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Rising Rates of Hepatocellular Carcinoma Leading to Liver Transplantation in Baby Boomer Generation with Chronic Hepatitis C, Alcohol Liver Disease, and Nonalcoholic Steatohepatitis-Related Liver Disease

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George Cholankeril at Stanford Medicine
George Cholankeril
Eric R Yoo
Eric R Yoo
Ryan B Perumpail
Ryan B Perumpail
Ryan B Perumpail
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Andy Liu at 台大
Andy Liu
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Abstract and Figures

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 Network for Organ Sharing (UNOS)/Organ Procurement Transplant Network (OPTN) database from 2003 to 2014 to compare HCC-related liver transplant surgery trends between two cohorts-the BB and non-BB-with a secondary diagnosis of HCV, ALD, or NASH. From 2003-2014, there were a total of 8313 liver transplant recipients for the indication of HCC secondary to HCV, ALD, or NASH. Of the total, 6658 (80.1%) HCC-related liver transplant recipients were BB. The number of liver transplant surgeries for the indication of HCC increased significantly in NASH (+1327%), HCV (+382%), and ALD (+286%) during the study period. The proportion of BB who underwent LT for HCC was the highest in HCV (84.7%), followed by NASH (70.3%) and ALD (64.7%). The recommendations for birth-cohort specific HCV screening stemmed from a greater understanding of the high prevalence of chronic HCV and HCV-related HCC within BB. The rising number of HCC-related LT among BB with ALD and NASH suggests the need for increased awareness and improved preventative screening/surveillance measures within NASH and ALD cohorts as well.
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diseases
Article
Rising Rates of Hepatocellular Carcinoma Leading to
Liver Transplantation in Baby Boomer Generation
with Chronic Hepatitis C, Alcohol Liver Disease,
and Nonalcoholic Steatohepatitis-Related
Liver Disease
George Cholankeril 1, Eric R. Yoo 2ID , Ryan B. Perumpail 3, Andy Liu 4, Jeevin S. Sandhu 1,
Satheesh Nair 5, Menghan Hu 6and Aijaz Ahmed 1, *
1
Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305,
USA; gcholankeril@gmail.com (G.C.); jsandhu@oxy.edu (J.S.S.)
2
Department of Medicine, Santa Clara Valley Medical Center, San Jose, CA 95128, USA; eric.r.yoo@gmail.com
3Division of Gastroenterology and Hepatology, University of California, Los Angeles, CA 90095, USA;
rperumpail@gmail.com
4Department of Medicine, California Pacific Medical Center, San Francisco, CA 94114, USA;
andyeliu@gmail.com
5Division of Gastroenterology and Hepatology, University of Tennessee Health Sciences Center, Memphis,
TN 38163, USA; snair@uthsc.edu
6Department of Biostatistics, Brown University School of Public Health, Providence, RI 02912, USA;
menghan_hu@brown.edu
*Corresponding: aijazahmed@stanford.edu; Tel.: +1-650-498-6091
Received: 28 August 2017; Accepted: 25 September 2017; Published: 26 September 2017
Abstract:
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 Network for Organ Sharing
(UNOS)/Organ Procurement Transplant Network (OPTN) database from 2003 to 2014 to compare
HCC-related liver transplant surgery trends between two cohorts—the BB and non-BB—with
a secondary diagnosis of HCV, ALD, or NASH. From 2003–2014, there were a total of 8313 liver
transplant recipients for the indication of HCC secondary to HCV, ALD, or NASH. Of the total, 6658
(80.1%) HCC-related liver transplant recipients were BB. The number of liver transplant surgeries for
the indication of HCC increased significantly in NASH (+1327%), HCV (+382%), and ALD (+286%)
during the study period. The proportion of BB who underwent LT for HCC was the highest in
HCV (84.7%), followed by NASH (70.3%) and ALD (64.7%). The recommendations for birth-cohort
specific HCV screening stemmed from a greater understanding of the high prevalence of chronic HCV
and HCV-related HCC within BB. The rising number of HCC-related LT among BB with ALD and
NASH suggests the need for increased awareness and improved preventative screening/surveillance
measures within NASH and ALD cohorts as well.
Keywords:
baby boomer; hepatitis C virus; alcoholic liver disease; non-alcoholic steatohepatitis;
liver transplantation
1. Introduction
The incidence of hepatocellular carcinoma (HCC) has been rising at an alarming rate with over
half a million new cases diagnosed annually worldwide [
1
]. In the United States (U.S.), HCC is the
Diseases 2017,5, 20; doi:10.3390/diseases5040020 www.mdpi.com/journal/diseases
Diseases 2017,5, 20 2 of 5
most rapidly rising cause of cancer and cancer-related deaths with an incidence that has tripled over
the last decade [
2
]. This rise in HCC incidence is largely due to the high prevalence of chronic hepatitis
C virus (HCV) infection, which has recently surpassed 3 million people [3].
The incidence of HCV has shown a disproportionate birth specific-cohort effect, with up to 80%
of HCV infection seen in baby boomers (BB), Americans born between 1945 and 1965 [
4
]. Due to
their long-standing chronic HCV infection, this aging birth specific-cohort has a higher likelihood for
developing HCC [
5
,
6
]. With an otherwise dismal prognosis, select HCC patients may be candidates
for liver transplantation (LT). The number of HCV-infected BB with HCC awaiting LT has already
increased nearly four-fold over the last two decades [
7
,
8
]. However, the impact of HCC LT among BB
within other leading liver disease etiologies, such as non-alcoholic steatohepatitis (NASH) and alcoholic
liver disease (ALD), has yet to be determined. We aim to study the impact of the BB birth-specific
cohort on LT recipients with HCV-related HCC, ALD-related HCC, and NASH-related HCC.
2. Methods
We utilized the registry data from the United Network for Organ Sharing (UNOS)/Organ
Procurement Transplant Network (OPTN) database to compare HCC LT trends in all adults (
age ≥18
)
from 2003 to 2014. Birth cohort-specific disparities in HCC LT were evaluated by categorizing patients
into two cohorts: BB and non-BB (non-baby boomers—born pre-1945 or post-1965). The underlying
etiology of HCC was determined by secondary diagnosis coding of liver disease etiology among
patients with HCC undergoing LT. Liver disease etiologies were categorized into HCV, ALD, or NASH.
In addition to using patients listed with a secondary diagnosis of NASH with HCC, we estimated
the number of patients with NASH in cryptogenic cirrhosis or cirrhosis due to unknown etiology
categories on a body mass index based on previously defined criteria [8].
We studied the proportion of HCC-related liver transplant surgeries according to their secondary
etiology and analyzed the annual trends in these breakdowns from 2003 and 2014. Additionally,
we compared demographic data (age, gender, ethnicity), and clinical comorbidities including hepatic
encephalopathy (HE), ascites, and diabetes within these two cohorts using chi-square testing for
categorical variables. Statistical significance was met using a two-tailed pvalue < 0.05. Post-transplant
survival was analyzed with Kaplan–Meier methods. All statistical analyses were performed with Stata
(Version 10; Stata Corporation, College Station, TX, USA).
3. Results
From 2003 to 2014, there were a total of 8313 HCC-related liver transplant surgeries for HCC
secondary to HCV, ALD, or NASH. HCV-related HCC had the highest proportion of LT (n= 6034,
72.6%) followed by NASH-related HCC (n= 1350, 16.2%) and ALD- related HCC (n= 929, 11.2%).
The BB cohort constituted 6658 (80.1%) of all HCC-related liver transplant recipients. From 2003 to 2014
the number of HCC-related liver transplant recipients increased nine-fold in NASH (+905%) and more
than doubled in HCV (+268%) and ALD (+208%). In a similar fashion, the number of liver transplant
surgeries for HCC among BB rose significantly in NASH (+1327%), HCV (+382%), and ALD (+286%).
The overall annual trends in HCC-related LT among BB for HCV, NASH, and ALD are depicted in
Table 1. The proportion of BB who underwent LT for HCC was the highest in HCV (84.7%), followed
by NASH (70.3%), and ALD (64.7%). The highest annual increment in BB proportion of HCC-related
LT was noted in NASH (+3.5%), followed by HCV (+2.6%), and ALD (+2.1%).
Demographic and clinical characteristics between BB and non-BB cohorts undergoing LT for HCC
among HCV, NASH, and ALD are outlined in Table 2. Compared to non-BB, HCC-related LT in BB
also had a higher prevalence of males in HCV (BB, 80.3% vs. non-BB, 66.1%, p< 0.01) and NASH (BB,
73.0% vs. non-BB, 65.1%, p< 0.01) (Table 2). The BB HCC cohort also had a higher prevalence of other
complications of end-stage liver disease including HE (BB, 40.2% vs. non- BB, 34.8%, p< 0.01) and
ascites (BB, 50.9% vs. non-BB, 46.8%, p< 0.01).
Diseases 2017,5, 20 3 of 5
Table 1.
Baby Boomer HCC Liver Transplantation Annual Trends with HCV, ALD, and NASH;
UNOS 2003–2014.
HCV NASH ALD
BB †Overall Percent BB Overall Percent BB Overall Percent
2003 149 216 69.0% 11 19 57.9% 22 37 59.5%
2004 167 224 74.6% 20 38 52.6% 16 33 48.5%
2005 218 297 73.4% 22 47 46.8% 28 59 47.5%
2006 271 351 77.2% 37 71 52.1% 36 75 48.0%
2007 373 461 80.9% 54 90 60.0% 38 85 44.7%
2008 427 505 84.6% 80 124 64.5% 48 79 60.8%
2009 460 540 85.2% 96 151 63.6% 56 76 73.7%
2010 492 585 84.1% 101 132 76.5% 45 66 68.2%
2011 567 632 89.7% 91 128 71.1% 81 107 75.7%
2012 619 707 87.6% 127 168 75.6% 77 106 72.6%
2013 646 722 89.5% 153 191 80.1% 69 92 75.0%
2014 719 794 90.6% 157 191 82.2% 85 114 74.6%
Total 5108 6034 84.7% 949 1350 70.3% 601 929 64.7%
APC
‡+2.6% +3.5% +2.1%
†BB = Baby Boomer; ‡APC = Annual Percent Change.
Table 2.
Demographic and Clinical Characteristics in HCC Liver Transplant Recipients among Baby
Boomers versus Non-Baby Boomers; UNOS 2003–2014.
HCV NASH ALD
BB
n= 5108
Non-BB
n= 926 pBB
n= 949
Non-BB
n= 401 pBB
n= 601
Non-BB
n= 328 p
Age, median 57 66 <0.01 59 67 <0.01 58 67 <0.01
Gender
Male 80.3% 66.1% <0.01 73.0% 65.1% <0.01 90.5% 89.6% 0.67
Ethnicity
White 67.7% 59.1% <0.01 75.9% 77.6% 0.50 69.6% 78.7% <0.01
Black 13.3% 11.1% 0.07 5.4% 3.7% 0.20 3.8% 1.2% 0.02
Hispanic 13.6% 17.6% <0.01 14.7% 14.5% 0.93 14.7% 14.5% 0.14
Asian 4.1% 11.1% <0.01 2.6% 2.2% 0.67 3.0% 1.2% 0.89
Other 9.9% 1.1% <0.01 1.4% 2.0% 0.49 8.9% 4.4% <0.05
HE 40.2% 34.8% <0.01 43.4% 41.4% <0.50 50.3% 43.9% 0.09
Diabetes 23.6% 28.4% <0.01 47.7% 47.7% <0.01 35.1% 33.5% 0.63
Ascites 50.9% 46.8% <0.05 55.2% 55.2% 0.84 68.6% 62.5% 0.06
There 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).
Diseases 2017,5, 20 4 of 5
Diseases 2017, 5, 20 4 of 5
Figure 1. Kaplan–Meier Survival Curves in HCC Post-Liver Transplantation among Baby Boomers
with HCV, ALD, and NASH.
4. Discussion
Since the implementation of the Model for End Stage Liver Disease (MELD) for liver allocation,
the number of HCC patients who underwent LT has risen significantly. While previous studies have
attributed this rising trend in HCC incidence and surgical intervention to BB cohort, these studies
only evaluated its impact on HCV-related HCC [9]. Although HCV continues to be the leading liver
disease etiology for HCC-related LT, there is a significant rise in NASH-related HCC and ALD-
related HCC leading to LT. Our analysis suggests that the BB cohort has influenced the rise in overall
HCC-related LT in all three liver disease etiologies. Aside from the birth specific-cohort effect, our
current allocation policy has also influenced the dramatic rise in the number HCC-related LT.
Candidates with HCC awaiting LT are eligible to receive a MELD exception resulting in higher
priority and increased likelihood of undergoing liver transplant surgery [10].
As the BB generation age, they have an increased risk of developing and suffering from chronic
health conditions and present a complicated challenge for healthcare providers in the future.
Therefore, there will be an increasing demand to allocate resources on policies highlighting
preventative health in the BB cohort. The 2012 guideline set by the Centers for Disease Control and
Prevention, the 2013 guideline set by the United States Preventative Services Task Force (USPSTF),
and the 2014 guideline set by the American Association for the Study of Liver Disease (AASLD) in
conjunction with the Infectious Disease Society of America have highlighted the increasing evidence
of the benefits of age-based HCV testing [1,11]. The recommendations for birth-cohort specific HCV
screening stemmed from a greater understanding of the high prevalence of chronic HCV and HCV-
related HCC within the BB generation. However, the rising number of HCC-related LT among BB
generation with ALD and NASH suggests the need for increased awareness and improved
preventative screening/surveillance for HCC in these sub-cohorts.
Author Contributions: George Cholankeril—study concept and design, acquisition of data, analysis and
interpretation of data, and drafting of the initial and final manuscript; Eric R. Yoo—study concept and design,
interpretation of data, drafting of the manuscript, and critical revision of the manuscript; Ryan B. Perumpail—
study concept and design, interpretation of data, drafting of the manuscript, and critical revision of the
manuscript; Andy Liu—study concept and design, interpretation of data, drafting of the manuscript, and critical
revision of the manuscript; Jeevin S. Sandhu—study concept and design, interpretation of data, drafting of the
Figure 1.
Kaplan–Meier Survival Curves in HCC Post-Liver Transplantation among Baby Boomers
with HCV, ALD, and NASH.
4. Discussion
Since the implementation of the Model for End Stage Liver Disease (MELD) for liver allocation,
the number of HCC patients who underwent LT has risen significantly. While previous studies have
attributed this rising trend in HCC incidence and surgical intervention to BB cohort, these studies only
evaluated its impact on HCV-related HCC [
9
]. Although HCV continues to be the leading liver disease
etiology for HCC-related LT, there is a significant rise in NASH-related HCC and ALD-related HCC
leading to LT. Our analysis suggests that the BB cohort has influenced the rise in overall HCC-related
LT in all three liver disease etiologies. Aside from the birth specific-cohort effect, our current allocation
policy has also influenced the dramatic rise in the number HCC-related LT. Candidates with HCC
awaiting LT are eligible to receive a MELD exception resulting in higher priority and increased
likelihood of undergoing liver transplant surgery [10].
As the BB generation age, they have an increased risk of developing and suffering from chronic
health conditions and present a complicated challenge for healthcare providers in the future. Therefore,
there will be an increasing demand to allocate resources on policies highlighting preventative health
in the BB cohort. The 2012 guideline set by the Centers for Disease Control and Prevention, the 2013
guideline set by the United States Preventative Services Task Force (USPSTF), and the 2014 guideline
set by the American Association for the Study of Liver Disease (AASLD) in conjunction with the
Infectious Disease Society of America have highlighted the increasing evidence of the benefits of
age-based HCV testing [
1
,
11
]. The recommendations for birth-cohort specific HCV screening stemmed
from a greater understanding of the high prevalence of chronic HCV and HCV-related HCC within the
BB generation. However, the rising number of HCC-related LT among BB generation with ALD and
NASH suggests the need for increased awareness and improved preventative screening/surveillance
for HCC in these sub-cohorts.
Diseases 2017,5, 20 5 of 5
Author Contributions:
George Cholankeril—study concept and design, acquisition of data, analysis and
interpretation of data, and drafting of the initial and final manuscript; Eric R. Yoo—study concept and design,
interpretation of data, drafting of the manuscript, and critical revision of the manuscript; Ryan B. Perumpail—study
concept and design, interpretation of data, drafting of the manuscript, and critical revision of the manuscript;
Andy Liu—study concept and design, interpretation of data, drafting of the manuscript, and critical revision of
the manuscript; Jeevin S. Sandhu—study concept and design, interpretation of data, drafting of the manuscript,
and critical revision of the manuscript; Satheesh Nair—study concept and design, interpretation of data, drafting
of the manuscript, and critical revision of the manuscript; Menghan Hu—study concept and design, interpretation
of data, drafting of the manuscript, and critical revision of the manuscript; Aijaz Ahmed—study concept and
design, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript,
and study supervision.
Conflicts of Interest: The authors declare no conflicts of interest.
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... 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]. ...
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... 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. ...
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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.
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... 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. ...
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... 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]. ...
Hepatocellular Carcinoma-Related Mortality in the USA, 1999–2018
Article
Full-text available
  • Aug 2022
  • DIGEST DIS SCI
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.
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... 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]. ...
Resource Management through Artificial Intelligence in Screening Programs—Key for the Successful Elimination of Hepatitis C
Article
Full-text available
  • Jan 2022
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.
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... 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. ...
Hepatitis C Antibody Screening Among Baby Boomers by a Community-Based Health Insurance Company
Article
Full-text available
  • Nov 2020
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.
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... 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. ...
Multidisciplinary Approach for Liver Transplantation in Patients with Nonalcoholic Steatohepatitis: It Takes a Village
Article
  • Mar 2020
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.
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... 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]. ...
New horizons in hepatitis B and C in the older adult
Article
  • Oct 2018
  • AGE AGEING
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.
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Prevention and Treatment of Viral Hepatitis
Chapter
  • Jun 2019
The most common hepatotropic viruses observed after solid organ transplantation (SOT) are hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis E virus (HEV). The direct-acting agents against HCV allowed to definitely clear the virus in the large majority of SOT patients and candidates to organ transplantation. The actual challenge is the timing of starting anti-HCV therapy: before or after transplantation? Because of the efficacy of nucleos(t)ide analogue (NA) therapy, HBV-related severe liver disease has become an uncommon indication for liver transplantation in Western countries. HBV prevalence is also quite low both in dialysis patients and in kidney transplant patients. HEV infection has been shown to be responsible for chronic hepatitis in SOT patients. It can also be associated to extrahepatic manifestations. Its treatment relies mainly on the reduction of immunosuppression and ribavirin.
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Altekruse SF, McGlynn KA, Reichman ME. Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol. 27 (9): 1485-1491
Article
Full-text available
  • Mar 2009
  • J CLIN ONCOL
Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. Incidence rates are increasing in the United States. Monitoring incidence, survival, and mortality rates within at-risk populations can facilitate control efforts. Age-adjusted incidence trends for HCC were examined in the Surveillance, Epidemiology, and End Results (SEER) registries from 1975 to 2005. Age-specific rates were examined for birth cohorts born between 1900 and 1959. Age-adjusted incidence and cause-specific survival rates from 1992 to 2005 were examined in the SEER 13 registries by race/ethnicity, stage, and treatment. United States liver cancer mortality rates were also examined. Age-adjusted HCC incidence rates tripled between 1975 and 2005. Incidence rates increased in each 10-year birth cohort from 1900 through the 1950s. Asians/Pacific Islanders had higher incidence and mortality rates than other racial/ethnic groups, but experienced a significant decrease in mortality rates over time. From 2000 to 2005, marked increases in incidence rates occurred among Hispanic, black, and white middle-aged men. Between 1992 and 2004, 2- to 4-year HCC survival rates doubled, as more patients were diagnosed with localized and regional HCC and prognosis improved, particularly for patients with reported treatment. Recent 1-year survival rates remained, however, less than 50%. HCC incidence and mortality rates continue to increase, particularly among middle-aged black, Hispanic, and white men. Screening of at-risk groups and treatment of localized-stage tumors may contribute to increasing HCC survival rates in the United States. More progress is needed.
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Birth Cohort-Specific Disparities in Hepatocellular Carcinoma Stage at Diagnosis, Treatment, and Long-term Survival
Article
  • Sep 2015
Background and aims: Individuals born between 1945 and 1965 account for nearly 75% of hepatitis C virus (HCV) infections in the U.S. As this cohort ages, progressive HCV-related liver disease leading to cirrhosis and hepatocellular carcinoma (HCC) will place a significant burden on the healthcare system. We aim to evaluate birth cohort-specific disparities in HCC stage at diagnosis, treatment rates, and overall survival with a focus on the 1945-1965 birth cohort. Methods: A population-based retrospective cohort study of adult patients with HCC identified in the Surveillance, Epidemiology, and End Results 2003-2011 registry evaluated birth cohort-specific disparities in prevalence and outcomes of HCC, including multivariate logistic regression models to evaluate disparities in HCC stage at diagnosis and HCC treatment received. Birth cohort-specific survival was evaluated with Kaplan Meier methods and multivariate Cox proportional hazard models. Results: The proportion of HCC represented by the 1945-1965 cohort increased by 64% from 2003-2011, and accounted for 57.4% of all HCC in 2011. Compared to patients born after 1965, the 1945-1965 cohort were more likely to have HCC within Milan criteria (OR, 3.66; 95% CI, 3.13-4.28; p<0.001). However, among patients with HCC within Milan criteria, the 1945-1965 cohort had no difference in receipt of surgical treatment, but had higher overall long-term survival (HR, 0.82; 95% CI, 0.69-0.97; p<0.03). Conclusions: The 1945-1965 birth cohort accounts for the majority of HCC in the U.S. Despite earlier HCC stage at diagnosis, no difference in receipt of surgical treatment was observed, but higher overall survival was achieved.
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Current concepts: hepatocellular carcinoma
Article
  • Sep 2011
Each year, hepatocellular carcinoma is diagnosed in more than half a million people worldwide, including approximately 20,000 new cases in the United States.(1,2) Liver cancer is the fifth most common cancer in men and the seventh in women. Most of the burden of disease (85%) is borne in developing countries, with the highest incidence rates reported in regions where infection with hepatitis B virus (HBV) is endemic: Southeast Asia and sub-Saharan Africa (Fig. 1).(3) Hepatocellular carcinoma rarely occurs before the age of 40 years and reaches a peak at approximately 70 years of age. Rates of liver cancer among men are two to four times as high as the rates among women. Hepatocellular carcinoma related to infection with hepatitis C virus (HCV) has become the fastest-rising cause of cancer-related death in the United States, and during the past two decades, the incidence of hepatocellular carcinoma in the United States has tripled while the 5-year survival rate has remained below 12%(2) (Fig. 2). The greatest proportional increase in cases of hepatocellular carcinoma has been seen among Hispanics and whites between 45 and 60 years of age.(4)
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Screening for Hepatitis C
Article
  • May 2015
  • J Am Med Assoc
This JAMA Clinical Guidelines Synopsis summarizes the most recent US Preventive Services Task Force guidelines on screening for hepatitis C virus infection in adults. Box Section Ref ID Guideline title Screening for Hepatitis C Virus Infection in Adults: US Preventive Services Task Force Recommendation Statement Developer US Preventive Services Task Force (USPSTF) Release date June 25, 2013 (online); September 3, 2013 (print) Prior version March 2004 Funding source Agency for Healthcare Research and Quality (AHRQ) Target population Asymptomatic adults without known liver disease or functional abnormalities Major recommendations Screen all persons at high risk of hepatitis C virus (HCV) infection and offer one-time HCV screening to all adults born between 1945 and 1965 (B recommendation)
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Screening for Hepatitis C Virus Infection in Adults: U.S. Preventive Services Task Force Recommendation Statement
Article
  • Sep 2013
Description: Update of the 2004 U.S. Preventive Services Task Force (USPSTF) recommendation on screening for and treatment of hepatitis C virus (HCV) infection in asymptomatic adults. Methods: The Agency for Healthcare Research and Quality commissioned 2 systematic reviews on screening for and treatment of HCV infection in asymptomatic adults, focusing on evidence gaps identified in the previous USPSTF recommendation and new studies published since 2004. The evidence on screening for HCV in pregnant women was also considered. Population: This recommendation applies to all asymptomatic adults without known liver disease or functional abnormalities. Recommendation: The USPSTF recommends screening for HCV infection in persons at high risk for infection. The USPSTF also recommends offering 1-time screening for HCV infection to adults born between 1945 and 1965. (B recommendation).
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Excess Mortality on the Liver Transplant Waiting List: Unintended Policy Consequences and Model for End-Stage Liver Disease (MELD) Inflation
Article
  • Jan 2015
  • HEPATOLOGY
Unlabelled: The Model for End-Stage Liver Disease (MELD) allocation system for liver transplantation provides "exceptions" for diseases such as hepatocellular carcinoma (HCC). It was the aim of this study to assess equipoise between exception candidates and nonexception candidates on the waiting list and to assess if the exception system contributes to steadily increasing regional MELD at transplant. In all, 78,595 adult liver transplant candidates between January 2005 and December 2012 were analyzed. Yearly trends in waiting list characteristics and transplantation rates were analyzed for statistical association with MELD exceptions. Regional variations in these associations and the effect of exceptions on regional MELD scores at transplant were also analyzed. 27.29% of the waiting list was occupied by candidates with exceptions. Candidates with exceptions fared much better on the waiting list compared to those without exceptions in mean days waiting (HCC 237 versus non-HCC 426), transplantation rates (HCC 79.05% versus non-HCC 40.60%), and waiting list death rates (HCC 4.49% versus non-HCC 24.63%). Strong regional variation in exception use occurred but exceptions were highly correlated with waiting list death rates, transplantation rates, and MELD score at removal in all regions. In a multivariate model predicting MELD score at transplant within regions, the percentage of HCC MELD exceptions was the strongest independent predictor of regional MELD score at transplant. Conclusion: Liver transplant candidates with MELD exceptions have superior outcomes compared to nonexception candidates and the current MELD exception system is largely responsible for steadily increasing MELD scores at transplant independent of geography.
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Curing Chronic Hepatitis C - The Arc of a Medical Triumph
Article
  • Apr 2014
  • NEW ENGL J MED
Chronic hepatitis C is a major cause of liver cirrhosis and hepatocellular carcinoma worldwide. Some 130 million to 170 million people, or about 3% of the world's population, are chronically infected with the hepatitis C virus (HCV). In the United States, chronic hepatitis C, the most common cause of liver-related death and reason for liver transplantation, recently eclipsed human immunodeficiency virus (HIV) infection as a cause of death. The development of direct-acting antiviral agents (DAAs) has revolutionized HCV treatment by offering genuine prospects for the first comprehensive cure of a chronic viral infection in humans. This success can be traced . . .
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Projected future increase in aging hepatitis C virus–infected liver transplant candidates: A potential effect of hepatocellular carcinoma
Article
  • Dec 2012
  • LIVER TRANSPLANT
In the United States, the peak hepatitis C virus (HCV) antibody prevalence of 4% occurred in persons born in the calendar years 1940-1965. The goal of this study was to examine observed and projected age-specific trends in the demand for liver transplantation (LT) among patients with HCV-associated liver disease stratified by concurrent hepatocellular carcinoma (HCC). All new adult LT candidates registered with the Organ Procurement and Transplantation Network for LT between 1995 and 2010 were identified. Patients who had primary, secondary, or text field diagnoses of HCV with or without HCC were identified. There were 126,862 new primary registrants for LT, and 52,540 (41%) had HCV. The number of new registrants with HCV dramatically differed by the age at calendar year, and this suggested a birth cohort effect. When the candidates were stratified by birth year in 5-year intervals, the birth cohorts with the highest frequency of HCV were as follows (in decreasing order): 1951-1955, 1956-1960, 1946-1950, and 1941-1945. These 4 birth cohorts, spanning from 1941 to 1960, accounted for 81% of all new registrants with HCV. A 4-fold increase in new registrants with HCV and HCC occurred between the calendar years 2000 and 2010 in the 1941-1960 birth cohorts. By 2015, we anticipate that an increasing proportion of new registrants with HCV will have HCC and be ≥60 years old (born in or before 1955). In conclusion, the greatest demand for LT due to HCV-associated liver disease is occurring among individuals born between 1941 and 1960. This demand appears to be driven by the development of HCC in patients with HCV. During the coming decade, the projected increase in the demand for LT from an aging HCV-infected population will challenge the transplant community to reconsider current treatment paradigms. Liver Transpl, 2012. © 2012 AASLD.
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Nonalcoholic Steatohepatitis Is the Most Rapidly Growing Indication for Liver Transplantation in Patients With Hepatocellular Carcinoma in the U. S.
Article
  • Jun 2014
  • HEPATOLOGY
Unlabelled: Nonalcoholic steatohepatitis (NASH) is currently the third leading indication for liver transplantation (LT) in the U.S. and is predicted to become the leading indication for LT in the near future. The trends in NASH-related hepatocellular carcinoma (HCC) among LT recipients in the U.S. remain undefined. We performed a retrospective cohort study to evaluate trends in the etiology of HCC among adult LT recipients in the U.S. from 2002 to 2012, using national data from the United Network for Organ Sharing registry. From 2002-2012, there were 61,868 adults who underwent LT in the U.S., including 10,061 patients with HCC. The total number and proportion of HCC LT recipients demonstrated a significant increase following the implementation of the Model for Endstage Liver Disease (MELD) scoring system in 2002 (3.3%, n=143 in 2000 versus 12.2%, n=714 in 2005 versus 23.3%, n=1336 in 2012). The proportion of hepatitis C virus (HCV)-related HCC increased steadily from 2002 to 2012, and HCV remained the leading etiology of HCC throughout the MELD era (43.4% in 2002 versus 46.3% in 2007 versus 49.9% in 2012). NASH-related HCC also increased significantly, and NASH is the second leading etiology of HCC-related LT (8.3% in 2002 versus 10.3% in 2007 versus 13.5% in 2012). From 2002 to 2012, the number of patients undergoing LT for HCC secondary to NASH increased by nearly 4-fold, and the number of LT patients with HCC secondary to HCV increased by 2-fold. Conclusion: NASH is the second leading etiology of HCC leading to LT in the U.S. More important, NASH is currently the most rapidly growing indication for LT in patients with HCC in the U.S.
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Fattovich G, Stroffolini T, Zagni I, Donato F.. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology 127: S35-S50
Article
  • Dec 2004
  • GASTROENTEROLOGY
Emerging data indicate that the mortality rate of hepatocellular carcinoma (HCC) associated with cirrhosis is rising in some developed countries, whereas mortality from non-HCC complications of cirrhosis is decreasing or is stable. Cohort studies indicate that HCC is currently the major cause of liver-related death in patients with compensated cirrhosis. Hepatitis C virus (HCV) infection is associated with the highest HCC incidence in persons with cirrhosis, occurring twice as commonly in Japan than in the West (5-year cumulative incidence, 30% and 17%, respectively), followed by hereditary hemochromatosis (5-year cumulative incidence, 21%). In hepatitis B virus (HBV)-related cirrhosis, the 5-year cumulative HCC risk is 15% in high endemic areas and 10% in the West. In the absence of HCV and HBV infection, the HCC incidence is lower in alcoholic cirrhotics (5-year cumulative risk, 8%) and subjects with advanced biliary cirrhosis (5-year cumulative risk, 4%). There are limited data on HCC risk in cirrhosis of other causes. Older age, male sex, severity of compensated cirrhosis at presentation, and sustained activity of liver disease are important predictors of HCC, independent of etiology of cirrhosis. In viral-related cirrhosis, HBV/HCV and HBV/HDV coinfections increase the HCC risk (2- to 6-fold relative to each infection alone) as does alcohol abuse (2- to 4-fold relative to alcohol abstinence). Sustained reduction of HBV replication lowers the risk of HCC in HBV-related cirrhosis. Further studies are needed to investigate other viral factors (eg, HBV genotype/mutant, occult HBV, HIV coinfection) and preventable or treatable comorbidities (eg, obesity, diabetes) in the HCC risk in cirrhosis.
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