Abstract Background and Aims The risk of hepatocellular cancer (HCC) after sustained virological response (SVR) with direct acting antivirals (DAA) is unclear. Our aim was to examine the risk and ...determinants of HCC in patients cured with DAA. Methods We conducted a retrospective cohort study of HCV patients who were treated with DAA in any of the 129 Veterans Health Administration hospitals between 1/1/2015 and 12/31/2015. We calculated the annual incidence rates for HCC by SVR. We used Cox regression models to compare the risk of HCC in patients with vs . those without SVR and to identify factors associated with incident HCC among patients with SVR. We reviewed a sample of HCC patients for tumor size and stage at diagnosis. Results Among 22,500 patients treated with DAA (19,518 with SVR; 2,982 without SVR), the mean (SD) age was 61.6 (6.1) year, and 39.0% had cirrhosis. There were 271 new cases of HCC, including 183 in patients with SVR. Compared to patients without SVR, those with SVR had a significantly reduced risk of HCC (0.90 vs. 3.45 HCC/100 PY; adjusted hazard ratio HR, 0.28, 95% CI=0.22–0.36). Patients with cirrhosis had the highest annual incidence of HCC after SVR (1.82 vs. 0.34/100 PY in patients without cirrhosis; adjusted HR, 4.73. 95% CI, 3.34-6.68). Most (>44.8%) HCC were classified as stage I. Maximum size of the largest lesion was ≤5 cm in over 75% of cases. Conclusions Among patients treated with DAA, SVR was associated with a considerable reduction in the risk of HCC. We did not find any evidence to suggest that DAAs promote HCC. However, in patients with SVR, the absolute HCC risk remained high in patients with established cirrhosis. These patients should be considered for ongoing HCC surveillance.
Background and Aims
The surge in unhealthy alcohol use during the COVID‐19 pandemic may have detrimental effects on the rising burden of alcohol‐associated liver disease (ALD) on liver ...transplantation (LT) in the USA. We evaluated the effect of the pandemic on temporal trends for LT including ALD.
Approach and Results
Using data from United Network for Organ Sharing, we analyzed wait‐list outcomes in the USA through March 1, 2021. In a short‐period analysis, patients listed or transplanted between June 1, 2019, and February 29, 2020, were defined as the “pre‐COVID” era, and after April 1, 2020, were defined as the “COVID” era. Interrupted time‐series analyses using monthly count data from 2016‐2020 were constructed to evaluate the rate change for listing and LT before and during the COVID‐19 pandemic. Rates for listings (P = 0.19) and LT (P = 0.14) were unchanged during the pandemic despite a significant reduction in the monthly listing rates for HCV (−21.69%, P < 0.001) and NASH (−13.18%; P < 0.001). There was a significant increase in ALD listing (+7.26%; P < 0.001) and LT (10.67%; P < 0.001) during the pandemic. In the COVID era, ALD (40.1%) accounted for more listings than those due to HCV (12.4%) and NASH (23.4%) combined. The greatest increase in ALD occurred in young adults (+33%) and patients with severe alcohol‐associated hepatitis (+50%). Patients with ALD presented with a higher acuity of illness, with 30.8% of listings and 44.8% of LT having a Model for End‐Stage Liver Disease–Sodium score ≥30.
Conclusions
Since the start of COVID‐19 pandemic, ALD has become the most common indication for listing and the fastest increasing cause for LT. Collective efforts are urgently needed to stem the rising tide of ALD on health care resources.
Background and Aims
In patients with NAFLD, those with type 2 diabetes mellitus (DM) have a high risk of progression to HCC. However, the determinants of HCC risk in these patients remain unclear.
...Approach and Results
We assembled a retrospective cohort of patients with NAFLD and DM diagnosed at 130 facilities in the Veterans Administration between 1/1/2004 and 12/31/2008. We followed patients from the date of NAFLD diagnosis to HCC, death, or 12/31/2018. We used landmark Cox proportional hazards models to determine the effects of anti‐DM medications (metformin, insulin, sulfonylureas) and glycemic control (percent of follow‐up time with hemoglobin A1c < 7%) on the risk of HCC while adjusting for demographics and other metabolic traits (hypertension, obesity, dyslipidemia). We identified 85,963 patients with NAFLD and DM. In total, 524 patients developed HCC during a mean of 10.3 years of follow‐up. Most common treatments were metformin monotherapy (19.7%), metformin‐sulfonylureas (19.6%), insulin (9.3%), and sulfonylureas monotherapy (13.6%). Compared with no medication, metformin was associated with 20% lower risk of HCC (HR, 0.80; 95% CI, 0.93–0.98). Insulin had no effect on HCC risk (HR, 1.02; 95% CI, 0.85–1.22; p = 0.85). Insulin in combination with other oral medications was associated with a 1.6 to 1.7‐fold higher risk of HCC. Adequate glycemic control was associated with a 31% lower risk of HCC (HR, 0.69; 95% CI, 0.62–0.78).
Conclusions
In this large cohort of patients with NAFLD and DM, use of metformin was associated with a reduced risk of HCC, whereas use of combination therapy was associated with increased risk. Glycemic control can serve as a biomarker for HCC risk stratification in patients with NAFLD and diabetes.
BACKGROUND AND AIMS
Nonalcoholic fatty liver disease (NAFLD) is now the most common liver condition. Predicting its progression could help clinicians manage and potentially prevent complications. We ...evaluated the independent and joint effects of metabolic traits on the risk of cirrhosis and hepatocellular carcinoma (HCC) among patients with NAFLD.
APPROACH AND RESULTS
We assembled a retrospective cohort of patients with NAFLD diagnosed at 130 facilities in the Veterans Administration between January 1, 2004, and December 31, 2008, with follow‐up through December 31, 2015. We performed competing risk‐adjusted cause‐specific Cox models to evaluate the effects of metabolic traits (diabetes, hypertension, dyslipidemia, obesity) as additive or combined indicators on time to develop cirrhosis or HCC or a composite endpoint of both. Of the 271,906 patients, 22,794 developed cirrhosis, and 253 developed HCC during a mean of 9 years follow‐up. At baseline, the mean body mass index was 31.6 (SD, 5.6), 28.7% had diabetes, 70.3% had hypertension, and 62.3% had dyslipidemia with substantial overlap among these traits. The risk of progression was the lowest in patients with only one or no metabolic trait. There was a stepwise increase in risk with each additional metabolic trait. Compared with patients with no metabolic trait, patients with both hypertension and dyslipidemia had 1.8‐fold higher risk of progression to cirrhosis/HCC (hazard ratio HR = 1.8, 95% confidence interval CI = 1.59‐2.06); the risk was 2.6‐fold higher in patients with diabetes, obesity, dyslipidemia, and hypertension (HR = 2.6, 95% CI = 2.3‐2.9). These associations were stronger for HCC. Diabetes had the strongest association with HCC in this cohort.
CONCLUSIONS
Each additional metabolic trait increased the risk of cirrhosis and HCC in patients with NAFLD. Diabetes conferred the highest risk of progression to HCC. Patients with diabetes and coexisting hypertension and obesity may be important targets for secondary prevention.
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.
Health care delivery is increasingly evaluated according to quality measures, yet such measures are underdeveloped for cirrhosis. The Practice Metrics Committee of the American Association for the ...Study of Liver Diseases was charged with developing explicit process‐based and outcome‐based measures for adults with cirrhosis. We identified candidate measures from comprehensive reviews of the literature and input from expert clinicians and patient focus groups. We conducted an 11‐member expert clinician panel and used a modified Delphi method to systematically identify a set of quality measures in cirrhosis. Among 119 candidate measures, 46 were identified as important measures to define the quality of cirrhosis care, including 26 process measures, 7 clinical outcome measures, and 13 patient‐reported outcome measures. The final process measures captured care processes for ascites (n = 5), varices/bleeding (n = 7), hepatic encephalopathy (n = 4), hepatocellular cancer (HCC) screening (n = 1), liver transplantation evaluation (n = 2), and other care (n = 7). Clinical outcome measures included survival, variceal bleeding and rebleeding, early‐stage HCC, liver‐related hospitalization, and rehospitalization within 7 and 30 days. Patient‐reported outcome measures covered physical symptoms, physical function, mental health, general function, cognition, social life, and satisfaction with care. The final list of patient‐reported outcomes was validated in 79 patients with cirrhosis from nine institutions in the United States. Conclusion: We developed an explicit set of evidence‐based quality measures for adult patients with cirrhosis. These measures are a tool for providers and institutions to evaluate their care quality, drive quality improvement, and deliver high‐value cirrhosis care. The quality measures are intended to be applicable in any clinical care setting in which care for patients with cirrhosis is provided.
The risk of nonalcoholic fatty liver disease (NAFLD) and its progression may differ between men and women. We conducted a systematic review and meta-analysis to determine the relationship between sex ...and NAFLD, nonalcoholic steatohepatitis (NASH), and advanced NAFLD fibrosis.
Studies reporting sex-stratified NAFLD prevalence among population-based samples and either NASH or advanced fibrosis among patients with biopsy-proven NAFLD were identified from MEDLINE, EMBASE, and Cochrane databases through December 2017. We calculated pooled relative risk ratios comparing women vs men for each outcome.
Our final analysis comprised 54 studies. Samples sizes were 62,239 for the NAFLD analysis, 5428 for the NASH analysis, and 6444 for the advanced fibrosis analysis. Women had a 19% lower risk of NAFLD than men in the general population (pooled risk ratio RR, 0.81; 95% CI, 0.68-0.97; I
= 97.5%). Women had a similar risk of NASH (RR, 1.00; 95% CI, 0.88-1.14; I
= 85.1%), and a 37% higher risk of advanced fibrosis (RR, 1.37; 95% CI, 1.12-1.68; I
= 74.0%) than men. Age modified the effect of sex on NAFLD severity. Risks of NASH (RR, 1.17; 95% CI, 1.01-1.36) and advanced fibrosis (RR, 1.56; 95% CI, 1.36-1.80; I
= 0) were substantially higher in women in study populations with average ages of 50 years and older; sex differences in NASH and advanced fibrosis were attenuated in younger populations.
In a systematic review and meta-analysis, we found women to have a lower risk of NAFLD than men. However, once NAFLD is established, women have a higher risk of advanced fibrosis than men, especially after age 50 years.
Background
The risk and determinants of HCC in patients with primary biliary cholangitis (PBC) are unclear. We conducted a systematic review and meta-analysis of the incidence of HCC and risk factors ...associated with HCC risk among patients with PBC.
Methods
We searched PubMed, EMBASE, MEDLINE, Cochrane databases and reference lists from relevant articles to identify cohort studies that examined incidence of HCC in patients with PBC from inception through November 2019.
Results
A total of 29 studies including 22,615 patients met the eligibility criteria. The median cohort size was 292 patients followed for an average of 76 months. The pooled incidence rate for patients with PBC was 4.17 per 1000 patient-years (95% CI 3.17–5.47). On subgroup analysis, the incidence of HCC in patients with PBC cirrhosis was 15.7 per 1000 patient-years (95% CI 8.73–28.24). The HCC incidence rate was 9.82 per 1000 person-years (95% CI 5.92–16.28) in men and 3.82 per 1000 person-years (95% CI 2.85–5.11) in women.
Conclusions
Cirrhosis is the strongest risk factor for HCC in patients with PBC. Male gender was also a risk factor. Our meta-analysis supports current recommendations of HCC surveillance in patients with PBC cirrhosis. Further studies are needed to evaluate risk factors in this population.
Background and Aims
The long‐term risk of disease for patients with nonalcoholic fatty liver disease (NAFLD) in the absence of elevated enzymes is unclear. We conducted a retrospective cohort study ...using the Corporate Data Warehouse of the Veterans Health Administration.
Approach and Results
We classified patients into three groups: patients with steatosis/normal alanine aminotransferase (ALT), steatosis/elevated ALT, and no steatosis/normal ALT. We examined incidence rates for cirrhosis and hepatocellular carcinoma (HCC) and conducted cause‐specific hazard models to evaluate the risk of cirrhosis and HCC. We identified 3,522 patients with steatosis/normal ALT, 15,419 patients with steatosis/elevated ALT, and 9,267 patients with no steatosis/normal ALT. The mean age in each group was 58.9, 54.7 and 59.3 years, respectively; over 90% were men. Compared to patients with hepatic steatosis/normal ALT, those with steatosis/elevated ALT were younger and more likely to be obese (both P < 0.01). In patients with steatosis/normal ALT, the incidence rates of cirrhosis and HCC were 1.22 (95% confidence interval CI: 0.83‐1.74) and 0.20 (95% CI: 0.06‐0.46) per 1,000 person‐years, respectively; this was lower than in patients with steatosis/elevated ALT (cirrhosis: 3.85; 95% CI: 3.50‐4.23, and HCC: 0.37; 95% CI: 0.26‐0.49). Patients with steatosis/elevated ALT had a higher risk of developing cirrhosis (adjusted hazard ratio: 3.37; 95% CI: 2.34‐4.86; P < 0.01) than patients with steatosis/normal ALT; they also had a higher risk of HCC, although it did not reach statistical significance (hazard ratio: 2.07; 95% CI: 0.82‐5.28; P = 0.13). The risk of cirrhosis and HCC in patients with steatosis/normal ALT and those without steatosis was not significantly different.
Conclusions
Patients with hepatic steatosis with persistently normal ALT are at lower risk for cirrhosis compared to those with steatosis and elevated ALT and not different from the risk in a clinical cohort without hepatic steatosis.
Summary
Background
The hepatitis C virus (HCV) care cascade has changed dramatically following the introduction of direct‐acting anti‐virals (DAAs). Up‐to‐date estimates of the cascade are needed to ...monitor progress, identify key gaps and inform policy.
Aim
To estimate the current and future HCV care cascade in the United States, nationally and in select subpopulations of interest.
Methods
We used a previously validated mathematical model to simulate the landscape of HCV in the United States from 2011 onwards, accounting for HCV screening policy updates, newer HCV treatments and rising HCV incidence.
Results
By the end of 2018, of 4.29 million HCV persons alive, 2.71 million (63%) were actively viremic, 2.24 million (52%) aware and 1.58 million (37%) cured. By 2030, under the status quo, of 3.65 million HCV persons alive, 1.88 million (51%) would be viremic, 2.25 million (62%) aware and 1.77 million (49%) cured. The HCV care cascade in 2018 differed substantially by subpopulation: of 1.34 million incarcerated HCV persons, 96% were viremic, 36% aware and 4% cured; of 0.87 million HCV persons in Medicare, 31% were viremic, 72% aware and 69% cured; and of 0.37 million HCV persons in Medicaid, 49% were viremic, 54% aware and 51% cured. Implementing universal screening, providing unrestricted treatment and controlling HCV incidence were factors found to have the largest effect on improving the HCV care cascade.
Conclusions
Since the launch of DAAs, the HCV care cascade has shifted towards higher awareness and treatment rates; however, additional interventions are needed to move towards HCV elimination.
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