Impact of Longitudinal Alcohol Use Patterns on Long-Term Risk of Cirrhosis Among US Veterans With Steatotic Liver Disease.

BACKGROUND & AIMS: Conflicting data exist on the impact of alcohol use on risk of liver disease progression in patients with steatotic liver disease. We aimed to evaluate the effect of longitudinal alcohol use on risk of cirrhosis among veterans with steatotic liver disease. METHODS: US veterans with steatotic liver disease were identified from January 2010 through December 2022. Alcohol use was assessed using documented Alcohol Use Disorders Identification Test-Concise (AUDIT-C) scores and categorized as no alcohol (AUDIT-C = 0), low-risk alcohol use (AUDIT-C 1-2 for women and 1-3 for men), and high-risk alcohol (AUDIT-C ≥ 3 for women and ≥ 4 for men). Incidence of cirrhosis was evaluated with competing risks Nelson-Aalen methods. Adjusted multivariable regression models evaluated risks of cirrhosis associated with baseline alcohol use and changes in alcohol use during follow-up. RESULTS: There were 1,156,189 veterans with steatotic liver disease identified (54.2% no alcohol, 34.6% low-risk alcohol, and 11.2% high-risk alcohol). Veterans with steatotic liver disease and high-risk alcohol have a 43% higher incidence of cirrhosis compared with patients reporting no alcohol use. Compared with patients with baseline high-risk alcohol who reported no change in alcohol use, those who decreased their alcohol use during follow-up experienced a 39% reduction in long-term risk of cirrhosis (hazard ratio, 0.61; 95% CI, 0.45-0.83; P < .01). CONCLUSIONS: One in 9 veterans with steatotic liver disease report concurrent high-risk alcohol use, which is associated with 43% greater risk of cirrhosis compared with no alcohol use. However, reducing alcohol use lowers risk of cirrhosis, emphasizing the importance of timely alcohol use assessment and early interventions to address high-risk alcohol use in steatotic liver disease.

Sex Differences in Treatment Response to Nucleos(t)ide Therapy in Chronic Hepatitis B: A Multicenter Longitudinal Study.

BACKGROUND & AIMS: It is unclear if there may be sex differences in response to nucleos(t)ide analogs including virologic response (VR), biochemical response (BR), complete response (CR), and hepatocellular carcinoma (HCC) incidence among hepatitis B patients. We compared nucleos(t)ide analog treatment outcomes by sex. METHODS: We performed a retrospective cohort study of 3388 treatment-naïve adult hepatitis B patients (1250 female, 2138 male) from the Real-World Evidence from the Global Alliance for the Study of Hepatitis B Virus consortium who initiated therapy with either entecavir or tenofovir from 22 sites (Argentina, Korea, Japan, Taiwan, and the United States). We used propensity-score matching to balance background characteristics of the male and female groups and competing-risks analysis to estimate the incidence and subdistribution hazard ratios (SHRs) of VR, BR, CR, and HCC. RESULTS: Females (vs males) were older (52.0 vs 48.6 y); less likely to be overweight/obese (49.3% vs 65.7%), diabetic (9.9% vs 13.1%), or cirrhotic (27.9% vs 33.0%); and had a lower HBV DNA level (5.9 vs 6.0 log10 IU/mL) and alanine aminotransferase level (91 vs 102 IU/L) (all P < .01). However, after propensity-score matching, relevant background characteristics were balanced between the 2 groups. Females (vs males) had similar 5-year cumulative VR (91.3% vs 90.3%; P = .40) and HCC incidence rates (5.1% vs 4.4%; P = .64), but lower BR (84.0% vs 90.9%; P < .001) and CR (78.8% vs 83.4%; P = .016). Males were more likely to achieve BR (SHR, 1.31; 95% CI, 1.17-1.46; P < .001) and CR (SHR, 1.16; 95% CI, 1.03-1.31; P = .016), but VR and HCC risks were similar. CONCLUSIONS: Sex differences exist for treatment outcomes among hepatitis B patients. Male sex was associated with a 16% higher likelihood of clinical remission and a 31% higher likelihood of biochemical response than females, while virologic response and HCC incidence were similar between the 2 groups.

Impact of HIV Infection on Liver and Cardiovascular Outcomes in Veterans With Metabolic Dysfunction-Associated Steatotic Liver Disease.

INTRODUCTION: Hepatic steatosis is highly prevalent in people living with HIV. It remains unclear whether HIV in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with greater risks of liver disease progression and cardiovascular disease (CVD). We aim to evaluate the impact of HIV infection on risks of liver and CVD outcomes among US Veterans with MASLD. METHODS: Using national Veterans Administration data from 2010 to 2022, we created a propensity score-matched cohort of MASLD patients with vs without HIV. Primary outcomes were incidence of cirrhosis and hepatocellular carcinoma (HCC) among patients with vs without HIV and patients with MASLD-HIV on antiretroviral therapy (ART) vs not on ART. Secondary outcomes included incidence of major adverse cardiovascular events and overall survival. RESULTS: The propensity-matched cohort included 920 MASLD patients with HIV and 920 MASLD patients without HIV and was similar in demographics and comorbidities. Compared with MASLD patients without HIV, incidences of cirrhosis and HCC were similar among MASLD with HIV. Compared with MASLD patients without HIV, incidence of major adverse cardiovascular event was higher among MASLD patients with HIV (5.18 vs 4.48 per 100 person-years, P = 0.03). Overall 5-year survival was significantly lower among MASLD patients with HIV and even lower among those not on ART. DISCUSSION: Among US Veterans with MASLD, concurrent HIV infection, and particularly not being on ART, is associated with greater risks of CVD and decreased overall survival. No differences in risks of cirrhosis or HCC were observed.

Antiviral therapy response in patients with chronic hepatitis B and fatty liver: A systematic review and meta-analysis.

The impact of concurrent fatty liver (FL) on response to antiviral therapy in chronic hepatitis B (CHB) patients has not been well characterized. We aimed to systematically review and analyse antiviral treatment response in CHB patients with and without FL. We searched PubMed, Embase, Web of Science and the Cochrane Library databases from inception to 31 May 2023 for relevant studies. Biochemical response (BR), complete viral suppression (CVS) and hepatitis B e antigen (HBeAg) seroconversion in CHB patients with FL (CHB-FL) and without FL (non-FL CHB) were compared. In an initial pool of 2101 citations, a total of 10 studies involving 2108 patients were included. After 12 weeks of treatment, CHB-FL patients as compared with non-FL CHB patients had lower BR rate (48.37% [108/227] vs. 72.98% [126/174], p = .04) but similar trend for CVS (36.86% [80/227] vs. 68.81% [114/174], p = .05) and similar rates of HBeAg seroconversion (6.59% [7/103] vs. 7.40% [7/110], p = .89). However, at week 48, there were no statistically significant differences between CHB-FL and non-FL CHB patients in any of the outcomes, including BR (60.03% [213/471] vs. 69.37% [314/717], p = .67), CVS (65.63% [459/746] vs. 73.81% [743/1132], p = .27) and HBeAg seroconversion (10.01% [30/275] vs. 14.06% [65/453], p = .58) with similar findings for week 96. BR rate was lower in CHB-FL patients after 12 weeks of antiviral treatment. However, after a longer follow-up of either 48 or 96 weeks, no statistically significant differences were observed in BR, CVS or HBeAg seroconversion rates between CHB patients with and without FL.

Cost-effectiveness of MRE versus VCTE in staging fibrosis for nonalcoholic fatty liver disease (NAFLD) patients with advanced fibrosis.

INTRODUCTION: NAFLD is a common cause of liver disease. To determine the optimal testing strategy for NAFLD patients with advanced fibrosis, several factors such as diagnostic accuracy, failure rates, costs of examinations, and potential treatment options need to be considered. The purpose of this study was to determine the cost-effectiveness of combination testing involving vibration-controlled transient elastography (VCTE) versus magnetic resonance elastography (MRE) as a frontline imaging strategy for NAFLD patients with advanced fibrosis. METHODS: A Markov model was developed from the US perspective. The base-case scenario in this model included patients aged 50 years with a Fibrosis-4 score of ≥2.67 and suspected advanced fibrosis. The model included a decision tree and a Markov state-transition model including 5 health states: fibrosis stage 1-2, advanced fibrosis, compensated cirrhosis, decompensated cirrhosis, and death. Both deterministic and probabilistic sensitivity analyses were performed. RESULTS: Staging fibrosis with MRE cost $8388 more than VCTE but led to an additional 1.19 Quality-adjusted life years (QALYs) with the incremental cost-effectiveness ratio of $7048/QALY. The cost-effectiveness analysis of the 5 strategies revealed that MRE+biopsy and VCTE+MRE+biopsy were the most cost-effective with the incremental cost-effectiveness ratios of $8054/QALY and $8241/QALY, respectively. Furthermore, sensitivity analyses indicated that MRE remained cost-effective with a sensitivity of ≥0.77, whereas VCTE became cost-effective with a sensitivity of ≥0.82. CONCLUSIONS: MRE was not only cost-effective than VCTE as the frontline modality for staging NAFLD patients with Fibrosis-4 ≥2.67 with incremental cost-effectiveness ratio of $7048/QALY but also remained cost-effective when used as a follow-up in instances of VCTE failure to diagnose.

Primary prophylaxis for spontaneous bacterial peritonitis is linked to antibiotic resistance in the Veterans Health Administration.

Spontaneous bacterial peritonitis (SBP) is a major cause of mortality. Although SBP primary prophylaxis (SBPPr) with fluoroquinolones and trimethoprim-sulfamethoxazole (TMP-SMX) is often used, resistance could reduce its benefit. AIM: Analyze peritoneal fluid resistance patterns in patients with a first SBP episode with/without SBPPr using the Veterans Health Administration corporate data warehouse and to evaluate national antibiograms. Corporate data warehouse data were extracted using validated International Classification of Disease-9/10 codes, culture, resistance data, and outcomes of 7553 patients who developed their first inpatient SBP between 2009 and 2019 and compared between those with/without SBPPr. Escherichia coli ( E. coli ) and Klebsiella pneumoniae ( K. pneumoniae ) sensitivity to ciprofloxacin and TMP-SMX was calculated using 2021 Veterans Health Administration antibiogram data from all states. The most common isolates were E. coli , K. pneumoniae , and Staphylococcus species. Veterans taking ciprofloxacin SBBPr had higher fluoroquinolone resistance (34% vs 14% no SBPPr, p <0.0001); those taking TMP-SMX had higher TMP-SMX resistance (40% vs 14%, p <0.0001). SBPPr patients showed higher culture positivity, greater length of stay, higher second SBP, and higher probability of liver transplant rates versus no SBPPr. Multivariable models showed SBBPr to be the only variable associated with gram-negative resistance, and SBPPr was associated with a trend toward longer length of stay. E. coli ciprofloxacin sensitivity rates were 50%-87% and 43%-92% for TMP-SMX. K. pneumoniae ciprofloxacin sensitivity was 76%-100% and 72%-100% for TMP-SMX. CONCLUSION: Among patients who developed their first SBP episode, there was a higher prevalence of antibiotic resistance in those on SBPPr, with a high rate of fluoroquinolone resistance across the Veterans Health Administration sites.

Antiviral therapy substantially reduces HCC risk in patients with chronic hepatitis B infection in the indeterminate phase.

BACKGROUND AND AIMS: 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. APPROACH AND RESULTS: 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

Cost-effectiveness study of FIB-4 followed by transient elastography screening strategy for advanced hepatic fibrosis in a NAFLD at-risk population.

BACKGROUND & AIMS: The cost-effectiveness to screen hepatic fibrosis in at-risk population as recommended by several professional societies has been limited. This study aimed to investigate the cost-effectiveness of this screening strategy in the expanded at-risk population recently proposed by several societies. METHODS: A combined model of the decision tree and Markov models was developed to compare expected costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) between screening and no screening groups. The model included liver disease-related health states and cardiovascular disease (CVD) states as a base-case analysis. Screening strategy consisted of fibrosis-4 index (FIB-4) followed by vibration-controlled transient elastography (VCTE) and intensive lifestyle intervention (ILI) as a treatment for diagnosed patients. RESULTS: Cost-effectiveness analysis showed that screening the at-risk population entailed $298 incremental costs and an additional 0.0199 QALY per patient compared to no screening (ICER $14 949/QALY). Screening was cost-effective based on the implicit ICER threshold of $25 000/QALY in Korea. When the effects of ILI on CVD and extrahepatic malignancy were incorporated into the cost-effectiveness model, the ICER decreased by 0.85 times from the base-case analysis (ICER $12 749/QALY). In contrast, when only the effects of liver disease were considered in the model, excluding cardiovascular disease effects, ICER increased from the baseline case analysis to $16 305. Even when replacing with medical costs in Japan and U.S., it remained cost-effective with the estimate below the countries' ICER threshold. CONCLUSIONS: Our study provides compelling evidence supporting the cost-effectiveness of FIB-4-based screening the at-risk population for advanced hepatic fibrosis.

Impact of Income-to-Poverty Ratio on Long-Term Mortality of Persons with Chronic Liver Disease in the US, 1999-2018.

INTRODUCTION: Chronic liver disease (CLD) is associated with increased morbidity and mortality. Understanding health disparities can inform appropriate interventions. We aimed to study mortality outcomes of those with CLD by income-level (income-to-poverty ratio <5 as lower-income and > 5 as higher-income). METHODS: In this retrospective-cohort study, we analyzed data of adults from the National Health and Nutrition Examination Survey, 1999-2018. CLD included viral hepatitis, nonalcoholic fatty liver disease (NAFLD), and alcohol-associated liver disease (ALD). RESULTS: We analyzed 59,204 adults: 47,224 without CLD and 11,980 with CLD. The CLD group was older, more likely male, racial/ethnic minority groups or foreign-born, and had lower educational and income levels (P<0.001). Most (80.02%) CLD participants did not have college degrees and had lower-income (79.18%). Among CLD participants, similar differences were observed between lower and higher-income groups. Lower-income participants with CLD had significantly higher 10-year cumulative mortality compared to higher-income CLD participants (15.26% vs 8.00%, P<0.001), with consistent findings in viral hepatitis and NAFLD subgroups (P<0.001) but not ALD (P=0.71). Adjusting for age, sex, race, birthplace, lower-income CLD participants were 2.01 (HR: 2.01; 95% CI: 1.79-2.26) times more likely to die overall and in viral hepatitis (HR: 2.05; 95% CI: 1.31-3.24) and NAFLD subgroups (HR: 2.32; 95% CI: 1.69-3.18) but not ALD (HR: 1.17; 95% CI: 0.55-2.51). CONCLUSION: Lower-income, foreign-born, and racial/ethnic minority groups were disproportionately represented among those with CLD, with lower-income and CLD individuals having double the mortality risk compared to their higher-income counterparts. Interventions should be culturally appropriate and address socioeconomic barriers.

Telehepatology Satisfaction Is Associated with Ethnicity: The Real-World Experience of a Vulnerable Population with Fatty Liver Disease.

BACKGROUND: Since the coronavirus disease 2019 (COVID-19) pandemic began, telemedicine use has transformed healthcare delivery. Yet there is concern that telemedicine may widen care disparities for vulnerable populations, and patient experience data are limited. AIMS: We aimed to assess patient satisfaction with hepatology-related telemedicine (telehepatology) for delivery of fatty liver disease (FLD) care in a safety-net healthcare system. METHODS: Adult patients with FLD were surveyed regarding satisfaction with telehepatology. Clinical, demographic, resources, and social determinants of health (SDoH) data were collected to identify factors associated with satisfaction through multivariable modeling. RESULTS: From June 2020 to March 2022, 220 participants were enrolled: the median age was 52 years, 37% were men, and 68% were Hispanic. One hundred nineteen (54%) had prior telehepatology experience. Overall, satisfaction was high; 70% reported being somewhat or very satisfied. On univariate analysis, Hispanic ethnicity (versus non-Hispanic, OR 0.34, 95% CI 0.1-0.9, p = 0.03) and limited access to personal cellphone/internet (OR 0.16, 95% CI 0.04-0.6, p = 0.01) were associated with lower satisfaction. On multivariable logistic regression modeling adjusted for pandemic duration, age, sex, severity of liver disease, and coexisting liver disease, Hispanic ethnicity and lack of personal cellphone/internet remained independently associated with lower telehepatology satisfaction (OR 0.24, 95% CI 0.07-0.9, p = 0.03 and OR 0.2, 95% CI 0.04-0.9, p = 0.04, respectively). The association remained statistically significant after inclusion of various SDoH in the multivariable model. CONCLUSIONS: Satisfaction with telehepatology among FLD patients in a safety-net clinical setting was high overall. However, Hispanic ethnicity and lack of personal cellphone/internet were independently associated with lower telehepatology satisfaction. A better understanding of patients' experience with telehepatology is needed to identify reasons for dissatisfaction, and in-person visits should remain an option for patients to ensure equitable care.

Disparities in Antiviral Treatment among Adults with Hepatitis B Cirrhosis: An Analysis of the National Veterans Affairs Cohort.

Timely antiviral therapy is critical in chronic hepatitis B (CHB) cirrhosis, to prevent further liver complications. Among a national cohort of US Veterans with CHB cirrhosis, only 52% were initiated on antiviral therapy; treatment was significantly lower among patients of non-Asian ethnicity, high-risk alcohol use, and in rural settings.

Global incidence of non-alcoholic fatty liver disease: A systematic review and meta-analysis of 63 studies and 1,201,807 persons.

BACKGROUND & AIMS: The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing. We aimed to estimate the pooled global NAFLD incidence. METHODS: We performed a systematic review and meta-analysis of cohort studies of adults without NAFLD at baseline to evaluate the global incidence of ultrasound-diagnosed NAFLD. RESULTS: A total of 63 eligible studies (1,201,807 persons) were analyzed. Studies were from Mainland China/Hong Kong (n = 26), South Korea (n = 22), Japan (n = 14), other (n = 2, Sri Lanka, Israel); 63.8% were clinical center studies; median study year 2000 to 2016; 87% were good quality. Among the 1,201,807 persons at risk, 242,568 persons developed NAFLD, with an incidence rate of 4,612.8 (95% CI 3,931.5-5,294.2) per 100,000 person-years and no statistically significant differences by study sample size (p = 0.90) or study setting (p = 0.055). Males had higher incidence vs. females (5,943.8 vs. 3,671.7, p = 0.0013). Both the obese (vs. non-obese) and the overweight/obese groups (vs. normal weight) were about threefold more likely to develop NAFLD (8,669.6 vs. 2,963.9 and 8,416.6 vs. 3,358.2, respectively) (both p <0.0001). Smokers had higher incidence than non-smokers (8,043.2 vs. 4,689.7, p = 0.046). By meta-regression, adjusting for study year, study setting, and study location, study period of 2010 or after and study setting were associated with increased incidence (p = 0.010 and p = 0.055, respectively). By country, China had a higher NAFLD incidence compared to non-China regions (p = 0.012) and Japan a lower incidence compared to non-Japan regions (p = 0.005). CONCLUSIONS: NAFLD incidence is increasing with a current estimate of 4,613 new cases per 100,000 person-years. Males and overweight/obese individuals had significantly higher incidence rates compared to females and those of normal weight. Public health interventions for prevention of NAFLD are needed with a special emphasis on males, overweight/obese individuals, and higher risk regions. IMPACT AND IMPLICATIONS: Non-alcoholic fatty liver disease (NAFLD) affects approximately 30% of people worldwide and appears to be increasing, but data to estimate the incidence rate are limited. In this meta-analytic study of over 1.2 million people, we estimated an incidence rate of NAFLD of 46.13 per 1,000 person-years with significant differences by sex, BMI, geography, and time-period. As treatment options for NAFLD remain limited, prevention of NAFLD should remain the focus of public health strategies. Studies such as these can help policy makers in determining which and whether their interventions are impactful.

Utilization of Antiviral Therapy for Patients With Hepatitis B-Related Hepatocellular Carcinoma: A Nationwide Real-World US Study.

BACKGROUND & AIMS: Although oral antiviral therapy (OAV) is reported to improve outcomes in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), it is underutilized. We determined the rate and factors associated with OAV utilization among patients with HBV-related HCC in a US population with health insurance. METHODS: Patients with HBV-related HCC were identified from the de-identified administrative health claims database for patients with private insurance, Optum Clinformatics (2003-2021). RESULTS: We identified 2129 patients with HBV-related HCC: 71% male, mean age 62.7 ± 12.5 years, 40% Asian individuals, 72% with cirrhosis, and 37% received OAV. The treatment rate improved over time (40.5% after 2010 vs 26.3% earlier; P < .001). Significantly lower treatment rates were noted for females, non-Asian patients, noncirrhotic patients, and patients without gastroenterologist/hepatologist or infectious disease (GI/ID) specialist care (P < .0001). OAV treatment predictors included Asian race and ethnicity (adjusted odds ratio [aOR], 3.6; 95% CI, 2.8-4.5; P < .001), male sex (aOR, 1.6; 95% CI, 1.3-2.0; P < .001), seeing a GI/ID specialist (aOR, 1.5; 95% CI, 1.10-1.99; P = .0091), having compensated cirrhosis (aOR, 2.2; 95% CI, 1.7-2.8; P < .001), and being treated from 2011 to 2021 (aOR, 2.3; 95% CI, 1.8-3.0; P < .001); being younger (aOR, 0.98; 95% CI, 0.98-0.99; P < .001) was less likely for treatment. OAV initiated at or before HCC diagnosis was associated independently with improved survival (adjusted hazard ratio, 0.84; 95% CI, 0.72-0.99; P = .037). CONCLUSIONS: Among patients with HBV-related HCC, only 1 in 3 received OAV despite having insurance coverage. Efforts must continue to develop ways to improve HBV OAV treatment, especially among females, non-Asian patients, and patients without cirrhosis or not seen by specialists.

Racial and Ethnic Disparities in Characteristics and Care Patterns of Chronic Hepatitis B Patients in the United States.

BACKGROUND & AIMS: Chronic hepatitis B (CHB) disproportionately impacts foreign-born patients and those of Asian or Black race. Given the paucity of data, we aimed to study the impact of race and ethnicity on CHB patient characteristics and management. METHODS: A retrospective analysis of adult CHB patients using data recorded in the deidentified Optum Clinformatics Data Mart Database (January 2003‒March 2021) was performed. We characterized and examined the rates of receiving adequate treatment evaluation (measuring hepatitis B virus DNA and alanine transaminase) and hepatitis B virus treatment among the racial and ethnic groups. RESULTS: The study cohort included 42,140 patients: age, 51.9 ± 15.1 years; 56.1% male; 47% Asian; 26% White; 11% Black; and 7% Hispanic. Thirty-three percent of White and 48% of Asian patients had an annual household income greater than $100,000 US compared with 16% for Black and 25% for Hispanic patients (P < .001), with similar disparities in educational levels. Approximately one third of White (29.3%), Black (35.1%), and Hispanic (35.4%), and half of Asian (49.9%) patients received adequate evaluation (P < .001). Among patients who met American Association for the Study of Liver Diseases treatment criteria, treatment rates were similar among White (60.8%; P = .09) and Black (62.8%; P = .48), but lower among Hispanic (54.7%; P = .03), as compared with Asian patients (65.4%). On multivariable logistic regression adjusted for age, sex, provider type, viral co-infection, and fatty liver disease, Hispanic patients were less likely to receive treatment (adjusted hazard ratio, 0.69; 95% CI, 0.53‒0.91; P = .01) compared with Asian patients. CONCLUSIONS: Compared with Asian CHB patients, non-Asian patients were less likely to undergo adequate evaluation and Hispanic patients were less likely to receive treatment for CHB. Additional efforts are needed to improve CHB management, especially for non-Asian patients.

Poor Diagnostic Efficacy of Noninvasive Tests for Advanced Fibrosis in Obese or Younger Than 60 Diabetic NAFLD patients.

BACKGROUND & AIMS: Serum-based noninvasive tests (NITs) have been widely used to assess liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). However, the diagnostic efficacy of NITs across ranges of age, body mass index (BMI), and presence of type 2 diabetes (T2DM) may vary and have not been well-characterized. METHODS: We analyzed 1489 patients with biopsy-proven NAFLD from 6 centers in Japan, Taiwan, and Korea. Using histology as the gold standard, we compared the areas under the receiver operating characteristic (AUROCs) of Fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), and the new Hepamet fibrosis score (HFS), with a focus on performance in subgroups as stratified by age, BMI, and the presence of T2DM. RESULTS: By histology, 44.0% of the overall cohort (655/1489) had F2-4, and 20.6% (307/1489) had F3-4 fibrosis. FIB-4 had the highest AUROCs for both F2-4 (0.701 vs NFS 0.676 and HFS 0.682, P = .001) and F3-4 (0.767 vs NFS 0.736 and HFS 0.752, P = .002). However, for F3-4 fibrosis, the AUROCs of all 3 NITs were generally higher in older (>60 years), nonobese (BMI <25 kg/m2), and non-diabetic patients, although overall the best performance was observed with FIB-4 among nonobese (BMI<25) diabetic patients (AUROC, 0.92). The worst performance was observed in younger patients with T2DM for all NITs including FIB-4 (AUROC, 0.63-0.66). CONCLUSIONS: FIB-4 had higher diagnostic efficacy for F3-4 than NFS or HFS, but this varied greatly by age, BMI, and T2DM, with better performance in older, nonobese, and nondiabetic patients. However, all NITs including FIB-4 had unacceptably poor performance in young or obese diabetic patients.

Global treatment rate and barriers to direct-acting antiviral therapy: A systematic review and meta-analysis of 146 studies and 1 760 352 hepatitis C virus patients.

BACKGROUND: Global data on the treatment rate with direct-acting antivirals (DAAs) for chronic hepatitis C (CHC) are sparse. We aimed to evaluate the CHC treatment rate and barriers to treatment in the DAA era. METHODS: We searched PubMed, EMBASE and Cochrane from inception to 5 August 2021, for relevant articles. Patients treated with DAAs without interferon (IFN) therapy were categorized as IFN-free DAAs. Patients receiving DAA with IFN or unclear IFN status were categorized as DAA/IFN. RESULTS: We identified and analysed data from 146 studies (1 760 352 CHC patients). DAA/IFN treatment rate was 16.0% (95% CI: 9.9-23.3, 49 studies, 886 535 patients). IFN-free DAA treatment rate was 52.3% (95% CI: 46.2-58.4, 123 studies, 1 276 754 patients): 45.4% in North America, 64.2% in South America (1 study), 90.4% in Africa (most data from Egypt), 54.4% in Europe, 60.7% in Australia and 60.5% in Asia, (p < .0001); 49% with hepatitis B co-infection and 32.3% with hepatocellular carcinoma (HCC). Treatment was not a priority in 22.8% of patients in Europe and 16.7% in Australia, compared to only 4.8% in North America and 2.1% in Asia (p < .0001). Poor adherence to clinical follow-up was the cause of no treatment in 74.7% of patients in Australia, 37.0% in North America, 7.9% in Europe and 14.3% in Asia (p < .0001). CONCLUSION: Though a marked improvement from IFN/DAA, the treatment rate with IFN-free DAA remains suboptimal (52.3% overall, 32.3% in HCC patients). Non-adherence to clinical follow-up and lack of disease awareness were treatment barriers.

Incidence of Cirrhosis and Hepatocellular Carcinoma Among Veterans With Noncirrhotic Metabolic Dysfunction-associated Fatty Liver Disease.

BACKGROUND AND AIMS: Despite the high prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD), the long-term incidence of cirrhosis or hepatocellular carcinoma (HCC) among adults with MAFLD is not well described. Using a national cohort of United States Veterans, we evaluated the overall incidence and predictors of cirrhosis and HCC among adults with noncirrhotic MAFLD. METHODS: Data from the 2010 to 2022 Veterans Affairs database were used to identify adults with noncirrhotic MAFLD using established definitions. Five and 10-year incidence of cirrhosis and HCC were assessed and stratified by demographics and relevant clinical variables. Multivariate Cox proportional hazard models were utilized to determine predictors of cirrhosis and HCC. RESULTS: Among 969,253 patients with noncirrhotic MAFLD (94.5% males, 70.2% non-Hispanic white, mean age of 62.7 ± 12.2 y), the 10-year incidence of cirrhosis and HCC was 3.70% (95% CI: 3.66-3.74) and 0.69% (95% CI: 0.67-0.70), respectively. When stratified by race/ethnicity, the 10-year incidence of cirrhosis was lowest among Asians (2.63%, 95% CI: 2.37-2.88) and highest among Hispanics (4.60%, 95% CI: 4.45-4.75), a pattern also observed with HCC. Significant disparities in risk of cirrhosis or HCC were observed when stratified by sex, substance use, and comorbidities. Risks of cirrhosis and HCC were highest in patients with baseline fibrosis-4 >2.67. CONCLUSION: This large study provides important epidemiological data describing the natural history of adults with MAFLD. Disparities in risk of cirrhosis and HCC were observed by demographic and clinical characteristics, emphasizing the importance of early identification of MAFLD with modifiable high-risk features to implement earlier interventions to improve long-term outcomes.

Transient Elastography and Serum-Based Tests for Diagnosis of Fatty Liver and Advanced Fibrosis in a Community Cohort: A Cross-Sectional Analysis.

BACKGROUND: Noninvasive tests (NITs) are necessary for knowing the true prevalence of fatty liver (FL) and advanced fibrosis. NITs for diagnosis of FL and fibrosis were compared. METHODS: Data were obtained from the National Health and Examination Survey (2017-2018). Participants were excluded with other liver diseases, missing data for NIT calculation, and/or excessive alcohol use. Area under the receiver operating characteristic (AUROC) compared the accuracy of 4 FL NITs (CAP, HSI, FLI, USFLI) among themselves and to CAP value of 285 dB/m and 5 fibrosis NITs (transient elastography, APRI, NFS, FIB-4, HEPAmet) among themselves and to LSM ≥8.7 kPa. RESULTS: Among 2,051 participants (average age 47 (±17.7), 48% males, 62% white, 73% overweight/obese, 39% metabolic syndrome), demographics were similar among NIT groups (CAP = 812; HSI = 1,234; FLI = 935; USFLI-824). FL prevalence by NIT: 39% CAP, 58% HSI, 47% FLI, 37% USFLI. Advanced fibrosis prevalence by test: LSM (≥8.7 kPa) 10-14%; FIB-4 (≥2.67) and APRI (≥0.7) 1.3-2.7%; HEPAmet (>0.47) 14-21%. Compared to CAP ≥285, FLI (AUROC = 0.823) and USFLI (AUROC = 0.833) performed better than HSI (AUROC: 0.798). Compared to LSM ≥8.7 kPa, only NFS (AUROC = 0.722) performed well (FIB-4 AUROC = 0.606; APRI = 0.647; HEPAmet = 0.629). Among the CAP cohort, the strongest FL predictor was obesity (OR: 15.2, 95% CI: 7.97-28.9, p < 0.001); the only fibrosis predictor was elevated AST (OR: 1.06, 95% CI: 1.00-1.12, p = 0.04). The addition of CAP or LSM as a second NIT reduced the number of indeterminate patients especially for FL. CONCLUSIONS: Regardless of diagnostic method in 2017-2018, the prevalence of NAFLD was >35%. NITs for FL performed well but not for advanced fibrosis. CAP and LSM as a second NIT reduced those considered indeterminate.

Liver Complications in Untreated Treatment-Ineligible versus Treated Treatment-Eligible Patients with Hepatitis B.

BACKGROUND: A substantial number of patients who do not meet treatment criteria for chronic hepatitis B (CHB) later develop adverse outcomes such as cirrhosis and hepatocellular carcinoma (HCC). Our aim was to determine whether current practice guidelines adequately identify CHB patients who will benefit from antiviral therapy. METHODS: We performed a retrospective cohort study comparing the incidence of adverse liver outcomes (cirrhosis and/or HCC) in untreated treatment-ineligible (at baseline and throughout follow-up) versus treated treatment-eligible patients according to standard American Association for the Study of Liver Diseases (AASLD) 2018 guidance (alanine aminotransferase [ALT] >70/50 U/L for men/women plus hepatitis B virus [HBV] DNA >20,000/2,000 IU/mL for HBeAg+/-) and with a sensitivity analyses using a lower threshold (ALT >40 U/L and HBV DNA >2,000 IU/mL). RESULTS: We reviewed records of 5,840 patients from 5 clinics in California and identified 2,987 treatment-naive non-HCC CHB patients. Of those, 271 patients remained untreated treatment-ineligible, 514 patients were treatment-eligible and initiated treatment, with 5-year cumulative adverse liver incidences of 12.5% versus 7.2%, p = 0.074. On multivariable analysis adjusting for age, sex, diabetes, albumin, platelet count, and HBV DNA, compared to treated treatment-eligible patients, untreated treatment-ineligible patients had a significantly higher risk of adverse liver outcomes (adjusted hazard ratio: 2.38, 95% confidence interval 1.03-5.48, p = 0.04) in main analysis by AASLD 2018 criteria but not in sensitivity analysis using the lower treatment threshold (p = 0.09). CONCLUSION: Patients never meeting standard AASLD 2018 criteria for antiviral therapy and never treated had twice the risk of developing cirrhosis and/or HCC when compared to eligible and treated patients.

Characteristics and Outcomes of Elderly Hepatocellular Carcinoma Patients following Surgical Resection: Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Due to ageing of the global population, hepatocellular carcinoma (HCC) is increasingly common among elderly patients, but outcomes after curative hepatic resection are unclear. Using a metanalytic approach, we aimed to estimate overall survival (OS), recurrence free survival (RFS) and complication rates in elderly HCC patients undergoing resection. METHODS: We searched PubMed, Embase, and Cochrane databases from inception to Nov 10, 2020 for studies reporting outcomes in elderly (age ≥ 65 years) patients with HCC undergoing curative surgical resection. Pooled estimates were generated using a random-effects model. RESULTS: We screened 8,598 articles and included 42 studies (7,778 elderly patients). The mean age was 74.45 years (95% CI 72.89-76.02), 75.54% were male (95% CI 72.53-78.32) and 66.73% had cirrhosis (95% CI 43.93-83.96). The mean tumor size was 5.50 cm (95% CI 4.71-6.29) and 16.01% had multiple tumors (95% CI 10.74-23.19). The 1-year (86.02% versus 86.66%, p=0.84) and 5-year OS (51.60% versus 53.78%) between non-elderly versus elderly patients were similar. Likewise, there were no differences in the 1-year (67.32% versus 73.26%, p=0.11) and 5-year RFS (31.57% versus 30.25%, p=0.67) in non-elderly versus elderly patients. There was a higher rate of minor complications (21.95% versus 13.71%, p=0.03) among elderly patients compared with non-elderly patients, but no difference in major complications (p=0.43) Conclusion: This data shows that overall survival, recurrence and major complications after liver resection for HCC are comparable between elderly and non-elderly patients, and may inform clinical management of HCC in this population.