Liver Cirrhosis Causes, Prevention and Early Diagnosis

The main causes of liver cirrhosis are chronic hepatitis B, chronic hepatitis C, long-term heavy alcohol use and fatty liver disease linked to obesity and diabetes. Each does its damage over 10 to 15 years without symptoms, so people with these risk factors need regular blood tests, an ultrasound and a fibroscan to catch cirrhosis early, while it can still be held in check.

For Dr. Sandeep K Jha, then Consultant Liver Transplant, Manipal Hospital, New Delhi, India, the purpose of testing people at risk is to catch cirrhosis early, before complications develop. This article covers the causes he set out for referring doctors, how each is treated, and how early cirrhosis is detected. The overview of the whole masterclass is in the liver cirrhosis complete guide.

The causes of liver cirrhosis differ by region

Cirrhosis is the common end point of many different injuries. Dr. Jha described a clear geographic split in the leading causes:

• In the East, hepatitis B and hepatitis C are the major causes.
• In the West, hepatitis C and alcohol-related liver disease are the most common.

Beyond these, he showed a chart of less common causes, many of them rare, which can produce the same shrunken, hardened liver if they persist in the body for long enough. Among the recognised examples are autoimmune hepatitis, primary biliary cholangitis, Wilson disease and haemochromatosis. In children, biliary atresia is the leading cause, as described in the complete guide.

Viral hepatitis: which viruses cause cirrhosis

Five hepatitis viruses infect the liver: A, B, C, D and E. They behave very differently.

The distinction matters for counselling. A patient recovering from hepatitis A or E needs reassurance that the infection will not cause cirrhosis, even though in rare cases it can cause sudden liver failure. The exception is hepatitis E in people with weakened immunity, such as organ transplant recipients, in whom it can become chronic and progress to cirrhosis. A patient with hepatitis B or C needs long-term treatment and monitoring.

Hepatitis B treatment: controlled, not cured

Dr. Jha described today's hepatitis B drugs as excellent compared with those of 10 years ago. He named tenofovir and entecavir as very effective, with low levels of resistance, and able to control the virus in practice.

Control is not cure. Hepatitis B hides inside the liver cells and can reactivate after years, or even a decade. Dr. Jha was explicit that no permanent cure exists at present.

Hepatitis C treatment: elimination is now achievable

Hepatitis C has been transformed by the directly acting antiviral agents. Dr. Jha cited sofosbuvir and velpatasvir as very effective drugs that eliminate the virus from the body.

The limit of antiviral treatment

The timing of treatment is everything. When hepatitis B or C is treated before cirrhosis develops, the patient can be spared cirrhosis altogether. Once cirrhosis has formed, Dr. Jha warned, the liver will not become normal again even if medication eliminates the virus. The scarring that remains still needs surveillance.

Because effective drugs now exist for both viruses, Dr. Jha expects the incidence of cirrhosis caused by hepatitis B and C to fall over the next 10 to 15 years.

Hepatitis B precautions for family members

Hepatitis B spreads through blood, through sexual contact and from mother to child. Dr. Jha acknowledged that, in theory, a household exposure such as contact with blood from a cut can transmit the virus. The protocol he described has three parts:

1. The infected person takes treatment.
2. Every family member is vaccinated against hepatitis B, so that each has enough protective antibodies to withstand an accidental exposure.
3. Personal items that can carry blood, such as razor blades, are never shared.

The same logic protects couples. When one partner carries hepatitis B, an adequately vaccinated spouse is considered protected against the virus, even within a sexual relationship.

Alcohol-related liver disease

Alcohol taken in excessive quantities over a prolonged period, which Dr. Jha described as 10 to 15 years, can cause both cirrhosis and liver cancer. Stopping alcohol completely is part of the management of cirrhosis of any cause, not only alcohol-related disease.

Fatty liver disease and cirrhosis: the fastest-growing cause

Non-alcoholic fatty liver disease (NAFLD) is the build-up of fat in the liver in people who drink little or no alcohol. It occurs in people with diabetes, obesity or dyslipidaemia (abnormal levels of cholesterol and triglycerides). The condition was recently renamed metabolic dysfunction-associated fatty liver disease (MAFLD), and international nomenclature now uses metabolic dysfunction-associated steatotic liver disease (MASLD); the inflamed form, non-alcoholic steatohepatitis (NASH), is now termed metabolic dysfunction-associated steatohepatitis (MASH).

In Dr. Jha's account, the incidence of fatty liver disease is rising very rapidly, driven by sedentary lifestyles and the growth of obesity and diabetes, and it is quickly becoming the most important cause of cirrhosis and of liver transplantation. The figures he presented make the scale plain:

• At least 60% to 70% of people with obesity have fatty liver disease.
• Between 15% and 50% of people with obesity have NASH, the inflamed form, and many progress to cirrhosis.
• In the United States, fatty liver disease is projected to overtake hepatitis C as the leading cause of liver transplants.

Steatohepatitis is reversible; cirrhosis is not

Steatohepatitis is the stage at which the fatty liver is inflamed. Dr. Jha's first step with such a patient is to establish whether cirrhosis has already developed, using one of two tests: a fibroscan or a liver biopsy.

The answer splits management in two:

• Steatohepatitis without fibrosis: if the risk factors are controlled, the inflammation improves and can disappear completely. Medication is added where needed.
• Cirrhosis already present: the patient is kept under regular follow-up for life, because there is no way of knowing when a cirrhotic liver will begin to fail.

Managing fatty liver disease: metabolic control first, then diet

Dr. Jha's approach starts with the metabolic risk factors rather than the liver itself:

1. Reduce weight in patients with obesity.
2. Control diabetes.
3. Control raised cholesterol and triglycerides.
4. Treat hypothyroidism.

Once those are controlled, the dietary prescription is simple. Where obesity is the driver, he recommends a low-calorie, low-fat, high-protein diet, restricted to under 2,000 kilocalories in 24 hours, with a strict diet chart, regular exercise and weight loss. When liver function tests are elevated, he sometimes adds medication. He does not recommend any particular food item: the broad guideline is calorie control and a diet low in carbohydrate and fat and high in protein.

Early symptoms of cirrhosis: why it is easy to miss

The most important fact about early cirrhosis, in Dr. Jha's words, is that it causes no symptoms. Most of the time, the only way to catch it is a fibroscan.

The textbook physical signs (jaundice, ascites, oedema, spider angiomas or small spider-shaped clusters of skin blood vessels, palmar erythema or reddened palms, and gynaecomastia, the enlargement of breast tissue in men) are the telltale findings on examination, but they appear only in advanced cirrhosis. The aim is to diagnose patients before these complications develop. Advanced cirrhosis, by contrast, is often easy to diagnose: the abdomen is swollen with fluid, the patient may vomit blood, the jaundice is obvious and the spleen may be very large.

Who should be tested for cirrhosis

Dr. Jha monitors every patient with a significant risk factor:

• Long-term alcohol intake.
• Hepatitis B infection.
• Hepatitis C infection.
• Diabetes.
• Severe obesity.

Tests for early diagnosis of cirrhosis

For patients under follow-up, Dr. Jha's panel is:

1. Complete blood count.
2. Liver function tests.
3. Kidney function tests.
4. Prothrombin time, a measure of how well the liver makes clotting proteins.
5. Ultrasound of the whole abdomen.

Together these show whether the liver is functioning optimally. More recently, his team has added the fibroscan to this panel.

Fibroscan versus liver biopsy

A fibroscan (transient elastography) uses an ultrasound-based probe to measure the stiffness of the liver: the more fibrosis, the stiffer the organ. It is painless, takes minutes and can be repeated.

Dr. Jha considers a liver biopsy unnecessary for diagnosing cirrhosis in 99% of cases. A good fibroscan can diagnose early cirrhosis, and he regards an ultrasound or fibroscan done proactively as the better route to diagnosis before complications develop. When a biopsy is performed, periportal or bridging fibrosis (scarring that extends from, or links, the portal tracts of the liver) signals advancing disease.

From diagnosis to surveillance

Once cirrhosis is confirmed, the strategy shifts from detection to surveillance. Patients are tested every six months, and deterioration in those results, or new fluid in the abdomen, marks the point at which the liver is failing. What happens next, from the complications of decompensation to the scores that time a transplant, is covered in decompensated cirrhosis, MELD and Child-Pugh scoring. The questions doctors raised on these topics during the session are on the Live Discussion page.