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Kaplan–Meier Survival Curves in HCC Post-Liver Transplantation among Baby Boomers with HCV, ALD, and NASH.
Source publication
We aim to study the impact of the baby boomer (BB) generation, a birth-specific cohort (born 1945-1965) on hepatocellular carcinoma (HCC)-related liver transplantation (LT) in patients with chronic hepatitis C virus (HCV), alcoholic liver disease (ALD), and non-alcoholic steatohepatitis (NASH). We performed a retrospective analysis using the United...
Context in source publication
Context 1
... was no statistical difference (p > 0.05) in short-term (one-year) post-transplant survival rate among BB vs. non-BB HCC-related LT in HCV (BB, 76.1% vs. non-BB, 77.2%), NASH (BB, 76.0% vs. non-BB, 75.6%), or ALD (BB, 77.4% vs. non-BB, 79.0%). However, when comparing post-transplant survival in BB within the three liver disease etiologies, post-transplant survival was highest in ALD, followed by NASH and HCV (Figure 1). ...
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Citations
... A significant part of the deaths observed due to complications of these liver diseases are due to CL, the final stage of liver fibrosis (LF), which develops as a result of a progressive violation of the architecture of the liver 2,4,7-10 . Deaths from HCC in recent years account for more than 30% of deaths from cancer worldwide, not only due to tumors arising in the gastrointestinal tract 3,11,12 . By country or region, the mortality rate from liver cirrhosis in China, the USA and Western European countries is significantly lower than in Central Asian countries. ...
Since the prevalence of acute and especially severe chronic liver diseases of various etiologies increases from year to year, this pathology is recognized as the main burden on health worldwide. Currently, it has been established that the use of drugs based on essential phospholipids and plant origin with antioxidant and hepatoprotective activity is very effective in the prevention and treatment of liver diseases. In this regard, we studied under experimental conditions the effect of phytocomposition of soy lecithin, glycyrrhizic acid, lycopene and ecdysterone (conditional name hepalipin) and proanthacyanidin (conditional name yantacin) isolated from the plant Alhagi pseudalhagi on cytolytic-cholestatic liver damage, as well as on the development of fibrosis. In this study, we evaluated the hepatoprotective and antifibrotic effects of a new combination called Hepatocin obtained in a 1:1 ratio (100 mg/kg of Hepalipin and 100 mg/kg of Yantacin). All the studies conducted were conducted on adult nonlinear rats, while the experimental animals were divided into a control group infected with heliotrin, a substance with hepatotoxic action, a group receiving hepatocin, and an intact group that was not infected with heliotrin at the same time. In the conducted studies, hepatocin significantly inhibited the development of cytolytic-cholestatic liver damage, helped to maintain the functions of the liver synthesizing protein and glycogen, and when administered to experimental animals against the background of a chronic disease developing as a result of damage by heliotrin, it has an antioxidant effect. In addition, the use of hepatocin for more than two months in chronic liver damage or early stage fibrosis led to the restoration of serum enzymes of experimental animals, as well as regulators of cytochrome P450 and b5 fibrogenesis in liver tissues, PCNA, PDGF-BB to levels almost close to the initial (intact) values. Thus, in experimental conditions of chronic severe hepatitis or early stage fibrosis, hepatocin showed statistically significant advantages over Phosphogliv in terms of the intensity of hepatoprotective or antifibrotic action.
... Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide [1]; the global burden of liver cancer is projected to increase by 32% by 2040 [2][3][4]. Hepatitis C virus (HCV) is the most common cause of HCC in Western countries and disproportionately affects Americans born between 1945 and 1965 who consequently are at an increased risk of developing HCC [5]. The approval of direct-acting antiviral agents (DAA) has changed the landscape of HCV treatment with achievement of cure being associated with a reduction in HCC risk [6][7][8][9]. ...
Background and Aims
The burden of hepatocellular carcinoma (HCC) is increasing, and certain groups may be at higher risk.
Methods
We analyzed trends in HCC-related mortality in the USA (1999–2018) using national death data. Age-adjusted trends in death rates (annual percentage change, APC) were calculated using joinpoint regression analysis.
Results
HCC-related death rates increased by 2.1% (95% CI 1.9 to 2.3) annually. Hepatitis C (HCV)-related HCC death rates increased from 1999 to 2012 (8.9%, 95% CI 7.6 to 10.2) followed by a −1.3% (95% CI −3.5 to 0.9) decrease annually. For adults > 65 years, HCV-related HCC death rates increased (7.3% annually, 95% CI 6.5 to 8.1), especially for rural areas (11.1% annually, 95% CI 6.9 to 15.5) with high rates among African-Americans and Hispanics. Increases in non-HCV-related HCC death rates were larger: 13.5% annually (95% CI 3.6 to 24.3, 2005–2010) followed by 4.2% annually (95% CI 2.3 to 6.2, 2010–2018). Annual rates of increase were similar for men (6.8%, 95% CI 5.9 to 7.8) and women (7.0%, 95% CI 5.5 to 8.4) from 1999 to 2018. Rate of increase across races was Whites 8.3% (95% CI 7.2 to 9.4, 1999–2018), African-Americans 11.2% (95% CI −6.6 to 32.3, 2015–2018), and Hispanics 3.7% (95% CI 1.0 to 6.5, 2012–2018).
Conclusion
HCC-related mortality has increased, driven by increases in non-HCV-related mortality with important demographic and regional trends. In addition, HCV-HCC mortality remains high particularly in older persons and those in rural areas despite advances in HCV therapy. These data underscore the need for targeted approaches to mitigate the burden of HCC-related mortality similar to efforts for other cancers.
... Nevertheless, HCC mortality rates as a whole have not followed the same downward trend, unlike other gastroenterological (GI)-related malignancies. As of 2021, HCC remains the third leading cause of cancerrelated death worldwide [2, 3], largely due to the increase in the number of HCC cases caused by alcohol-related liver disease (ALD) and NAFLD [3]. In order to combat this rise in HCC-related mortality, it is imperative to understand the patterns underlying these increasing numbers and more importantly identify interventions in order to prevent the rise of non-HCV related chronic liver disease. ...
... Early detection of the virus is important for the physical and mental health of the individuals because only the screened, diagnosed and linked to care can benefit from DAAs' potential [25]. Without screening, a late diagnosis is translated in hospitalization and death due to rising rates of hepatocellular carcinoma [27]. ...
Background:
The elimination of the Hepatitis C virus (HCV) will only be possible if rapid and efficient actions are taken. Artificial neural networks (ANNs) are computing systems based on the topology of the biological brain, containing connected artificial neurons that can be tasked with solving medical problems.
Aim:
We expanded the previously presented HCV micro-elimination project started in September 2020 that aimed to identify HCV infection through coordinated screening in asymptomatic populations and developed two ANN models able to identify at-risk subjects selected through a targeted questionnaire.
Material and method:
Our study included 14,042 screened participants from a southwestern region of Oltenia, Romania. Each participant completed a 12-item questionnaire along with anti-HCV antibody rapid testing. Hepatitis-C-positive subjects were linked to care and ultimately could receive antiviral treatment if they had detectable viremia. We built two ANNs, trained and tested on the dataset derived from the questionnaires and then used to identify patients in a similar, already existing dataset.
Results:
We found 114 HCV-positive patients (81 females), resulting in an overall prevalence of 0.81%. We identified sharing personal hygiene items, receiving blood transfusions, having dental work or surgery and re-using hypodermic needles as significant risk factors. When used on an existing dataset of 15,140 persons (119 HCV cases), the first ANN models correctly identified 97 (81.51%) HCV-positive subjects through 13,401 tests, while the second ANN model identified 81 (68.06%) patients through only 5192 tests.
Conclusions:
The use of ANNs in selecting screening candidates may improve resource allocation and prioritize cases more prone to severe disease.
... Chronic HCV infection may progress to liver cirrhosis, end-stage liver disease, and hepatocellular carcinoma, with late diagnosis associated with more severe outcomes, including death. 12 A majority of acute HCV infections are asymptomatic, and about half of all chronically infected individuals are unaware of their infection status. 13 Antiviral regimens for HCV are well tolerated and result in a >90% cure rate. ...
Infection with the hepatitis C virus (HCV) is the most commonly reported bloodborne infection in the United States. Individuals born between 1945-1965, the baby boomers, account for approximately 75% of all chronic HCV infections in the United States. The purpose of this study was to determine if a 6-week intervention, including outreach, education, and incentive, by a community-based health insurance company could improve uptake of HCV antibody screening among the 1945-1965 birth cohort. Individuals were eligible to participate in this campaign if they were born on or after January 1, 1945 and on or before December 31, 1965, had health insurance with Sendero Health Plans during the intervention period, and had no evidence of having received an HCV antibody test prior to the campaign start date. The 6-week campaign period was from November 14, 2018 through December 31, 2018. A gift card incentive was provided if HCV screening was completed on or before December 31, 2018. A total of 5287 individuals were eligible to participate in the campaign. Members who were baby boomers were 3.36 times more likely to receive HCV antibody screening during the intervention period in 2018 than during a similar period in 2017 (prevalence ratio = 3.36; P < 0.0001; 95% confidence interval: 2.71, 4.16). Health officials have established the identification, treatment, and elimination of HCV as a national policy objective. Using an outreach, education, and incentive approach, Sendero Health Plans improved uptake of HCV antibody screening among the high-risk baby boomer population.
... 26 The proportion of baby boomer LT recipients with NASH also increased incrementally, coming in second after recipients with HCV. 27 While the number of waitlist registrants with NASH is rapidly increasing, earlier studies demonstrated that patients with NASH are less likely to receive an LT when compared with patients with HCV; the NASH patients were ultimately more likely to be delisted or die before receiving an LT. 28 However, in an analysis of the UNOS data from 2002 to 2016, Thuluvath et al demonstrated that patients with NASH are not disadvantaged by higher waitlist removal or lower transplant rates when compared with their counterparts with other liver disease etiologies. ...
Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease in Western countries, and its aggressive form, nonalcoholic steatohepatitis (NASH), is a leading cause of cirrhosis and end-stage liver disease. The total number of new liver transplantation waitlist registrants with NASH continues to increase rapidly, making NASH the second most common indication for liver transplantation. Compared with recipients for other etiologies, patients with NASH often have higher rates of obesity, diabetes, dyslipidemia, hypertension, kidney disease, and cardiac disease. Many of these medical comorbidities are independently associated with increased preoperative risk and both short- and long-term complications. The presence of these particular risk factors necessitates the need for early detection, medical optimization, and careful preoperative care. Bariatric surgery is an effective strategy for weight loss and ultimately reducing obesity-related medical complications. In select patients, bariatric surgery—before, during, or after liver transplantation—may be useful to help improve posttransplant outcomes. NAFLD/NASH can present after liver transplantation and occurs as either recurrent or de novo disease. Posttransplant NAFLD occurs in the setting of metabolic syndrome, immunosuppression use, and genetic determinants. Future studies and efforts should focus on optimizing medical management strategies to further improve transplant outcomes in patients with NAFLD.
... Liver transplantation is a definitive and effective treatment option for HCC, but there are strict eligibility criteria for the liver transplantation waitlist. Studies have shown that liver transplantation rates for HCC have doubled in the US over the past decade [20]. According to a study using the United Network for Organ Sharing (UNOS) data from 2003 to 2014, Cholankeril et al. noted that while overall liver transplantation rates for HCV-related HCC have more than doubled, liver transplantation rates have tripled in BB, constituting 80.1% of all HCC-related liver transplants in the US [20]. ...
... Studies have shown that liver transplantation rates for HCC have doubled in the US over the past decade [20]. According to a study using the United Network for Organ Sharing (UNOS) data from 2003 to 2014, Cholankeril et al. noted that while overall liver transplantation rates for HCV-related HCC have more than doubled, liver transplantation rates have tripled in BB, constituting 80.1% of all HCC-related liver transplants in the US [20]. Our retrospective cohort study using the HCUP-NIS database has several limitations. ...
Introduction and objectives:
Three fourths of chronic hepatitis C virus (HCV) infected adult patients in the United States (US) are born between 1945 and 1965, also known as baby boomers (BB). Prevalence of hepatocellular carcinoma (HCC) is raising in BB due to their advancing age and prolonged HCV infection. We evaluated inpatient hospitalization and mortality in BB associated with HCC.
Materials and methods:
It is a retrospective cohort study utilizing the Healthcare Utilization Project-National Inpatient Sample (HCUP-NIS) database. From 2003 to 2012, top five primary cancer related hospitalization and mortality among BB were studied.
Results:
Among 48,733 hospitalizations related to HCC in HCUP-NIS database from 2003 to 2012, BB accounted for 49.6% (24,210) whereas non-BB 50.4% (24,523). Within BB cohort, the top five cancers with the highest proportion of hospitalizations were HCC (46%), prostate (43%), kidney (41%), pancreas (33%), and bladder (21%). From 2003 to 2012, the proportion of HCC related hospitalizations represented by BB almost doubled (33.5 to 57.8%) whereas there was one-third reduction (66.4 to 42.1%) among non-BB. Similarly, HCC-related inpatient mortality in BB decreased by 28% (6.1 to 2.7 per 100,000 hospitalization) but it remained unchanged in non-BB (11.1 to 10.6). HCC accounted for 2nd highest mortality (4960 total deaths) among hospitalized BB behind pancreatic cancer. HCC related to HCV was disproportionately higher in BB compared to non-BB (50.6% vs. 19%; P<0.001).
Conclusion:
HCC ranks number one among the top five cancers with highest proportion of inpatient burden. Future studies should focus on understanding the underlying reasons for this ominous trend.
... In the USA, up to 80% of individuals infected with HCV were born during the 'baby boom' between 1946 and 1964 [27]. Data suggests that individuals born during this period are five times more likely to have chronic HCV infection than other adults [28]. ...
Hepatitis C (HCV) and hepatitis B (HBV), are blood-borne viruses that can cause acute hepatitis; but are clinically relevant because chronic infection is associated with development of cirrhosis and hepatocellular carcinoma. Both these viruses are becoming more common in the older population, due to the ageing of generations exposed to the risk factors associated with infection; intravenous drug use, multiple sexual partners and men who have sex with men. This review will cover the natural history and epidemiology of these infections as well as the revolution in drug therapy that now allows cure of HCV infection and complete control of HBV infection.
... Rates of HCC among the 1945-1965 birth cohort have increased in incidence by 58.7% over the past decade and are expected to continue growing over time. (13) Using data from the Centers for Disease Control and Prevention, the National Cancer Institute, and the North American Association of Central Cancer Registries, Ryerson et al. (2) reported that while overall U.S. cancer deaths for men and women combined declined by 1.5% per year from 2003 to 2012, liver cancer incidence rates overall increased sharply, and deaths from liver cancer increased at the highest rates of all cancer sites (mean annual percentage increase of 3.4%). The authors did not specifically evaluate trends in HCC diagnosed among the 1945-1965 birth cohort, and few studies have focused on the national burden of HCC among the 1945-1965 birth cohort. ...
... This highlights the continued increasing burden of HCC among this cohort and emphasizes the importance of timely implementation of HCC screening and surveillance among 1945-1965 birth cohort patients at high risk of developing HCC. (13,14) HCV remains a major driver in the increasing number of registrants and recipients for liver transplantation in the 1945-1965 birth cohort. (14)(15)(16)(17) An estimated 3.3% of the 1945-1965 birth cohort have the HCV antibody and account for nearly 75% of all U.S. HCV infections. ...
... (18) The availability of highly effective direct-acting antivirals for the treatment of chronic HCV will likely translate into reductions in HCV-associated HCC; however, overall trends in HCC may not necessarily peak, given the emergence of nonalcoholic steatohepatitis (NASH)-related HCC. (19)(20)(21) Cholankeril et al. (13) performed a retrospective analysis using the United Network for Organ Sharing/Organ Procurement Transplant Network database from 2003 to 2014 to compare HCC-related liver transplant trends between 1945 and 1965 and non-1945-1965 birth cohorts. They reported that 80.1% of all HCC-related liver transplants were of the 1945-1965 birth cohort alone. ...
Individuals from the 1945‐1965 birth cohort account for the majority of hepatocellular carcinoma (HCC) cases in the United States. Understanding trends in HCC among this birth cohort is vital given the increasing burden of chronic liver disease among this group. We retrospectively evaluated trends and disparities in HCC tumor stage at the time of diagnosis among the 1945‐1965 birth cohort in the United States using the Surveillance, Epidemiology, and End Results (SEER) cancer registry. Tumor stage at the time of HCC diagnosis was assessed using Milan criteria and SEER HCC staging systems. Among 38,045 patients with HCC within the 1945‐1965 birth cohort (81.6% male, 50.1% non‐Hispanic white, 16.2% African American, 12.6% Asian, 19.8% Hispanic), 66.2% had Medicare or commercial insurance, 27.2% had Medicaid, and 6.6% were uninsured. During the period 2004‐2006 to 2013‐2014, the number of patients with HCC from the 1945‐1965 birth cohort increased by 58.7% (5.9% increase per year). While the proportion of patients with HCC within the Milan criteria increased with time (36.4% in 2003‐2006 to 46.3% in 2013‐2014; P < 0.01), less than half were within the Milan criteria. On multivariate analysis within the Milan criteria, men were 12% less likely to have HCC compared to women, and African Americans were 27% less likely to have HCC compared to non‐Hispanic whites (odds ratio, 0.73; 95% confidence interval, 0.68‐0.78; P < 0.01). Conclusion : From 2004 to 2014, the burden of newly diagnosed HCC among the 1945‐1965 birth cohort increased by 5.9% per year. While improvements in earlier staged HCC at diagnosis were observed, the majority of patients with HCC among the 1945‐1965 birth cohort were beyond the Milan criteria at diagnosis; this may reflect poor utilization or suboptimal performance of HCC screening tests.
... 14 In a retrospective study of liver transplant (LT) recipients in the United States from 2002 to 2012, NASH was noted to be the second leading etiology of HCC-related liver transplantation, 15 whereas other similarly designed studies also have shown or projected the presence of an increasing trend. 2,[16][17][18][19][20] All this is accompanied by an alarming conundrum in the field of NAFLD and NASH: despite rapid growth in the burden of the disease, there are no validated diagnostic or prognostic noninvasive biomarkers for NASH and related fibrosis, and there are no effective pharmacologic therapies with proven efficacy and safety. [21][22][23] In earlier studies, NASH increasingly was shown to contribute to the cohort of patients who receive a liver transplant in the United States, including those who received a transplant because of HCC. ...
... [21][22][23] In earlier studies, NASH increasingly was shown to contribute to the cohort of patients who receive a liver transplant in the United States, including those who received a transplant because of HCC. 2,15,16,18,20 It is plausible that patients with NASH actually may present late in the course of their disease with more advanced liver disease and a higher stage of HCC, both of which potentially can affect their status on the transplant list and their post-LT outcomes. Therefore, the aim of our study was to use the most recent longitudinal data from a national registry to assess changes in LT listings for HCC according to underlying etiologies of liver disease and to compare their on-the-list and post-LT outcomes. ...
Background:
While hepatitis B and C have been the main drivers of hepatocellular carcinoma (HCC), non-alcoholic steatohepatitis (NASH) has recently become an important cause of HCC. The aim of this study was to assess the causes of HCC among liver transplant (LT) candidates in the U.S.
Methods:
The Scientific Registry of Transplant Recipients (2002-2016) was used to estimate the trends in prevalence of HCC in LT candidates with the most common types of chronic liver disease: alcoholic liver disease (ALD), chronic hepatitis B (CHB), chronic hepatitis C, and NASH.
Results:
158,347 adult LT candidates were included. Of these, 26,121 (16.5%) had HCC; this proportion increased from 6.4% (2002) to 23.0% (2016) (trend p<0.0001). Over the study period, CHC remained the most common etiology for HCC (65%). The proportions of HCC accounted for by CHC and ALD remained stable (both trend p>0.10), the proportion of CHB decreased 3.1-fold (p<0.0001), while the proportion of NASH in HCC increased 7.7-fold (from 2.1% to 16.2%, p<0.0001). Furthermore, since 2002, the prevalence of HCC in LT candidates with NASH increased 11.8-fold, while this rate increased 6.0-fold in CHB, 3.4-fold in ALD and 2.3-fold in CHC (all p<0.0001); the increasing trend in NASH was steeper than that for any other etiology (p<0.0001 in a trend regression model). The proportion of LT candidates with HCC who were ultimately transplanted or died while waiting did not differ between etiologies (p>0.05).
Conclusions:
Non-alcoholic steatohepatitis is the most rapidly growing cause of HCC among U.S. patients listed for liver transplantation.
