Claude Couinaud Helped Change How Surgeons Operate on the Liver

From the hepatocentrism of ancient Mesopotamia to the Greek myth of Prometheus to Christian iconography, the liver has held a venerated role in mythology and medicine for millennia. Despite the integral role of the liver in human health and disease, it was only in the 20th century that physicians and anatomists began to fully understand its intricate anatomy. This historical retrospective traces the understanding of liver anatomy from ancient times to the present, with particular attention to the contributions of Hugo Rex, James Cantlie, and Claude Couinaud.

Classical Anatomists: Early Studies of the Liver

Among the earliest surviving anatomical models of the liver are Babylonian clay models of the trilobar sheep liver used to teach divination and hepatoscopy. The earliest descriptions of the human liver come from Galen of Pergamum (129–216 CE), whose studies in animals proposed that the liver is “of a good size […] Where it is applied to the diaphragm, it is arched and smooth. Below, toward the cavity and vena cava, it is concave and irregular.”

Galen also described the liver as the “source of the veins and the principal instrument of blood production” and as sharing with the heart and brain “in the triple control of the natural, animal and vital souls” (De Hippocratis et Platonis Decretis, 2nd century CE). Galen’s contemporary Aretaeus of Cappadocia proposed that the vena cava originated from the liver, and thus “the roots of all the veins unite to form the liver,” which contributed to the belief that “the formation of the blood is in the liver, and hence the distribution of it over the whole system.”

Even Renaissance anatomist Andreas Vesalius presented the liver as erroneously having five lobes in his Tabulae Anatomicae Sex (1538), though this was corrected to a bilobar liver in his pioneering anatomy textbook De Humani Corporis Fabrica (1543). William Harvey, the English anatomist who described the circulatory system in 1628, believed that a five-lobed liver was the origin of all veins.

In 1654, English anatomist Francis Glisson (1597–1677) published Anatomia hepatis, the first book devoted exclusively to liver anatomy. This textbook contained an early detailed description of the liver capsule (Glisson’s capsule), blood supply, and biliary anatomy. Anatomy textbooks as late as the mid-19th century continued to refer to the lobes using external landmarks, namely the falciform ligament, as the plane of division. Swiss anatomist Albrecht von Haller later divided the liver into four lobes: right, left, quadrate, and caudate.

Although Dr. Couinaud is among the best-known liver anatomists, his work built on generations of research on the internal anatomy of the liver using corrosion casting. In corrosion casting, a substance is injected into the internal structures of the liver, including the portal venous, hepatic arterial, hepatic venous, and biliary systems. Once the resin hardens, the liver parenchyma is dissolved, leaving a cast that preserves the deep internal structures of the liver in their original three-dimensional framework.

Hugo Rex (1861–1936) was one of the most important early liver anatomists, and his pioneering studies influenced subsequent liver anatomy research. Working at the German University in Prague (Deutsche Universität Prag), Rex was among the first to comprehensively study the internal anatomy of the liver. Using corrosion casts, Rex demonstrated that the portal vein divided into right and left branches supplying distinct portions of the liver. His use of internal anatomy to define the portal division of the liver was a departure from previous descriptions based primarily on external anatomy and the falciform ligament.

Rex published his findings in “Beiträge zur Morphologie der Säugerleber” (Contributions to the Morphology of the Mammalian Liver) in 1888. Despite the limitations of early corrosion-casting methods, Rex described second-order portal divisions that helped establish the concept of segmental liver anatomy. Rex is remembered today in the eponymous Rex recess, the space between segments 3 and 4 that contains an intrahepatic portion of the left portal vein and can be targeted in meso-Rex shunting procedures for extrahepatic portal vein obstruction.

“The Surgery of the Liver Will Be Advanced a Step”: James Cantlie

James Cantlie (1851–1926) was a Scottish surgeon whose clinical observations fundamentally changed the study of liver anatomy. He completed his medical studies at Aberdeen and his surgical training at London’s Charing Cross Hospital in 1877. He started his career at Charing Cross but soon turned his research and clinical interests toward tropical diseases.

In 1887, Dr. Cantlie moved to Hong Kong, where he made an observation that would influence the study of the liver. During an autopsy, he observed that the right side of the liver was reduced to a mass of fibrotic tissue, whereas the “almost elephantine” left side showed marked hypertrophy. He hypothesized that destruction of the right side had resulted in compensatory hypertrophy of the contralateral liver. Importantly, this included the quadrate lobe (segment 4), which conventionally was considered a right-sided structure according to external anatomy.

Dr. Cantlie published these findings in the Proceedings of the Anatomical Society of Great Britain and Ireland in 1897. Dr. Cantlie wrote, “The hypertrophy of the left side joined with the atrophied right side, at a line drawn through the fundus of the gallbladder to the center of the inferior vena cava at the back of the liver.” His contributions are reflected in Cantlie’s Line, a theorized plane extending from the gallbladder fossa to the inferior vena cava that defines the functional division between the right and left sides of the liver.

Dr. Cantlie corroborated his clinical observations by injecting the divisions of the portal vein with colored dyes, showing that the injected areas met along his proposed line. He stated, “It is theoretically possible to tie the vessels of one side at the gate of the liver, supplying an abnormal growth in one or other of the liver lobes, leaving the other side to do the work,” anticipating principles that underpin modern hepatic surgery and assessment of the future liver remnant.

Dr. Cantlie continued, “I commend this subject to all those who are working at the surgery of the liver; and I believe that if, in the hands of future observers, the statements I have made receive closer investigation, the surgery of the liver will be advanced a step.” Dr. Cantlie returned to London in 1897 and became a founder of the London School of Tropical Medicine.

Following Dr. Cantlie’s clinical observations, several important anatomical studies contributed to the understanding of liver anatomy. Sir Archibald H. McIndoe, MB ChB, FACS, and Virgil S. Counseller, MD, two surgeons working at Mayo Clinic in Rochester, Minnesota, used cellulose nitrate (celloidin) corrosion casts in their landmark 1927 study, “The Bilaterality of the Liver,” published in Archives of Surgery.

Drs. McIndoe and Counseller observed a “striking and constant result,” with the left and right branches of the portal vein, hepatic artery, and bile duct consistently demonstrating a line of division extending through the gallbladder fossa, confirming Dr. Cantlie’s earlier experiments. They wrote, “Our experiments clearly show that the liver of man is constantly and regularly divided into halves, according to distribution of the portal vein, by a plane passing through the fossa for the gallbladder and the entrance of the hepatic veins into the inferior vena cava […] the falciform ligament is of secondary importance.”

In 1951, Carl-Herman Hjortsjö of Sweden proposed a segmental classification based on biliary anatomy using a combination of corrosion specimens and cholangiograms. Hjortsjö concluded that the bile duct and portal vein accompanied each other, which served as a prelude to Dr. Couinaud’s later studies. However, Hjortsjö’s model largely fell out of favor because of its irregular boundaries and limited practicality for clinical use.

In 1953, John E. Healey Jr., MD, and Paul C. Schroy at Jefferson Medical College in Philadelphia proposed what was then the most comprehensive nomenclature. Based on vinyl acetate corrosion casts, they proposed a model of the liver with four “segments”: the left lobe with medial and lateral segments, and the right lobe with anterior and posterior segments, largely based on biliary anatomy. Each segment was then divided into superior and inferior areas, for a total of eight areas plus three additional areas in the caudate lobe. In a subsequent publication, Healey noted that limited understanding of the intrahepatic vascular and biliary anatomy had hindered advances in liver resection.

“Although radical operations upon the liver were performed as early as 1886, little advancement has been made in the surgical technic of such resections. This is due mainly to the fact that surgeons (and anatomists) have been totally unaware of the intrahepatic course and distribution of the larger vascular, and biliary channels and that, therefore, incisions through the hepatic parenchyma have been largely performed somewhat blindly. It is not surprising, therefore, that the present day mortality rate for partial hepatectomies is little changed from the mortality rate for similar procedures in 1897,” he said.

In 1957, Neal A. Goldsmith, MD, and Russell T. Woodburne, PhD, at the University of Michigan, published a portal venous-based model with four segments, each having two subsegments. They proposed that “in major hepatic resections, relative freedom from morbidity and mortality is dependent to a considerable extent upon adherence to sound surgical principles and anatomic facts.” The Goldsmith-Woodburne model closely resembles the Couinaud classification and appears to have been developed nearly concurrently and in parallel with Dr. Couinaud’s work in France.

Claude Couinaud: Finding Order in Disorder

Claude Couinaud (1922–2008) was a French surgeon-anatomist whose extensive studies of segmental liver anatomy laid the foundation for the eponymous nomenclature system that remains widely used today.

Dr. Couinaud was born in Argentan, France, in 1922. He completed his medical education at the École de Médecine in Paris in 1946 and his surgical training in Paris in 1951. Following his training, he undertook research in the anatomy laboratory of André Delmas in Paris. Delmas charged Dr. Couinaud with investigating arterial cross-perfusion in the hepatic hilum and suggested corrosion casting as an alternative to dissection alone. Dr. Couinaud developed a technique using vinyl chloride acetate resins dissolved in acetone. The material was sufficiently fluid to fill small intrahepatic structures while producing durable casts.

Dr. Couinaud answered his initial research question by demonstrating intrahepatic arterial anastomoses in the hilum. During this investigation, however, he also observed a regular pattern of hepatic pedicle segmentation that would shape the future course of his research.

Dr. Couinaud began full-time surgical practice in Paris, dividing his days between morning clinics and operations with Henri Mondor and afternoon research in the laboratory.

During this period, he created more than 100 corrosion casts of the liver and observed a regular vascular-biliary segmentation pattern that was consistent from one liver to another. He classified the liver into eight functionally independent segments based on portal venous anatomy.

Each segment has its own portal inflow and biliary drainage, while hepatic veins run along intersegmental boundaries. In 1952, he published “Hépatectomies gauches lobaires et segmentaires,” detailing the segmental anatomy of the left liver, followed in 1953 by “Les hépato-cholangiostomies digestives,” which presented the segmental anatomy of the entire liver. He also proposed a sectoral classification based on second-order branching of the portal vein, with hepatic veins between the sectors. His landmark treatise on liver anatomy, Le Foie: Études anatomiques et chirurgicales, was published in 1957, with a foreword by Delmas.

Perhaps most influential was Dr. Couinaud’s ability to apply his anatomic knowledge to surgery. Following the report of a modern anatomic hepatectomy by Jean-Louis Lortat-Jacob in 1952, Dr. Couinaud performed a “controlled” hepatectomy by controlling and ligating Glissonian sheaths as a single unit during resection of segments 2 and 3 in 1953. He followed this with a formal left hepatectomy in 1956. Dr. Couinaud’s work in biliary bypass similarly reflected his applied anatomical knowledge.

His 1953 publication “Les hépato-cholangiostomies digestives” outlined the anatomic basis of biliary bypass procedures above the left-right biliary confluence. He described a case series using a technique for accessing the intrahepatic left bile duct at the base of segment 4, now known as the eponymous Hepp-Couinaud procedure, in a 1956 paper with Jacques Hepp. He also described a distal segment 3 biliary bypass in a 1957 paper with Robert Soupault.

In an era of disparate liver anatomy classifications, Dr. Couinaud’s segmental nomenclature became the dominant system and remains widely used. The system was simple and consistent, using readily defined anatomic boundaries and numeric 1–8 nomenclature. It also provided surgical guidance for segmental resections based on portal inflow and hepatic venous outflow. French surgeons who led the development of hepatobiliary surgery in the mid-20th century applied Dr. Couinaud’s anatomical descriptions to surgical resection and imaging, including computed tomography.

Dr. Couinaud’s nomenclature informed the International Hepato-Pancreato-Biliary Association’s Brisbane 2000 Terminology of Liver Anatomy and Resections, developed under the leadership of Steven M. Strasberg, MD, FACS, of Washington University in St. Louis, Missouri. The Brisbane terminology uses Dr. Couinaud’s classification for segmental anatomy while standardizing terminology for larger anatomic divisions of the liver.

Dr. Couinaud donated his remaining collection of 116 liver casts to the Université de Paris’ Delmas-Orfila-Rouvière anatomy museum. In 2015, the collection was moved to the Conservatoire d’Anatomie at the Université de Montpellier, where it was combined with Paul E. Rapp’s collection of 134 liver casts to form a unique collection of 250 casts.

The studies of liver anatomy by Rex, Dr. Cantlie, Dr. Couinaud, and others helped lay the foundation for modern liver surgery. Hepatobiliary surgeon Jean-Nicolas Vauthey, MD, FACS, dedicated his 2012 Americas Hepato-Pancreato-Biliary Association Presidential Address to Dr. Couinaud and “the seven virtues of hepato-pancreato-biliary surgery.”

A deeper understanding of liver anatomy and compensatory hypertrophy has supported the development of therapies including preoperative portal vein embolization and associating liver partition and portal vein ligation for staged hepatectomy. After generations of study, surgeons are closer to summiting the “Mount Everest” of organs, yet the liver continues to challenge the bright and the bold.

Dr. Brendan Lovasik is a transplant surgeon at Mayo Clinic in Jacksonville, Florida.

Dr. Aaron Delman is a transplant surgery fellow at Washington University in St. Louis, Missouri.

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