Donna L. White

The changing pattern of epidemiology in hepatocellular carcinoma

Primary liver cancer (PLC) represents approximately 4% of all new cancer cases diagnosed worldwide. The purpose of this review is to describe some of the latest international patterns in PLC incidence and mortality, as well as to give an overview of the main etiological factors. We used two databases, GLOBOCAN 2002 and the World Health Organization (WHO) mortality database to analyze the incidence and mortality rates for PLC in several regions around the world. The highest age adjusted incidence rates (>20 per 100,000) were reported from countries in Southeast Asia and sub-Saharan Africa that are endemic for HBV infection. Countries in Southern Europe have medium-high incidence rates, while low-incidence areas (<5 per 100,000) include South and Central America, and the rest of Europe. Cirrhosis is present in about 80-90% of HCC patients and is thereby the largest single risk factor. Main risk factors include HBV, HCV, aflatoxin and possibly obesity and diabetes. Together HBV and HCV account for 80-90% of all HCC worldwide. HBV continues to be the major HCC risk factor worldwide, although its importance will most likely decrease during the coming decades due to the widespread use of the HBV vaccine in the newborns. HCV has been the dominant viral cause in HCC in North America, some Western countries and Japan. Obesity and diabetes are increasing at a fast pace throughout the world, and if they are proven to be HCC risk factors, they would account for more HCC cases in the future.

Association between nonalcoholic fatty liver disease and risk for hepatocellular cancer, based on systematic review.

BACKGROUND & AIMS Nonalcoholic fatty liver disease (NAFLD) has been implicated as a cause of hepatocellular carcinoma (HCC). We performed a systematic review of epidemiology studies to confirm the association between these disorders. METHODS We searched PubMed for original reports published from January 1992 to December 2011 that evaluated the association between NAFLD, nonalcoholic steatohepatitis (NASH), cryptogenic cirrhosis presumed to be NASH-related, and the risk of HCC. Studies were categorized as offering potential direct evidence (eg, cohort studies) or indirect evidence (eg, case-control, cross-sectional, or case-series studies) for an association. We analyzed data from a total of 17 cohort studies (3 population based, 9 clinic based [6 limited to patients with cirrhosis], and 5 natural history), 18 case-control and cross-sectional studies, and 26 case series. RESULTS NAFLD or NASH cohorts with few or no cases of cirrhosis cases had a minimal risk for HCC (cumulative HCC mortality of 0%-3% for study periods up to 20 y). Cohorts with NASH and cirrhosis had a consistently higher risk (cumulative incidence ranging from 2.4% over 7 y to 12.8% over 3 y). However, the risk for HCC was substantially lower in these cohorts than for cohorts with hepatitis C-related cirrhosis. Factors that increased risk among cohorts with NASH and cirrhosis could not be determined, because most studies were not sufficiently powered for multivariate analysis. CONCLUSIONS This systematic review shows that despite several limitations, there is epidemiologic evidence to support an association between NAFLD or NASH and an increased risk of HCC; risk seems to be limited to individuals with cirrhosis.

Hepatitis C infection and risk of diabetes: a systematic review and meta-analysis.

BACKGROUND/AIMS Several studies found hepatitis C (HCV) increases risk of Type II diabetes mellitus (DM). However, others found no or only sub-group specific excess risk. We performed meta-analyses to examine whether HCV infection does increase DM risk in comparison to the general population and in other sub-groups with increased liver disease rates including with hepatitis B (HBV). METHODS We followed standard guidelines for performance of meta-analyses. Two independent investigators identified eligible studies through structured keyword searches in relevant databases including PubMed. RESULTS We identified 34 eligible studies. Pooled estimators indicated significant DM risk in HCV-infected cases in comparison to non-infected controls in both retrospective (OR(adjusted)=1.68, 95% CI 1.15-2.20) and prospective studies (HR(adjusted)=1.67, 95% CI 1.28-2.06). Excess risk was also observed in comparison to HBV-infected controls (OR(adjusted)=1.80, 95% CI 1.20-1.40) with suggestive excess observed in HCV+/HIV+ cases in comparison to HIV+ controls (OR(unadjusted)=1.82, 95% CI 1.27-2.38). CONCLUSIONS Our finding of excess DM risk with HCV infection in comparison to non-infected controls is strengthened by consistency of results from both prospective and retrospective studies. The excess risk observed in comparison to HBV-infected controls suggests a potential direct viral role in promoting DM risk, but this needs to be further examined.

Experimental and Clinical Basis for the Use of Statins in Patients With Ischemic and Nonischemic Cardiomyopathy

Over the past 2 decades our understanding of the pathologic mechanisms that lead to heart failure (HF) has evolved from simplistic hemodynamic models to more complex models that have implicated neurohormonal activation and adverse cardiac remodeling as important mechanisms of disease progression. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have become a standard part of the armamentarium in the prevention and treatment of coronary artery disease. Apart from their lipid-lowering capabilities, statins seem to have non-lipid-lowering effects that impact neurohormonal activation and cardiac remodeling. This review will examine the potential benefits of statins in HF patients with ischemic and nonischemic cardiomyopathy as well as potential concerns regarding the use of statins in these patients.

Advanced Imaging Technologies Increase Detection of Dysplasia and Neoplasia in Patients With Barrett's Esophagus: A Meta-analysis and Systematic Review

BACKGROUND & AIMS US guidelines recommend surveillance of patients with Barretts esophagus (BE) to detect dysplasia. BE conventionally is monitored via white-light endoscopy (WLE) and a collection of random biopsy specimens. However, this approach does not definitively or consistently detect areas of dysplasia. Advanced imaging technologies can increase the detection of dysplasia and cancer. We investigated whether these imaging technologies can increase the diagnostic yield for the detection of neoplasia in patients with BE, compared with WLE and analysis of random biopsy specimens. METHODS We performed a systematic review, using Medline and Embase, to identify relevant peer-review studies. Fourteen studies were included in the final analysis, with a total of 843 patients. Our metameter (estimate) of interest was the paired-risk difference (RD), defined as the difference in yield of the detection of dysplasia or cancer using advanced imaging vs WLE. The estimated paired-RD and 95% confidence interval (CI) were obtained using random-effects models. Heterogeneity was assessed by means of the Q statistic and the I(2) statistic. An exploratory meta-regression was performed to look for associations between the metameter and potential confounders or modifiers. RESULTS Overall, advanced imaging techniques increased the diagnostic yield for detection of dysplasia or cancer by 34% (95% CI, 20%-56%; P < .0001). A subgroup analysis showed that virtual chromoendoscopy significantly increased the diagnostic yield (RD, 0.34; 95% CI, 0.14-0.56; P < .0001). The RD for chromoendoscopy was 0.35 (95% CI, 0.13-0.56; P = .0001). There was no significant difference between virtual chromoendoscopy and chromoendoscopy, based on Student t test analysis (P = .45). CONCLUSIONS Based on a meta-analysis, advanced imaging techniques such as chromoendoscopy or virtual chromoendoscopy significantly increase the diagnostic yield for identification of dysplasia or cancer in patients with BE.

Intimate Partner Aggression Perpetrated and Sustained by Male Afghanistan, Iraq, and Vietnam Veterans With and Without Posttraumatic Stress Disorder

Veterans with posttraumatic stress disorder (PTSD) consistently evidence higher rates of intimate partner aggression perpetration than veterans without PTSD, but most studies have examined rates of aggression among Vietnam veterans several years after their deployment. The primary aim of this study was to examine partner aggression among male Afghanistan or Iraq veterans who served during Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) and compare this aggression to that reported by Vietnam veterans with PTSD. Three groups were recruited, OEF/OIF veterans with PTSD (n = 27), OEF/OIF veterans without PTSD (n = 31), and Vietnam veterans with PTSD (n = 28). Though only a few comparisons reached significance, odds ratios suggested that male OEF/OIF veterans with PTSD were approximately 1.9 to 3.1 times more likely to perpetrate aggression toward their female partners and 1.6 to 6 times more likely to report experiencing female perpetrated aggression than the other two groups. Significant correlations among reports of violence perpetrated and sustained suggested many men may have been in mutually violent relationships. Taken together, these results suggest that partner aggression among Iraq and Afghanistan veterans with PTSD may be an important treatment consideration and target for prevention.

Irritable bowel syndrome and dyspepsia among women veterans: prevalence and association with psychological distress

Background  The burden of functional GI disorders and their associations with psychological distress in women veterans is unclear.

Higher Serum Testosterone is associated with Increased Risk of Advanced Hepatitis C-related Liver Disease in Males

Males have strikingly increased risk of advanced liver disease. However, the association between testosterone and risk of hepatitis C virus (HCV)‐related advanced liver disease is unknown. We performed a cross‐sectional study in male veterans with chronic HCV. Blood samples were obtained to measure total serum testosterone and perform the FibroSURE‐ActiTest. Other risk‐factor data were obtained through systematic questionnaires (e.g., alcohol), physical measurements (e.g., body mass index), and serological tests (e.g., viral load). The association between total testosterone and risk of advanced hepatic fibrosis (F3 and F3/F4) and inflammatory activity (A3 and A2/3) measured by the FibroSURE‐ActiTest was evaluated with logistic regression. A total of 308 eligible study participants were prospectively recruited (mean age: 57; 52% African‐American). There were 105 cases with advanced fibrosis and 203 mild fibrosis controls as well as 88 cases with advanced inflammatory activity and 220 mild activity controls. Mean total serum testosterone was significantly higher in advanced fibrosis cases as well as advanced inflammatory activity cases, compared to mild disease controls (6.0 versus 5.3 ng/mL and 5.9 versus 5.4 ng/mL, respectively). We observed a significant 25% increase in advanced fibrosis risk and 15% increase in advanced inflammatory activity risk for each 1‐ng/mL increase in total serum testosterone. Total testosterone in the upper tertile was associated with an even greater excess risk of advanced fibrosis than advanced inflammatory activity (odds ratio [OR]adjusted advanced fibrosis = 3.74; 95% CI: 1.86‐6.54 versus ORadjusted advanced inflammatory activity = 2.23; 95% CI: 1.07‐4.93, respectively). Conclusions: Total serum testosterone is associated with an increased risk of both advanced hepatic fibrosis and advanced hepatic inflammatory activity in HCV‐infected men. Testosterone may be important in the pathogenesis of HCV‐related advanced liver disease in males. (Hepatology 2011)

Trauma history and risk of the irritable bowel syndrome in women veterans

Aliment Pharmacol Ther 2010; 32: 551–561

Trends in the Burden of Nonalcoholic Fatty Liver Disease in a United States Cohort of Veterans.

BACKGROUND & AIMS Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in the United States. However, few data are available on recent trends in the incidence and prevalence of NAFLD in the U.S. METHODS We analyzed the national Veterans Administration databases from 2003 to 2011 and calculated the age-adjusted prevalence and incidence of NAFLD for the overall sample of patients and by demographic subgroups. We used a previously validated algorithm to define NAFLD, which was based on persistent increases in levels of liver enzymes in the absence of positive results from tests for hepatitis C or hepatitis B or evidence of excessive alcohol use. RESULTS Of the 9,784,541 patients with at least 1 visit to the Veterans Administration between 2003 and 2011, 1,330,600 patients (13.6%) had NAFLD. The annual incidence rates of NAFLD remained stable (from 2.2% to 3.2%) during the study duration. The prevalence of NAFLD increased from 6.3% in 2003 (95% confidence interval, 6.26%-6.3%) to 17.6% in 2011 (95% confidence interval, 17.58%-17.65%), a 2.8-fold increase. The incidence and prevalence increased at significantly greater rates in patients younger than 45 years vs older patients. CONCLUSIONS In a U.S. population, the annual incidence of NAFLD ranges from 2% to 3%. The prevalence of NAFLD more than doubled from 2003 through 2011; it is likely to continue to increase because of a steady overall incidence coupled with a rising incidence in younger individuals.