The largest of the internal organs, the liver monitors essentially all materials absorbed from the diet, converting nutrients to useable form and eliminating potential toxins; it also manufactures de novo a number of substances essential for life. Disease of the liver typically progresses slowly, because the organ has large capacity and can regenerate. It is subject, however, to numerous insults that over time can it ultimately to fail, with devastating consequences. Current research is directed at the following areas:

Infection by hepatitis B and hepatitis C viruses, with emphasis on modes of transmission, determinants of severe disease and the immune response to these viruses.
Diseases of bile ducts, including the endoscopic management of primary sclerosing cholangitis, biliary tumors and stones.
Understanding the liver's response to injury and managing the formation of scar tissue ("fibrosis" or "cirrhosis").
Liver transport including the determinants of bile formation; inherited jaundice
The root causes and management of the complications of chronic liver disease, including fluid retention, altered consciousness ("encephalopathy"), decreased kidney function and internal bleeding.
Investigation of the molecular basis and treatment of liver cancer.

Liver Transplantation

For many patients with acute or chronic end-stage liver disease, transplantation may be the only option. The UCSF Liver Transplant Program, which integrates the efforts of gastroenterologists and surgeons, is one of only three centers selected by the National Institutes of Health to be part of its liver transplant database. It is one of the leading programs in the US in terms of patient volume (over 100 transplants every year) and innovative research. Survival statistics are among the very best in the country. Current areas of faculty interest include:

Testing of an artificial liver
Research on rejection and recurrent viral infection
Identifying approaches to minimizing cost and morbidity without compromising outcome

Inflammatory Bowel Disease

The inflammatory bowel diseases, ulcerative colitis and Crohn's Disease, are chronic conditions that once were considered largely untreatable. However, research has led to new insight into the immunological and metabolic disturbances that underlie these diseases and has generated a number of promising new therapeutic options. The UCSF Center for Inflammatory Bowel Diseases, situated at the Mount Zion campus, integrates patient care and research in an inter-disciplinary approach. Patients have access to expert medical and surgical gastrointestinal evaluation as well as nutrition, psychological assessment and alternative medicine. All patients, including those with difficult or refractory disease, may participate in clinical trials of the latest biologicals.

Areas of research emphasis include:

The altered immunological response of the bowel leading to chronic inflammation.
Evaluation of experimental anti-inflammatory and immunosuppressive medications for ulcerative colitis and Crohn's disease
Biochemical and genetic comparisons of normal intestinal cells with those from patients with ulcerative colitis to find the underlying cellular trigger of disease
Development of new nutritional, social and psychological support systems for patients with inflammatory bowel disease and their families
Development of applied molecular techniques for the early detection of colon cancer complicating colitis

Cancer of the Colon and Esophagus

A subgroup of patients with colon cancer come from families with several cases, indicating the presence of inherited factors. These families have provided important insight into the genes that are critical for normal cell growth in the colon and, conversely, the genes in which mutation leads to cancer. The Colon Cancer Risk-Assessment Program, at the Mount Zion campus and the Veterans Affairs Hospital, is focused on patients from families with two or more cases, particularly when the cancer appears before the age of 50. The Program maintains a registry that now includes more than 200 families in the Bay Area. Enrolled patients and their relatives can receive genetic screening and counseling while participating in studies, as follows:

Surveys to uncover new genes that predict the risk of cancer
Cancer-prevention protocols centering on anti-inflammatory compounds, including selective cyclooxygenase-2 inhibitors
The biology that underlies the neoplastic transformation of the lining cells of the colon
Experimental treatment of colon cancer metastatic to the liver, in collaboration with the Division of Medical Oncology and Department of Surgery

Also important is cancer of the esophagus, in particular that related to the condition known as Barrett's esophagus, in which the lower part of the organ acquires a lining resembling that of the intestine. Patients with this type of lining are at risk for adenocarcinoma of the esophagus. Research is focused on defining the predictors of risk and measures to prevent evolution to cancer.

Obesity, Diabetes and the Liver Disease of Obesity

Obesity and obesity-associated diabetes are increasing at a striking rate in the highly developed countries of the world, most notably in the United States. "Morbid" obesity is weight gain that interferes with normal daily tasks, often preventing gainful employment. The Division offers a multi-disciplinary approach to the management of morbid obesity. One component is evaluation of diabetes, in collaboration with the UCSF Metabolic Research Unit. Another component is "gastric bypass" surgery, carried out by the Department of Surgery. A particular research focus is the low grade inflammation that occurs in the liver of many obese patients, notably those who also have diabetes. Known as "non-alcoholic steatohepatitis", or NASH, it appears to be increasing in frequency and in some individuals progresses to the point of requiring liver transplantation. Investigators in the Division are examining possible genetic factors, related to abnormal fat handing by the liver, that may contribute to disease progression.

Bowel Motility Disorders

Abnormal bowel motility ("dysmotility") can involve the swallowing apparatus, the esophagus, the stomach or the intestine, particularly the colon. It is seldom life-threatening but typically is chronic and may account for more lost workdays, in aggregate, than any other gastrointestinal condition. Investigators from the Division of Gastroenterology are testing the hypothesis that altered connections between the brain and the gut are responsible for dysmotility in at least some patients. The role of dietary constituents also is being examined.