explanation.
- The researchers adjusted their analyses for various health and lifestyle factors measured at baseline. But these things – such as cardiovascular fitness – may not have remained consistent during life. There are also a number of possible contributing factors, such as alcohol consumption, smoking and diet, which weren't considered that could have had an influence.
- BMI was only measured at the start of the study. It's highly likely this varied during the course of the follow-up period.
- The links also aren't entirely linear – that is, there's not a consistent pattern of increasing risk with increasing BMI across the results. This means the relationship isn't completely clear, and further raises the possibility other factors are having an influence.
- This study involved a specific population sample of Swedish men conscripted to national service. We don't know the outcomes for the exempt population (such as men with an illness or disability), women, or populations from other countries and cultures. That said, from what we know about the link between obesity and liver disease, it would be surprising if women weren't subject to the same risks as men.
Being overweight or obese is a known risk factor for a number of health conditions. While this study isn't able to prove this is responsible for an increased risk of severe liver disease, the results are in line with previous research.