Hepatitis C                                              Helen S. Te, MD, AGAF                              University of ...
Focused Clinical Updates, May 18 & 19, 2008groups. The authors’ conclusion was that the non-invasive GBT and hyaluronic ac...
Focused Clinical Updates, May 18 & 19, 2008hepatitis C patients. We do expect the BMI to be positively correlated with ins...
Focused Clinical Updates, May 18 & 19, 2008center, they were presumably already vaccinated by their referring physicians, ...
Focused Clinical Updates, May 18 & 19, 2008and treatment for hepatitis B and C. The US Preventive Task Force guidelines fo...
Focused Clinical Updates, May 18 & 19, 2008Abstracts DiscussedTITLE: Quantitative measure of liver function using 13C-Gala...
Focused Clinical Updates, May 18 & 19, 2008The AUCs for the separation of mild/moderate from advanced fibrosis were 0.810 ...
Focused Clinical Updates, May 18 & 19, 2008other diseases or those taking medications or alcohol (> 20 gm /day) were exclu...
Focused Clinical Updates, May 18 & 19, 2008patients during weekly 2-hour telemedicine clinics using a standardized, case-b...
Focused Clinical Updates, May 18 & 19, 2008made between different practice specialties, using one-way ANOVA with Bonferron...
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  1. 1. Hepatitis C Helen S. Te, MD, AGAF University of Chicago Medical Center, Chicago, Illinois Helen S. Te, MD, AGAF is an Assistant Professor of Medicine in the Section of Gastroenterology at The University of Chicago Medical Center in Chicago, Illinois. She is the Medical Director of the Adult Liver Transplant Program of the University of Chicago Medical Center. Dr. Te specializes in the diagnosis and management of viral hepatitis, chronic liver disease and liver transplantation. Her research interests include the prevention of post transplant rejection, fatty liver disease, and viral hepatitis. Dr. Te has been involved in several clinical trials studying treatment regimens in patients with chronic hepatitis C, including patients who are nonresponsive to current therapies. Her work has been published in The American Journal of Gastroenterology, Liver Transplantation, Transplantation, andGastroenterology and Hepatology. She has served as a reviewer for a number of medical journals, includingArchives of Internal Medicine, Digestive Diseases and Sciences, American Journal of Gastroenterology, andGastroenterology. Certified by the American Board of Internal Medicine, with a subspecialty in gastroenterology aswell as transplant hepatology, Dr. Te is a member of the American Association for the Study of Liver Diseases(AASLD) and serves on the Surgery and Liver Transplantation Committee of the AASLD. She is also a Fellow of theAmerican Gastroenterological Association, and is a member of the American Society of Transplant Physicians andthe Gastroenterology Research Group.In this session, we will review the most recent data that was presented at DDW® on the topic of hepatitis C. Mostof these are clinical abstracts that were submitted to the AGA. There are other abstracts that have been presented tothe other societies participating in this meeting, so I am going to touch on a few that have similar topics as the onesin your handout, and other exciting ones as well if we have enough time. This morning’s session will be dividedinto these topics 1) non-invasive markers of fibrosis in hepatitis C, 2) hepatitis C and insulin resistance, 3) oneabstract that addresses what happens to hepatitis C when the patient is treated with Rituximab (I’m often askedquestions by oncology colleagues when they have patients with hepatitis C who need to be given Rituxan for theirhematologic malignancies), and 4) three abstracts that highlight some practices regarding hepatitis C screening andmanagement out in the community. In my opinion, the most exciting abstracts this year are those that addressupdates on the treatment for hepatitis C.Abstract S2069: “Quantitative measure of liver function using 13 C-Galactose (GBT) and 13 C-Methacetin(MBT) breath tests and hyaluronic acid as serum markers in patients with chronic hepatitis B or chronichepatitis C.”The aim of this study was to determine whether these non-invasive tests (the two kinds of breath tests along with theserum marker hyaluronic acid) would be adequate to diagnose fibrosis of the liver, particularly in the earlier stagesof the liver disease. In clinical practice, the currently available serum markers are quite good in distinguishing thetwo extremes of the whole spectrum; the very early stage (no fibrosis) or the very advanced stage (cirrhosis). In themiddle of the whole spectrum, I think there is a big void that has to be filled - how to use non-invasive measurementof those F2-F3 categories. These investigators took 89 patients, about half of whom (41) had hepatitis C. All ofthese patients had a biopsy within six months. They had the galactose breath test (GBT) and the methacetin breathtest (MBT). In addition, they took 31 healthy controls to compare the results. They saw that the controls hadessentially the same results with the breath tests (both GBT and MBT) as the people with no fibrosis, which is agood validation. As far as distinguishing between cirrhosis and non-cirrhosis, the GBT and the hyaluronic acidwere quite good in distinguishing those patients with a very significant positive correlation in terms of the Metavirscoring with F1-F4. The MBT, however, was not a good test to distinguish that. When looking at early fibrosis, todistinguish F0-F1 versus F2-F3 from the later stages, neither GBT, MBT or hyaluronic acid could distinguish these
  2. 2. Focused Clinical Updates, May 18 & 19, 2008groups. The authors’ conclusion was that the non-invasive GBT and hyaluronic acid was pretty good indistinguishing cirrhosis from non-cirrhosis but MBT was not. None of these three tests were able to distinguishearly stages of fibrosis in either hepatitis B or hepatitis C. This is the same problem we have in practice.Abstract S2078: “The APRI and FIB-4 are equivalent in the estimation of fibrosis in chronic hepatitis C.”These authors wanted to compare the accuracy of the AST to platelet ratio index (APRI) and FIB-4 (an inexpensiveand accurate marker of fibrosis in HCV infection) in predicting fibrosis. They enrolled about 277 patients andperformed biopsies at the time of the blood draw. They utilized the Ludwig criteria in staging liver biopsies wheremild fibrosis was assigned as F0-F1 and significant fibrosis was F2-F4. They then used a different category wherethey combined mild and moderate fibrosis as F0-F2 and advanced fibrosis as F3-F4. When they compared the twotests, FIB-4 and APRI, they had nearly identical area under the curve results with pretty good correlation of 0.85 foreach. The tests are similar in terms of predicting mild fibrosis and distinguishing that from significant fibrosis.When looking at mild to moderate fibrosis, to distinguish that from advanced fibrosis, there was a decent negativepredictive value but the positive predictive value fell down to relatively lower levels; to 69% for APRI and 77% forFIB-4. The authors concluded that both tests were good at separating mild from significant fibrosis and inpredicting the absence of advanced fibrosis, but they were not as accurate in predicting the presence of advancedfibrosis. The APRI and FIB-4 are easier indices to obtain in our day-to-day practice since the labs are typicalcomponents of our management of hepatitis C patients. However, we may have to utilize more than one tool if weare aiming for a more accurate non-invasive means of assessing fibrosis. Utilizing a single formula or a particularinstrument is probably not going to give us the best result. A problem in this study, as with others, is that they areutilizing liver biopsies as the gold standard. We are all aware that liver biopsy has its own pitfalls in terms ofsampling error. We probably have about a 15%, or even up to 30%, sampling error with liver biopsies. When weare comparing a variable against a gold standard that has its own problems, it becomes more difficult to determinewhich one is the better test.Abstract S2065: “Minimal visceral fat accumulation is a prerequisite for a persistent normal serum ALT level inchronic hepatitis C patients.”The authors wanted to determine if there was any relationship between visceral fat accumulation and the serumALT of patients with hepatitis C. The study patients had CT scans performed to evaluate the amount of visceral fatin their abdomen. There were two categories - normal ALT (less than 30) or elevated ALT (greater than or equal to31). The insulin resistance was calculated by the homeostasis model assessment (HOMA) and the quantitativeinsulin-sensitivity check index (QUICKI). The investigators had a total of 95 patients - 22 had a normal ALT andthe rest had an elevated ALT. The patients in the normal group were a little older and they had a lower BMI. Theirvisceral fat accumulation was lower as well. Investigators found that the HOMA and the QUICKI indices weresignificantly correlated to the visceral fat area; meaning that visceral fat accumulation was positively correlatedwith an increased insulin resistance. The more visceral fat, the more likely the patient was insulin resistant, whichis expected. They found that the normal ALT patients were also those who had low visceral fat. If a patient had alean body, they were more likely to have a normal serum ALT compared to someone who has more visceral fataccumulation.Abstract M1771: “The prevalence of insulin resistance in patients with chronic hepatitis C and B.”The authors wanted to assess the prevalence of insulin resistance using the HOMA index among non-cirrhotic, non-diabetic naïve hepatitis B and C patients, and compare the indices between hepatitis B and C patients. The studyenrolled 102 hepatitis C patients and 27 hepatitis B patients. The demographic data, the BMI, the waistcircumference, the free fatty acid levels, the histological activity index (HAI), and fibrosis and steatosis scores werevery similar between the hepatitis B and hepatitis C patients. There was a slight divergence in that there were moremales and Asians in the hepatitis B patients and there were surprisingly more patients with elevated serumcholesterol. There was no significant difference in the prevalence of insulin resistance between hepatitis B (30%)and C (38%) patients, although we have to remember that the number of hepatitis B patients is so small (27patients). The authors did note that BMI a nd the HAI were independent risk factors for insulin resistance in2 To claim CME credit please visit the Education and Training section of www.gastro.org
  3. 3. Focused Clinical Updates, May 18 & 19, 2008hepatitis C patients. We do expect the BMI to be positively correlated with insulin resistance, and the HAIpotentially might be a sequela instead of a causative factor in insulin resistance development. I think that insulinresistance, in terms of those who have excessive weight and metabolic syndrome, will remain to be a continuingchallenge for us to treat our patients with hepatitis C and get them to respond to treatment. It is so much easier totreat the hepatitis C itself than for them to try to lose the weight.Abstract 383: “Hepatitis C virus (HCV) flares in patients with hematological malignancies treated with anti-CD20 antibody rituximab including regimens.”The authors evaluated the role of rituximab in inducing significant increases in transaminases in patients withhepatitis C. There were about 104 patients who were treated with rituximab-containing regimens in their institutionwithin a two-year period. Nine of these patients who had hepatitis C were followed for up to twelve months aftertheir chemotherapy ended. A hepatitis flare was defined as an ALT of more than five times normal. Theinvestigators found that among the nine hepatitis C patients, three of them had elevation in ALT to more than fivetimes baseline, whereas there was no elevation at all in non-hepatitis C patients. That is a 33% incidence of ahepatitis flare that occurs while the hepatitis C patient is receiving rituximab. Fortunately, none of these flaresended up in either hepatic failure or death for the patients and they all were able to continue their chemotherapy.This is very helpful information. My oncology colleagues often ask if a patient can receive rituximab for hepatitisC, or would it increase the hepatitis C viral replication. The problem with this abstract is that the hepatitis Cdiagnosis was made with a hepatitis C antibody rather than hepatitis C RNA, and the authors did not mention whathappened to the viral load during the times that patients were given treatment. It would have been very interestingto see if there was also a correlation with the viral load going up during the time of flare. That may be something tomonitor during the treatment of patients with rituximab and might help anticipate a flare before it actually happens.I don’t know if they will present this information in their oral presentation tomorrow, but that would be interestingto see.Abstract 380: “Project ECHO (Extension for Community Healthcare Outcomes): Knowledge networks expandaccess to hepatitis C (HCV) treatment with pegylated interferon and ribavirin in rural areas and prisons. Care isas safe and effective as a university HCV clinic.”Project ECHO (Extension for Community Healthcare Outcomes) is a very elaborate and sophisticated model of anoutreach into the underserved rural areas, prisons where hepatitis C patients have not been treated before, by usingtelemedicine and computer networking. The specialists in the tertiary care center provide the guidance for theprimary care physicians, physician’s assistants and nurse practitioners, to allow them to treat the HCV patients.They have treated about 327 hepatitis C patients with this project and the majority of the patients (about two-thirds)are minorities including Hispanic, Native American or African American. About 24% were cirrhotic, which is anexpected fraction. Depression was quite high, with a 41% prevalence in this population. There was about 60%genotype 1 with a high viral load. The early virologic response (EVR) was about 85%, 82% and 93% respectivelyfor the university, prison and rural patients. The authors did not report on the sustained virologic response (SVR).The significant adverse event (SAE) rate was about 12% and those who had SAE’s were patients who were olderand had a lower serum albumin, probably representing advanced disease. The platelet count was also lower, sothese patients were more likely to have cirrhotic livers. They also were the ones who had the history of depression.The authors conclude that hepatitis C treatment delivered to patients in rural areas and prisons using this model wasquite safe and as effective as a university clinic treating hepatitis C.Abstract S1058: “Hepatitis A and B immunization practices among community physicians of chronic hepatitis Cpatients.”The authors wanted to evaluate the frequency of vaccination of hepatitis C patients in the community in accordancewith AASLD practice guidelines. They studied patients who were referred to their hepatology practice for a year.Eighty-nine of these patients have been diagnosed with hepatitis C for at least one year, to give the primary carephysician and the referring physician time to screen these patients for hepatitis A and B immune status, so theycould be vaccinated if they were not immune to hepatitis A and B. When the patients were seen at the referral To claim CME credit please visit the Education and Training section of www.gastro.org 3
  4. 4. Focused Clinical Updates, May 18 & 19, 2008center, they were presumably already vaccinated by their referring physicians, so the authors evaluated the immunestatus to hepatitis A or hepatitis B in these patients. Of the 89 patients, about 46% were immune to hepatitis A,which could represent either prior exposure or vaccination. Fifty-eight percent had evidence of previous hepatitis Bexposure or vaccination as well. The authors tried to compare these incidents of immunity to hepatitis A and B tothe number of patients who had a previous screening colonoscopy within five years, to have a comparative gauge ofadherence to preventive healthcare practice guidelines. Sixty-five percent of the patients had a screeningcolonoscopy within five years, which is higher than the prevalence of immunity to hepatitis A or B in these patients.The authors also compared their results with previously published prevalence of hepatitis A and B immunity inhepatitis C patients. In hepatitis A, this is reported to be about 38% and in hepatitis B, 59%. The authors concludedthat hepatitis A or B immunity in the patients who were referred to them was very similar to the hepatitis A or Bimmunity status as previously reported in hepatitis C patients who have not been immunized to hepatitis A or B.This suggests that perhaps none of these referred patients were vaccinated by the referring physicians, as a higherrate of immunity would have been expected if immunization was given. There was a higher compliance withcolonoscopy than the vaccination for hepatitis A and B. Patients are screened for colon cancer more commonlybecause colon cancer has such a high profile. The consequence of colon cancer is also graver than that of lack ofimmunization to hepatitis A and B. I think the level of awareness on the part of the referring physician regardinghepatitis A and B vaccine is not as high as their level of awareness regarding the need for colonoscopies. I think itis that the gravity of the situation is very different. These results indicate that we have improved the level ofawareness in the primary or referring physicians for the need to immunize these patients. There were only 89patients in this study, and I have heard of adult primary care clinics not necessarily stocking the vaccine because itis not very commonly used in the adult population, unlike in pediatric offices. There are also patients who receivethe first dose but then don’t go back for the second and the third dose. Recalling these patients is not likely toalways be done by each clinic.Abstract S2079: “The impact of hepatitis B (HBV), hepatitis C (HCV) and non-alcoholic fatty liver disease(NAFLD) guidelines on clinical practices.”These investigators were trying to assess the attitudes of primary care physicians, gastroenterologists andhepatologists regarding hepatitis B, C and NAFLD. They sent out surveys that had specific questions aboutNAFLD, HBV, and HCV, but the number of surveys sent out was not specified. One hundred sixty-one surveyswere returned, but the response rate can not be determined. One hundred one responses came from primary carephysicians, 30 from gastroenterologists and 26 from hepatologists, which might reflect a similar proportion ofphysicians to whom the survey was sent. Most of the physicians practice in urban and suburban settings, with veryfew in rural areas. When it comes to screening, the primary care physicians considered hepatitis C to be lesscommon in the population than the gastroenterologists and the hepatologists. The primary care physicians alsothought NAFLD was more common, which is a realistic perception. The survey results showed that 40% ofprimary care physicians were not aware of guidelines for any of these diseases compared to about 13% ofgastroenterologists and 4% of hepatologists. Most hepatologists were familiar with the AASLD guidelines, althoughonly 40% of gastroenterologists were aware of the AASLD guidelines for HBV, HCV and NAFLD. I would haveexpected a higher number in this group. Primary care physicians were most likely to follow the United StatesPreventive Service Task Force guidelines, followed by the American Academy of Family Practice guidelines,followed by the American College of Physicians guidelines and then least, AASLD guidelines. That is notsurprising, as most primary care physicians would follow the preventive task force guidelines. The hepatologists orgastroenterologists typically do not follow the American Academy of Family Practice guidelines. The primary carephysicians also rated themselves less knowledgeable about hepatitis B guidelines than the gastroenterologists andthe hepatologists, as well as less knowledgeable about the hepatitis C guidelines. The primary care physicians haveless use of the guidelines when they make a decision to screen for hepatitis B and C. The hepatologists ratedeffectiveness of hepatitis B treatment higher than the primary care physicians, whereas the primary care physiciansrated the effectiveness of treatment for NAFLD higher than the hepatologists. I thought this was quite interesting,considering many hepatologists still find the treatment of NAFLD to be quite lacking. Side effects of hepatitis Band NAFLD treatment were rated to be more harmful by the primary care physicians than the hepatologists. Theconclusion is that although there are several practice guidelines available out there, there is still a lack of familiarityand adaptation of these guidelines into clinical practice, particularly in the primary care setting as far as screening4 To claim CME credit please visit the Education and Training section of www.gastro.org
  5. 5. Focused Clinical Updates, May 18 & 19, 2008and treatment for hepatitis B and C. The US Preventive Task Force guidelines for screening for hepatitis C do notadvocate screening for hepatitis C in asymptomatic patients or low risk patients and had a neutral stand on screeningfor hepatitis C in high-risk patients, which is really interesting. This is based on the lack of conviction thatscreening is going to translate to cost effectiveness in terms of increasing patients’ survival. This is the only set ofpreventive guidelines that did not take a strong stand for hepatitis C screening in high-risk patients.Abstract S2081: “Peginterferon and ribavirin for treatment of hepatitis C and HIV co-infection: A meta-analysisof randomized controlled trials.”These authors did a meta-analysis of all randomized controlled trials comparing peginterferon and ribavirin versusstandard interferon and ribavirin in HIV and hepatitis C infected patients. They had five trials included into theirmeta-analysis with about 13,000 patients. The majority of these patients (85%) were on highly active anti-retroviraltherapy (HAART) therapy. The bottom line is that there was a higher sustained viral response (SVR) with peg-interferon and ribavirin compared to standard interferon, with a very similar side effect profile between the twogroups. This is not new news; as we are expecting the pegylated interferon would be a better form of treatment forthe co-infected population than the standard interferon. To claim CME credit please visit the Education and Training section of www.gastro.org 5
  6. 6. Focused Clinical Updates, May 18 & 19, 2008Abstracts DiscussedTITLE: Quantitative measure of liver function using 13C-Galactose (GBT) and 13C-Methacetin (MBT) breath tests andhyaluronic acid as serum markers in patients with chronic Hepatitis B or chronic Hepatitis CABSTRACT FINAL ID: S2069AUTHORS (FIRST NAME, LAST NAME): Krista Stibbe1, Claudia Verveer1, Jan Francke1, Bettina E. Hansen2, Pieter E.Zondervan3, Ernst J. Kuipers1, Robert J. de Knegt1, Anneke van Vuuren1ABSTRACT BODY: Background Quantification of fibrosis is essential in chronic hepatitis patients (HBV or HCV) todetermine progression of fibrosis or cirrhosis, necessity for treating patients, and efficacy of treatment. Liver biopsy is thegolden standard, however the procedure is invasive, with a significant morbidity rate, and problems like sampling error andobserver variability.Aims To determine whether non-invasive tests (breath tests and a serum marker) could be used as alternatives for diagnosingliver fibrosis, especially in the earlier stages of liver fibrosis.Methods 89 patients (48 HBV and 41 HCV), who had a liver biopsy within previous 6 months, were included for GBT and/orMBT. Both breath tests were metabolized via different pathways in the liver. Biopsies were classified via Metavir score (F0-F4). In addition, 31 healthy controls (C) with normal liver biochemistry were included for both breath tests. Breath sampleswere taken frequently up to 3 hours (T=0, 10, 20, 30, 40, 60, 90, 120, 150 and 180 min) to measure the expired 13CO2/12CO2isotope ratio. Hyaluronic acid (HA) was measured in serum of all participants.Results In Metavir group F0, F1, F2, F3 and F4, resp. 8, 34, 14, 11, 15 patients attended GBT and resp. 9, 32, 14, 11, 15patients attended MBT. Controls (n=31; mean AUC= 20.4) were not significantly different from patients in F0 (17.8) for GBT,neither for MBT controls vs F0 (68.2 vs.74.3).GBT as well as HA results distinguished between non-cirrhotic and cirrhotic patients. GBT: (C+ F0-3) vs F4 (17.5 vs 14.3,p=0.01) and HA: (36.6 vs 182.3, p<0,001). Linear regression showed a significant positive correlation between Metavir scoringand GBT as well as HA (both p<0.001).However, neither GBT, MBT nor HA could discriminate early fibrosis stages from late stages (F0-1 vs F2-3) (GBT: 16.7 vs15.2; p=0.113) (MBT: 71.6 vs 66.1; p=0.180) (HA: 38.4 vs 47.0; p=0.544) (T-test).In addition, GBT mean was lower in men compared to women (-0.29, p=0.002) and MBT and BMI of the patients wereinversely related (0.24; p=0.011). Both measured by linear regression.Expiration patterns were different: the peak and time of expired 13CO2 in GBT is significantly lower and later in time in F3-4compared with C+ F0-2 (both p<0,001). In MBT the peak in F3-4 is significantly lower (p=0.037), but not significantly later(p=0.085). Also HA measurement is significantly different between F0-2 vs F3-4 (p=0.03,T-test).Conclusion The non-invasive GBT and HA distinguish reliably between cirrhotic and non-cirrhotic patients, unfortunatelyMBT cannot. However, GBT, MBT and HA had not enough accuracy to diagnose early stages of fibrosis in patients with HBVor HCV.TITLE: The APRI and FIB-4 Are Equivalent in the Estimation of Fibrosis in Chronic Hepatitis CABSTRACT FINAL ID: S2078AUTHORS (FIRST NAME, LAST NAME): Ned Snyder1, Tony Trang1, Shu-Yuan Xiao2, John R. Petersen2ABSTRACT BODY: Background: Several hepatic fibrosis markers utilizing simple biochemical tests or components of thehepatic extracellular matrix are useful in predicting broad categories of fibrosis in chronic hepatitis C (HCV). Two tests that caneasily be calculated from routine data are the APRI and FIB-4.Aims: We compared the accuracy of the APRI and the FIB 4 in the separation of mild from significant fibrosis, and alsomild/moderate fibrosis from advanced fibrosis.Methods: The 277 patients studied were enrolled in a prospective study of hepatic fibrosis markers in chronic HCV. Blood wasdrawn at the time of staging liver biopsy. The biopsies were staged using Batts Ludwig criteria (F0-F4) by a single pathologistwho only knew the patients had HCV. Patients with co-infection, an organ transplant, or HCC were excluded. The APRI andFIB-4 were calculated as below. Mild fibrosis was defined as F0-F1, significant fibrosis: F2-F4, Mild/moderate fibrosis: F0-F2,and advanced fibrosis: F3-F4.Results:Construction of Receiver Operating Characteristic curves revealed that the FIB-4 and APRI had near identical AreasUnder the Curve (AUC)of 0.859 and 0.850 respectively for the separation of mild and significant fibrosis. Utilizing cut offs or0.85 and 1.80, the FIB-4 predicted 68 of 75 for mild fibrosis (NPV=90.7%) and 78 of 86 for significant fibrosis (PPV=90.8%)with an indeterminate zone (0.86-1.79) of 116 patients (41.1%). Using cut-offs of 0.42 and 1.2, the APRI predicted 50 of 56with mild fibrosis (NPV=89.3%).and 82 of 91 for significant fibrosis (PPV=92%) with an indeterminate zone of 123 patients(45.5%)6 To claim CME credit please visit the Education and Training section of www.gastro.org
  7. 7. Focused Clinical Updates, May 18 & 19, 2008The AUCs for the separation of mild/moderate from advanced fibrosis were 0.810 and 0.798 for the FIB-4 and APRIrespectively. Using cut-offs of 0.85 and 1.80, the FIB-4 predicted 127 of 146 for mild/moderate fibrosis (NPV=87%) and 28 of36 for advanced fibrosis (NPV=77.8%). The indeterminate zone was 88 patients (32.6%). Using cut-offs of 0.75 and 2.05, theAPRI predicted 114 of 127 (NPV=89.8%) for mild/moderate fibrosis and 29 of 42 (PPV=69%) for advanced fibrosis. Theindeterminate zone was 101 patients (37.4%). Conclusion: The FIB-4 and the APRI are equal in their ability to separate mildfrom significant fibrosis, and mild/moderate fibrosis from advanced fibrosis since they have near identical predictive values,AUC’s, and indeterminate zones. While both are good at separating mild and significant fibrosis, and negatively predictingadvanced fibrosis, neither is very accurate in the positive predictive of advanced fibrosis.FIB-4= Age(years) x AST (U/L)/Platelets (109/L)xALT(U/L)1/2APRI= AST/ULN x 100 /Platelets (109//L)TITLE: Minimal visceral fat accumulation is a prerequisite for a persistent normal serum ALT level in chronic hepatitis Cpatients.ABSTRACT FINAL ID: S2065AUTHORS (FIRST NAME, LAST NAME): Noriko Oza1, Yuichiro Eguchi1, Shunya Nakashita1, 2, Eriko Ishibashi1, 2,Takahisa Eguchi 2, Aki Matsunobu1, 2, Yoichiro Kitajima2, Shigetaka Kuroki 2, Iwata Ozaki 1, Yasunori Kawaguchi1, YasushiIde1, Tsutomu Yasutake1, Ryuichi Iwakiri1, Toshihiko Mizuta 1, Naofumi Ono2, Kazuma Fujimoto1ABSTRACT BODY: Background/aims: Serum ALT level, an indication of the activity of hepatitis, is an important maker inthe progression of hepatitis C. Namely, progression of hepatitis C was correlated with the serum ALT level. There might bemany factors which regulate serum ALT level of liver diseases and recent study demonstrated visceral fat tissue mightinfluence damage of liver tissues via various adipocytokines. This study aimed to determine an effect of visceral fataccumulation on serum ALT level in patients with chronic hepatitis C. Methods: Patients with chronic hepatitis C weresequentially enrolled in the study during November 2005 to April 2007. After gaining informed consent, the subjects underwentabdominal CT to measure the amount of visceral fat for cross-sectional assessment. Amount of visceral fat was assessed usingthe visceral fat area (VFA cm2) on the umbilical cross section. Patients were classified into either a normal (serum ALTlevel 30 IU/L) or increased (serum ALT level 31 IU/L) group. Insulin resistance in the liver was assessed using ahomeostasis model of insulin resistance (HOMA-IR). Insulin resistance in skeletal muscle was assessed using the QuantitativeInsulin Sensitivity Check Index (QUICKI). Patients of HBs antigen-positive; consumption of greater than 20 g alcohol per day;autoimmune liver disease; and advanced chronic hepatitis (histological stage of fibrosis=F3 or F4 in liver biopsy) wereexcluded. Correlation was evaluated using Pearson’s correlation coefficient. Results: A total of 95 patients (46 males, 49females, mean age: 54.6±11.6) were included in the study (22 patients in the ALT normal group, 73 patients in the increasedALT group). Age was significantly higher in the normal group than the increased group (60.6±9.8 vs 52.8±11.5, p<0.05). BMIwas significantly lower in the normal group (21.9±2.3 vs 24.6±3.7, p<0.01). VFA was lower in the normal group with nopatient with excessive visceral fat (VFA 100 cm2) in this group (normal: 57.3±24.8, increased: 89.0±49, p<0.05). HOMA-IRand QUICKI were significantly correlated with visceral fat area (HOMA-IR: r=0.614, p<0.01; QUICKI: r=-0.558, p<0.01).Serum ALT level was correlated with HOMA-IR and QUICKI (HOMA-IR: r=0.553, p<0.01; QUICKI r=-0.462, p<0.01).Conclusion: Visceral fat accumulation leads to an increase in insulin resistance in the liver and skeletal muscle. To have apersistent normal serum ALT level, patients with chronic hepatitis C must be free from visceral fat obesity. To confirm thishypothesis, it should be evaluated whether visceral fat reduction improves increase in ALT level in chronic hepatitis C.TITLE: The prevalence of insulin resistance in patients with chronic hepatitis C and BABSTRACT FINAL ID: M1771AUTHORS (FIRST NAME, LAST NAME): Wael Soliman1, Magdalena Kuczynski1, I.George Fantus2, Jenny Heathcote1ABSTRACT BODY: Background: The presence of insulin resistance (IR) may predict the subsequent development ofdiabetes. Diabetes is associated with chronic hepatitis C (CHC). The prevalence of IR in non-cirrhotic CHC patients has notbeen well assessed and similarly prevalence of IR in chronic hepatitis B (CHB) remains unknown.Aim: To assess the prevalence of IR defined as [Homeostasis Model assessment (HOMA-IR) ≥ 2.1] among treatment naïve,non-cirrhotic, non-diabetic (fasting serum glucose < 7mmol/l) patients with CHC and CHB (controls).Methods: IR measured by HOMA test [fasting insulin (microunits per milliliter) × fasting glucose (millimoles per liters) / 22.5]was determined in treatment naïve, non-cirrhotic (biopsy proven), non-diabetic patients with CHC and CHB. Patients with To claim CME credit please visit the Education and Training section of www.gastro.org 7
  8. 8. Focused Clinical Updates, May 18 & 19, 2008other diseases or those taking medications or alcohol (> 20 gm /day) were excluded. Demographic data (sex, race, age) andmetabolic parameters [body mass index (BMI), waist circumference, lipid profile and free fatty acids] were collected in thepatients studied. A series of t-tests (continuous) and chi-square test (categorical) were used to determine the differencesbetween the CHC and CHB patient groups. A series of logistic regression analyses were performed to determine theindependent predictors of IR (HOMA ≥ 2.1) among CHC and CHB. This study was approved by our hospital research ethicsboard.Results: IR status was determined in 102 CHC and 27 CHB patients. BMI, waist circumference, free fatty acids, histologicalactivity index (HAI), hepatic fibrosis and steatosis scores were not significantly different between CHC and CHB patients(p=0.3092, p=0.1587, p=0.9486, p=0.4455, p=0.7871, p=0.4079 respectively).The two groups were different in that male sex(p=0.0247) , Asian race (p<0.0001) and elevated serum cholesterol (p=0.0330) were more common in patients with CHB butthere was no significant difference in the prevalence of IR (HOMA ≥ 2.1) among patients with CHC (38%) and CHB (30%)(p=0.4087). Multivariate analysis indicated that the prevalence of IR among patients with CHC was independently associatedwith BMI [p= 0.0054, overweight odds ratio (OR) = 6.78 & obesity OR = 17.13] and HAI (p=0.0344, activity grade 2 OR =3.69), which was not the case in CHB.Conclusion: The prevalence of IR was 38% in CHC and 30% in CHB. BMI and HAI are independent risk factors for insulinresistance (HOMA ≥ 2.1) but only in CHC.TITLE: Hepatitis c virus (HCV) flares in patients with hematological malignancies treated with anti-CD 20 antibody(rituximab)-including regimens.ABSTRACT FINAL ID: 383AUTHORS (FIRST NAME, LAST NAME): Manuela Mangone1, Stefano Angeletti1, Michela Di Fonzo1, Fabio Attilia1, SaraGallina1, Marcella Epifani1, Bruno Monarca2, Antonella Ferrari2, Caterina Tatarelli2, Gianfranco Delle Fave1, MassimoMarignani1ABSTRACT BODY: Background: Limited data are available on transaminases increases in HCV-positive (HCV+) patientsaffected by haematological malignancies treated with the anti-CD 20 antibody (rituximab)-based regimens.Aim: To evaluate in this group of patients the possible role of rituximab in inducing significant increases in transaminases.Material and methods: the data regarding 104 patients consecutively treated for haematological malignancies at our Institutionduring the period from January 2004 to December 2006 with anti-CD 20 antibody (rituximab)-including regiments (55M, 49 F,median age 63.6 yrs, range 23-92) were retrospectively evaluated. HCV+ and HCV-negative (HCV-) patients were identifiedand the trend of serum alanine aminotransferase (ALT) during treatment collected. Patients experiencing an increase in ALT >5times normal value were defined to have an hepatitis flare and followed up to 12 months after completing their chemotherapytreatment.Results: 9 patients were HCV antibody positive before treatment (4M, 5F, median age 62yrs, range 37-72; 8.6% of total). Nostatistical difference was detected in age and sex distribution between the HCV+ and the HCV- groups. An ALT flare wasidentified in 3 of the 9 HCV+ patients (33%) and in none of the HCV- (p<0.0005, Fisher test). None of these patients hadclinical or histological stigmata of end stage liver disease (ESLD). One of the HCV+ experiencing the increase in ALT evolvedto an icteric hepatitis picture. None showed hepatic failure or died because of the hepatitis flare. Chemotherapeutic treatmentwas continued in all three patients.Conclusions: HCV+ patients undergoing treatment with anti-CD 20 antibody (rituximab)-based regimens may experiencesignificant increases of ALT but this event is to be considered benign in patients without end stage liver disease.TITLE: Project ECHO (Extension for Community Healthcare Outcomes): Knowledge Networks Expand Access to Hepatitis C(HCV) Treatment with Pegylated Interferon and Ribavirin in Rural Areas and Prisons. Care is as Safe and Effective as aUniversity HCV Clinic.ABSTRACT FINAL ID: 380AUTHORS (FIRST NAME, LAST NAME): Sanjeev Arora1, Glen H. Murata2, Karla Thornton1, Brooke Parish3, Steven M.Jenkusky3, Jeffrey C. Dunkelberg1, Richard M. Hoffman2, Miriam Komaromy4ABSTRACT BODY: Objective: To conduct a prospective cohort study to evaluate the safety and efficacy of HCV treatmentby primary care providers in rural areas and prisons in comparison to university clinic. Methods: Project ECHO is a newmethod of healthcare delivery and clinical education for the management of complex, common and chronic diseases, inunderserved areas, using HCV as a model. Project ECHO is a partnership of University of New Mexico, eight prisons, andthirteen rural health clinics dedicated to providing best practices and protocol-driven healthcare in rural areas. Telemedicineand internet connections enable specialists to co-manage HCV patients using case-based knowledge networks and to trackoutcomes. Project ECHO partners (nurse practitioners, primary care physicians, physician assistants) present HCV positive8 To claim CME credit please visit the Education and Training section of www.gastro.org
  9. 9. Focused Clinical Updates, May 18 & 19, 2008patients during weekly 2-hour telemedicine clinics using a standardized, case-based format that includes discussion of history,physical examination and test results. In these case-based learning clinics, partners rapidly gain deep domain expertise in HCVas they collaborate with university specialists in hepatology, psychiatry and substance abuse in co-managing their patients.Results: Since June of 2003, 185 HCV knowledge network clinics have been conducted with 2640 case presentations of HCVpatients. Of 327 patients treated via Project ECHO, 63.5% were members of a minority (Hispanic in 53.2%, Native Americanin 4.4%, and African American in 2.0%). Cirrhosis was present in 24.1% and depression in 41.4%. Genotype 1 was found in61.1%, while the average log viral load was 5.94 ± 0.94. Early Virological Response was seen in 82/96 (85%), 61/74 (82%) and105/113 (93%) of university, prison and rural patients. Significant adverse events (SAE) occurred in 24 (11.8%). Compared topatients without SAE, those with events were significantly older (48.7 ± 6.9 vs 43.6 ± 9.3 years; P=0.002); had lower serumalbumin (3.69 ± 0.58 vs 4.08 ± 0.49 gm/dl; P=0.009), and platelet count (156 ± 75 vs 190 ± 81 x1000; P=0.047); and morelikely to have cirrhosis of liver (50.0% vs 21.0%; P=0.002), and report a history of depression (66.7% vs 38.1%; P=0.008).Logistic regression showed that cirrhosis of liver [adjusted odds ratio (OR) 4.59; 95% confidence interval (CI) 1.66 – 12.7),depression (OR 4.77; 95% CI 1.66 – 13.7), were independent determinants of SAE (Hosmer-Lemeshow P=0.927; ROC area0.742). No differences in genotype distribution, SAE or response to treatment were found across sites. Conclusions: HCVtreatment delivered to patients in rural areas and prisons using the Project ECHO model is as safe and effective as a universityHCV clinic.TITLE: Hepatitis A and B immunization practices among community physicians of chronic hepatitis C patientsABSTRACT FINAL ID: S1058AUTHORS (FIRST NAME, LAST NAME): Yasmin Metz1, Ketan Kulkarni2, Maya Gambarin-Gelwan2, Ira M. Jacobson2ABSTRACT BODY: PURPOSE: We sought to determine if chronic hepatitis C (CHC) patients are being appropriatelyvaccinated in the community in accordance with AASLD practice guidelines (Strader DB et al. Hepatology 2004; 39: 1147-71).METHODS: Patients with CHC initially seen in our hepatology practice between 7/06-7/07 were identified. Subjects wereeither self-referred, referred by their primary care provider or gastroenterologist. Charts were reviewed to ascertain date ofdiagnosis, demographic data, hepatitis serologies and stage of liver disease. Screening colonoscopy status in age-appropriatesubjects was also reviewed to assess compliance with another recommended preventive health measure. Patients were onlyincluded in the final analysis if they had well-compensated liver disease and had known CHC for at least one year prior to re-ferral to permit time for immunization. RESULTS: One hundred and fifteen consecutive new CHC referrals were identified. 89of them had been diagnosed at least one year prior to referral with a mean of 6.6±4 years. 41 patients (46%, n=89) were HAVIgG +, suggesting either prior vaccination or natural immunity. Among 86 patients for whom complete HBV serologies wereavailable, 50 (58%) had serum markers of past HBV infection or vaccination (isolated HBcAb+ n=5, HBsAb+ n=45). Of 66patients over 50 years old for whom colonoscopy history was documented, 43 (65%) had a screening colonoscopy within 5years. Prior studies have shown the prevalence of natural immunity to HAV and HBV among CHC patients is 38% and 59%,respectively (Siddiqui F et al. Am J Gastroenterol 2001; 96: 858-63). There was no difference between the prevalence ofimmunity to HAV (p=0.13) or HBV (p=0.91) among our population when compared to the expected prevalence of naturalimmunity. The prevalence of colonoscopy screening was greater than that of immunity to HAV (p=0.02) but not for HBV (p=0.41). CONCLUSION: The prevalence of immunity to HAV and HBV among our CHC patients was similar to the prevalenceof natural immunity previously reported. Since the immunogenicity of HAV and HBV vaccinations is high in patients withwell-compensated disease, ineffective seroconversion could only account for a small percentage of unvaccinated subjects.Hence, immunity to HAV and HBV in our population of HCV-infected subjects was not adequately ensured by referringphysicians. Patients were more likely to have undergone colonoscopy than have immunity to HAV. Greater awareness isneeded among physicians so that immunization against HAV and HBV becomes part of routine health maintenance for CHCpatients.TITLE: The Impact of Hepatitis B (HBV), Hepatitis C (HCV) and Non-Alcoholic Fatty Liver Disease (NAFLD) Guidelineson Clinical PracticesABSTRACT FINAL ID: S2079AUTHORS (FIRST NAME, LAST NAME): Jillian Kallman2, 1, Aimal Arsalla1, 2, Angela M. Wheeler1, Ruben D. Aquino2,Kathy L. Terra1, Rebekah Euliano1, Zobair M. Younossi1, 2ABSTRACT BODY: Although guidelines for HBV and HCV and position statements for NAFLD have been put forth bydifferent societies, awareness of these guidelines and their impact on the physician practices have not been measured. Aim: Toassess the attitudes of primary care physicians (PCP), gastroenterologists (GE), and hepatologists (HEP) regarding HBV, HCVand NAFLD. Design: An in-depth questionnaire was sent to PCP, GE, and HEP, assessing their familiarity with issues relatedto HBV, HCV and NAFLD. The survey contained 29 NAFLD items, 35 HBV items, and 35 HCV items. Comparisons were To claim CME credit please visit the Education and Training section of www.gastro.org 9
  10. 10. Focused Clinical Updates, May 18 & 19, 2008made between different practice specialties, using one-way ANOVA with Bonferroni adjustments. Results: A total of 161surveys have been received (101 PCP, 30 GE, 26 HEP). Demographics of survey respondents included age (46.9 years +/-12.4), gender (Male = 59.9%), practice environment (42.8% Urban, 46.6% Suburban, 3.3% Rural, 7.3% multipleenvironments), with a median of 60 patients seen per week. The majority of PCP, GE, and HEP agreed on most screeningissues related to HBV, HCV and NAFLD. However, some important differences exist. PCP considered HCV to be lesscommon than both GE (p=.0001) and HEP (.001) and NAFLD more common than HEP (.0001). Over 40% of PCP reportedbeing unaware of any official guidelines for HBV, HCV or NAFLD, compared to 13% of GE and 4% of HEP. A majority ofHEP (88%) and 40% of GE were familiar with and followed AASLD guidelines. PCPs were most likely to be familiar with anduse USPSTF guidelines (24%) followed by AAFP (15%), ACP (14%) and AASLD guidelines (5%). Neither HEP nor GEreported following AAFP guidelines. Further, PCP rated themselves significantly less knowledgeable of HBV guidelines thanboth GE and HEP (p=.003 and p=.0001, respectively) as well as for HCV guidelines (p=.0001 each). PCP also reportedsignificantly less reliance on guidelines when making a decision to screen for HBV and HCV (P<0.05). Although PCP, GE andHEP did not differ in rating the effectiveness of HCV treatment, HEP rated the effectiveness of HBV treatment higher thanPCPs (p=.0001) and PCPs rated the effectiveness of treatment for NAFLD higher than HEP (p=.0001). Furthermore, sideeffects of HBV and NAFLD treatment were rated as more harmful by PCP than HEP (p=.001) or GE (p=.009). Conclusions:Although practice guidelines for three common liver diseases exist, there continues to be a lack of familiarities and practicevariation in clinical practice. As expected, specialists are more aware about these guidelines than primary care physicians. Inorder to increase knowledge base about important liver diseases, efforts should be focused on primary care practices.TITLE: Peginterferon and Ribavirin for Treatment of Hepatitis C and HIV Co-infection: A Meta-Analysis of RandomizedControlled TrialsABSTRACT FINAL ID: S2081AUTHORS (FIRST NAME, LAST NAME): Ajitinder S. Grewal1, Abhishek Choudhary1, Matthew L. Bechtold1, Srinivas R.Puli1, Mohamed O. Othman1, Praveen K. Roy1ABSTRACT BODY: Background and Purpose: Hepatitis C (HCV) co-infection is a significant contributor of morbidity andmortality among HIV patients. The progression of liver disease is accelerated in these patients. Combined treatment withpeginterferon (PEG) and ribavirin (RBV) is the standard treatment for HCV mono-infected patients. Recently, several studieshave reported the efficacy and adverse effects of treating the HIV/HCV co-infected patients with peginterferon and ribavirin.We conducted a meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and side effects of peginterferonand ribavirin versus standard interferon (INF) and ribavirin. Methods: MEDLINE, Cochrane Central Register of ControlledTrials & Database of Systematic Reviews, PubMed, and recent abstracts from major conference proceedings were searched(through 10/07). RCTs enrolling adult subjects and comparing PEG/RBV with INF/RBV were included. Studies were assigneda quality score using Jadad score. Standard forms were used to extract data by two independent reviewers. Pooled estimates ofthe following outcomes were obtained: End of treatment response (ETR), sustained viral response (SVR), and side effects.Separate analyses were performed for each outcome by using odds ratio (OR). Publication bias was assessed. Heterogeneityamong studies was assessed by calculating I2 measure of inconsistency and if noted, a random effects model was performed.Results: Five trials satisfied the inclusion criteria (1,335 patients). The mean age ranged from 37-45 years. 86.2% of patientswere on HAART therapy. Two trials used PEG alpha-2a (180 mcg per week) & 3 trials used PEG alpha-2b (2 trials used 1.5mcg/kg/week & 1 trial used 100-150 mcg/week). Dose of RBV was 800-1,200 mg daily. PEG/RBV achieved a higher SVRcompared to INF/RBV (OR 2.94, 95% CI: 1.70–5.08, NNT 5). ETR was also higher with the PEG/RBV (OR 3.17, 95% CI:1.93–5.17, NNT 5). SVR was significantly higher with PEG/RBV, regardless of the genotype. The side effects profile wassimilar among the treatment groups (OR 1.04, 95% CI: 0.82–1.32, p=0.73). However, influenza-like symptoms were morecommon in the INF/RBV group (OR 1.68, 95% CI: 1.06–2.60, NNH 12). No significant publication bias was present.Conclusion: Peginterferon and ribavirin achieves a higher SVR compared to standard interferon and ribavirin therapy inHCV/HIV co-infected patients (NNT=5). Influenza-like symptoms were more common in patients treated with standardinterferon and ribavirin. However, other side effects were similar in the two treatment groups.10 To claim CME credit please visit the Education and Training section of www.gastro.org