Robert P. Perrillo M.D.

Terrault, N. A., Wahed, A. S., Feld, J. J., Cooper, S. L., Ghany, M. G., Lisker-Melman, M., Perrillo, R., Sterling, R. K., Khalili, M., Chung, R. T., Rosenthal, P., Fontana, R. J., Sarowar, A., Lau, D. T. Y., Wang, J., Lok, A. S. and Janssen, H. L. A. (2022). “Incidence and prediction of HBsAg seroclearance in a prospective multi-ethnic HBeAg-negative chronic hepatitis B cohort.” Hepatology 75(3): 709-723.

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BACKGROUND AND AIMS: Achieving HBsAg loss is an important landmark in the natural history of chronic hepatitis B (CHB). A more personalized approach to prediction of HBsAg loss is relevant in counseling patients. This study sought to develop and validate a prediction model for HBsAg loss based on quantitative HBsAg levels (qHBsAg) and other baseline characteristics. METHODS: The Hepatitis B Research Network (HBRN) is a prospective cohort including 1240 untreated HBeAg-negative patients (1150 adults, 90 children) with median follow-up of 5.5 years. Incidence rates of HBsAg loss and hepatitis B surface antibody (anti-HBs) acquisition were determined, and a predictor score of HBsAg loss using readily available variables was developed and externally validated. RESULTS: Crude incidence rates of HBsAg loss and anti-HBs acquisition were 1.6 and 1.1 per 100 person-years (PY); 67 achieved sustained HBsAg loss for an incidence rate of 1.2 per 100 PY. Increased HBsAg loss was significantly associated with older age, non-Asian race, HBV phenotype (inactive CHB vs. others), HBV genotype A, lower HBV-DNA levels, and lower and greater change in qHBsAg. The HBRN-SQuARe (sex,∆quantHBsAg, age, race) score predicted HBsAg loss over time with area under the receiver operating characteristic curve (AUROC) (95% CIs) at 1 and 3 years of 0.99 (95% CI: 0.987-1.00) and 0.95 (95% CI 0.91-1.00), respectively. In validation in another cohort of 1253 HBeAg-negative patients with median follow-up of 3.1 years, HBRN SQuARe predicted HBsAg loss at 1 and 3 years with AUROC values of 0.99 (0.98-1.00) and 0.88 (0.77-0.99), respectively. CONCLUSION: HBsAg loss in predominantly untreated patients with HBeAg-negative CHB can be accurately predicted over a 3-year horizon using a simple validated score (HBRN SQuARe). This prognostication tool can be used to support patient care and counseling.

Perrillo, R.P., Burton, J.R., Jr. and Westbrook, L.M. (2022). “Herbal hepatitis due to use of alternative medicines for Lyme disease.” Proc (Bayl Univ Med Cent) 35(1): 104-105.

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Lyme disease often leaves patients with chronic symptoms of fatigue, easy confusion, and even cardiac arrhythmias. We report a case in which Lyme disease was treated with an herbal mixture due to protracted symptoms despite intravenous antibiotics. This mixture was associated with hepatotoxicity. General providers should be aware of the fact that homeopathic remedies may be associated with hepatotoxicity, and herbalists need better understanding of the safety risks of the individual components in remedy mixtures.

Terrault, N.A., Wahed, A.S., Feld, J.J., Cooper, S.L., Ghany, M.G., Lisker-Melman, M., Perrillo, R., Sterling, R.K., Khalili, M., Chung, R.T., Rosenthal, P., Fontana, R.J., Sarowar, A., Lau, D., Wang, J., Lok, A.S. and Janssen, H. (2021). “Incidence and Prediction of HBsAg Seroconversion in a Prospective Multi-ethnic HBeAg-Negative Chronic Hepatitis B Cohort.” Hepatology Nov 7. [Epub ahead of print].

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BACKGROUND & AIMS: Achieving HBsAg loss is an important landmark in the natural history of chronic hepatitis B. A more personalized approach to prediction of HBsAg loss is relevant in couseling patients. This study sought to develop and validate a prediction model for HBsAg loss based on quantitative HBsAg levels and other baseline characteristics. METHODS: Hepatitis B Research Network (HBRN) is a prospective cohort including 1240 untreated HBeAg-negative patients (1150 adults, 90 children) with median follow-up of 5.5 years. Incidence rates of HBsAg loss and anti-HBs acquisition were determined and a predictor score of HBsAg loss using readily available variables was developed and externally validated. RESULTS: Crude incidence rates of HBsAg loss and anti-HBs acquisition were 1.6 and 1.1 per 100 person-years (PY); 67 achieved sustained HBsAg loss for an incidence rate of 1.2 per 100 PY. Increased HBsAg loss was significantly associated with older age, non-Asian race, HBV phenotype (inactive carrier vs others), HBV genotype A, lower HBV DNA levels and lower and greater change in quantitative HBsAg (∆qHBsAg). The HBRN-SQuARe (sex,∆quantHBsAg, age, race) score predicted HBsAg loss over time with AUROC (95% confidence intervals) at 1 and 3 years of 0.99 (95% CI: 0.987-1.00) and 0.95 (95% CI 0.91-1.00), respectively. Validation in another cohort of 1253 HBeAg-negative patients with median follow-up of 3.1 years, HBRN-SQuARe predicted HBsAg loss at 1 and 3 years with AUROC values of 0.99 [0.98-1.00] and 0.88 [0.77-0.99], respectively. CONCLUSION: HBsAg loss in predominantly untreated patients with HBeAg-negative chronic hepatitis B can be accurately predicted over a 3-year horizon using a simple validated score (HBRN-SQuARe). This prognostication tool can be used to support patient care and counseling.

Lok, A.S., Perrillo, R., Lalama, C.M., Fried, M.W., Belle, S.H., Ghany, M.G., Khalili, M., Fontana, R.J., Sterling, R.K., Terrault, N., Feld, J.J., Di Bisceglie, A.M., Lau, D.T.Y., Hassan, M. and Janssen, H.L.A. (2020). “medLow Incidence of Adverse Outcomes in Adults with Chronic Hepatitis B Virus Infection in the Era of Antiviral Therapy.” Hepatology Sep 16. [Epub ahead of print.].

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BACKGROUND AND AIMS: Outcomes of persons with chronic HBV infection in the era of antiviral therapy are not well characterized. We determined the incidence and factors associated with clinical outcomes in a multiethnic, North American cohort of adults with chronic HBV infection, who were not on antiviral therapy at enrollment. METHODS: Adults with chronic HBV infection, not receiving antiviral therapy, and without a history of decompensation, HCC or OLT were prospectively followed. Participants with known HIV, HCV or HDV coinfection were excluded. During follow-up, treatment could be initiated per standard of care. Clinical outcomes included: incident cirrhosis, decompensation, HCC, OLT and HBV-related death. RESULTS: Among 1418 participants analyzed, 51.5% were women, median age 41.1 years, 75% Asian, 10% white, 13% black, 24% HBeAg(+), and 1.5% cirrhosis at baseline. During the study, 274 started treatment, 83 had an ALT flare, 118/330 initially HBeAg(+) became HBeAg(-), and 90/1329 became HBsAg(-). After 6641 person-years follow-up, 8 participants (4/21 with baseline cirrhosis) had 12 clinical outcomes (2 decompensation, 5 HCC, 2 OLT, 3 HBV-related deaths) and 19/1397 had incident cirrhosis. 21/26 participants had first outcome before treatment, none had become HBsAg(-) while 5/9 HBeAg(+) had become HBeAg(-) at time of first outcome. Cumulative percentage of clinical outcomes was 16% at year 4 in participants with baseline cirrhosis, and 2% (including incident cirrhosis) at year 7 in those without. CONCLUSIONS: Incidence of adverse outcomes was low in this closely monitored large cohort of North American adults with predominantly inactive, non-cirrhotic chronic HBV. Our data highlight the benefits of HBsAg loss and the importance of early diagnosis and treatment to prevent cirrhosis and other complications of chronic HBV infection.

Brouwer, W. P., Q. Zhao, B. E. Hansen, D. Lau, M. Khalili, N. A. Terrault, A. M. Di Bisceglie, R. P. Perrillo, M. W. Fried, D. Wong, J. J. Feld, S. H. Belle and H. L. A. Janssen (2020). “HBV Genotype-Specific Levels of Hepatitis B Surface Antigen Improve HBV Phenotype Definition.” Clin Gastroenterol Hepatol 18(1): 259-261.

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Controversies exist regarding the classification of the different clinical phases of chronic hepatitis B (CHB) because hepatitis B virus (HBV) DNA and alanine aminotransferase levels fluctuate over time. To improve the distinction of clinical phases and the associated spectrum of clinical outcome, hepatitis B surface antigen (HBsAg) levels may be of help. We hypothesize that HBV genotype specific HBsAg levels are needed for the identification of different clinical HBV disease phases.