Gregory T. Everson, MD
Jennifer DeSanto, RN
Chief Study Coordinator
Andrea Herman, RN
Steve Helmke, PhD
Our laboratory is interested in new and emerging therapies for the treatment of chronic hepatitis C and chronic hepatitis B. As a result, our team conducts a large number of clinical trials funded by pharmaceutical companies, government grants and contracts, and private foundations. Examples include studies maintenance therapy with peginterferon to prevent disease progression in patients with chronic hepatitis C (HALT-C), collaborations with companies developing new antivirals for hepatitis C (Vertex, Roche, Wyeth, Bristol-Meyers-Squibb, Intermune, Human Genome Sciences) and hepatitis B (Gilead), and drugs for combating cytopenias induced by antiviral therapy (GSK, OrthoBiotech). We are also studying pre-transplant antiviral strategies for prevention of post-transplant recurrence of hepatitis C (LADR-A2ALL).
An additional significant interest is development and implementation of methods for measuring hepatic function in man. Currently we are using multiple quantitative tests of liver function (QLFTs) to study hepatic function in chronic hepatitis C patients enrolled in the HALT-C trial. We have correlated these tests to other measures of disease severity and are developing models for use of QLFTs that could translate into clinical practice. We are also using QLFTs to define the magnitude of functional loss after right lobe donation in the setting of LDLT. This study is a key sub-study of the NIH-sponsored A2ALL study. Additionally, we are examining hepatic functional impairment in patients with chronic hepatitis C and minimal fibrosis.
One test that we have developed in my laboratory, that shows great promise as a clinically relevant function test is the cholate shunt. The following figure demonstrates the relationship of cholate shunt to hepatic fibrosis.
The test demonstrates progressive rise in shunt (worse function) as the amount of liver fibrosis increases. The relationship is not linear, but exponential, indicating that at higher stages of fibrosis there is a greater decline in function or increase in shunt for a given increase in additional fibrosis. This is the functional equivalent for the clinical phenomenon we term “decompensation” or “falling off the table” or “wheels falling off the wagon”.
The test also shows promise for predicting risk of decompensation and for tracking change in hepatic function over time. This test is likely applicable to all patients with liver disease, not just patients with chronic hepatitis C.
Recent Publications 2005 - 2006
- Everson GT. Management of cirrhosis due to chronic hepatitis C. Journal of Hepatology 42 (2005) S65-S74.
- Everson GT. Should we treat patients with chronic hepatitis C on the waiting list? Journal of Hepatology 2005; April 42(4):456-62.
- Everson GT. Antiviral Therapy in the Liver Transplant Candidate and Recipient. Current Hepatitis Report 2005; 4:75-82.
- Everson GT. Treatment of Hepatitis C in the Patient with Decompensated Cirrhosis. Clin Gastro and Hepatology, 2005;3:S106-S112.
- Trotter J, Pieramici E, Everson GT. Chronic Albumin Infusions to Achieve Diuresis in Patients with Ascites Who Are Not Candidates for Transjugular Intrahepatic Portosystemic Shunt (TIPS). Digestive Dis and Sciences 2005 Jul; 50(7):1356-60.
- Everson GT, Trotter J, Forman L, Kugelmas M, Halprin A, Fey, B, Ray C. Treatment of Advanced Hepatitis C with a Low Accelerating Dosage Regimen (LADR) Of Antiviral Therapy. Hepatology 2005, 42(2):255-262.
- Lok AS, Ghany MG, Goodman ZD, Wright EC, Everson GT, Sterling RK, Everhart JE, Lindsay KL, Bonkovsky HL, Di Bisceglie AM, Lee WM, Morgan TR, Dienstag JL, Morishima C, the HALT-C Trial Group. Predicting cirrhosis in Patients with Hepatitis C Based on Standard Laboratory Tests: Results of the HALT-C Cohort. Hepatology 2005, 42(2):282-292.
- Everson GT. Treatment of Hepatitis C in Patients who have Decompensated Cirrhosis. Clinics in Liver Disease 2005, Aug; 9(3):473-86.
- Sieja KS, Everson Gt. De Novo Hepatocellular Carcinoma in a Patient with Chronic Hepatitis C 5 years after Sustained Virologic Response to Interferon/Ribavirin Therapy. Dig Dis Sci, 2006 Mar;51(3):600-2.
- Everson GT, Balart L, Lee SS, Reindollar RW, Shiffman ML, Minuk GY, Pockros PJ, Govindarajan S, Lopez-Talavera JC, Heathcote EJ. Histologic benefits of Peginterferon alfa-2a monotherapy in patients with hepatitis C and advanced fibrosis or cirrhosis. Submitted J Hepatology, October 2005.
- Swize L, Everson GT. Chronic Hepatitis C: Reasons to Treat Besides the Liver. Submitted, July 2005.
- Fontana RJ, Di Bisceglis AM, Sanyal AJ, Mehta S, Doherty MC, Everson GT, Kahn JA, Malet PF, Sheikh MY, Chung RT, Ghany MG, Gretch DR, Everhart JE, and the HALT-C Trial Group. Portal Hypertensive Gastropathy in Chronic Hepatitis C Patients with Bridging Fibrosis and Compensated Cirrhosis: Results from the HALT-C Trial. Am J Gastroenterol. 2006 Mar 30.
- Kulig CC, Beresford TP, Everson GT. Rapid, Accurate, and Sensitive Fatty Acid Ethyl Ester Determination by Gas Chromatography-Mass Spectometry. J Lab Clin Med. 2006 Mar;147(3):133-8.
- Moore PA, Balan V, Nelson D, Sulkowski M, Everson G, Lambiase L, Neumann A, Garcia A, Osborn B, Bagchi P, Novello L, Freimuth W, Subramanian M. Modulation of Interferon Specific Gene Expression by Albuferon in Subjects with Chronic Hepatitis C and Correlation with Anti-Viral Response. In preparation, 2005.
- Lok, ASF, Everhart JE, Chung Rt, Padmanabhan L, Greenson JK, Shiffman ML, Everson GT, Lindsay KL, Bonkovsky HL, DiBisceglie AM, Lee WM, Morgan TR, Ghany MG, Morishima C, and the HALT C Trial Group. Hepatic Steatosis is associated with Fibrosis and Impaired Antiviral Response in Non-Diabetics with Hepatitis C: Analysis of Data from the HALT-C Trial. Submitted, 2005.
- Sanyal AJ, Fontana RJ, Di Bisceglie AM, Everhart JE, Doherty MC, Everson GT, Donovan JA, Malet PF, Mehta S, Morgan TR, Reid AE, Ghany MG, Gretch DR and the HALT-C Trial Group. Esophageal Varices in Subjects with Hepatitis C and Advanced Fibrosis. Submitted to Gastroenterology, 2005.
- Terrault NA, Shiffman ML, Lok AS, Saab S, Gillespie BW, Brown RS, Everson GT, Reddy KR, Farr JH, Kulik LM, Pruett TL, Seeff LB, and A2ALL Study Group. Outcomes in Hepatitis C Virus Infected Recipients of Living Donor Versus Deceased Donor Liver Transplantation. Submitted, 2005.
- Balan V, Nelson D, Sulkowski M, Everson G, Lambiase L, Wiesner RH, Dickson RC, Novello LA, Garcia A, Moore PA, Yu R, Subramanian GM. Modulation of interferon Specific Gene Expression in Peripheral Blood by Albumin-interferon Alfa in Subjects with Chronic Hepatitis C and Correlation with Antiviral Responses. Submitted, J Viral Hepatitis, October 2005.
- McHutchison JG, Patel K, Schiff ER, GItlin N, Mur RE, Everson GT, Carithers RL, Davis GL, Marcellin P, Shiffman ML, Harvey J, Albrecht JK. Interferon Alfa-2b Continuous Long-Term Therapy Versus Repeated 24-Week Cycles for Retreating Chronic Hepatitis C. Submitted to Hepatology, 2005.
- Bonkovsky HL, Snow KK, Malet PF, Back-Madruga C, Hoofnagle JH, HALT C Trial Group. Health-Related Quality of Life in Chronic Hepatitis C Patients with Advanced Fibrosis. In preparation, 2005
- Lindsay KL, Morishima C, Wright EC, Dienstag JL, HALT C Trial Group. Systemic Factors are Associated with Lack of Virologic Response during Peginterferon and Ribavirin Therapy of Choronic Hepatitis C: Results from the Lead-In Phase of the Heaptitis C Long-Term Treatment Against Cirrhosis (HALT-C) Trial. In Preparation, 2005.
- Balan V, Nelson DR, Sulkowski MS, Everson GT, Lambiase LR, Wiesner RH, Dickson RC, Post AB, Redfield RR, Davis GL, Neumann AU, Osborn BL, Freimuth WW, Subramanian GM. A Phase I/II study evaluating escalating doses of recombinant human albumin-interferon-alpha fusion protein in chronic hepatitis C patients who have failed previous interferon-alpha-based therapy. Antivir Ther. 2006;11(1):35-45.
- Schlenker C, Trotter JF, Shah RJ, Everson G, Chen YK, Antillon D, Antillon MR. Endoscopic gallbladder stent placement for treatment of symptomatic cholelithiasis in patients with end-stage liver disease. Am J Gastroenterol. 2006 Feb;101(2):278-83.
- Bonkovsky HL , Naishadham D, Lambrecht RW, Chung RT, Hoefs JC, Nash SR, Rogers TE, Banner BF, Sterling RK, Donovan JA, Fontana RJ, DiBisceglie AM, Ghany MG, Morishima C, and the HALT-C Trial Group. Influence of Iron and HFE Mutations on Severity and Response to Therapy during Retreatment of Advanced Chronic Hepatitis C in the HALT-C Trial. Submitted to Gastroenterology, February 2006.
- Everson GT, Hoefs JC, Seeff LB, Bonkovsky HL, Naishadham D, Shiffman ML, Kahn JA, Lok ASF, Di Bisceglie AM, Lee WM, Dienstag JL, Ghany MG, Morishima C, and the HALT-C Trial Group. Impact of Disease Severity on Outcome of Antiviral Therapy for Chronic Hepatitis C: Lessons from the HALT-C Trial. Submitted to Hepatology, April 2006
- Shiffman ML, Ghany MG, Morgan TR, Wright EC, Everson GT, Lindsay KL, Lok ASF, Bonkovsky HL, Di Bisceglie AM, Lee WM, Dienstag JL, Gretch DR, and the HALT-C Trial Group. Impact of reducing peginterferon alfa-2a and ribavirin dose on virologic response in patients with chronic hepatitis C. Submited to Gastroenterology, April 2006.
- MorishimaC, Morgan TR, Everhart JE, Wright EC, Shiffman ML, Everson GT, Lindsay KL, Lok ASF, Bonkovsky HL, Di Bisceglie AM, Lee WM, Dienstag JL, Ghany MG, Gretch DR, and the HALT-C Trial Group. HCV RNA Detection by TMA during the hepatitis C antiviral long-term treatment against cirrhosis (HALT-C) Trial. Submitted to Hepatology, March 2006.