Abstract
Background
Chronic hepatitis B (CHB) and fatty liver (FL) are common, natural history data on concurrent FL and CHB (FL-CHB) are limited. This study aimed to evaluate the effect of FL on ...cirrhosis, hepatocellular carcinoma (HCC), and hepatitis B surface antigen (HBsAg) seroclearance incidence in CHB patients.
Methods
In a retrospective cohort study of 6786 adult CHB patients, we used propensity score matching (PSM) to balance the FL-CHB and non-FL CHB groups. Kaplan-Meier methods were used to compare cumulative cirrhosis, HCC, and HBsAg seroclearance rates between subgroups.
Results
Before PSM, compared to non-FL CHB, FL-CHB patients had lower 10-year cumulative rates of cirrhosis, HCC, and a higher HBsAg seroclearance rate. Similar results were found in the matched FL-CHB and non-FL CHB patients, as well as in the antiviral-treated PSM cohort. Cox proportional hazards model indicated FL to remain significantly and strongly associated with lower risk of cirrhosis and HCC (hazard ratio HR, 0.19 95% confidence interval {CI}, .12–.33, P < .001 and HR, 0.21 95% CI, .09–.51, P = .001, respectively) in antiviral-treated patients but not in untreated patients.
Conclusions
FL was significantly associated with lower cirrhosis and HCC risk and higher HBsAg seroclearance. Further studies are needed to confirm our funding and investigate the mechanisms underlying the impact of FL on CHB.
In this retrospective cohort study of 6786 adult patients with chronic hepatitis B (CHB), we observed a consistently lower incidence of cirrhosis, hepatocellular carcinoma, and higher incidence of hepatitis B surface antigen seroclearance in CHB patients’ concurrent fatty liver (FL), compared to non-FL CHB patients.
Background and Aims
Real‐world data for treatment effectiveness and renal outcomes in chronic hepatitis B (CHB) patients who were switched to the new and safer prodrug tenofovir alafenamide (TAF) ...from tenofovir disoproxil fumarate (TDF) are limited. Therefore, we aimed to evaluate treatment and renal outcomes of this population.
Approach and Results
We analyzed 834 patients with CHB previously treated with TDF for ≥12 months who were switched to TAF in routine practice at 13 US and Asian centers for changes in viral (HBV DNA < 20 IU/mL), biochemical (alanine aminotransferase ALT < 35/25 U/L for male/female), and complete (viral+biochemical) responses, as well as estimated glomerular filtration rate (eGFR; milliliters per minute per 1.73 square meters) up to 96 weeks after switch. Viral suppression (P < 0.001) and ALT normalization (P = 0.003) rates increased significantly after switch, with a trend for increasing complete response (Ptrend = 0.004), while the eGFR trend (Ptrend > 0.44) or mean eGFR (P > 0.83, adjusted for age, sex, baseline eGFR, and diabetes, hypertension, or cirrhosis by generalized linear modeling) remained stable. However, among those with baseline eGFR < 90 (chronic kidney disease CKD stage ≥2), mean eGFR decreased significantly while on TDF (P = 0.029) but not after TAF switch (P = 0.90). By week 96, 21% (55/267) of patients with CKD stage 2 at switch improved to stage 1 and 35% (30/85) of CKD stage 3‐5 patients improved to stage 2 and 1.2% (1/85) to stage 1.
Conclusions
Overall, we observed continued improvement in virologic response, ALT normalization, and no significant changes in eGFR following switch to TAF from TDF.
Alterations in the immune system during pregnancy have been associated with reactivation of hepatitis B virus (HBV) in chronic hepatitis B (CHB) women. However, the effects of pregnancy on CHB remain ...not well understood. The goal of this study was to examine flares in HBV DNA and serum alanine aminotransferase (ALT) during pregnancy and postpartum in CHB women untreated prior to pregnancy.
This was a multicenter retrospective study of 113 pregnancies in 101 CHB women who presented during pregnancy at two community gastroenterology clinics and two tertiary medical centers in the United States during 1997-2015. Outcomes analyzed included onset, severity, and resolution of flares in HBV and ALT that occurred prior to starting antiviral therapy, if antiviral therapy was subsequently initiated. Women who initiated antiviral therapy during pregnancy were not included in the analysis of postpartum flares.
HBV DNA flares were observed in 9% (8/90) of women during pregnancy and 4% (2/48) of women during postpartum. Flares in ALT (99-2522 U/l) were observed in 6% (7/112) of women during pregnancy and 10% (5/51) of women within the first 3 months of delivery. Age, HBeAg positivity, baseline HBV DNA, baseline ALT, gravida, and parity were not found to be significant predictors of flare.
Flares in HBV DNA and ALT can occur during late pregnancy and early postpartum in CHB women, and can be severe. Women with CHB should therefore be closely monitored during pregnancy and early postpartum.
Seroclearance of hepatitis B surface antigen (HBsAg) is a marker for clearance of chronic hepatitis B virus (HBV) infection, but reported annual incidence rates of HBsAg seroclearance vary. We ...performed a systematic review and meta-analysis to provide more precise estimates of HBsAg seroclearance rates among subgroups and populations.
We searched PubMed, Embase, and the Cochrane library for cohort studies that reported HBsAg seroclearance in adults with chronic HBV infection with more than 1 year of follow-up and at least 1 repeat test for HBsAg. Annual and 5-, 10-, and 15-year cumulative incidence rates were pooled using a random effects model.
We analyzed 34 published studies (with 42,588 patients, 303,754 person-years of follow-up, and 3194 HBsAg seroclearance events), including additional and updated aggregated data from 19 studies. The pooled annual rate of HBsAg seroclearance was 1.02% (95% CI, 0.79–1.27). Cumulative incidence rates were 4.03% at 5 years (95% CI, 2.49–5.93), 8.16% at 10 years (95% CI, 5.24–11.72), and 17.99% at 15 years (95% CI, 6.18–23.24). There were no significant differences between the sexes. A higher proportion of patients who tested negative for HBeAg at baseline had seroclearance (1.33%; 95% CI, 0.76–2.05) than those who tested positive for HBeAg (0.40%; 95% CI, 0.25–0.59) (P < .01). Having HBsAg seroclearance was also associated with a lower baseline HBV DNA level (6.61 log10 IU/mL; 95% CI, 5.94–7.27) vs not having HBsAg seroclearance (7.71 log10 IU/mL; 95% CI, 7.41–8.02) (P < .01) and with a lower level of HBsAg at baseline (2.74 log10 IU/mL; 95% CI, 1.88–3.60) vs not having HBsAg seroclearance (3.90 log10 IU/mL, 95% CI, 3.73–4.06) (P < .01). HBsAg seroclearance was not associated with HBV genotype or treatment history. Heterogeneity was substantial across the studies (I2 = 97.49%).
In a systematic review and meta-analysis, we found a low rate of HBsAg seroclearance in untreated and treated patients (pooled annual rate, approximately 1%). Seroclearance occurred mainly in patients with less active disease. Patients with chronic HBV infection should therefore be counseled on the need for lifelong treatment, and curative therapies are needed.
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Endoscopic screening is used widely to minimize the rates of colorectal cancer cases and deaths. During highly virulent infectious disease pandemics such as the coronavirus disease 2019 (COVID-19) ...pandemic, it is essential to weigh the risks and benefits of receiving endoscopy, especially in regions with moderately high viral infection rates. An observational study was conducted to assess the number of patients seen for endoscopic procedure at 2 of our surgery centers. Reasons for their procedure were collected in addition to information regarding any positive COVID-19 cases. This study considers the rate of severe acute respiratory syndrome coronavirus 2 infection along with the number of colorectal cancer cases encountered at a community endoscopy center to suggest that the benefits of undergoing endoscopic evaluation may outweigh the risks of attending an endoscopy procedure during the COVID-19 pandemic. One of the main reasons patients underwent endoscopic procedure was for colon cancer screenings (41.9%), and 5 of 1020 patients seen during the observation period were diagnosed with cancer. Of these 1020 patients, 8 were found to have positive tests for COVID-19 within 2 to 4 weeks after their procedure.
HCC risk in chronic hepatitis B (CHB) is higher in the indeterminate phase compared with the inactive phase. However, it is unclear if antiviral therapy reduces HCC risk in this population. We aimed ...to evaluate the association between antiviral therapy and HCC risk in the indeterminate phase.
We analyzed 855 adult (59% male), treatment-naïve patients with CHB infection without advanced fibrosis in the indeterminate phase at 14 centers (USA, Europe, and Asia). Inverse probability of treatment weighting (IPTW) was used to balance the treated (n = 405) and untreated (n = 450) groups. The primary outcome was HCC development. The mean age was 46±13 years, the median alanine transaminase was 38 (interquartile range, 24-52) U/L, the mean HBV DNA was 4.5±2.1 log 10 IU/mL, and 20% were HBeAg positive. The 2 groups were similar after IPTW. After IPTW (n = 819), the 5-, 10-, and 15-year cumulative HCC incidence was 3%, 4%, and 9% among treated patients (n = 394) versus 3%, 15%, and 19%, among untreated patients (n = 425), respectively ( p = 0.02), with consistent findings in subgroup analyses for age >35 years, males, HBeAg positive, HBV DNA>1000 IU/mL, and alanine transaminase<upper limit of normal. In multivariable Cox proportional hazards analysis adjusted for age, sex, HBeAg, HBV DNA, alanine transaminase, diabetes, and platelets, antiviral therapy remained an independent predictor of reduced HCC risk (adjusted HR = 0.3, 95% CI: 0.1-0.6, p = 0.001).
Antiviral therapy reduces HCC risk by 70% among patients with indeterminate-phase CHB. These data have important implications for the potential expansion of CHB treatment criteria.
Nonalcoholic fatty liver disease (NAFLD) is typically associated with obesity. Little is known about the prevalence of cirrhosis in patients with NAFLD and a normal body mass index (BMI).
We ...determined prevalence of cirrhosis, cardiovascular disease (CVD), and metabolic abnormalities among participants in all BMI categories in the TARGET-NASH study. A total of 3386 patients with NAFLD were enrolled from August 2016 through March 2019. The odds ratios of cirrhosis, CVD, and metabolic abnormalities were estimated by age and race, adjusting for sex and center type.
Based on standard BMI cutoff values, 12.8% of study subjects were lean, 27.1% were overweight, 26.5% had class 1 obesity, and 33.7% had class 2 or 3 obesity. Asians accounted for 48.7% of lean participants, and proportions decreased as BMI categories increased (P < .0001). Lower proportions of lean participants had cirrhosis (22.6% vs 40.2% of non-lean participants), CVD history (9.0% vs 14.8% of nonlean participants), diabetes (32.6% vs 53.5% of non-lean participants), hypertension (47.8% vs 67.4% of non-lean participants), or dyslipidemia (54.0% vs 64.1% of non-lean participants). Asian participants had a lower prevalence of cirrhosis, history of CVD, cardiovascular events, and diabetes compared with non-Asians, independent of BMI category. After we adjusted for age, sex, and center type and site, the odds of NAFLD-associated cirrhosis in Asians who were lean was almost half the odds of NAFLD-associated cirrhosis in non-Asians who were lean (odds ratio, 0.47; 95% CI, 0.29-0.77).
More than 10% participants in a cohort of persons with NAFLD in the United States are lean; Asians account for almost half of the lean persons with NAFLD. Lean participants had a lower prevalence of cirrhosis, CVD, and metabolic abnormalities than non-lean persons with NAFLD. Asian participants had a significantly lower prevalence of cirrhosis, CVD, and metabolic abnormalities than non-Asians in all BMI categories. ClinicalTrials.gov, Number: NCT02815891.
Topic models e.g., probabilistic latent semantic analysis, latent Dirichlet allocation (LDA), and supervised LDA have been widely used for segmenting imagery. However, these models are confined to ...crisp segmentation, forcing a visual word (i.e., an image patch) to belong to one and only one topic. Yet, there are many images in which some regions cannot be assigned a crisp categorical label (e.g., transition regions between a foggy sky and the ground or between sand and water at a beach). In these cases, a visual word is best represented with partial memberships across multiple topics. To address this, we present a partial membership LDA (PM-LDA) model and an associated parameter estimation algorithm. This model can be useful for imagery, where a visual word may be a mixture of multiple topics. Experimental results on visual and sonar imagery show that PM-LDA can produce both crisp and soft semantic image segmentations; a capability previous topic modeling methods do not have.
First-line treatment for nonalcoholic fatty liver disease (NAFLD) focuses on weight loss through lifestyle modifications.1,2 Weight loss ≥5% results in reduction of steatosis and weight loss ≥10% has ...been associated with improvement in hepatic inflammation and fibrosis.3 The incidence and sustainability of weight loss among patients with NAFLD were estimated and associating factors identified.
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