James M. Wantuck

Review article: the epidemiology and therapy of chronic hepatitis C genotypes 4, 5 and 6

The global burden of hepatitis C (HCV) infection is mostly found in Africa, the Middle East and Asia, where HCV genotypes 4, 5 and 6 are common. The literature on these genotypes is sparse and this synopsis will review characteristics of patients infected with these genotypes.

Mo1045 Compared to HCC Patients With Chronic Viral Hepatitis (Viral HCC), Hcc Patients With Nonviral Etiologies (Nonviral HCC) Were Less Likely to Undergo HCC Screening, Presented With More Advanced Tumors, and Had Poorer Overall Survival

Purpose: HCC rarely occurs in patients without chronic liver disease, and the clinical outcomes of HCC patients may differ by etiologies of underlying liver disease. Routine HCC screening/surveillance is recommended for those with chronic hepatitis B and cirrhosis of all etiologies, but it is unclear if there are differences in adherence in different populations. Our goal was to compare screening adherence and clinical outcomes of viral vs. nonviral HCC patients. Methods: This is a retrospective cohort study of 200 consecutive nonviral HCC patients (67 with alcoholic liver disease [ALD], 73 with cryptogenic/nonalcoholic fatty liver disease [NAFLD] and 52 with others) and 396 patients with viral HCC (268 with chronic hepatitis C, 119 with chronic hepatitis B and 9 with both) randomly selected from a total cohort of 1,214 patients with viral HCC who presented at a U.S. medical center in 1991-2011. HCC patients were identified via ICD-9 electronic query with data collected in all cases by individual chart review and National Death Index search. HCC screening adherence was optimal if US or CT/MRI were done every 6-12 months. Results: Compared to viral HCC patients, those with nonviral HCC were older (65±13 vs. 57±11, p<0.0001) and more likely to be non-Asian (74% vs. 51%, p<0.001), but had similar CPT scores (6.6 ±1.7 vs. 6.9±1.8, p=0.13). While the majority of viral HCC patients had a history of optimal HCC screening (69%), almost none of the nonviral HCC patients did (1%). Compared to viral HCC patients, nonviral HCC patients were much more likely to present withBLCL Stage C/D (42% vs. 19%), p<0.001) and beyond the Milan criteria for liver transplantation (75% vs. 54%, p<0.001). Nonviral HCC patients had significantly lower 5-year survival compared to their viral HCC counterparts: 48% vs 57% (p=0.036) (Figure). Similarly, patients who received optimal screening had significantly higher 5-year overall survival compared to those with suboptimal or no screening (62% vs. 47%, p=0.012). Onmultivariate analysis also inclusive of age, sex and ethnicity, independent predictors for lower mortality were HCC screening (OR=0.50, p=0.015), in addition to viral liver disease etiology (OR= 0.39, p=0.002). Conclusions: Nonviral HCC patients were much less likely to have a history of HCC screening, presented with higher tumor stages, and had poorer survival. The lack of HCC screening in nonviral HCC patients may be due to poor adherence and access to care as may be seen in those with ALD or underdiagnosis of chronic liver disease/cirrhosis as may be seen in those with cryptogenic or NAFLD. Further studies and efforts should be focused on early diagnosis of underlying liver disease, cirrhosis, and improvingHCC screening compliance in at-risk patients; which is especially important with the rising obesity epidemic and projected increase of HCC incidence due to NAFLD.

Letter: response‐guided treatment of hepatitis C virus genotype 5 may be feasible – authors’ reply

1. Wantuck JM, Ahmed A, Nguyen MH. Review article: the epidemiology and therapy of chronic hepatitis C genotypes 4, 5 and 6. Aliment Pharmacol Ther 2014; 39: 137–47. 2. Karatapanis S, Tsoplou P, Papastergiou V, et al. Hepatitis C virus genotyping in Greece: unexpected high prevalence of genotype 5a in a Greek island. J Med Virol 2012; 84: 223–8. 3. Papastergiou V, Skorda L, Lisgos P, et al. Hepatitis C virus genotype 5: prospective evaluation of peginterferon/ribavirin treatment efficacy and predictive value of on-treatment virological responses for sustained virological response. J Clin Gastroenterol 2014; 48: 160–5. 4. Papastergiou V, Dimitroulopoulos D, Skorda L, et al. Predictors of sustained virological response in Greek and Egyptian patients with hepatitis C genotype 4: does ethnicity matter? J Med Virol 2012; 84: 1217–23. 5. Antaki N, Bibert S, Kebbewar K, et al. IL28B polymorphisms do not predict response to therapy in chronic hepatitis C with HCV genotype 5. Gut 2012; 61: 1640–1.

716 Differential Survival in Patients With Hepatitis B Virus-Related Hepatocellular Carcinoma (HBV/HCC) Compared to Hepatitis C Virus-Related Hepatocellular Carcinoma (HCV/HCC)

Background/Aims: Detection of circulating tumor cells (CTC) is associated with poor progression free and overall survival in patients with breast, prostate, and colon cancer. There is limited information about the prognostic value of CTC in patients with cholangiocarcinoma (CCA). The aim of this study are (1) to quantify circulating tumor cells in the peripheral blood of patients with CCA; and (2) to test the hypothesis that the presence of circulating tumor cells is associated with larger tumor burden of CCA and poor overall survival. Methods: A total of 45 patients with CCA seen at Mayo Clinic Rochester were prospectively enrolled between June 2010 and September 2012. 10 ml peripheral blood was drawn into CellSave Preservative Tubes. Blood samples were processed within 96 hours after the blood draw. The CellSearch system by Veridex was used for the capture, enrichment, identification and enumeration of CTC of epithelial origin in 7.5 ml of peripheral blood from the patients. The CellSearch system has an estimated sensitivity of approximately 20-30% for detecting CTC at a prognostic level . The association between baseline characteristics and detection of CTC was analyzed. Overall survival was estimated by the Kaplan Meier method and compared using the Log Rank test. Results: The mean age of patients was 61 and 29 (64%) patients were male. CTC were detected in 13 (28%) patients. Patients with CTC tended to have larger tumor size, more tumor nodules, a higher CA19-9 level, increased CEA, lymph node involvement, and metastatic disease compared to patients without CTC. (Table) There was no significant association between CTC and demography (age, gender, and race) or underlying liver dysfunction . There was a trend towards poorer survival in patients with CTC compared to patients without CTC (p=0.09). Conclusion: CTC are detectable in patients with cholangiocarcinoma. The presence of CTC was associated with tumor burden and metastatic cancer. The prognostic implications of CTC in patients with CCA need further validation in a larger patient group.

Mo2026 Epidemiology and Clinical Outcomes of Asians With Hepatocellular Carcinoma (HCC) Compared to Non-Asian Patients

Background : Endoscopic ultrasonography (EUS) is considered to be the best modality to predict the neoplastic polyps of the gallbladder. However, EUS has several limitations following as 1) the considerable experience of investigators, 2) presence of the interobserver variations and 3) unavailability of EUS in some centers. Multidetector computed tomography (MDCT) provides fine section image of gallbladder and allows to reduce the interobserver variations. We evaluated the accuracy of MDCT combined with high resolution ultrasonography (HRUS) for gallbladder polyps smaller than 2cm compared with EUS. Methods : From Dec 2005 to June 2010, 109 patients who underwent cholecystectomy due to gallbladder polyps were enrolled. Subjects were divided in two groups (reference group : 63 patients who were performed MDCT and HRUS vs. validation group : 46 patients who underwent MDCT, HRUS, and EUS). New scoring system was developed from reference group, and applied to validation group, while previously reported EUS scoring system was applied to the same validation group. Results : In reference group, size (p,0.001), number (p=0.015), shape (p=0.001), and CT/US size ratio of polyps (p=0.008) were significant variables in univariate analysis. Area under the ROC curve draw by new scoring system was 0.859 and cut-off value was set to 3. In validation group, new scoring system showed comparable accuracy (65.2%) with previously reported EUS scoring system(73.9%, p=0.434). Conclusion : MDCT combined with HRUS provide comparatively high accuracy in small gallbladder polyps in distinguishing between neoplastic and non-neoplastic polyps as preoperative diagnostic modality.

613 Hepatitis C Virus (HCV) Diagnosis and Clinical Outcomes of Patients With HCV-Related Hepatocellular Carcinoma (HCC): A Comparative Study of Asians Versus Non-Asians

BACKGROUND AND AIMS: In addition to hepatitis B virus, HCV is also an important cause of HCC in Asians; however, it is often overlooked. This study aims to examine baseline characteristics, timing of HCV diagnosis and long-term survival of HCV-related HCC in Asians compared to non-Asian patients. METHODS: We conducted a retrospective cohort study of 798 consecutive Asian (n=220) and non-Asian (n=572) patients with HCV-related HCC who were identified via computer query using ICD-9 diagnosis at a U.S. university medical center between 7/1996 and 6/2012. Individual records were reviewed. RESULTS: Asians were much older (66 [38-88] vs. 56 [31-87] years, P ,0.0001) and more likely to be female (33% vs. 19%, P,0.0001). A significantly larger proportion of Asians were also diagnosed with HCC within only 2 years of HCV diagnosis compared to non-Asians (35% vs. 20%, p=0.001). Non-Asians were more likely to have decompensated liver disease and had higher median Child-Turcotte-Pugh score (6 [5-11] vs. 7 [5-13], P ,0.0001). Asian patients were more likely to undergo liver-directed palliative therapy (46% vs. 28%) and much less likely to be listed for liver transplantation(20% vs. 48%) (P ,0.001), despite similar rates of meeting Milan criteria for liver transplantation (52 vs.58%, P=0.16). Overall, there was a trend for higher median survival rates in Asians compared to non-Asians (30 vs. 21 months, P=0.091). Among those who were listed for liver transplantation, there was no statistically significant difference in survival between Asians and non-Asians in the first 2 years (72% vs. 68%) but there was divergence with Asians having higher survival afterwards (61% vs. 51%) (Figure 1). However, among those undergoing liver-directed palliative therapy, Asians had significantly higher long-term survival compared to non-Asians (5-year survival: 28% vs. 10%, P,0.0001) (Figure 2). On multivariate Cox proportional hazards model also inclusive of age, sex, BCLC staging, Child-Pugh score, meeting Milan criteria, liver transplantation listing, non-Asian ethnicity was an independent predictor for lower overall survival (HR=0.70 [0.52-0.86]). CONCLUSIONS: Despite being older and having a lower rate of liver transplantation listing, Asian HCV/HCC patients had higher median survival compared to non-Asian patients, particularly among those undergoing palliative therapy. Non-Asians were more likely to have decompensated liver disease and non-Asian ethnicity was an independent predictor for poorer long-term survival. Compared to non-Asians, Asians with HCV-related HCCwere also muchmore likely to have delayed HCV diagnosis. Improved strategies in HCV screening in Asians are needed as it may lead to earlier diagnosis and treatment of HCV infection and possible prevention of HCC development in this ethnic population with a disproportionate HCC disease burden.