Hepatocellular carcinoma in patients with non-alcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States and represents an increasingly important etiology of hepatocellular carcinoma (HCC) with annual cumulative incidence rates ranging from 2% to 12% in cohorts of NAFLD cirrhosis. While the risk of progression of NAFLD to HCC remains higher among patients with fibrosis or cirrhosis, an increasing amount of literature describes NAFLD-HCC as a disease that can occur in the absence of cirrhosis. Efforts to characterize the pathogenesis of NAFLD-HCC have suggested mechanisms that strongly associate with states of hyperinsulinemia and chronic inflammation, cellular mechanisms including adaptive immune responses and hepatic progenitor cell populations, and genetic polymorphisms including mutations of PNPLA3. Current literature describes NAFLD-HCC mostly as a disease of late presentation with lower rates of receipt of curative therapy and worse prognosis. However, a growing body of evidence has reported comparable and potentially more favorable disease-free and overall survival rates among patients with NAFLD-HCC after receipt of curative treatment. This review summarizes current evidence of epidemiology, pathophysiology, disease presentation, demand and receipt of curative therapy, post-treatment outcomes, and overall survival of NAFLD-associated HCC.

Poor adherence and low persistency rates for hepatocellular carcinoma surveillance in patients with chronic hepatitis B.

Our goal was to examine rates and predictors for hepatocellular carcinoma (HCC) surveillance adherence and persistency, since studies of such adherence and persistency in patients with chronic hepatitis (CHB) are currently limited.Consecutive CHB patients (N = 1329) monitored for ≥1 year at 4 US clinics from January 1996 to July 2013 were retrospectively studied. Surveillance adherence was evaluated based on the American Association for the Study of Liver Diseases guidelines. Kaplan-Meier method was used to analyze surveillance persistency of 510 patients who had initially fair adherence (having at least annual surveillance imaging with further follow-up).Mean age was 48, with the majority being male (58%), Asian (92%), foreign-born (95%), and medically insured (97%). Patients with cirrhosis and those seen at university liver clinics were more likely to have optimal HCC surveillance than those without cirrhosis and those seen at community clinics (38.4% vs 21.6%, P <0.001 and 33.5% vs 14.4%, P < 0.001, respectively). HCC diagnosed in optimally adherent patients trended toward smaller tumor size (P < 0.08). On multivariate analysis also inclusive of age, sex, clinical visits, cirrhosis, clinic setting and antiviral therapy use, strong independent predictors for having at least annual imaging were a history of more frequent clinical visits (odds ratio [OR] = 2.5, P < 0.001) and university-based care (OR = 5.2, P < 0.001). Even for those with initially fair adherence, persistency dropped to 70% at 5 years.Adherence and persistency to HCC surveillance in CHB patients is generally poor. More frequent clinic visits and university-based settings were significant and strong predictors of at least annual HCC surveillance adherence.

Sustained virological response and its treatment predictors in hepatitis C virus genotype 4 compared to genotypes 1, 2, and 3: a meta-analysis.

BACKGROUND: Pegylated interferon and ribavirin (PEG-IFN+RBV) may be more cost-effective than direct-acting antivirals in resource-limited settings. Current literature suggests sustained virological response (SVR) in hepatitis C virus genotype 4 (HCV-4) is similar to genotype 1 (HCV-1), but worse than 2 and 3 (HCV-2/3). However, few studies have compared treatment response between these groups and these have been limited by small sample sizes with heterogeneous designs. We performed a meta-analysis of SVR predictors in HCV-4 versus HCV-1, 2, and 3 patients treated with PEG-IFN+RBV. METHODS: In November 2013, we searched for 'genotype 4' in MEDLINE/EMBASE databases and scientific conferences. We included original articles with ≥25 treatment-naïve HCV-4 and comparisons to HCV-1, 2, and/or 3 patients treated with PEG-IFN+RBV. Random effects modelling was used with heterogeneity defined by Cochrane Q-test (p value<0.10) and I(2) statistic (>50%). RESULTS: Five studies with 20 014 patients (899 HCV-4; 12 033 HCV-1; and 7082 HCV-2/3 patients) were included. SVR was 53% (CI 43% to 62%) for HCV-4, 44% (CI 40% to 47%) for HCV-1; and 73% (CI 58% to 84%) for HCV-2/3. SVR with EVR (early virological response) was 75% (CI 61% to 86%) in HCV-4; 64% (CI 46% to 79%) in HCV-1; and 85% (CI 71% to 93%) in HCV-2/3. SVR without EVR was 10% (CI 6% to 17%) for HCV-4; 13% (CI 12% to 15%) for HCV-1; and 23% (CI 16% to 33%) for HCV-2/3. CONCLUSIONS: SVR rates are similar in HCV-4 (∼50%) and HCV-1 (∼40%). Lack of EVR is a good stopping rule for HCV-4 and HCV-1 since only 10% subsequently achieve SVR. In HCV-4 patients with EVR, three-quarters can expect to achieve SVR with PEG-IFN+RBV.

Meta-analysis: influence of host and viral factors in patients with chronic hepatitis C genotype 4 treated with pegylated interferon and ribavirin.

The burden of hepatitis C virus genotype 4 (HCV-4) is high in Africa and East Mediterranean countries. Previous reports estimate sustained virologic response (SVR) rates in HCV-4 to be ∼20-70%. However, many of these studies are limited by different study designs and small sample sizes. Our aim was to evaluate treatment outcome and host/viral factors on SVR in HCV-4 patients treated with pegylated interferon and ribavirin (PEG IFN+RBV) in a systematic and quantitative manner. A comprehensive literature search in MEDLINE and EMBASE for 'genotype 4' was conducted in November 2013. Abstracts from American Association for the Study of Liver Diseases, Asian Pacific Study of the Liver, Digestive Disease Week, and European Association for the Study of the Liver in 2012/2013 were reviewed. Inclusion criteria were original studies with at least 25 treatment-naive HCV-4 patients treated with PEG IFN+RBV. Exclusion criteria were coinfection with HIV, hepatitis B virus, or other genotypes. Effect sizes were calculated using random-effects models. Heterogeneity was determined by Cochrane Q-test (P<0.05) and I statistic (>50%). We included 51 studies (11 102 HCV-4 patients) in the primary analysis. Pooled SVR was 53% [95% confidence interval (CI): 50-55%] (Q-statistic=269.20, P<0.05; I=81.43). On subgroup analyses, SVR was significantly associated with lower viral load, odds ratio (OR) 3.05 (CI: 1.80-5.17, P<0.001); mild fibrosis, OR 3.17 (CI: 2.19-4.59, P<0.001); and favorable IL28B polymorphisms, rs12979860 CC versus CT/TT, OR 4.70 (CI: 2.87-7.69, P<0.001), and rs8099917 TT versus GT/GG, OR 5.21 (CI: 2.31-11.73, P<0.001). HCV-4 patients treated with PEG IFN+RBV may expect SVR rates of ∼50%. Lower viral load, mild fibrosis, and favorable IL28B (rs12979860 CC and rs8099917 TT) are positively associated with SVR.

Hepatocellular carcinoma incidence in noncirrhotic patients with chronic hepatitis B and patients with cirrhosis of all etiologies.

BACKGROUND: Hepatocellular carcinoma (HCC) causes approximately a half million deaths annually with the majority related to chronic hepatitis B (CHB) and cirrhosis. Results on HCC incidence in CHB patients without cirrhosis are conflicting. GOALS: This study aimed to examine HCC incidence in 2 high-risk groups: (1) patients with noncirrhotic CHB and 45 years of age or older; and (2) patients with cirrhosis of all etiologies and any age. RESULTS: Through electronic query using ICD-9 diagnosis codes for CHB and cirrhosis (070.32 and 571.5, respectively) between January 2001 and January 2008, a total of 949 patients with 12 months of follow-up or longer were identified and reviewed. Over 4231.5 person-years of observation, HCC developed in 15 of the 741 noncirrhotic CHB patients and 30 of the 208 cirrhotic patients. Male and female noncirrhotic CHB patients had significantly lower annual HCC incidences than those found in male and female patients with cirrhosis regardless of etiologies (0.7% vs. 4.1%, P<0.0001 and 0.1% vs. 2.7%, P<0.0001). Annual HCC incidence increased significantly with age in both sexes of noncirrhotic CHB patients. In noncirrhotic CHB patients, annual HCC incidence was very low in young females, but increased to 0.3% to 0.4% in females 55 years of age or older. An HCC incidence rate of 1.1% per year was seen in noncirrhotic CHB men aged 55 or older. CONCLUSIONS: Although annual HCC incidence in cirrhotic patients did not differ significantly among different age groups, rates among noncirrhotic patients were significantly higher in older patients and up to 1.1% in males above 55 years.

Barriers and facilitators to adherence to screening colonoscopy among African-Americans: a mixed-methods analysis.

This mixed-methods study reports barriers and facilitators to screening colonoscopy among inner-city African-Americans. A purposive sample of 29 African-Americans ≥ 50 years old with average risk of colorectal cancer (CRC) was recruited from CRC education programs in an urban setting (June 2011-April 2012). A demographic survey collected quantitative data (e.g., socioeconomic status), and a semi-structured interview assessed qualitative data (e.g., perspectives of colonoscopies). Sample and between-group analyses were conducted using descriptive statistics and content analysis of quantitative and qualitative data, respectively. The sample consisted of 17 people who completed a colonoscopy and 12 who had not. Mean age was 68 years; 79 % completed at least high school, and all had health care coverage and had visited a physician within the last year. Physician recommendation was prevalent among both groups (15/17 in completers vs. 8/12 in non-completers) and thus did not fully explain the differences in adherence. The greatest barrier for the non-colonoscopy group was lack of knowledge about the importance of screening while the commonest facilitator for the colonoscopy group was physician recommendation. Improved knowledge about colonoscopies is a significant facilitator to adherence, while physician recommendation was not significantly different between groups. Promotion of screening colonoscopies by both physicians and community programs has the potential to improve adherence rates in the African-American population.

Culturally targeted patient navigation for increasing african americans' adherence to screening colonoscopy: a randomized clinical trial.

BACKGROUND: Patient navigation has been an effective intervention to increase cancer screening rates. This study focuses on predicting outcomes of screening colonoscopy for colorectal cancer among African Americans using different patient navigation formats. METHODS: In a randomized clinical trial, patients more than 50 years of age without significant comorbidities were randomized into three navigation groups: peer-patient navigation (n = 181), pro-patient navigation (n = 123), and standard (n = 46). Pro-patient navigations were health care professionals who conducted culturally targeted navigation, whereas peer-patient navigations were community members trained in patient navigation who also discussed their personal experiences with screening colonoscopy. Two assessments gathered sociodemographic, medical, and intrapersonal information. RESULTS: Screening colonoscopy completion rate was 75.7% across all groups with no significant differences in completion between the three study arms. Annual income more than $10,000 was an independent predictor of screening colonoscopy adherence. Unexpectedly, low social influence also predicted screening colonoscopy completion. CONCLUSIONS: In an urban African American population, patient navigation was effective in increasing screening colonoscopy rates to 15% above the national average, regardless of patient navigation type or content. IMPACT: Because patient navigation successfully increases colonoscopy adherence, cultural targeting may not be necessary in some populations.

Prevalence, risk factors, and disease knowledge of chronic hepatitis B infection in Vietnamese Americans in California.

Our goal is to examine the prevalence, risk factors, and disease knowledge of chronic hepatitis B (CHB) among Vietnamese Americans in California. We also examined treatment eligibility and linkage to care among patients who tested positive for CHB. We enrolled 717 subjects from ten different hepatitis B virus (HBV) screening events in five locations from January 2009 to June 2010 in California. HBV status was determined by hepatitis B surface antigen (HBsAg) and antibody. Data were collected by a 36-question survey. A total of 99 patients (13.8 %) had positive HBsAg, especially those aged 31-40 years (23.6 %), and 177 (24.7 %) were still susceptible to HBV infection. A significant proportion of those who were HBsAg positive or still susceptible reported a history of HBV vaccination (10 and 20 %, respectively). Following adjustments for age and sex, significant predictors for HBsAg positivity were lack of healthcare coverage (OR=2.4, p=0.004), having a family history of CHB (OR=2.1, p=0.009), and prior occupational exposure (OR=3.0, p=0.007). Of those who tested positive, 13.3 % met criteria for antiviral therapy, but none had been initiated on treatment. HBV prevalence in Vietnamese Americans in California was high (13.8 %), especially in those between 31 and 40 years of age. Patient disease and treatment knowledge was poor, as were follow-up and management of those found to have CHB and/or have indication for antiviral therapy.

Cancer care in East and Central Harlem: community partnership needs assessment.

In the largely African American and Hispanic communities of East and Central Harlem in New York City (NYC), health inequities are glaring. Mortality from cancer is 20-30 % higher than in Manhattan and 30-40 % higher than rates in the general population in NYC. Despite advances in risk assessment, early detection, treatment, and survivorship, individuals in Harlem and similar urban communities are not benefiting equally. Guided by community-based participatory research, this study serves as an important step in understanding cancer care needs and the range of factors that impact the disparate rates of cancer in East and Central Harlem. Forty individual interviews were conducted with community leaders and residents. Major themes included: need for appropriate supportive services; health care access and financial challenges; beliefs related to stigma, trust, and accountability; and the impact of the physical environment on health. Education was seen as a critical area of need and intervention.

Tenofovir monotherapy and tenofovir plus entecavir combination as rescue therapy for entecavir partial responders.

BACKGROUND AND AIMS: Despite high potency, a significant proportion of patients treated with entecavir achieve only partial viral suppression. Our goal was to examine the complete viral suppression rate (undetectable HBV DNA PCR levels) with alternative therapies in such patients. METHODS: We retrospectively studied 42 consecutive patients with partial response to entecavir (detectable HBV DNA at ≥12 months of therapy) who were treated at three clinics with rescue therapies: entecavir + adefovir (n = 5), tenofovir (n = 6), and entecavir + tenofovir (n = 31). Antiviral resistance was excluded by negative mutation analysis and/or absence of virologic breakthrough (increase >1 log(10)IU/mL from nadir). RESULTS: All patients were Asian and 57 % were male with a median age of 36 (22-64) years. Only a few patients had prior exposure to lamivudine (7 %) or adefovir (7 %). Almost all patients (95 %) had positive HBeAg. Overall, the complete viral suppression rate was 79 %, and the alanine aminotransferase normalization rate was 83 % in entecavir partial responders after 6 months on rescue therapies. Cumulative complete viral suppression rates were significantly different (P = 0.0164) among the entecavir + adefovir, tenofovir, and entecavir + tenofovir treatment groups at 6 months (20 vs. 83 vs. 83 %, respectively) and 12 months (20 vs. 100 vs. 97 %). All three patients without complete viral suppression on entecavir + adefovir became aviremic 6 months after switching to entecavir + tenofovir. CONCLUSIONS: Virologic response to entecavir + tenofovir combination therapy and tenofovir monotherapy appeared to be similar in most patients, but not with the entecavir + adefovir combination.

High rate of complete viral suppression with combination therapy in patients with chronic hepatitis B and prior treatment failure.

BACKGROUND: Combination therapy for chronic hepatitis B virus (HBV) infection is recommended for patients with antiviral resistance (AVR) or partial response (PR) to earlier antiviral therapy; however, data on outcomes are limited. GOALS: To determine the rate of complete viral suppression (CVS) with combination therapy and to compare CVS among different indications and treatment regimens. METHODS: A cohort of 109 consecutive patients with chronic hepatitis B from 3 liver clinics in Northern California was retrospectively studied. All patients started combination therapy between April 2004 and August 2009 for the following indications: AVR (n = 29), PR (n = 60), or others (n = 20). Combination treatments included lamivudine (LAM), adefovir (ADV), telbivudine (LdT), entecavir (ETV), tenofovir (TDF), and emtricitabine (FTC). CVS was defined as undetectable serum HBV DNA <100 IU/mL. RESULTS: Among the patients, who were nearly all Asian (99%), 73% had ≥ 2 prior treatments and 82% had treatment failure (AVR or PR). Median treatment duration of combination therapy was 21 months (range, 6 to 50 mo). The majority (77%) achieved CVS after 6 months of various combination regimens: 80% for ETV+TDF, 76% for TDF+LAM or FTC or LdT, 75% for ETV+ADV, and 69% for ADV+LAM or LdT (P = 0.86). After 6 months of therapy, CVS was observed in a similar proportion of patients treated for PR and AVR (72% and 74%, respectively). CONCLUSIONS: Although the majority of 109 treatment-experienced patients had prior treatment failure, high rates of CVS were rapidly achieved and did not significantly differ between indications of AVR and PR or between ETV-based and TDF-based regimens.

Adherence to screening for hepatocellular carcinoma among patients with cirrhosis or chronic hepatitis B in a community setting.

BACKGROUND: Screening for hepatocellular carcinoma (HCC) has been shown to improve survival via earlier cancer detection. Although HCC screening is considered standard of care in the USA, little is known of the adherence to this practice, especially in a community setting. AIMS: Our primary goal was to evaluate adherence to HCC screening and to find predictors of screening adherence in a community setting. Our secondary objective was to determine the impact of screening on survival. METHODS: We studied a cohort of 557 consecutive patients at high risk for HCC: patients with cirrhosis and older chronic hepatitis B (CHB) patients without cirrhosis (≥45 years old). Patients initiated screening 1/2001-1/2005 and were monitored ≥12 months to 12/2008 in two community gastroenterology clinics in Northern California. HCC screening was categorized into four groups based on combined frequency of serum alpha-fetoprotein and imaging: optimal, suboptimal, poor, and no screening. RESULTS: About 40.6% of our cohort received poor or no screening. Noncirrhotic CHB patients had worse screening than cirrhotic patients. Multivariate analysis revealed that patients with a greater number of clinical visits per year were 3.4 times more likely to have regular screening than patients with fewer clinical visits per year (P<0.001). There was a trend for association between HCC screening and greater access to curative treatment. CONCLUSION: Since more frequent clinic visits is a strong independent predictor of improved screening adherence, regular routine clinic visits may help improve adherence to HCC screening, which may also lead to improved clinical outcomes.