By Donald M. Jensen, MD
In retrospect, it seems like it was the dark ages. When I was a medical resident at Rush in the mid-’70s, hepatology had few therapies and even less ability to change the course of chronic liver disease.
We had neomycin for hepatic encephalopathy (a complication of advanced liver disease that affects your behavior, mood, speech and other neurologic functions); corticosteroids for autoimmune hepatitis (liver inflammation), and diuretics for ascites and edema (swelling in the abdomen and legs). That was about it.
However, I was fortunate to have three attending hepatologists (unusual for any medical center in those days): A.W. (Bill) Holmes, John Payne and Richard B. Capps. I was struck by how smart they were and how they could glean so much information from a patient’s history and physical examination. Perhaps as important, each had a sense that liver disease would continue to grow as a specialty, and that bright new things were on the horizon. How right they were.
Over the next decade, liver transplantation, antiviral therapy and other large and small advances came forward. During my year as chief resident at Rush, Dr. Holmes suggested that I look into a fellowship in England. He said that many exciting things were coming out of King’s College Hospital in London under the direction of Roger Williams. I liked the idea of going abroad and applied for (and, ultimately, received) an invitation to be a fellow in the liver unit at King’s.
Focus on research
King’s was indeed a magical place. They had a fledgling liver transplant program combined with Sir Roy Calne at Cambridge University’s Addenbrook Hospital; a two-bed liver intensive care unit for patients with fulminant hepatitis (it was the start of the Tylenol overdose time period), and a large laboratory that had just published 56 papers the prior year.
I had some clinical duties: taking call in the acute liver failure unit, as well as traveling to Cambridge to manage patients after liver transplantation. However, my major focus was on research.
I spent my first month visiting each physician/investigator at their research bench and learning about their studies — which included studies about autoimmune hepatitis, primary biliary cholangitis (PBC), hemochromatosis, viral hepatitis, immunology, and extracorporeal hemoperfusion for acute liver failure. At the end of the month, I had to choose an area to study. I decided to focus on an idea to develop a novel radioimmunoassay to detect antibodies against the liver plasma membrane in autoimmune hepatitis.
Over the next 12 months, my mentor, Adrian Eddlestein, and I purified rabbit, and then human, liver membrane antigen known as liver-specific lipoprotein (LSP). We found a novel way to radiolabel it and established a unique assay incorporating the IgG Fc-binding properties of staphylococcus protein A.
During this time, I had been collecting blood and liver biopsy samples from both patients with autoimmune hepatitis, as well as hepatitis B and other chronic liver diseases. Our pathologist, Bernard Portman, independently scored all the liver biopsies for their different histological features. We were certainly able to detect anti-LSP antibodies, some of very high titer, but the eureka moment came when we matched up those results with the biopsy findings.
It turned out that anti-LSP was most common in autoimmune hepatitis and that it correlated remarkably with piecemeal necrosis – the hallmark biopsy lesion of autoimmune hepatitis. We decided that the finding was novel enough that we should aim to publish in a prestige medical journal — and we submitted our manuscript (after 12 revisions!) to the New England Journal of Medicine. It was accepted and published the following July as the lead paper. And, I was hooked on a career in academic hepatology.
Recently, I was invited back to the liver unit at King’s for its 50-year reunion. I was asked to give a brief talk about my experience at King’s during its 10th year. It seemed like completing the circle.
Parenthetically, my 18 months at King’s also featured my marriage to Donna Hanlon who has been my wife for the past 41 years. It was a truly remarkable time.
Donald M. Jensen, MD, is a hepatologist at Rush who specializes in autoimmune hepatitis, hepatitis B, hepatitis C, cirrhosis and liver cancer.