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Mei Lu,1 Christopher L Bowlus,2 Keith Lindor,3 Carla V Rodriguez-Watson,4 Robert J Romanelli,5 Irina V Haller,6 Heather Anderson,7 Jeffrey J VanWormer,8 Joseph A Boscarino,9 Mark A Schmidt,10 Yihe G Daida,11 Amandeep Sahota,12 Jennifer Vincent,13 Jia Li,1 Sheri Trudeau,1 Loralee B Rupp,14 Stuart C Gordon15 On Behalf of the FOLD Investigators1Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA; 2University of California Davis School of Medicine, Sacramento, CA, USA; 3College of Health Solutions, Arizona State University, Phoenix, AZ, USA; 4Center for Health Research Kaiser Permanente Mid-Atlantic Research Institute, Rockville, MD; Reagan-Udall Foundation for the FDA, Washington, DC, USA; 5Palo Alto Medical Foundation Research Institute, Palo Alto, CA, USA; 6Essentia Institute of Rural Health, Essentia Health, Duluth, MN, USA; 7Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; 8Marshfield Clinic Research Foundation, Marshfield, WI, USA; 9Department of Population Health Sciences, Geisinger Clinic, Danville, PA, USA; 10Center for Health Research, Kaiser Permanente Northwest, Portland, OR, USA; 11Center for Integrated Health Care Research, Kaiser Permanente Hawai’i, Honolulu, HI, USA; 12Department of Research and Evaluation, Kaiser Permanente Southern California, Los Angeles, CA, USA; 13Baylor, Scott & White Research Institute, Temple, TX, USA; 14Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, MI, USA; 15Division of Gastroenterology and Hepatology, Henry Ford Health System; and Wayne State University School of Medicine, Detroit, MI, USACorrespondence: Mei LuDepartment of Public Health Sciences, Henry Ford Health System, 3E One Ford Place, Detroit, MI 48202, USATel +1 313 874 6413Fax +1 313 874 6730Email mlu1@hfhs.orgBackground: Biopsy remains the gold standard for determining fibrosis stage in patients with primary biliary cholangitis (PBC), but it is unavailable for most patients. We used data from the 11 US health systems in the FibrOtic Liver Disease Consortium to explore a combination of biochemical markers and electronic health record (EHR)-based diagnosis/procedure codes (DPCs) to identify the presence of cirrhosis in PBC patients.Methods: Histological fibrosis staging data were obtained from liver biopsies. Variables considered for the model included demographics (age, gender, race, ethnicity), total bilirubin, alkaline phosphatase, albumin, aspartate aminotransferase (AST) to platelet ratio index (APRI), Fibrosis 4 (FIB4) index, AST to alanine aminotransferase (ALT) ratio, and > 100 DPCs associated with cirrhosis/decompensated cirrhosis, categorized into ten clusters. Using least absolute shrinkage and selection operator regression (LASSO), we derived and validated cutoffs for identifying cirrhosis.Results: Among 4328 PBC patients, 1350 (32%) had biopsy data; 121 (9%) were staged F4 (cirrhosis). DPC clusters (including codes related to cirrhosis and hepatocellular carcinoma diagnoses/procedures), Hispanic ethnicity, ALP, AST/ALT ratio, and total bilirubin were retained in the final model (AUROC=0.86 and 0.83 on learning and testing data, respectively); this model with two cutoffs divided patients into three categories (no cirrhosis, indeterminate, and cirrhosis) with specificities of 81.8% (for no cirrhosis) and 80.3% (for cirrhosis). A model excluding DPCs retained ALP, AST/ALT ratio, total bilirubin, Hispanic ethnicity, and gender (AUROC=0.81 and 0.78 on learning and testing data, respectively).Conclusion: An algorithm using laboratory results and DPCs can categorize a majority of PBC patients as cirrhotic or noncirrhotic with high accuracy (with a small remaining group of patients’ cirrhosis status indeterminate). In the absence of biopsy data, this EHR-based model can be used to identify cirrhosis in cohorts of PBC patients for research and/or clinical follow-up.Keywords: primary biliary cirrhosis, cholangitis, race/gender/ethnicity, gender, ethnicity, decompensated cirrhosis, ursodeoxycholic acid, UCDA

Hemophagocytic lymphohistiocytosis (HLH) is a rare condition characterized by a pathologic immune dysregulation resulting in extreme inflammation. Clinical manifestations are varied but can include severe multiorgan failure and death. HLH has been associated with malignancies, autoimmune diseases, and infections, such as histoplasmosis. Histoplasmosis commonly has subclinical manifestations but can also present in its disseminated form. We present the case of an immunocompromised patient with worsening liver function caused by hepatic histoplasmosis that later triggered HLH with severe multiorgan dysfunction.

BackgroundBiopsy remains the gold standard for determining fibrosis stage in patients with primary biliary cholangitis (PBC), but it is unavailable for most patients. We used data from the 11 US health systems in the FibrOtic Liver Disease Consortium to explore a combination of biochemical markers and electronic health record (EHR)-based diagnosis/procedure codes (DPCs) to identify the presence of cirrhosis in PBC patients.MethodsHistological fibrosis staging data were obtained from liver biopsies. Variables considered for the model included demographics (age, gender, race, ethnicity), total bilirubin, alkaline phosphatase, albumin, aspartate aminotransferase (AST) to platelet ratio index (APRI), Fibrosis 4 (FIB4) index, AST to alanine aminotransferase (ALT) ratio, and >100 DPCs associated with cirrhosis/decompensated cirrhosis, categorized into ten clusters. Using least absolute shrinkage and selection operator regression (LASSO), we derived and validated cutoffs for identifying cirrhosis.ResultsAmong 4328 PBC patients, 1350 (32%) had biopsy data; 121 (9%) were staged F4 (cirrhosis). DPC clusters (including codes related to cirrhosis and hepatocellular carcinoma diagnoses/procedures), Hispanic ethnicity, ALP, AST/ALT ratio, and total bilirubin were retained in the final model (AUROC=0.86 and 0.83 on learning and testing data, respectively); this model with two cutoffs divided patients into three categories (no cirrhosis, indeterminate, and cirrhosis) with specificities of 81.8% (for no cirrhosis) and 80.3% (for cirrhosis). A model excluding DPCs retained ALP, AST/ALT ratio, total bilirubin, Hispanic ethnicity, and gender (AUROC=0.81 and 0.78 on learning and testing data, respectively).ConclusionAn algorithm using laboratory results and DPCs can categorize a majority of PBC patients as cirrhotic or noncirrhotic with high accuracy (with a small remaining group of patients' cirrhosis status indeterminate). In the absence of biopsy data, this EHR-based model can be used to identify cirrhosis in cohorts of PBC patients for research and/or clinical follow-up.

Although direct‐acting antiviral (DAA) therapies for chronic hepatitis C virus (HCV) infection have demonstrated high rates of sustained virologic response, virologic failure may still occur, potentially leading to the emergence of viral resistance, which can decrease the effectiveness of subsequent treatment. Treatment options for patients who failed previous DAA‐containing regimens, particularly those with nonstructural protein 5A inhibitors, are limited and remain an area of unmet medical need. This phase 2, open‐label study (MAGELLAN‐1) evaluated the efficacy and safety of glecaprevir (GLE) + pibrentasvir (PIB) ± ribavirin (RBV) in HCV genotype 1–infected patients with prior virologic failure to HCV DAA‐containing therapy. A total of 50 patients without cirrhosis were randomized to three arms: 200 mg GLE + 80 mg PIB (arm A), 300 mg GLE + 120 mg PIB with 800 mg once‐daily RBV (arm B), or 300 mg GLE + 120 mg PIB without RBV (arm C). By intent‐to‐treat analysis, sustained virologic response at posttreatment week 12 was achieved in 100% (6/6, 95% confidence interval 61‐100), 95% (21/22, 95% confidence interval 78‐99), and 86% (19/22, 95% confidence interval 67‐95) of patients in arms A, B, and C, respectively. Virologic failure occurred in no patients in arm A and in 1 patient each in arms B and C (two patients were lost to follow‐up in arm C). The majority of adverse events were mild in severity; no serious adverse events related to study drug and no relevant laboratory abnormalities in alanine aminotransferase, total bilirubin, or hemoglobin were observed. Conclusion: The combination of GLE and PIB was highly efficacious and well tolerated in patients with HCV genotype 1 infection and prior failure of DAA‐containing therapy; RBV coadministration did not improve efficacy. (Hepatology 2017;66:389–397).

OBJECTIVES: Asian and Pacific Islanders (APIs) constitute less than 6% of the US population, but account for more than half of Americans with chronic hepatitis B virus (HBV) infection. We sought to examine the effect of country of origin on HBV testing and chronic HBV infection prevalence among APIs. METHODS: We analyzed demographic and clinical data collected for adults from Kaiser Permanente Hawaii with 1 or more healthcare encounters during 2006 to 2008, 12 months or more of follow-up before 2009, and no HBV-related diagnosis within 6 months of enrollment. Persons who received a test and a positive test result for HBV surface antigen or HBV DNA were classified “tested” and with “chronic HBV infection”, respectively. RESULTS: Of 92,687 eligible APIs, 53,573 (58%) had country-of-origin data available. Among those, 41,263 were US born; 28.3% were tested; and 1.8% of those tested had chronic HBV infection. Of 12,310 foreign-born APIs, 30.5% were tested and 7.4% of those tested had chronic HBV infection. Foreign-born APIs had higher odds of being tested (odds ratio [OR] = 1.15) and testing positive (OR = 4.18) compared with US-born APIs. Persons with 2 or more abnormal tests for alanine aminotransferase (ALT) levels had higher odds of getting tested (OR = 6.12) and of testing positive (OR = 1.86) compared with persons with other ALT levels. CONCLUSIONS: Less than one-third of this managed care API population (29% of 53,573) was tested, yet the prevalence of chronic HBV infection (3.2%) was 12 times higher than that of the general US population. These findings underscore the importance of adherence to HBV testing guidelines to identify persons with infection so they may be linked to care.

Background & Aims Little is known about factors associated with a sustained virologic response (SVR) among patients with hepatitis C virus (HCV) infection to treatment with protease inhibitors. Methods Previously untreated patients (from the Serine Protease Inhibitor Therapy 2 [SPRINT-2] trial) and those who did not respond to prior therapy (from the Retreatment with HCV Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol 2 [RESPOND-2] trial) received either a combination of peginterferon and ribavirin for 48 weeks or boceprevir, peginterferon, and ribavirin (triple therapy) after 4 weeks of peginterferon and ribavirin (total treatment duration, 28–48 wk). A good response to interferon was defined as a ≥1 log 10 decrease in HCV RNA at week 4; a poor response was defined as a 10 decrease. We used multivariate regression analyses to identify baseline factors of the host (including the polymorphism interleukin [ IL ]- 28B rs12979860) associated with response. The polymorphism IL - 28B rs8099917 also was assessed. Results In the SPRINT-2 trial, factors that predicted a SVR to triple therapy included low viral load (odds ratio [OR], 11.6), IL-28B genotype (rs 12979860 CC vs TT and CT; ORs, 2.6 and 2.1, respectively), absence of cirrhosis (OR, 4.3), HCV subtype 1b (OR, 2.0), and non-black race (OR, 2.0). In the RESPOND-2 trial, the only factor significantly associated with a SVR was previous relapse, compared with previous nonresponse (OR, 2.6). Most patients with rs12979860 CC who received triple therapy had undetectable levels of HCV RNA by week 8 (76%–89%), and were eligible for shortened therapy. In both studies, IL-28B rs12979860 CC was associated more strongly with a good response to interferon than other baseline factors; however, a ≥1 log 10 decrease in HCV-RNA level at week 4 was associated more strongly with SVR than IL-28B rs12979860. Combining the rs8099917 and rs12979860 genotypes does not increase the association with SVR. Conclusions The CC polymorphism at IL-28B rs12979860 is associated with response to triple therapy and can identify candidates for shorter treatment durations. A ≥1 log 10 decrease in HCV RNA at week 4 of therapy is the strongest predictor of a SVR, regardless of polymorphisms in IL-28B . ClinicalTrials.gov; numbers NCT00705432 and NCT00708500.

The HCV council 2011 convened 11 leading clinicians and researchers in hepatitis C virus from academic medical centers in the United States to provide a forum for the practical and comprehensive evaluation of current data regarding best practices for integrating new direct-acting antiviral agents into existing treatment paradigms. The council investigated 10 clinical practice statements related to HCV treatment that reflect key topical areas. Faculty members reviewed and discussed the data related to each statement, and voted on the nature of the evidence and their level of support for each statement. In this new era of DAAs, a comprehensive and critical analysis of the literature is needed to equip clinicians with the knowledge necessary to design, monitor, and modify treatment regimens in order to optimize patient outcomes.