Hepatopulmonary syndrome historical perspective

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Soroush Seifirad, M.D.[2]

• In 1884, Flückiger was the first to report the association between liver dysfunction and the development of hypoxemia. (Flückiger M. Vorkommen von trommelschlagel-formigen fingerendphalangen ohne chronische veranderungeng an den lungen oder am herzen. Wien Med Wochenschr. 1884;34:1457.) The term “hepatopulmonary syndrome” was first suggested by Kennedy and Knudson almost 100 years later,in 1977 during describing a patient with the classic findings of hepatopulmonary syndrome.

• In 1884, Flückiger was the first to report the association between liver dysfunction and the development of hypoxemia. (Flückiger M. Vorkommen von trommelschlagel-formigen fingerendphalangen ohne chronische veranderungeng an den lungen oder am herzen. Wien Med Wochenschr. 1884;34:1457.)
• The term “hepatopulmonary syndrome” was first suggested by Kennedy and Knudson almost 100 years later,in 1977 during describing a patient with the classic findings of hepatopulmonary syndrome.^[1]

• Currently the only definitive treatment is liver transplantation. Alternative treatments such as supplemental oxygen or somatostatin to inhibit vasodilation remains anecdotal.
• Here are the landmarks of liver transplantation pathway.

• In the 1960s, Thomas Starzl used dogs as the first animals for research on liver transplantation in Boston and Chicago.
• In 1963, the first liver transplant in humans was attempted by a surgical team led by Dr. Thomas Starzl of Denver, Colorado, United States.
• Dr. Starzl performed many additional transplants until he was successful in 1967 with the first one-year survival post-transplantation.
• In 1970, the regimen for immunosuppressive therapy following transplant was introduced, but azathioprine and steroids did not improve survival rates of patients.
• In the 1980s, with the introduction of cyclosporine by Sir Roy Calne, there was an improvement in rejection rates.
• In 1983, liver transplantation was no longer an experimental modality, but a clinically accepted form of therapy for both adult and pediatric patients with appropriate indications.
• In 1986, the introduction of monoclonal antibodies such as muromonab-CD3 [OKT3] further contributed to improvement of quality of immunosuppressive therapy used in patients, with significant decline in rejection rates.
• In 1988, University of Wisconsin (UW) solution was developed, which ensured a smooth surgery and longer preservation period.
• In 1992, the concept of xenotransplantation and cloning techniques were introduced by Starzl.
• In 1999, approximately 5000 procedures were carried out, in contrast to 100 which had been performed a decade earlier.
• Recently, the introduction of newer immunosuppressive agents such as IL-2 receptor blockers and tacrolimus, have drastically increased patient survival ratesto 1 and 5-year rates of approximately 85 and 70 percent respectively.
• In December 2016, 147,128 liver transplants were performed in the US as compared to 7217 in 1998 based on data from the United Organ Sharing (UNOS) network.