Gia L. Tyson

Risk factors for cholangiocarcinoma

Cholangiocarcinoma (CC) is the second most common primary hepatic malignancy after hepatocellular cancer. CC accounts for approximately 10%‐25% of all hepatobiliary malignancies. There are considerable geographic and demographic variations in the incidence of CC. There are several established risk factors for CC, including parasitic infections, primary sclerosing cholangitis, biliary‐duct cysts, hepatolithiasis, and toxins. Other less‐established potential risk factors include inflammatory bowel disease, hepatitis C virus, hepatitis B virus, cirrhosis, diabetes, obesity, alcohol drinking, tobacco smoking, and host genetic polymorphisms. In studies where the distinction between intra‐ and extrahepatic CC was used, some potential risk factors seem to have a differential effect on CC, depending on the site. Therefore, the consistent use of a more refined classification would allow a better understanding of risk factors for CC. (HEPATOLOGY 2011;)

Prevalence and predictors of hepatitis B virus coinfection in a United States cohort of hepatitis C virus‐infected patients

There are sparse epidemiologic data on coinfection of hepatitis B (HBV) and hepatitis C (HCV) in the United States. Therefore, the aim of this study was to determine the prevalence and predictors of HBV coinfection in a large U.S. population of HCV patients. We used the National Veterans Affairs HCV Clinical Case Registry to identify patients tested for HCV during 1997‐2005. Patients were categorized based on HCV exposure (any two +HCV tests or one test with a diagnostic code), HCV infection (+RNA or genotype), HBV exposure (any +HBV test, excluding +HBsAb only), and HBV infection (+HBsAg, HBV DNA, or HBeAg). The prevalence of HBV exposure among patients with HCV exposure and that of HBV infection among patients with HCV infection were determined. Multivariate logistic regression evaluated potential demographic and clinical predictors of HBV coinfection. Among 168,239 patients with HCV exposure, 58,415 patients had HBV exposure for a prevalence of 34.7% (95% confidence interval [CI] 34.5‐35.0). Among 102,971 patients with HCV infection, 1,431 patients had HBV coinfection for a prevalence of 1.4% (95% CI 1.3‐1.5). Independent associations with HBV coinfection compared with HCV monoinfection were age ≤50 years, male sex, positive HIV status, history of hemophilia, sickle cell anemia or thalassemia, history of blood transfusion, cocaine and other drug use; there was decreased risk in patients of Hispanic ethnicity. Conclusion: This is the largest cohort study in the U.S. on the prevalence of HBV coinfection in HCV patients. Among veterans with HCV, exposure to HBV is common (∼35%), but HBV coinfection is relatively low (1.4%). Several possible risk factors were identified. (Hepatology 2013;58:538–545)

Referral and receipt of treatment for hepatocellular carcinoma in United States veterans: effect of patient and nonpatient factors.

The delivery of treatment for hepatocellular carcinoma (HCC) could be influenced by the place of HCC diagnosis (hospitalization versus outpatient), subspecialty referral following diagnosis, as well as physician and facility factors. We conducted a study to examine the effect of patient and nonpatient factors on the place of HCC diagnosis, referral, and treatment in Veterans Administration (VA) hospitals in the United States. Using the VA Hepatitis C Clinical Case Registry, we identified hepatitis C virus (HCV)‐infected patients who developed HCC during 1998‐2006. All cases were verified and staged according to Barcelona Clinic Liver Cancer (BCLC) criteria. The main outcomes were place of HCC diagnosis, being seen by a surgeon or oncologist, and treatment. We examined factors related to these outcomes using hierarchical logistic regression. These factors included HCC stage, HCC surveillance, physician specialty, and facility factors, in addition to risk factors, comorbidity, and liver disease indicators. Approximately 37.2% of the 1,296 patients with HCC were diagnosed during hospitalization, 31.0% were seen by a surgeon or oncologist, and 34.3% received treatment. Being seen by a surgeon or oncologist was associated with surveillance (adjusted odds ratio [aOR] = 1.47; 95% CI: 1.20‐1.80) and varied by geography (1.74;1.09‐2.77). Seeing a surgeon or oncologist was predictive of treatment (aOR = 1.43; 95% CI: 1.24‐1.66). There was a significant increase in treatment among patients who received surveillance (aOR = 1.37; 95% CI: 1.02‐1.71), were seen by gastroenterology (1.65;1.21‐2.24), or were diagnosed at a transplant facility (1.48;1.15‐1.90). Conclusion: Approximately 40% of patients were diagnosed during hospitalization. Most patients were not seen by a surgeon or oncologist for treatment evaluation and only 34% received treatment. Only receipt of HCC surveillance was associated with increased likelihood of outpatient diagnosis, being seen by a surgeon or oncologist, and treatment. (HEPATOLOGY 2013;)

Level of α-Fetoprotein Predicts Mortality Among Patients With Hepatitis C–Related Hepatocellular Carcinoma

BACKGROUND & AIMS Hepatocellular carcinoma (HCC) can result from hepatitis C virus (HCV)-related liver disease and is the fastest-growing cause of cancer-related death in the United States. α-fetoprotein (AFP) has been used as a prognostic factor for HCC, but the value of AFP as a prognostic factor for HCV-related HCC in the United States is unknown. We investigated whether higher levels of AFP at the time of diagnosis are associated with increased mortality of patients with HCV-related HCC. METHODS In a retrospective study, we collected data from a cohort of HCV-infected veterans, identifying incident HCC cases from October 1, 1998, to January 1, 2007 (n = 1480 patients). The mean serum levels of AFP, obtained within 60 days before to 30 days after HCC diagnosis, were determined for 1064 patients and categorized as less than 10 ng/mL (18%), 10 to less than 100 ng/mL (30%), 100 to less than 1000 ng/mL (22%), or 1000 ng/mL or more (29%). Cox proportional hazard models were used to associate serum levels of AFP with mortality, adjusting for demographic features, clinical factors, and treatment. RESULTS The median survival times were significantly lower among patients with higher levels of AFP: 709 days for patients with less than 10 ng/mL, 422 days for patients with 10 to less than 100 ng/mL, 208 days for patients with 100 to less than 1000 ng/mL, and 68 days for patients with 1000 ng/mL or more. In the multivariate analysis, increased levels of AFP (10 to <100, 100 to <1000, and ≥1000) were associated significantly with increased mortality, compared with a serum AFP level of less than 10; hazard ratios were 1.50, 2.23, and 4.35, respectively. CONCLUSIONS Serum AFP level at the time of diagnosis with HCV-related HCC is an independent predictor of mortality.

Dietary fructose intake and severity of liver disease in hepatitis C virus-infected patients.

Background and Goals: Dietary fructose intake in the United States has been increasing, and fructose intake has been associated with the metabolic syndrome and hepatic steatosis. This study aimed to determine whether dietary fructose intake is associated with advanced hepatic fibrosis and inflammation in an hepatitis C virus (HCV)-infected male population. Study: We conducted a cross-sectional study of HCV-infected male veterans. The main exposure variable was daily dietary fructose calculated from the National Cancer Institute Diet History Questionnaire and the main outcome variables were FibroSURE-ActiTest determined hepatic fibrosis (F0-F3=mild vs. F3/F4-F4=advanced) and inflammation (A0-A2=mild vs. A2/A3-A3=advanced). We examined this association in logistic regression adjusting for demographic, clinical, and other dietary variables. Results: Among 313 HCV+ males, 103 (33%) had advanced fibrosis and 89 (28%) had advanced inflammation. Median daily fructose intake was 46.8 g (interquartile range, 30.4 to 81.0). Dietary fructose intake across quartiles among males with advanced versus mild fibrosis was 21.4% versus 25.2%, 32.0% versus 24.8%, 24.3% versus 25.2%, and 22.3% versus 24.8%, respectively, and among males with advanced versus mild inflammation was 20.2% versus 25.5%, 41.6% versus 21.4%, 22.5% versus 25.9%, and 15.7% versus 27.2%, respectively. In multivariate analysis, there were no significant associations between daily fructose intake and advanced fibrosis. There was a significant association only between the second quartile of daily fructose intake (30 to 48 g) and advanced inflammation. Conclusions: There were no significant associations between dietary fructose intake and hepatic fibrosis risk, as assessed by FibroSURE, in HCV-infected males. Additional research is needed to clarify the potential role of fructose intake and HCV-related hepatic inflammation.

The Temporal Trends in Incidence of Intra and Extrahepatic Cholangiocarcinoma in the United States and the Impact of Klatskin Tumor Classification

Background and Aims: Previous studies of cholangiocarcinoma have reported an increasing incidence of intrahepatic (ICC) and a decreasing incidence of extrahepatic (ECC) in the United States. Hilar cholangiocarcinomas (Klatskin tumors) are anatomically defined as ECC and could have affected these trends. In version 1 of the International Classification of Diseases for Oncology (ICD-O) (1973-1991), Klatskin tumors were not assigned a unique ICD-O code and may have been coded as either ICC or ECC. In ICD-O version 2 (19922000), they were assigned a unique histology code (8162/3) which was cross-referenced to ICC. ICD-O version 3 (2000-present) cross-referenced Klatskin tumors to either ICC or ECC. Thus, Klatskin tumors may have been misclassified as ICC under all versions of ICDO. We conducted this study to determine 1) the secular trends of ICC and ECC from 19922007 and 2) the potential impact of misclassification bias on these trends. Methods: Using data from the Surveillance, Epidemiology and End Results (SEER) program, age-adjusted incidence rates of ICC and ECC were calculated in two consecutive time periods (19922000, 2001-2007). Following definitions were used: ICC: topography codes C22.0 (Liver) and C22.1 (Intra-hepatic bile duct) and histology codes 8140, 8160, 8161, 8020, and 8010. ECC: topography code C24.0; histology codes 8010, 8020, 8041, 8070, 8140, 8144, 8160, 8161, 8260, 8310, 8480, 8490, and 8560. Klatskin: histology code 8162/3. We calculated the annual percent change (APC) in incidence rates, utilizing a weighted least squares method. Results: We identified 4297 patients with ICC and 2679 patients with ECC during 1992-2007. The age adjusted rates (per 100,000) for ICC excluding Klatskin tumors (i.e., true ICC rate) decreased from 1.5 during 1992-2000 to 1.4 in 2001-2007 with an APC of -0.3% (95% C.I.: 1.5, 0.8), whereas true ECC rates, including Klatskin tumors significantly increased from 0.8 to 1.1 during the same time periods with an APC of 3.3% (95% C.I.: 2.0, 4.5). The increased incidence of ECC was more pronounced in males (APC 3.6%, 95% C.I.: 2.0, 5.1), Asians and pacific islanders (APC 4.5%) and in the 65+ age group (APC 3.9%). During 1992-2000, 208/224 (93%) cases of Klatskin tumors were misclassified as ICCs. This proportion dropped to 60/144 (42%) in 2001-2007. However, even with misclassification the incidence rate for ICC (including Klatskin tumors) declined from 1.6 to 1.4 per 100,000 during the two time periods with an APC of -0.9% (95% C.I -2.1, 0.3). Conclusions: Contrary to recent data, the incidence rates of ICC in the US have remained stable during the period 1992-2007, whereas ECC rates have risen. Improved classification of Klatskin tumors may explain some but not all of these trends.