Bruce F. Scharschmidt (born March 6, 1946) is an American physician-scientist whose career has spanned academic, business and non-profit sectors. He was a major contributor to the care of patients with liver disease and advancement of liver transplantation.
Scharschmidt was born in East Cleveland, Ohio. He now lives in San Francisco, California with his wife, Peggy S. Crawford M.D. [1] Their son and daughter, Drs. Brent and Tiffany Scharschmidt and their families also live in the San Francisco Bay Area.
Scharschmidt graduated from Shaw High School in East Cleveland [2] and completed his undergraduate and medical education in Northwestern University’s Honors (6-year) Program in Medical Education. [3] After completing his residency training in Internal Medicine at the University of California, San Francisco (UCSF) in 1972, Scharschmidt worked for three years as a Clinical Associate at the National Institutes of Health, where he was a founding member of the Liver Disease Research Branch of NIDDK. [4]
Scharschmidt returned to UCSF in 1975 for subspecialty training in gastroenterology, and in 1977 joined the UCSF faculty. In 1985, he became a Professor of Medicine and, in 1990, was named Chief of the Gastroenterology division. [5]
While at UCSF, for two decades Scharschmidt led an independent NIH-funded research laboratory focused on liver physiology and the pathophysiology of liver disease. His research team elucidated cellular mechanisms of bile formation, including characterization of the hepatic uptake of organic anions such as bilirubin, [6] demonstrated that hepatic update of bile acids is sodium-coupled and electrogenic, [7] identified of the presence on the basolateral hepatocyte membrane of a sodium-coupled bicarbonate transporter critical to intracellular pH regulation, [8] [9] and reported of the initial evidence that hepatic bile acid secretion is mediated by an ATP-dependent transporter (later identified and shown to be mutated in progressive familial intrahepatic cholestasis type 2). [10] His team also collaborated in the identification of the gene that is responsible for progressive familial intrahepatic cholestasis type 1, previously known as Byler's disease, as well as benign recurrent intrahepatic cholestasis. [11]
Scharschmidt was an invited speaker at the 1982 NIH Consensus conference on Liver Transplantation, [12] where he reviewed and presented the results of liver transplantation, which at that time was carried out in only four centers worldwide, and authored the then definitive article on liver transplantation outcomes. [13] The NIH Consensus Conference concluded that liver transplantation was no longer experimental, which paved the way for its reimbursement and availability at centers throughout the US and worldwide. With his UCSF colleagues in surgery, Scharschmidt helped launch the UCSF liver transplant program. [14] [15] As a member of the Training and Workforce Committee of the American Association for the Study of Liver Diseases, [16] he worked with his colleagues to set current standards for training in hepatology, including special certification in transplant hepatology.
More than 15 individuals trained directly with Scharschmidt, several of whom became gastroenterology division chiefs, [17] and/or deans [18] and dozens more completed the UCSF gastroenterology training program for which he was responsible. [19] He authored an invited article on the topic of mentoring for Gastroenterology. [20]
In 1996, Scharschmidt moved to Chiron Corporation, [5] where he served as Corporate VP responsible for the clinical development of therapeutics and vaccines until its acquisition in 2006 by Novartis, where he remained for two years. While at Chiron and Novartis, his team was responsible for the successful clinical development and approval of therapeutics, including interleukin 2 for melanoma., [21] and participated in the development of several new vaccines approved in the US and/or Europe, including the first influenza vaccine manufactured using mammalian cell culture rather than the traditional fertilized chicken eggs, the first adjuvanted flu vaccine, [22] the meningococcal C vaccine [23] used to help curb deadly outbreaks in Canada and the UK, a tetravalent meningococcal vaccine effective against A, C, Y & W strains, [24] and the first vaccine against meningococcus B. [25]
In April 2008, Scharschmidt left Novartis to join Hyperion Therapeutics, a bay area biotech startup which was in early phase development of an ammonia lowering agent for patients with urea cycle disorders (UCDs). [26] As a member of Hyperion's management team, he was involved in taking the company public in 2012 (HPTX, NASDAQ), [27] Hyperion's successful secondary stock offering in 2013, [28] and sale of the company to Horizon Pharma in May 2015. [29]
Scharschmidt currently serves as Board Member and/or consultant to several biotechnology companies in the US and abroad. [30] [31]
Scharschmidt was elected to membership in the American Society for Clinical Investigation (ASCI) in 1982, [32] served as ASCI President from 1992-93 [33] and as Editor-in-Chief of the Journal of Clinical Investigation (JCI) from 1987-1992. [34] He is also a member of the Association of American Physicians.
Scharschmidt served as Associate Editor of Gastroenterology (1981-1986), [35] Associate Editor of the textbook Gastrointestinal and Liver Disease, (5th, 6th, and 7th Editions) [36] and as Editor of the Pocket Clinician textbook on Internal Medicine. [37] He received the Western Gastroenterological Association Research Award (1988), the University of Toronto Sheila Sherlock Research Award (1991), [38] was 1998 Honoree of the American Liver Foundation Northern CA Division's Salute to Excellence, [39] and was named 2010 Distinguished Northwestern Feinberg School of Medicine Alumnus of the year. [40]
Scharschmidt is inventor or co-inventor on multiple US (Patent Nos. 5,308,833, [41] 8,404,215, [42] 8,642,012, [43] 9,095,559, [44] 13,610,580, [45] ) and international patients with multiple patents pending.
Medical: Scharschmidt has authored over 200 research and review articles. The Hyperion clinical trials designed under Scharschmidt have resulted in over 20 publications, [46] address not only with the performance characteristics of RAVICTI, [47] but also the use of blood and urine metabolites for drug dosing and the optimal timing and target levels for blood ammonia in patients with urea cycle disorders so as to minimize the risk and frequency of hyperammonemic crises,. [48] [49] Bruce's team at Hyperion also designed and executed a large randomized, double-blind placebo controlled trial which demonstrated that lowering ammonia in patients with cirrhosis complicated by hepatic encephalopathy (HE) decreases the risk and frequency of HE episodes. [50] These findings, presented at the plenary session of American Association for the Study of Liver Disease, established that ammonia is not just a correlate, but a cause of HE and, as with UCDs, established the optimal timing and target levels for blood ammonia in cirrhotics so as to minimize their risk and frequency of HE episodes. [51] He also helped define the natural history of HE [52] as well as methodology for its diagnosis. [53]
Children’s Books: Scharschmidt has written and published several children’s books with others in production. Please visit brucescharschmidt.com.
As ASCI President, Scharschmidt initiated and obtained industry and NSF funding for a High School Science Teacher Summer Scholarship Program, [54] which paired science teachers with ASCI mentors so as to enable them to teach science as the exciting discipline of discovery. Bruce has served on the National Board of Directors of the American Liver Foundation, [55] on the External Advisory Board for the Clinical Translational Science Award at Northwestern/Feinberg School of Medicine, where he also served as President of the Medical Alumni Association Board from 2015 to 2017. [56] He has chaired the Translational Team of the Gladstone Institutes, where he is also a member of the President's Council. [57] He ran in the 2005 and 2006 Boston Marathons [58] and participated in the 2008 Mt. Shasta Climb [59] to raise funds for the American Liver Foundation, organized with his son in 2009 the “Biking For Burma’s Malnourished” bike ride from Central Thailand to the Burma Border to raise money for Global Health Access Program, [60] and in 2010 co-founded the ‘Cure the Cycle Challenge’ for the National Urea Cycle Disorders Foundation [61] in which he participated as a rider from 2010 through 2015.
Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pain, and diarrhea. Hepatitis is acute if it resolves within six months, and chronic if it lasts longer than six months. Acute hepatitis can resolve on its own, progress to chronic hepatitis, or (rarely) result in acute liver failure. Chronic hepatitis may progress to scarring of the liver (cirrhosis), liver failure, and liver cancer.
Ascites is the abnormal build-up of fluid in the abdomen. Technically, it is more than 25 ml of fluid in the peritoneal cavity, although volumes greater than one liter may occur. Symptoms may include increased abdominal size, increased weight, abdominal discomfort, and shortness of breath. Complications can include spontaneous bacterial peritonitis.
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide.
Alcoholic liver disease (ALD), also called alcohol-related liver disease (ARLD), is a term that encompasses the liver manifestations of alcohol overconsumption, including fatty liver, alcoholic hepatitis, and chronic hepatitis with liver fibrosis or cirrhosis.
Liver transplantation or hepatic transplantation is the replacement of a diseased liver with the healthy liver from another person (allograft). Liver transplantation is a treatment option for end-stage liver disease and acute liver failure, although availability of donor organs is a major limitation. The most common technique is orthotopic transplantation, in which the native liver is removed and replaced by the donor organ in the same anatomic position as the original liver. The surgical procedure is complex, requiring careful harvest of the donor organ and meticulous implantation into the recipient. Liver transplantation is highly regulated, and only performed at designated transplant medical centers by highly trained transplant physicians and supporting medical team. Favorable outcomes require careful screening for eligible recipients, as well as a well-calibrated live or deceased donor match.
Everolimus, sold under the brand name Afinitor among others, is a medication used as an immunosuppressant to prevent rejection of organ transplants and as a targeted therapy in the treatment of renal cell cancer and other tumours.
Autoimmune hepatitis, formerly known as lupoid hepatitis, plasma cell hepatitis, or autoimmune chronic active hepatitis, is a chronic, autoimmune disease of the liver that occurs when the body's immune system attacks liver cells, causing the liver to be inflamed. Common initial symptoms may include fatigue, nausea, muscle aches, or weight loss or signs of acute liver inflammation including fever, jaundice, and right upper quadrant abdominal pain. Individuals with autoimmune hepatitis often have no initial symptoms and the disease may be detected by abnormal liver function tests and increased protein levels during routine bloodwork or the observation of an abnormal-looking liver during abdominal surgery.
Portal hypertension is defined as increased portal venous pressure, with a hepatic venous pressure gradient greater than 5 mmHg. Normal portal pressure is 1–4 mmHg; clinically insignificant portal hypertension is present at portal pressures 5–9 mmHg; clinically significant portal hypertension is present at portal pressures greater than 10 mmHg. The portal vein and its branches supply most of the blood and nutrients from the intestine to the liver.
Primary sclerosing cholangitis (PSC) is a long-term progressive disease of the liver and gallbladder characterized by inflammation and scarring of the bile ducts, which normally allow bile to drain from the gallbladder. Affected individuals may have no symptoms or may experience signs and symptoms of liver disease, such as yellow discoloration of the skin and eyes, itching, and abdominal pain.
Ornithine transcarbamylase deficiency also known as OTC deficiency is the most common urea cycle disorder in humans. Ornithine transcarbamylase, the defective enzyme in this disorder, is the final enzyme in the proximal portion of the urea cycle, responsible for converting carbamoyl phosphate and ornithine into citrulline. OTC deficiency is inherited in an X-linked recessive manner, meaning males are more commonly affected than females.
Hepatic encephalopathy (HE) is an altered level of consciousness as a result of liver failure. Its onset may be gradual or sudden. Other symptoms may include movement problems, changes in mood, or changes in personality. In the advanced stages it can result in a coma.
Acute liver failure is the appearance of severe complications rapidly after the first signs of liver disease, and indicates that the liver has sustained severe damage. The complications are hepatic encephalopathy and impaired protein synthesis. The 1993 classification defines hyperacute as within 1 week, acute as 8–28 days, and subacute as 4–12 weeks; both the speed with which the disease develops and the underlying cause strongly affect outcomes.
Cholestasis is a condition where the flow of bile from the liver to the duodenum is impaired. The two basic distinctions are:
The Cahill cycle, also known as the alanine cycle or glucose-alanine cycle, is the series of reactions in which amino groups and carbons from muscle are transported to the liver. It is quite similar to the Cori cycle in the cycling of nutrients between skeletal muscle and the liver. When muscles degrade amino acids for energy needs, the resulting nitrogen is transaminated to pyruvate to form alanine. This is performed by the enzyme alanine transaminase (ALT), which converts L-glutamate and pyruvate into α-ketoglutarate and L-alanine. The resulting L-alanine is shuttled to the liver where the nitrogen enters the urea cycle and the pyruvate is used to make glucose.
Rifaximin, is a non-absorbable, broad spectrum antibiotic mainly used to treat travelers' diarrhea. It is based on the rifamycin antibiotics family. Since its approval in Italy in 1987, it has been licensed in over more than 30 countries for the treatment of a variety of gastrointestinal diseases like irritable bowel syndrome, and hepatic encephalopathy. It acts by inhibiting RNA synthesis in susceptible bacteria by binding to the RNA polymerase enzyme. This binding blocks translocation, which stops transcription. It is marketed under the brand name Xifaxan by Salix Pharmaceuticals.
Liver cancer, also known as hepatic cancer, primary hepatic cancer, or primary hepatic malignancy, is cancer that starts in the liver. Liver cancer can be primary in which the cancer starts in the liver, or it can be liver metastasis, or secondary, in which the cancer spreads from elsewhere in the body to the liver. Liver metastasis is the more common of the two liver cancers. Instances of liver cancer are increasing globally.
Paracetamol poisoning, also known as acetaminophen poisoning, is caused by excessive use of the medication paracetamol (acetaminophen). Most people have few or non-specific symptoms in the first 24 hours following overdose. These symptoms include feeling tired, abdominal pain, or nausea. This is typically followed by absence of symptoms for a couple of days, after which yellowish skin, blood clotting problems, and confusion occurs as a result of liver failure. Additional complications may include kidney failure, pancreatitis, low blood sugar, and lactic acidosis. If death does not occur, people tend to recover fully over a couple of weeks. Without treatment, death from toxicity occurs 4 to 18 days later.
Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage to the liver leads to repair of liver tissue and subsequent formation of scar tissue. Over time, scar tissue can replace normal functioning tissue, leading to the impaired liver function of cirrhosis. The disease typically develops slowly over months or years. Early symptoms may include tiredness, weakness, loss of appetite, unexplained weight loss, nausea and vomiting, and discomfort in the right upper quadrant of the abdomen. As the disease worsens, symptoms may include itchiness, swelling in the lower legs, fluid build-up in the abdomen, jaundice, bruising easily, and the development of spider-like blood vessels in the skin. The fluid build-up in the abdomen may develop into spontaneous infections. More serious complications include hepatic encephalopathy, bleeding from dilated veins in the esophagus, stomach, or intestines, and liver cancer. Stages of cirrhosis include compensated cirrhosis and decompensated cirrhosis.
A liver support system or diachysis is a type of therapeutic device to assist in performing the functions of the liver. Such systems focus either on removing the accumulating toxins, or providing additional replacement of the metabolic functions of the liver through the inclusion of hepatocytes to the device. This system is in trial to help people with acute liver failure (ALF) or acute-on-chronic liver failure.
Liver angiosarcoma also known as angiosarcoma of the liver or hepatic angiosarcoma is a rare and rapidly fatal cancer arising from endothelial that line the blood vessels of the liver. It is a type of angiosarcoma. Although very rare with around 200 cases diagnosed each year, it is still considered the third most common primary liver cancer, making up around 2% of all primary liver cancers. Liver angiosarcoma can be primary, meaning it arose in the liver, or secondary, meaning the angiosarcoma arose elsewhere and metastasized to the liver. This article covers PHA, however much is also applicable to secondary tumors.
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