Milestones in liver transplantation: how did alcoholic cirrhosis become a transplantation indication?

In 1954, Dr Joseph Murray and Dr Francis Moore in the United States performed the first successful kidney transplant. The organ was taken from an identical twin, marking the true beginning of organ transplantation. It is important to note that a pressing question immediately arose regarding the ethical implications of expo- sing a healthy donor to potential postoperative complications.
The first report on experimental liver transplantation was presented in October 1952 by an Italian surgeon Vittorio Staudacher from Milan at the 54^th Congress of the Italian Surgical Society in Venice.
In 1955, Stuart Welch (Albany Medical College) presented experimental research on liver transplantation as an auxiliary organ (heterotopic transplantation) supporting the recipient’s liver.
In 1956, Jack A. Cannon (UCLA – Los Angeles) conducted the first experimental, orthotopic liver transplantation.
In 1960, Thomas Starzl reported the results of the first 5 orthotopic liver transplants in dogs.
In 1960, azathioprine was introduced into the treatment of transplant recipients.
In 1963, the aforementioned Thomas Starzl performed the first human liver transplant (OLT). The indication for this transplant was hepatocellular carcinoma (HCC). The survival rates for this and subsequent patients were extremely low. It was not until 1967 that the eighth human transplant, carried out by Th. Starzl, assured 400-day survival.
The concept of brain death was formalised between 1967 and 1968. In 1968, Sir Roy Calne performed the first successful liver transplant in Europe, in Cambridge, England.
A significant breakthrough occurred in 1969 when Jean Francis Borel introduced cyclosporine – another immunosuppressive drug for post-transplant patients.
In 1976, Roy Calne conducted clinical trials that confirmed the efficacy of this drug in maintaining the transplanted organ.
A consensus was reached in Bethesda, USA in 1983, establishing liver transplantation as a standard of care for patients with irreversible liver failure.
It is also worth noting the dates of 1984 and 1985, when Henri Bismuth in Villejuif and Rudolf Pichlmayr in Hanover transplanted parts of the liver after reducing the size of the organ, so that it could be used for paediatric recipients.
In 1987, a preservation solution for transplant organs, known as UW solution (University of Wisconsin), was introduced.
In 1989, another immunosuppressive drug, tacrolimus, was introduced into clinical practice, which is still used effectively today.
The next significant milestone in liver transplantation was reached in 1989 when Russell Strong (Australia) performed a successful partial liver transplant from a living donor to a child. In 1994, Yoshio Yamaoka (Japan) transplanted the right lobe of the liver from a living donor to an adult recipient.
Another significant date is 2001, when the MELD scale, developed by Kameth and colleagues at the Mayo Clinic in the USA, was introduced to assess the severity of chronic liver disease. This scale is based on bilirubin, creatinine, and INR levels, with a range of 6-40 points.
In 2006, the concept of marginal donors was defined by Sandy Feng (USA) to expand the pool of donor organs, including those with significant steatosis, donors who had prolonged stays in the Intensive Care Unit, or high sodium levels.
In 2010, James Guarrera (USA) reported the first data on the use of a hypothermic liver perfusion device.
In recent years, indications for liver transplantation have been established. These include: advanced chronic liver failure, acute liver failure, liver tumours, and metabolic liver diseases. Patients with a MELD score above 15 points should be qualified for transplantation.
In 1998, the first studies were published indicating that liver failure caused by excessive alcohol consumption is also an indication for transplantation. At the same time, it was emphasized that patients with alcoholic cirrhosis (ALD) have a similar survival rate as those who were transplanted for other indications. In 2001, a consensus was reached that ALD is a suitable indication for OLT, with a recommendation that the patient abstain from drinking alcohol after transplantation.
Research in 2003 identified factors contributing to the relapse of alcohol abuse in approximately as many as 30% of post-transplant patients.
Predictive factors for relapse in patients with alcoholic liver disease include: other psychiatric disorders, lack of social support, previous rehabilitation attempts, lack of engagement in other activities, low self-esteem, co-existence of chronic diseases, polydrug abuse, and lack of coordinated care.
In Europe, a registry of patients who underwent OLT was established in 1968. By the end of 2023, nearly 170,000 patients were included in this registry. Analysing the registry reveals significant changes. Unfortunately, since the COVID-19 pandemic, the overall number of patients who underwent liver transplantation has decreased. However, on a positive note, the age limit of deceased donors has been shifted. Organs are increasingly being harvested from deceased donors over the age of 70. Moreover, recipients over the age of 70 are being accepted for transplantation.
The dominant group of patients undergoing liver transplantation are those with liver cirrhosis, accounting for approximately 70% of surgeries. Among these patients, a significant proportion have alcoholic cirrhosis, representing 36.7% of all indications for cirrhosis, and this percentage is still growing. In the overall European context, patients with alcoholic cirrhosis account for 19.6% of OLT patients, meaning that one in five transplant recipients has alcoholic cirrhosis. This raises the question of whether, in accordance with the principles of social justice and the ongoing organ shortage, this group of patients should “take” organs from patients with liver failure caused by other diseases.
According to the 2021 data published by the US OPTN/SRTR registries, alcoholic cirrhosis has not only rapidly increased as an indication for OLT but has now become the primary reason for liver transplant procedures.
This raises the question of whether the long-term survival rates of patients undergoing liver transplantation for alcoholic cirrhosis are comparable to those with other indications. The answer is affirmative: 5-, 10-, and even 20-year survival rates for these patients are similar to those of patients with cirrhosis caused by viral hepatitis.
In conclusion, alcoholic cirrhosis is currently a reco­gnized indication for liver transplantation.

DISCLOSURE

The author reports no conflict of interest.

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