The UK’s Problem with Liver Disease

By Dr Stephen David Ryder BMBS, MRCP, FRCP, DM, CSST

Liver disease: common, diagnosed late and frequently missed.

The UK has a problem with liver disease. In stark contrast to other causes of mortality, deaths from liver disease have shown a substantial increase over the last four decades while other disorders such as lung disease and heart disease fell. Liver disease is now the leading cause of working life years lost in men and the third highest cause in women.

Symptoms of liver disease occur very late. Chronic injury to liver cells does not cause symptoms and in the short term if a liver cell dies then it is replaced.

This regenerative ability of the liver is well known by the public but misinterpreted, it does not mean that the liver has an endless ability to repair. With chronic injury to liver cells, that ability to repair is accompanied by the putting down of scar tissue within the liver. It is this progressive accumulation of scar tissue which distorts the normal structure of the liver, termed cirrhosis, and if injury and scar accumulation continues, it leads to liver failure.

The accumulation of fibrosis in the liver is a long process, decades rather than years with almost all causes of liver injury. This has been best described in hepatitis C infection where the average time from infection with the virus to the development of cirrhosis has been shown to be over 30 years.

The symptoms of liver failure are dramatic and usually of sudden onset, fluid retention with ascites (intra-abdominal fluid) and leg swelling, vomiting blood from oesophageal varices and confusion (hepatic encephalopathy).

The signs of liver failure are abdominal ascites (fluid accumulation in the peritoneal cavity), liver cancer in a cirrhotic liver shown on CT scan, oesophageal varices, the result of scarring in the liver and high pressure in the portal vein transporting blood into the liver from the intestine and the dramatic view of bleeding varices down an endoscope. Jaundice would be seen in the eyes of someone with cirrhosis.

When these develop there are medical treatments which can help, but full repair of the underlying cirrhotic liver is impossible, and there are ongoing needs then for medical monitoring and the only potential curative therapy is liver transplantation, which is a resource that is restricted and not applicable to all. The quality of life of people with cirrhosis is often poor. Even if the overt symptoms of liver failure can be managed, the treatments are not without side effects and symptoms such as debilitating fatigue are common. In the UK, currently, over 50% of people with cirrhosis are only diagnosed when they are admitted to hospital with liver failure, and they have therefore very restricted treatment options.

Primary liver cancer, hepatocellular carcinoma, is a complication of chronic liver injury and usually occurs in people with cirrhosis. Although treatments for liver cancer are improving rapidly, prevention is better than cure. An early diagnosis of liver disease which is then treated before cirrhosis has developed will usually abolish the cancer risk totally. A diagnosis of cirrhosis will allow people affected to be regularly screened for liver cancer development, which is shown to detect cancers earlier when curative treatment is more likely to be possible.

Liver disease has a number of causes but more than 90% of them are preventable. The most common causes are:

  • Alcohol
  • Fatty liver related to weight gain, and
  • Viral hepatitis.

Diagnosing Liver Disease – Why is it Missed?

A major problem is that liver disease remains symptom-free until it is very advanced. Detection, therefore, relies on picking up abnormal blood tests, liver function tests, or recognising a risk factor for liver disease and proactively looking for it.

Liver function tests are badly named as the blood tests in the usually requested panel are not all function markers. Those that are, bilirubin and albumin, only become abnormal when the liver fails, which is very late in the disease process. The detection of liver disease early, therefore, relies on picking up what are often mild elevations of the liver enzymes.

Liver Function Test Panel  What It Means
Bilirubin Waste product from recycled red blood cells True function marker-removed from the blood by the liver and excreted in bile
Albumin Protein synthesised in the liver True function marker
Alanine aminotransferase (ALT) Damage marker Released from damaged hepatocytes
Alkaline phosphatase (ALP) Damage marker Released from damaged bile duct cells

As liver disease is very common in our society, over 60% of adults are overweight or obese and at risk of fatty liver while one in four adults drink at levels which put them at risk of alcohol related liver injury.  Liver function tests are done for reasons totally unconnected with chronic liver disease in the majority of people, either drug monitoring for things like statin prescribing in primary care or a non-specific catch all in hospitalised patients.  This means that when liver blood tests are checked there are elevated liver damage markers, mainly ALT, found in a large number of people who are apparently healthy.

The lack of appreciation of the long natural history of liver disease means such elevations are often written off as minor and irrelevant and are very often ignored. Only recently have liver fibrosis markers in blood tests and scan form become available outside specialist units, so from when liver disease rates started to rise in our population, probably the 1990s, until recently, detection of liver disease required identification of abnormal transaminases and undertaking a screen for liver disease.

This is partly history: alcohol intake, drug treatments and risk factors for viral liver disease which are birth in a high prevalence country for hepatitis B and medical treatment overseas or injecting drug use for hepatitis C and partly examination for obesity and signs of chronic liver disease plus a range of additional tests. These are an ultrasound scan of the liver which is a good way of spotting fatty liver as the fatty liver reflects more ultrasound back to the probe, so the liver appears “bright” and blood tests for specific liver disorders.

Disease Being Tested For Type of Disorder Test Requested
Hepatitis C Viral infection, often caught by contaminated needles in health care of substance use Hepatitis C antibodies
Hepatitis B Viral infection commonly transmitted from mother to child at birth or child to child in early life, common in many low to medium-income nations Hepatitis B surface antigen
Haemochromatosis An inherited disorder where excess iron is absorbed and stored in many body tissues causing liver injury Ferritin or transferrin saturation
Autoimmun Liver Disorders Disorders where the immune system inappropriately targets own body tissues, this can either be the liver cell, autoimmune hepatitis or the bile duct cell, primary biliary cholangitis Liver autoantibodies Immunoglobulins

These tests are not new or novel, these diagnostic tests and algorithms of when to investigate and what to do with abnormal test results have been around since the 1990s with numerous National and International guidelines being produced.

If a diagnosis is made, then there is treatment.

Hepatitis C now has widely available treatment with pills for which an 8–12-week treatment cures 97% of people and prevents the development of liver fibrosis. Hepatitis B has had effective anti-viral therapy now for two decades and although a cure is not possible, control with safe side effect free medicines is routine.

Auto-immune liver diseases have specific therapy now, again with an excellent chance of control of the disease, and again avoidance of long-term risk of liver fibrosis in the vast majority of people.

Alcohol excess, perhaps surprising to many, also has very effective treatment. Even where people are dependent on alcohol, engagement in an NHS approved treatment programme has around a 70% chance of reducing alcohol consumption to a physically safe level. This is far more effective than stop smoking programmes reflecting the less addictive nature of alcohol overall than tobacco.

Obesity, or more specifically central abdominal fat, causes fatty liver. While behaviour change and weight loss may be challenging to achieve, it can be done, and the knowledge of physical disease due to obesity is a motivator to undertake the exercise, 20 minutes, five times per week sufficient to sustain heart rate at 75% of maximal and weight loss of 7-10% of starting body weight which are proven to reverse fatty liver and to stop or slow progression.

What Are the Legal Implications of Missed Diagnosis?

If someone develops liver cancer or liver failure that could have been diagnosed at a “preventive” stage, and that opportunity was missed in earlier health care encounters, then that provider may be judged to have failed in their duty of care, as is shown in the case studies below.

Case Study 1

A 61-year-old man developed right upper abdominal pain and was referred by his GP on the NHS two week wait. A CT scan showed a 5cm diameter mass in the right lobe of the liver and changes elsewhere in the liver suggesting cirrhosis. On investigation, he was shown to have a serum ferritin of 6800 (normal up to 350) and on genetic testing was found to have genetic haemochromatosis. The liver lump was proven to be a hepatocellular carcinoma which was a direct result of the liver cirrhosis caused by his iron overload. He was treated by liver transplantation with a good initial prognosis.

He was aware that he had liver blood tests previously which had been abnormal. On review of his primary care records, he had an intermittently abnormal ALT, usually around 60-70 with the upper limit of normal of 45. The first reading which was abnormal had been some 25 years prior to his cancer diagnosis. The GP records noted “test abnormal” and an alcohol history (negative) was recorded but no further investigation was undertaken. Six further readings were taken in the decade following and were annotated as “unchanged minor abnormality.”  Had the simple blood tests, in this case ferritin, been undertaken, it is probable that his condition would have been diagnosed at a non-cirrhotic stage, and his cancer prevented. There is an additional twist in this case in that the patient brother was then tested for genetic haemochromatosis and he was also diagnosed with the disorder; there is a 1:4 chance statistically of this happening. The brother also had cirrhosis at diagnosis and therefore his diagnosis also was delayed.

Case Study 2

A 69-year-old man suddenly vomited fresh blood in large amounts and he was admitted to hospital as an emergency and investigation revealed that he had liver cirrhosis and the bleeding was from a direct complication of liver cirrhosis, the presence of oesophageal varices.  These were treated at endoscopy successfully. He was noted to have central obesity which had been present for the last 15 years and drank 25 units of alcohol per week, and again had done so for 15-20 years.

He had had gallbladder surgery 15 years previously after developing episodic upper abdominal pain and vomiting. Prior to surgery his GP had arranged an ultrasound scan, which had shown a bright liver as well as gallstones in the gallbladder. The surgeon noted at the time of laparoscopic cholecystectomy “the liver is fatty and enlarged”, but despite this no advice was given about his alcohol intake and weight. After suffering his variceal bleed, he stopped taking alcohol completely and lost 3 stone in weight. The patient contends that had he been made aware of the risk of liver disease related to his fatty liver, he would have undertaken those lifestyle changes at once, and as a result would have avoided developing a life-threatening complication of cirrhosis.

In Conclusion

Liver disease is increasingly common and there are tests which can provide effective early diagnosis. Not to use those tests is a failure of care which has serious implications for the individual who may unknowingly be at risk of life-threatening complications of a disease they did not know they had. Unfortunately, this is a relatively common scenario with many people having either abnormal blood tests or scans in the past which could and should have resulted in an earlier diagnosis.

About Dr Ryder

Dr Stephen Ryder, BMBS, MRCP,FRCP, DM, CSST, is a Consultant Physician in Hepatology and Gastroenterology.

Dr Ryder has particular interests in liver disease, viral hepatitis and abnormal liver blood tests. He won the award from the Nottingham Biomedical Research Unit for translational research in 2008.

Dr Ryder has been undertaking medico-legal work for over 20 years with his work splits approximately 40% claimant and 60% defendant.

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