Jennifer R. Kramer

Increasing Prevalence of HCC and Cirrhosis in Patients With Chronic Hepatitis C Virus Infection

BACKGROUND & AIMS Patients with hepatitis C virus (HCV) infection are at risk for developing costly and morbid complications, although the actual prevalence of these complications is unknown. We examined time trends in the prevalence of cirrhosis and its related complications, such as hepatic decompensation and hepatocellular carcinoma (HCC). METHODS We calculated the annual prevalence of cirrhosis, decompensated cirrhosis, and HCC in a national sample of veterans diagnosed with HCV between 1996 and 2006. Patients with HCV who had at least one physician visit in a given calendar year were included in the analysis of prevalence for that year. We used direct standardization to adjust the prevalence of cirrhosis and related complications for increasing age of the cohort as well as sex and changes in clinical characteristics. RESULTS In this cohort, the number of individuals with HCV increased from 17,261 in 1996 to 106,242 in 2006. The prevalence of cirrhosis increased from 9% in 1996 to 18.5% in 2006. The prevalence of patients with decompensated cirrhosis doubled, from 5% in 1996 to 11% in 2006, whereas the prevalence of HCC increased approximately 20-fold (0.07% in 1996 to 1.3% in 2006). After adjustment, the time trend in the prevalence of cirrhosis (and its complications) was lower than the crude trend, although it still increased significantly. CONCLUSIONS The prevalence of cirrhosis and HCC in HCV-infected patients has increased significantly over the past 10 years. An aging cohort of patients with HCV could partly explain our findings. Clinicians and health care systems should develop strategies to provide timely and effective care to this high-risk population of patients.

Obesity increases oesophageal acid exposure

Background: Obesity has been associated with gastro-oesophageal reflux disease (GERD); however, the mechanism by which obesity may cause GERD is unclear. Aim: To examine the association between oesophageal acid exposure and total body or abdominal anthropometric measures. Methods: A cross-sectional study of consecutive patients undergoing 24 h pH-metry was conducted. Standardised measurements of body weight and height as well as waist and hip circumference were obtained. The association between several parameters of oesophageal acid exposures and anthropometric measures were examined in univariate and multivariate analyses. Results: 206 patients (63% women) with a mean age of 51.4 years who were not on acid-suppressing drugs were enrolled. A body mass index (BMI) of >30 kg/m2 (compared with BMI<25 kg/m2) was associated with a significant increase in acid reflux episodes, long reflux episodes (>5 min), time with pH<4, and a calculated summary score. These significant associations have affected total, postprandial, upright and supine pH measurements. Waist circumference was also associated with oesophageal acid exposure, but was not as significant or consistent as BMI. When adjusted for waist circumference by including it in the same model, the association between BMI>30 kg/m2 and measures of oesophageal acid exposure became attenuated for all, and not significant for some, thus indicating that waist circumference may mediate a large part of the effect of obesity on oesophageal acid exposure. Conclusions: Obesity increases the risk of GERD, at least partly, by increasing oesophageal acid exposure. Waist circumference partly explains the association between obesity and oesophageal acid exposure.

Utilization of Surveillance for Hepatocellular Carcinoma Among Hepatitis C Virus–Infected Veterans in the United States

BACKGROUND Surveillance for hepatocellular carcinoma (HCC) is recommended for patients with hepatitis C virus (HCV) infection and cirrhosis. However, whether surveillance is being done as recommended is unknown. OBJECTIVE To examine the prevalence and determinants of HCC surveillance among HCV-infected patients with cirrhosis in Veterans Affairs (VA) health care facilities in the United States. DESIGN Retrospective cohort study of HCV-infected patients using data obtained from the national VA Hepatitis C Clinical Case Registry. SETTING 128 VA medical centers. PATIENTS HCV-infected patients with cirrhosis diagnosed between fiscal years 1998 and 2005. MEASUREMENTS Abdominal ultrasonography and measurement of α-fetoprotein for HCC surveillance were identified from administrative data by using a previously validated algorithm. Patients were categorized as having routine (tests done during at least 2 consecutive years in the 4 years after cirrhosis diagnosis), inconsistent (at least 1 test, but not routine), or no surveillance in the 4 years after cirrhosis diagnosis. Predictors of surveillance were identified by using hierarchical random-effects regression. RESULTS 126 670 patients with HCV were identified; 13 002 (10.1%) had cirrhosis. Approximately 42.0% of patients with cirrhosis received 1 or more HCC surveillance tests within the first year after the cirrhosis index date; however, a decline in receipt of surveillance was observed in the following 2 to 4 years. Among patients with cirrhosis and at least 2 years of follow-up, routine surveillance occurred in 12.0%, inconsistent surveillance in 58.5%, and no surveillance in 29.5%. Lower medical and psychological comorbid conditions, presence of varices, and the absence of decompensated liver disease were associated with a higher likelihood of receiving routine surveillance. LIMITATIONS Hepatocellular carcinoma surveillance tests were indirectly identified from registry data. Physician recommendations could not be captured. CONCLUSION Few HCV-infected veterans with cirrhosis received routine HCC surveillance. New strategies are needed to improve the implementation of HCC surveillance in clinical practice. PRIMARY FUNDING SOURCE Houston Veterans Affairs Health Services Research and Development Center of Excellence and the National Cancer Institute.

Meta-analysis: Four-Drug, Three-Antibiotic, Non-bismuth-Containing “Concomitant Therapy” Versus Triple Therapy for Helicobacter pylori Eradication

Background: Low success rates with triple therapy for Helicobacter pylori infections have prompted search for alternatives. In one, a proton‐pump inhibitor (PPI) and amoxicillin was followed by the PPI plus clarithromycin and a nitroimidazole (sequential therapy); in another, these four drugs were given concomitantly (concomitant therapy).

Abdominal obesity and the risk of Barrett's esophagus.

BACKGROUND:The association between overweight/obesity and the risk of Barretts esophagus (BE) is unclear. Further, the association between body fat distribution and the risk of BE is unknown.METHODS:We conducted a retrospective case–control study in patients who underwent endoscopy at a single large VA Medical Center between 2000 and 2003. Cases were patients with documented BE who had an abdominal CT scan within 1 yr of the endoscopy, whereas controls were patients without BE (with or without erosive esophagitis) who also had an abdominal CT scan. The surface areas of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were calculated from CT scan images at level of intervertebral disc between L4 and L5, and body mass index (BMI) in kg/m2 at the time of endoscopy was also recorded. Cases and controls were compared in univariate and multivariable analyses.RESULTS:We identified 36 cases and 93 controls. There were no significant differences between cases and controls in age (mean 63 yr), gender (98% men), or race (71% white Caucasian). BMI was significantly greater in cases than controls (27 vs 24; p = 0.006). BMI >30 kg/m2 was associated with a greater risk of BE than lower BMI (odds ratio 4.0; 95% CI: 1.4–11.1, p = 0.008). VAT was approximately 1.5-fold greater in cases than controls (183 vs 115 cm2; p < 0.0001), whereas SAT was less different (248 vs 200 cm2; p = 0.03). We estimated that each 10-cm2 increase in VAT was associated with 9% increase in risk of BE. Interestingly, VAT remained independently associated with BE in the model that adjusted for BMI, and in that model, BMI was not significantly associated with BE.CONCLUSIONS:Obesity seems to be associated with an increased risk of BE. Abdominal visceral adiposity might mediate most of this risk.

The validity of viral hepatitis and chronic liver disease diagnoses in Veterans Affairs administrative databases

Background  The validity of International Classification of Diseases‐9 codes for liver disease has not been determined.

Risk of hepatocellular carcinoma after sustained virological response in Veterans with hepatitis C virus infection

The long‐term prognosis in terms of risk or predictors of developing hepatocellular carcinoma (HCC) among patients with sustained virological response (SVR) remains unclear. We conducted a retrospective cohort study using data from the Veterans Affairs VA hepatitis C virus (HCV) Clinical Case Registry in patients with positive HCV RNA between October 1999 and August 2009 and follow‐up through December 2010. HCV treatment (interferon with or without ribavirin) and SVR (RNA test negative at least 12 weeks after the end of treatment) were determined. We used Coxs proportional hazards models to calculate hazard ratios (HRs) for potential predictors (demographic, virological, and clinical) associated with HCC development post‐SVR. We identified 33,005 HCV‐infected individuals who received treatment, of whom 10,817 achieved SVR. Among these patients, 100 developed new HCC during a total follow‐up of 30,562 person‐years for an overall incidence rate of 0.33% per year. Annual risk of HCC remained considerably high among patients with cirrhosis (1.39%) and those cured after age 64 (0.95%). Patients with diabetes (adjusted HR = 1.88; 1.21‐2.91) or genotype 3 infection (adjusted HR = 1.62; 0.96‐2.734) were significantly more likely to develop HCC. Conclusions: Risk of HCC after HCV cure, though considerably reduced, remains relatively high at 0.33% per year. Older age and/or presence of cirrhosis at the time of SVR are associated with a high enough risk to warrant surveillance. Diabetes is also a risk factor for post‐SVR HCC. (Hepatology 2016;64:130–137)

Risk of Hepatocellular Carcinoma after Sustained Virologic Response in Veterans with HCV‐infection

The long‐term prognosis in terms of risk or predictors of developing hepatocellular carcinoma (HCC) among patients with sustained virological response (SVR) remains unclear. We conducted a retrospective cohort study using data from the Veterans Affairs VA hepatitis C virus (HCV) Clinical Case Registry in patients with positive HCV RNA between October 1999 and August 2009 and follow‐up through December 2010. HCV treatment (interferon with or without ribavirin) and SVR (RNA test negative at least 12 weeks after the end of treatment) were determined. We used Coxs proportional hazards models to calculate hazard ratios (HRs) for potential predictors (demographic, virological, and clinical) associated with HCC development post‐SVR. We identified 33,005 HCV‐infected individuals who received treatment, of whom 10,817 achieved SVR. Among these patients, 100 developed new HCC during a total follow‐up of 30,562 person‐years for an overall incidence rate of 0.33% per year. Annual risk of HCC remained considerably high among patients with cirrhosis (1.39%) and those cured after age 64 (0.95%). Patients with diabetes (adjusted HR = 1.88; 1.21‐2.91) or genotype 3 infection (adjusted HR = 1.62; 0.96‐2.734) were significantly more likely to develop HCC. Conclusions: Risk of HCC after HCV cure, though considerably reduced, remains relatively high at 0.33% per year. Older age and/or presence of cirrhosis at the time of SVR are associated with a high enough risk to warrant surveillance. Diabetes is also a risk factor for post‐SVR HCC. (Hepatology 2016;64:130–137)

The effect of HIV coinfection on the risk of cirrhosis and hepatocellular carcinoma in U.S. veterans with hepatitis C.

OBJECTIVES:This study was conducted to determine whether HIV coinfection increases the risk of cirrhosis in HCV-infected patients in the HAART and pre-HAART eras. Further, the risk of hepatocellular carcinoma was also examined.METHODS:This retrospective cohort study was conducted among HCV-infected veterans who were seen at one of the 172 Veterans Health Administration hospitals between October 1, 1991 and September 30, 2000. Patients with prerecorded advanced liver disease were excluded. Incidence rates, cumulative incidence, and Cox proportional hazard ratios were calculated.RESULTS:There were 26,641 patients with HCV-only and 4,761 patients with HCV–HIV coinfection. The unadjusted incidence rate of cirrhosis was lower in patients with coinfection than HCV-only (p < 0.01). After controlling for demographics and confounders (including alcoholism and chronic hepatitis B), coinfection was not significantly associated with cirrhosis. However, there was an increased risk of cirrhosis in patients with coinfection compared to HCV-only during the pre-HAART era (before October 1, 1996) (hazard ratio = 1.48, 1.06–2.07, p= 0.02), but not among patients who entered the cohort during the HAART era. The unadjusted incidence rate of hepatocellular carcinoma in patients with coinfection and HCV-only was 1.3 and 2/1,000 person-years, respectively (p= 0.04). In the multivariate model, coinfection was not associated with hepatocellular carcinoma (hazard ratio = 0.84, p= 0.40).CONCLUSIONS:Coinfection was a significant risk factor for cirrhosis only during the pre-HAART era and was not associated with hepatocellular carcinoma, irrespective of time period.

Hepatocellular Carcinoma in the Absence of Cirrhosis in United States Veterans is Associated With Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS Hepatocellular carcinoma (HCC) can develop in individuals without cirrhosis. We investigated risk factors for development of HCC in the absence of cirrhosis in a U.S. METHODS We identified a national cohort of 1500 patients with verified HCC during 2005 to 2010 in the U.S. Veterans Administration (VA) and reviewed their full VA medical records for evidence of cirrhosis and risk factors for HCC. Patients without cirrhosis were assigned to categories of level 1 evidence for no cirrhosis (very high probability) or level 2 evidence for no cirrhosis (high probability), which were based on findings from histologic analyses, laboratory test results, markers of fibrosis from noninvasive tests, and imaging features. RESULTS A total of 43 of the 1500 patients with HCC (2.9%) had level 1 evidence for no cirrhosis, and 151 (10.1%) had level 2 evidence for no cirrhosis; the remaining 1203 patients (80.1%) had confirmed cirrhosis. Compared with patients with HCC in presence of cirrhosis, greater proportions of patients with HCC without evidence of cirrhosis had metabolic syndrome, nonalcoholic fatty liver disease (NAFLD), or no identifiable risk factors. Patients with HCC without evidence of cirrhosis were less likely to have abused alcohol or have hepatitis C virus infection than patients with cirrhosis. Patients with HCC and NAFLD (unadjusted odds ratio, 5.4; 95% confidence interval, 3.4-8.5) or metabolic syndrome (unadjusted odds ratio, 5.0; 95% confidence interval, 3.1-7.8) had more than 5-fold risk of having HCC in the absence of cirrhosis, compared with patients with HCV-related HCC. CONCLUSIONS Approximately 13% of patients with HCC in the VA system do not appear to have cirrhosis. NAFLD and metabolic syndrome are the main risk factors for HCC in the absence of cirrhosis.