Posters – Tuesday May 23, 2006 8:00AM Hepatitis C
HCV: Epidemiology, Natural History, Diagnosis
S. Batash; I. Khaykis; R. F. Raicht; E. J. Bini
Inadequate sterilization and re-use of medical equipment may have contributed to hepatitis C virus (HCV) transmission in the former Soviet Union. Although New York (NY) leads the nation in the number of Russian Americans (1.6 million in the NY Tri-State area), the epidemiology of HCV infection has not been evaluated in this population. The aims of this study were to determine the prevalence of and risk factors for HCV infection among Russian immigrants in the NY metropolitan area.
We conducted a 3-day community-based HCV screening program in the 2 boroughs of the NY Tri-State area with the highest density of Russian immigrants (Brooklyn and Queens). Russian radio and cable television were used to invite patients to come in for free HCV counseling and testing. In the last 2 days of screening, each person also completed a HCV risk factor questionnaire.
The overall prevalence of HCV positivity among the 283 subjects (age 51.9 ± 15.7 years; 53.4% female) was 28.3% (95% CI 23.0% - 33.5%). Although there was no difference in the prevalence of HCV infection between men and women (30.3% vs 26.5%, P = 0.48), there was a linear trend towards an increasing prevalence with age (21.4% in subjects <30 years old and 35.0% in those ≥70 years old). Among those who completed the questionnaire, the mean number of years in the U.S. was 10.7 ± 6.1, with the majority either from Uzbekistan (32.0%), Ukraine (29.9%), or Russia (18.6%). Prior injection drug use was uncommon (2.1%), and only 22.7% reported ≥10 lifetime sexual partners. The prevalence of HCV infection was 11.1% in immigrants from Russia, 29.0% from Uzbekistan, 31.0% from the Ukraine, and 36.8% from other regions. Although IM injections (OR=11.1; 95% CI 2.4 - 50.7), blood transfusion (OR=4.3; 95% CI 1.7 - 11.2), hospitalization (OR=4.2; 95% CI 1.4 - 12.2), and surgery (OR=3.3; 95% CI 1.1 - 9.7) were significantly associated with HCV positivity in univariate analysis, only IM injections (OR=9.1; 95% CI 2.0 - 42.4) and blood transfusion (OR=3.2; 95% CI 1.2 - 9.0) remained independently associated with HCV infection in multivariable analysis.
In this community-based HCV screening program, we found a high prevalence of HCV infection among Russian immigrants in the NY metropolitan area. It is likely that the use of inadequately sterilized medical equipment and blood transfusions were the primary modes of HCV transmission in this population. Given the high prevalence of HCV infection in Russian immigrants, universal HCV testing should be strongly considered in this population.
This study was funded by a grant from Roche Pharmaceuticals and the American Liver Foundation.
Abstract 550 – Low Prevalence of Advanced Fibrosis in African americans with chronic hepatitis C and persistently normal serum ALT : The case for conservative management
A. A. Mihas; M. L. Shiffman; H. R. Lippman; L. Pisney; D. M. Heuman
African Americans (AA) have poorer treatment responses than Caucasians (Cau), related to higher prevalence of genotype 1, higher viral titers, and genetic differences in biology of interferon response.If likelihood of success with antiviral therapy is low and disease course is indolent, expectant management may be preferable to treatment. Currently decisions regarding need for antiviral treatment are based mainly on liver biopsy, with its attendant risk, discomfort and cost.
The aim of this study was twofold: a) to assess the spectrum of liver histopathology among AAs with PNALT as compared to currently high ALT (HALT) or currently normal but intermittently high ALT (IHALT) and b) to determine whether the relationship of ALT pattern to fibrosis differs between AA and Cau patients.
375 consecutive AA and 206 Cau US veterans undergoing liver biopsy for evaluation of chronic hepatitis C were included . We utilized the DVA electronic records to review ALT going back as much as 23 years, extracting the highest-ever ALT value and the current ALT at time of liver biopsy. All patients had imaging of the liver as well as routine biochemical and serologic tests by standard laboratory techniques. Hepatic fibrosis was graded on a 0-6 scale according to the Ishak staging system by two blinded reviewers.
Approximately half the patients with a normal ALT at the time of liver biopsy were found to have had at least one previous documented ALT elevation. AA patients with IHALT and HALT had similar fibrosis scores (2.75 ± 0.15 and 3.1 ± 0.12 respectively), as well as similar prevalence of advanced fibrosis ( 48% and 54% , respectively) and cirrhosis (14% and 19%, respectively). In contrast, AA patients with PNALT had significantly lower fibrosis scores (1.22 ± 0.09, p< 0.01) and prevalence of cirrhosis was only 0.8%. The proportion of patients with PNALT was greater among African Americans than Caucasians ( 32% vs 22% %, p < 0.05), but in subgroups with PNALT, IHALT or HALT, no differences were found between races with respect to mean fibrosis scores or prevalence of advanced fibrosis or cirrhosis.
AA are more likely than Cau to have PNALT. The prevalence of cirrhosis among both AA and Cau with a well-documented PNALT is negligible. If long term followup is available for an HCV patient and ALT is persistently normal, liver biopsy is not needed and antiviral therapy can be deferred . This conservative approach to the PNALT patient is preferable especially in AA with HCV genotype 1 and high viral titer, in whom probability of sustained virological response to interferon and ribavirin is low.
X. Zhao; M. Ramaswamy; M. Tang; M. Black; X. Ma
Spontaneous clearance of hepatitis C virus (HCV) infection is the outcome of the interplay between host immunity and virus behavior. HCV has been shown to have different viral kinetics in African Americans (AA) as opposed to Caucasians. We look at the spontaneous clearance rate in these two groups and the association of viral clearance with race, environmental factors, and other viral coinfection.
Retrospective chart review was performed on 293 patients with positive HCV Ab who were followed at our liver clinic from 2002 to 2005. Patients with spontaneous clearance were identified as having positive HCV Ab confirmed by RIBA and undetectable viremia without prior treatment; chronically infected patients were identified as either having active viremia or negative viremia after treatment. Patients with diagnosed autoimmune diseases were excluded. Data were collected on patient demographics, risk factors, and clinical characteristics. Statistical analysis was performed using univariate and multivariate logistic regression analyses.
There were 191 AA, 74 Caucasians, 19 Asians, and 9 Latin-Americans in our study. The spontaneous clearance rate in AA and Caucasian patients was 9.4% (18/191) and 20.3% (15/74) respectively (P=0.021). No difference was observed in age, gender, and weight between the two groups. In univariate analysis, HBsAg positivity had a positive association with viral clearance (odds ratio [OR] 6.08; 95% CI 1.56-23.80; P=0.016); black race (OR 0.45; 95% CI, 0.22-0.91; P=0.027) and alcohol abuse (OR 0.23; 95% CI, 0.09-0.58; P=0.001) were associated with decreased HCV clearance; age, gender, and risk factors (IVDA, blood transfusion) did not show significant association with viral clearance. In multivariate analysis adjusting for gender, race, alcohol, and HBV coinfection, HBsAg remained positively associated with viral clearance (OR 14.15; 95% CI 2.74-72.97; P=0.001), while black race (OR 0.42; 95% CI 0.19-0.93; P=0.032) and alcohol abuse (OR 0.18; 95% CI 0.06-0.52; P=0.001) were still negatively associated with viral clearance.
Spontaneous clearance of HCV is lower in African Americans than in Caucasians; HBV coinfection is associated with increased likelihood of HCV clearance. The primary viral clearance may be negatively influenced by black race and alcohol abuse.
Abstract 552 – Prospective and independent validation of the Lok index for prediction of cirrhosis in patients with chronic hepatitis C: comparison with FibroScan, Fibrotest and APRI
L. Castera; J. Foucher; B. Le Bail; P. Bernard; J. Bertet; P. Couzigou; V. de Ledinghen
Background & Aim:
A novel noninvasive index based on standard laboratory tests (platelet count, AST/ALT ratio, and INR) has been recently proposed for prediction of cirrhosis in patients with chronic hepatitis C (CHC) (Lok et al. Hepatology 2005). The aim of this prospective study was to validate independently the accuracy of this index for the detection of cirrhosis in CHC patients, as compared with transient elastography (FibroScan) and other serum markers (FibroTest and APRI).
Patients & Methods:
412 consecutive CHC patients (231 males, mean age 52±12 yrs) who underwent a liver biopsy at our institution between january 2003 and november 2005 were studied. Of these patients, 264 also had the day of liver biopsy a FibroScan, a FibroTest, and laboratory tests allowing to calculate the APRI (AST/platelet) and Lok indexes. These patients did not differ from the total group for most characteristics including age, gender, and fibrosis stage distribution. Fibrosis was scored according to METAVIR by two independent pathologists. Diagnostic performances were assessed using areas under the receiving operating characteristic curve (AUROC).
Histological fibrosis score distribution was : F0-F1 24%; F2 36%; F3 20%; F4 20%. Mean liver biopsy length was: 19±8 mm. AUROC (95% CI) for the diagnosis of cirrhosis (F4) of Lok index was 0.81 (0.75-0.87). A Lok index < 0.2 to exclude cirrhosis would have misclassified 14,5% of patients with cirrhosis (Sensitivity 85%, specificity 43%, negative predictive value 76%), whereas a cut-off > 0.5 to confirm cirrhosis would misclassify 6% of patients (Sensitivity 50%; specificity 93%; positive predictive value 64%) ; 195 patients (47%) who were between these 2 values could not be correctly classified. Liver stiffness measurement could not be obtained in 12 patients (4.5%). In the 252 patients evaluated, AUROC (95% CI) for the diagnosis of cirrhosis of Lok index was 0.81 (0.74-0.88), compared with 0.95 (0.92-0.98) for FibroScan, 0.86 (0.81-0.91) for FibroTest, and 0.80 (0.73-0.86) for APRI.
Diagnostic performances of Lok index in our patients were similar to those of APRI but lower than those of FibroScan and FibroTest. FibroScan appears as the best method for prediction of cirrhosis in CHC patients.
K. Ario; T. Mizuta; Y. Eguchi; T. Kumagai; T. Yasutake; I. Ozaki; K. Fujimoto
It is well recognized that hepatic inflammation facilitates the progression of hepatic fibrosis and the occurrence of hepatic cancer in HCV-infected patients, but little is known about the factors associated with hepatic inflammation. Recent studies have indicated that insulin resistance might be an important factor related to hepatic fibrogenesis and carcinogenesis. The purpose of this study was to determine whether insulin resistance influences hepatic inflammation in patients with HCV-related chronic hepatitis.
Seventy-two HCV-positive chronic hepatitis patients (44 males, 28 females, mean age: 56.0±9.7, range: 36-73) who underwent liver biopsy and a 75g oral glucose tolerance test (OGTT) were included. Insulin resistance (or sensitivity) was evaluated with HOMA-IR and the insulin sensitivity index (ISI composite). Age, gender, glucose tolerance class (NGT, IGT, DM) in the OGTT, HOMA-IR, ISI composite, BMI, serum HCV core protein level, HCV genotype (1b, 2a, 2b), serum adiponectin level, histological stage of fibrosis (F1, F2, F3) and grade of steatosis (<10%, 10-30%, 30-60%, >60%) were analyzed for their association with serum ALT level and the histological grade of inflammation (A1, A2, A3) using correlation coefficients, the Mann-Whitney U test, Fisher’s exact probability test and logistic regression analysis.
Serum ALT level was correlated with HOMA-IR (r=0.464, p<0.0001) and ISI composite (r=-0.352, p=0.002), but not age, BMI, adiponectin and HCV core protein level. There was no difference in ALT levels according to gender, glucose tolerance class, HCV genotype, histological fibrosis or steatosis. Logistic regression analysis showed that HOMA-IR was the only factor associated with an ALT level of >80 IU/L (OR 3.12, p=0.024). There was a significant difference in ALT levels between cases with an HOMA-IR of <2 and >2 (63.9±34.0 vs. 97.2±59.2, respectively; p=0.002). ISI composite was the only factor related to a histological inflammation grade of >A2 (OR 0.064, p=0.022). With an ISI composite of <8 and >8, the ratios of those >A2 grade were 83.8% and 25%, respectively.
The present study showed that inflammatory activity in HCV-related chronic hepatitis is strongly related to insulin resistance. These data suggest that improvements in insulin resistance might lead to decreased inflammation in HCV-related hepatitis patients.
Abstract 554 – Diagnostic Liver Biopsy in Patients wWith Advanced Fibrosis and Cirrhosis
K. E. Sherman; Z. D. Goodman; S. T. Sullivan; S. Faris-Young
Liver biopsy is a key modality in the diagnosis and staging of liver disease. However, optimal biopsy technique in cirrhotic subjects whose samples are prone to fragmentation and suboptimal interpretation has not been established. We evaluated the effect of biopsy technique on specimen size, quality and other features in 923 biopsies in patients with advanced fibrosis/cirrhosis due to HCV infection.
Liver biopsy specimens were obtained during the course of a phase II, double-blind randomized placebo controlled multicenter trial designed to determine the safety and efficacy of interferon-gamma 1b in patients with hepatitis C (HCV) associated severe liver fibrosis or cirrhosis (Ishak stages 4-6). The investigators at individual sites were permitted to choose the approach and type of liver biopsy performed, but the protocol specified that specimens should be at least 20 mm in length, to ensure adequate sampling for evaluation of fibrosis. Biopsies were centrally reviewed. The following definitions were utilized: Adequate >6 portal tracts, Marginal 3-5 portal tracts, Inadequate <3 portal tracts.
Needle type was reported in 826 cases. Cutting needles were used for 595 of the biopsies (69.7%), aspiration needles for 250 (30%), while the remainder was unknown or another method. Fragmentation was observed in 39.2% of liver biopsies obtained using an aspiration technique, but in only 4.7% of samples collected using an automated cutting needle (p< 0.001). Biopsies performed with automated cutting needles were judged to be adequate in 553 (93%), marginally adequate in 36 (6%) and inadequate in 6 (1%). Aspiration biopsies were adequate in 207 (83%), marginal in 37 (15%) and inadequate in 6 (2%). Statistically, aspiration methods were much more likely to be judged inadequate than automated cutting needle techniques (p= 0.005). Mean biopsy length was 19.17 mm (SEM +0.31) across 886 biopsies evaluated. Mean length was 17.47 mm (S.E.M. + 0.52) for aspiration biopsies, 20.26 mm (S.E.M. + 0.37) for automated cutting needle biopsies, and 16.75 mm for other biopsy types. Analysis of variance indicates that automated cutting needles produced significant longer biopsies than other types (p<0.05). There were no serious adverse events associated with liver biopsy in any subject and no procedure related mortality.
Biopsy in advanced liver disease more often yields larger, unfragmented samples amenable to pathologic interpretation when performed with an automated cutting needle compared to aspiration (suction) biopsy. Adoption of this technique would facilitate accurate biopsy evaluation in patients with advanced fibrosis/cirrhosis.