Current epidemiology of hepatitis E virus infection in the United States: low seroprevalence in the National Health and Nutrition Evaluation Survey.

UNLABELLED: Analysis of the National Health and Nutrition Evaluation Survey (NHANES) 1988-1994 dataset found a relatively high seroprevalence (21%) of hepatitis E virus (HEV) infection in the U.S. general population. Using data obtained within the NHANES 2009-2010 survey, where a high performance assay for HEV was used, we estimated the weighted seroprevalence of HEV infection among U.S. individuals 6 years and older. We also evaluated factors associated with HEV seropositivity. A total of 8,814 individuals were included in the analysis. The median age of study participants was 37 years (interquartile range [IQR] 17-58 years), with 51.2% being female. The weighted national seroprevalence of HEV was 6% (95% confidence interval [CI] 5.1%-6.9%). About 0.5% of those with HEV had evidence of recent exposure (immunoglobulin M-positive). In the univariate analyses, factors associated with HEV seropositivity were increasing age (P-trend<0.001), birth outside of the U.S., Hispanic race, and "meat" consumption (>10 times/month). No significant association was observed with low socioeconomic status, water source, or level of education. In the multivariate analysis, only older age remained predictive of HEV seropositivity. CONCLUSION: The weighted national seroprevalence of HEV in the U.S. is much less than previously reported. Using data obtained with a high performance assay, the seroprevalence of HEV was estimated at 6.0% in the U.S. Based on these results, the seroprevalence of HEV is only one-third as high as previously reported.

Meta-analysis: superior treatment response in Asian patients with hepatitis C virus genotype 6 versus genotype 1 with pegylated interferon and ribavirin.

OBJECTIVE: Our goal was to systematically and quantitatively assess treatment response between Asian patients with hepatitis C virus genotype 6 (HCV-6) and hepatitis C virus genotype 1 (HCV-1) treated for 48 weeks with pegylated interferon and ribavirin. METHODS: We performed a literature search in MEDLINE and EMBASE for 'genotype 6' in August 2013. Additional abstracts from major international scientific conferences from 2012 to 2013 were reviewed. Studies included were original articles with ≥10 treatment-naïve Asian HCV-6 patients. Exclusion criteria were coinfections with hepatitis B virus, HIV and/or other liver diseases. Heterogeneity was defined as a Cochrane Q test with a p value of 0.10 and an I(2) statistic of >50%. RESULTS of a random-effects model are reported. RESULTS: A total of 1,046 (503 HCV-6; 543 HCV-1) patients from 12 studies were included in the analysis. The pooled sustained virologic response (SVR) rate was 80.2% (95% CI 74.3-85.0, Q statistic = 20.87, p < 0.035; I(2) = 47.3%) for HCV-6 and 62.5% (95% CI 41.9-79.4, Q statistic = 52.41, p < 0.001; I(2) = 92.37) for HCV-1 patients. HCV-6 patients had a significantly higher SVR rate compared to HCV-1 patients (odds ratio 2.73, 95% CI 1.69-4.41, p < 0.001). Approximately one fourth of patients without early virologic response (EVR) achieved SVR, regardless of genotype (HCV-1, n = 6/23; HCV-6, n = 4/21). CONCLUSIONS: Asian patients with HCV-6 can expect higher SVR rates (∼80%) than HCV-1 patients (∼63%). EVR as a stopping rule is less clear in Asian patients with HCV-6 and HCV-1.

Approximately one-half of patients with early-stage hepatocellular carcinoma meeting Milan criteria did not receive local tumor destructive or curative surgery in the post-MELD exception era.

BACKGROUND: Since 2002, priority Model for End-stage Liver Disease (MELD) exception status has been given to patients with hepatocellular carcinoma (HCC) who meet the Milan criteria. Since then, the number of liver transplantations performed in patients with HCC has increased, but to the authors' knowledge, few studies to date have examined the effect of MELD exception recommendations on therapy use and survival rates in a nationwide sample. The current study examines therapy use and long-term survival rates among patients with HCC tumors meeting the Milan criteria in the post-MELD exception era. METHODS: The current study is a retrospective cohort study of 2179 patients with localized HCC meeting the Milan criteria who were registered between 2004 and 2007 in the Surveillance, Epidemiology, and End Results database. RESULTS: A total of 43% of patients did not receive any specific therapy. Overall, the 5-year relative survival rate for patients receiving only supportive care was dismal at 24% (95% confidence interval [95% CI], 21%-27%), whereas that for patients undergoing liver transplantation was 77% (95% CI, 71%-82%). Long-term survival was found to be dependent on age, race/ethnicity, and type of therapy received. A multivariate Cox proportional hazards model adjusted for age, race/ethnicity, and type of therapy received demonstrated that, compared with white patients, black patients had significantly poorer survival outcomes (hazards ratio, 1.23; 95% CI, 1.03-1.47 [P = .02]), whereas Asian/Pacific Islander patients had significantly better survival rates when compared with white patients (HR, 0.66; 95% CI, 0.57-0.77 [P < .001]). CONCLUSIONS: Despite having localized disease that met transplantation criteria, nearly 50% of the large nationwide cohort of patients with HCC in the current study received only supportive care and had dismal 5-year relative survival rates, especially among black patients.

The changing epidemiology of hepatitis C virus infection in the United States: National Health and Nutrition Examination Survey 2001 through 2010.

BACKGROUND & AIMS: In light of the dramatically changing hepatitis C therapeutic landscape, knowledge of the current burden of HCV infection in the general population of the United States is critical. METHODS: The National Health and Nutrition Examination survey collects nationally representative data on HCV infection in the civilian population of the United States. Data from 2001 to 2010 were combined for this study. HCV testing was completed in 38,025 participants. RESULTS: The prevalence of anti-HCV in the United Sates decreased from 1.9% (95% CI 1.5%-2.5%) in 2001-2002 to 1.3% (95% CI 0.9%-1.8%) in 2005-2006, and remained stable up to 2010. About 67% of all infected persons were positive for HCV RNA, indicating 2.3 million people with chronic HCV infection, of whom 68% have genotype 1. Seventy percent of infected persons were born between 1945 and 1965, with prevalence of 3.5% (95% CI 2.2%-4.8%). The stable rate since 2006 is mostly related to prevalent cases and foreign born persons migrating into US. Other important risk factors include less education and low economic status. Race, HIV status, number of sexual partners, and blood transfusions are no longer associated with HCV infection. CONCLUSIONS: As of 2010, approximately 2.3 million persons were chronically infected with Hepatitis C in the US. Most of those infected are prevalent, rather than incident cases. The prevalence of HCV was on the decline, but has stabilized since 2006. Future studies should explore reasons for no decline in HCV prevalence since 2006.

Increased long-term survival among patients with hepatocellular carcinoma after implementation of Model for End-stage Liver Disease score.

BACKGROUND & AIMS: Assignment of Model for End-stage Liver Disease (MELD) exception points to patients with hepatocellular carcinoma (HCC) who fall within Milan criteria, which began in 2003, increases their priority on liver transplantation waitlists. However, little is known about how this change affected survival of all patients with HCC (transplant eligible and ineligible). We compared long-term survival of HCC patients before and after this change. METHODS: We performed a large population-based cohort study by using the Surveillance, Epidemiology, and End Results cancer registry to investigate survival times of patients with HCC before those who met the Milan criteria were given MELD exception points (1998-2003) and afterward (2004-2010) by using Kaplan-Meier methods. Multivariate Cox proportional hazards models evaluated independent predictors of survival. RESULTS: During 2004-2010, a significantly higher percentage of patients with HCC survived for 5 years compared with 1998-2003 (21.9% vs 13.0%, P < .001). This difference remained significant among all treatment groups (no therapy: 15.2% vs 10.2%, P < .001; local tumor destruction: 37.6% vs 22.1%, P < .001; resection: 55.5% vs 39.2%, P < .001; transplantation: 77.2% vs 73.1%, P = .12). Multivariate Cox proportional hazards models, inclusive of sex, age, ethnicity, Milan criteria, number and stage of tumor, and time period, showed increased survival of patients during 2004-2010 (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.83-0.91; P < .001). Compared with non-Hispanic whites, Asians (HR, 0.81; 95% CI, 0.77-0.86; P < .001) and Hispanics (HR, 0.89; 95% CI, 0.84-0.95; P < .001) had longer survival times, whereas blacks had a trend toward shorter survival times (HR, 1.05; 95% CI, 0.98-1.13; P = .16). CONCLUSIONS: Patients with HCC who met Milan criteria had significantly longer survival times after implementation of the MELD exception points, regardless of sex or ethnicity. Blacks continued to have the lowest rates of 5-year survival.

Prevalence, trends, and risk factors for fecal incontinence in United States adults, 2005-2010.

BACKGROUND & AIMS: We investigated the prevalence of and trends and risk factors for fecal incontinence (FI) in the United States among non-institutionalized adults from 2005 to 2010. METHODS: We analyzed data from 14,759 participants in the U.S. National Health and Nutrition Examination Survey (49% women, 20 years or older) from 2005 to 2010 (the FI Severity Index was added in 2005-2006). FI was defined as accidental leakage of solid or liquid stool or mucus at least once in preceding month. Sampling weights were used to obtain estimates for the national population. Logistic regression was used to identify risk factors for FI. RESULTS: The prevalence of FI among non-institutionalized U.S. adults was 8.39% (95% confidence interval, 7.76-9.05). It was stable throughout the study period: 8.26% in 2005-2006, 8.48% in 2007-2008, and 8.41% in 2009-2010. FI resulted in release of liquid stool in most cases (6.16%). Prevalence increased with age from 2.91% among 20- to 29-year-old participants to 16.16% (14.15%-18.39%) among participants 70 years and older. Independent risk factors for FI included older age, diabetes mellitus, urinary incontinence, frequent and loose stools, and multiple chronic illnesses. FI was more common among women only when they had urinary incontinence. CONCLUSIONS: FI is a common problem among non-institutionalized U.S. adults. Its prevalence remained stable from 2005-2010. Diabetes mellitus and chronic diarrhea are modifiable risk factors. Future studies on risk factors for FI should assess for presence of urinary incontinence.

Ethnic disparities and liver transplantation rates in hepatocellular carcinoma patients in the recent era: results from the Surveillance, Epidemiology, and End Results registry.

Hepatocellular carcinoma (HCC) is a leading cause of morbidity and mortality. After the implementation of the Model for End-Stage Liver Disease system, rates of liver transplantation (LT) for HCC patients increased. However, it is not clear whether this trend has continued into recent times. Using the Surveillance, Epidemiology, and End Results registry (1998-2010), we retrospectively analyzed trends for LT among HCC patients in 3 time periods: 1998-2003, 2004-2008, and 2009-2010. A total of 60,772 HCC patients were identified. In the more recent time periods, the proportion of localized-stage HCC increased (45.0% in 1998-2003, 50.4% in 2004-2008, and 51.7% in 2009-2010; P < 0.001). Although the proportion of HCC patients within the Milan criteria also increased with time (22.8% in 1998-2003, 31.8% in 2004-2008, and 37.1% in 2009-2010; P < 0.001), the proportion of those patients undergoing LT increased from 1998-2003 to 2004-2008 but decreased from 2004-2008 to 2009-2010. However, the actual frequencies of LT were similar in 2004-2008 (208.2 per year) and 2009-2010 (201.5 per year). A multivariate logistic regression, including sex, age, ethnicity, Milan criteria, tumor stage, tumor size and number, and time periods, demonstrated a lower likelihood of LT in 2009-2010 versus 1998-2003 [odds ratio (OR) = 0.63, 95% confidence interval (CI) = 0.57-0.71]. Blacks (OR = 0.48, 95% CI = 0.41-0.56), Asians (OR = 0.65, 95% CI = 0.57-0.73), and Hispanics (OR = 0.76, 95% CI = 0.68-0.85) were all less likely to undergo LT in comparison with non-Hispanic whites. Despite the increasing proportion of patients with HCC diagnosed at an earlier stage, LT rates declined in the most recent era. In addition, ethnic minorities were significantly less likely to undergo LT. The growing imbalance between the number of transplant-eligible HCC patients and the shortage of donor livers emphasizes the need to improve donor availability and curative alternatives to LT.

Prevalence of non-alcoholic fatty liver disease and risk factors for advanced fibrosis and mortality in the United States.

In the United States, non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and associated with higher mortality according to data from earlier National Health and Nutrition Examination Survey (NHANES) 1988-1994. Our goal was to determine the NAFLD prevalence in the recent 1999-2012 NHANES, risk factors for advanced fibrosis (stage 3-4) and mortality. NAFLD was defined as having a United States Fatty Liver Index (USFLI) > 30 in the absence of heavy alcohol use and other known liver diseases. The probability of low/high risk of having advanced fibrosis was determined by the NAFLD Fibrosis Score (NFS). In total, 6000 persons were included; of which, 30.0% had NAFLD and 10.3% of these had advanced fibrosis. Five and eight-year overall mortality in NAFLD subjects with advanced fibrosis was significantly higher than subjects without NAFLD ((18% and 35% vs. 2.6% and 5.5%, respectively) but not NAFLD subjects without advanced fibrosis (1.1% and 2.8%, respectively). NAFLD with advanced fibrosis (but not those without) is an independent predictor for mortality on multivariate analysis (HR = 3.13, 95% CI 1.93-5.08, p<0.001). In conclusion, in this most recent NHANES, NAFLD prevalence remains at 30% with 10.3% of these having advanced fibrosis. NAFLD per se was not a risk factor for increased mortality, but NAFLD with advanced fibrosis was. Mexican American ethnicity was a significant risk factor for NAFLD but not for advanced fibrosis or increased mortality.

Sustained virologic response to standard interferon or pegylated interferon and ribavirin in patients with hepatitis C virus genotype 5: systematic review and meta-analysis of ten studies and 423 patients.

BACKGROUND: Interferon (IFN)-free therapy has vastly improved therapeutic options for those with hepatitis C virus infection (HCV). However, the lack of data and the expense limit its use for lesser known genotypes such as HCV-5, especially in countries with financial limitations. Previous reports estimate sustained virologic response (SVR) rates in HCV-5 to be ~40-70%. AIM: Our goal was to estimate pooled SVR rates for HCV-5 treatment-naïve patients treated with IFN or peginterferon (PEG IFN) and ribavirin (RBV) combination therapy for 48 weeks. METHODS: We conducted a literature search to identify articles with HCV-5 patients treated with IFN/PEG IFN + RBV. Pooled SVR rates were reported by random effects modeling with 95% confidence intervals. Heterogeneity was defined by the Cochrane Q-statistic p ≤ 0.05 and I(2) statistic ≥50%. RESULTS: A total of 423 patients from ten studies were included in the analysis. The pooled SVR rate for HCV-5 patients treated with IFN/PEG IFN + RBV for 48 weeks was 58.0% (CI 53.1%-62.7%). There was no evidence of heterogeneity (I(2) = 0, p = 0.61) or publication bias (Egger's test = 0.26). Pooled analysis of HCV-5 patients treated with PEG IFN + RBV was 55.0% (CI 49.4-61.5%). There was no evidence of heterogeneity (I(2) = 0.00, p = 0.75) or publication bias (Egger's test = 0.71). Combination therapy with IFN/PEG IFN + RBV had a pooled EVR of 90.2% (CI 76.8-96.2%). CONCLUSIONS: SVR for HCV-5 treated with combination therapy (IFN/PEG-IFN + RBV for 48 weeks) was approximately 60%. Current data are insufficient to evaluate variable duration of treatment (24 vs. 48 weeks), presence or absence of cirrhosis, effects of high versus low viral loads, or degree of fibrosis. The optimal treatment duration for HCV-5 patients with IFN-based combination remains to be established. Data and drug access are needed for treatment for HCV-5 in more resource-limited areas.

Meta-analysis of patients with hepatitis C virus genotype 6: 48 weeks with pegylated interferon and ribavirin is superior to 24 weeks.

BACKGROUND: Hepatitis C virus genotype 6 (HCV-6) is common in patients from Southeast Asia and the surrounding regions. Optimal treatment duration for HCV-6 is unknown given the inconclusive evidence from studies with varying methodologies and small sample sizes. METHODS: A literature search for 'genotype 6' in MEDLINE and EMBASE in October 2013 produced 161 and 251 articles, respectively. Additional abstracts were identified from four major international GI/liver conferences in 2012/2013. Inclusion criteria were original studies with ≥10 HCV-6 treatment-naïve patients treated with pegylated interferon + ribavirin (PEG IFN+RBV). Exclusion criteria were coinfections with HBV, HIV, other HCV genotypes, and/or other liver diseases. Primary outcome was pooled sustained virologic response (SVR). Heterogeneity was defined by Cochrane Q test (p value of 0.10) and I (2) statistic (≥50 %). RESULTS: A total of 13 studies with 641 patients were included. The pooled SVR estimate was 77 % (CI 70-83 %) (Q value = 38.4, p value <0.001, I (2) = 68.7 %) overall, 79 % (CI 73-84 %) for the 48-week group and 59 % (CI 46-70 %) for 24-week group, respectively. In studies with direct comparison of the two groups, SVR was superior in patients treated for 48 versus 24 weeks, OR 1.9 (CI 1.08-3.2, p = 0.026). In studies with direct comparison of patients with rapid virologic response (RVR), there was no difference in SVR between 48 versus 24 weeks, OR 1.74 (CI 0.65-4.64, p = 0.27). CONCLUSION: Hepatitis C virus genotype 6 patients should be treated for 48 weeks, and those who achieve RVR may receive the shorter 24-week treatment duration. The high SVR (~80 %) with 48 weeks of PEG IFN+RBV therapy may be a cost-effective option for HCV-6 patients from resource-poor regions.