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Hepatocellular Carcinoma and Viral Hepatitis in New York City
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"From 2001-2012, 8,827 NYC residents were diagnosed with HCC, and of those, 5,166 (58.5%) had a report of HBV, HCV, or both
- The survival probability for those with HCC was low, with a median survival time of only 10.9 months, consistent with previously reported median survival times of 6-20 months [24]. Given that early diagnosis of HCC improves survival and increases the probability of cure [2], these findings highlight the importance of screening and early treatment of HBV and HCV, as well as screening for HCC in persons with HBV or HCV infection or cirrhosis of any etiology [8,25,26].
- In this study, viral hepatitis was the largest contributor to HCC in NYC. Though important for those with HBV and cirrhosis from any cause, screening for HCC has its limitations
- highly effective and curative HCV treatments may reduce liver damage and subsequent HCC in HCV-infected persons, and treatment for all those with HCV should be a priority.
- Unfortunately, HCC screening in the U.S. is not occurring according to recommendations. One study found that among non-cirrhotic patients with chronic HBV, only 6.7% were appropriately screened (one ultrasound every six months) and 33.7% did not receive HCC screening at all [27]. In another study ofthose with HCV and cirrhosis, fewer than 50% of patients received HCC surveillance in the first year following cirrhosis diagnosis and only 12% received ongoing surveillance as recommended [28]. In a retrospective study of patients diagnosed with cirrhosis, fewer than 20% of those who developed HCC had received regular screening [29]. To improve its use, HCC screening according to expert recommendations must be facilitated and covered by all health insurances.
- To further these efforts, health department activities to increase screening, linkage to care, and treatment for those with HCV, both through outreach and direct service programs, should continue to be supported with city, state, and federal funds.
- "The median age at HCC diagnosis was 62 years, ranging from55 years for HBV mono-infected persons to 68 years for non-infected persons
Persons with HCC often lived in neighborhoods with high or very high poverty, particularly among those with HCV mono-infection. Many risk factors for HCC, including HCV and HBV infection, alcoholism, obesity, and metabolic syndrome are also associated with low socioeconomic status [21]. Individuals who reside in neighborhoods with a high poverty rate might also have limited access to healthcare, which could limit access to viral hepatitis screening and treatment and HCC screening [22,23]......When examining all residents with HCC within a given neighborhood poverty level, the proportion with HCV increased with increasing neighborhood poverty. Among persons with HCC living in low-poverty neighborhoods, 32% had HCV mono-infection. This proportion increased to 36% in medium-poverty neighborhoods and to 39% and 46% in high and very high poverty level neighborhoods, respectively.
The median survival time after HCC diagnosis was 6.9 months for persons with neither infection, 13.1 months for persons with HCV mono-infection, and 22.3 months for those with HBV mono-infection (see supplementary table 2). The probability of survival 60 months after diagnosis varied from 37.5% among those with HBV mono-infection to 16.1% among those with neither infection.
Almost 60% of NYC residents with HCC had a viral hepatitis diagnosis; among those, 70% had HCV infection alone or with HBV, consistent with previous findings in the U.S"
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Hepatocellular Carcinoma and Viral Hepatitis in New York City
Clinical Infectious Diseases Advance Access published September 1, 2016
Miranda S. Moore1,2,*, Elena Ivanina1,*, Katherine Bornschlegel1, Baozhen Qiao3, Maria J. Schymura3, Fabienne Laraque1
1New York City Department of Health and Mental Hygiene, Queens, NY, 11101 USA
2CDC/CSTE Applied Epidemiology Fellowship, Atlanta, GA, 30341, USA
3New York State Department of Health, Albany, NY 12237USA
Abstract
Background. Hepatocellular carcinoma (HCC) incidence and mortality are increasing in the United States. Viral hepatitis infection is a primary risk factor for HCC. This study describes the relationship between viral hepatitis and HCC in New York City (NYC).
Methods. Viral hepatitis cases reported to the NYC Department of Health from 1999-2012 were matched to HCC cases diagnosed from 2001-2012 and reported to the New York State Cancer Registry. HCC cases were stratified by presence or absence of viral hepatitis. Demographic characteristics, factors associated with specific causes of death, and survival time were analyzed for all HCC cases.
Results. From 2001-2012, 8,827 NYC residents were diagnosed with HCC; 38.4% had hepatitis C (HCV) infection, 17.9% had hepatitis B (HBV) infection, and 2.2% had both infections. HCC patients were predominantly men (74.8%) and equally white non-Hispanic (28.6%) and Hispanic (28.9%). Those with HBV were primarily Asian/Pacific Islander (63.2%). The median survival time after HCC diagnosis for persons with HBV infection was 22.3 months, compared with 13.1 months for persons with HCV, and 6.9 months for non-infected persons. The five-year survival rate was 37.5% for those with HBV, 20.0% for those with HCV, 29.5% among coinfected individuals, and 16.1% for those with neither infection reported.
Conclusion.In NYC, most persons with HCC have viral hepatitis; the majority of viral hepatitis infections are due to HCV. Survival for persons with HCC differs widely by viral hepatitis status. This study highlights the importance of viral hepatitis prevention and treatment and HCC screening.
As has been true nationally, HCC incidence and mortality are increasing in New York City (NYC) [9]. However, the epidemiology of HCC in NYC, particularly its relationship with viral hepatitis, has not been described in the literature. Approximately 100,000 persons, or 1.2% of the NYC population, have HBV infection [10], while approximately 146,500 persons, or 2.4% of NYC residents 20 years of age and older, have HCV infection [11]. The majority of HBV and HCV infections are asymptomatic for years, thus many individuals are unaware of their infection and will not benefit from antiviral treatment and/orscreening for HCC. The aim of this study was to describe the relationship between HBV, HCV, HCC, and mortality in NYC.
RESULTS
From 2001-2012, 8,827 NYC residents were diagnosed with HCC, and of those, 5,166 (58.5%) had a report of HBV, HCV, or both (Table 1). Most persons with HCC were men (74.8%), particularly among those with HBV mono-infection (85.2%). The median age at HCC diagnosis was 62 years, ranging from55 years for HBV mono-infected persons to 68 years for non-infected persons. The majority of persons with HBV mono-infection were Asian/Pacific Islanders (63.2%), whereas persons with HCV mono-infection were most frequently Hispanic (35.0%) or black non-Hispanic (30.1%), and those with neither infection were mainly white non-Hispanic (36.5%) or Hispanic (32.0%).
While 41.4% of persons were diagnosed with HCC at a local stage, another 38.0% were diagnosed at a regional or distant stage (Table 1). Disease stage was not reported in one fifth of the cases. Persons with neither infection were less often diagnosed with HCC at a local stage and more often diagnosed with an unknown stage than those with any viral hepatitis infection. HCC cases with neither infection were more likely to be diagnosed during the beginning of the study period and via autopsy/death certificates.
A significantly greater proportion of individuals with HBV mono-infection (52%) and HCV mono-infection (56%) lived in neighborhoods with high or very high poverty compared with those with neither infection (47%) (Table 1). When examining all residents with HCC within a given neighborhood poverty level, the proportion with HCV increased with increasing neighborhood poverty. Among persons with HCC living in low-poverty neighborhoods, 32% had HCV mono-infection. This proportion increased to 36% in medium-poverty neighborhoods and to 39% and 46% in high and very high poverty level neighborhoods, respectively (Cochran-Armitage test for trend, p<0.001). In contrast, approximately half (52%) of persons with HCC residing in low-poverty neighborhoods had neither infection reported.
HBV mono-infected persons died at the youngest age (median: 57 years) and persons with neither infection died at the oldest age (median: 70 years) (Table 2). The groups with viral hepatitis had significantly greater proportions of premature death (death before the age of 65 years [18]) than the non-infected group. HCC was listed as the underlying cause of death for 66.1% of those who died.
Among persons who died, those with HBV mono-infection were more likely to die of HCC than those with neither infection (aOR 1.30, 95% CI 1.04-1.62); the odds of dying from HCC did not differ for those with HCV mono-infection or HBV/HCV coinfection (Table 3). Persons with HCV mono-infection hadgreater odds of dying of other liver disease compared with non-infected individuals, while non-infected individuals were more likely to die of cardiovascular diseases than those with HBV or HCV mono-infection.
Kaplan-Meier estimates revealed that persons without viral hepatitis had the shortest survival time after HCC diagnosis, while those with HBV mono-infection had the longest survival time (Figure 1a). Survival for each group was significantly different from that of almost all other groups (log-rank test, p<0.001), except for the HBV/HCV coinfected group compared with the HCV mono-infection group (p=0.40). The median survival time after HCC diagnosis was 6.9 months for persons with neither infection, 13.1 months for persons with HCV mono-infection, and 22.3 months for those with HBV mono-infection (see supplementary table 2). The probability of survival 60 months after diagnosis varied from 37.5% among those with HBV mono-infection to 16.1% among those with neither infection.
As expected, survival decreased with worsening stage of disease at diagnosis, regardless of infection status. Nevertheless, patients with HBV mono-infection continued to have longer survival than other groups for all disease stages (Figure 1b-d). For patients diagnosed with HCC at a local stage, median survival time was 94.5 months for HBV mono-infected individuals but only 28.1 months for HCV mono-infected individuals. Likewise, when diagnosed at a distant stage, median survival time was 3.7months for those with HBV mono-infection but 3.2 months for those with HCV mono-infection (see supplementarytable 2).
The risk of death for persons with HBV continued to be smaller than for those with neither infection, even after adjusting for numerous covariates (aHR=0.81, 95% CI: 0.73-0.89). At six months after HCC diagnosis, there was no significant difference in the risk of death for HCV mono-infected persons compared with those with neither infection (aHR=0.95, 95% CI: 0.90-1.02). However, the relative hazard of death increased over time and was significantly larger five years after HCC diagnosis (aHR=1.34, 95%
CI 1.20-1.51). The risk of death for those with HBV/HCV coinfection was not significantly different from those with neither infection (see supplementary Table 3).
Discussion
Almost 60% of NYC residents with HCC had a viral hepatitis diagnosis; among those, 70% had HCV infection alone or with HBV, consistent with previous findings in the U.S. [6,19]. Of note, 41% of HCC patients were not reported with either HBV or HCV infection, highlighting the importance of other HCC risk factors such as alcohol use and metabolic syndrome [20]. HCC patients with viral hepatitis were more likely to be diagnosed at a local stage and less likely to have an unknown stage, suggesting a higher degree of medical care. However, the proportion of diagnoses at a local stage was less than 50% for all groups, indicating improvements are needed in screening for HCC risk factors and early diagnosis of HCC.
Persons with HCC often lived in neighborhoods with high or very high poverty, particularly among those with HCV mono-infection. Many risk factors for HCC, including HCV and HBV infection, alcoholism, obesity, and metabolic syndrome are also associated with low socioeconomic status [21]. Individuals who reside in neighborhoods with a high poverty rate might also have limited access to healthcare, which could limit access to viral hepatitis screening and treatment and HCC screening [22,23].
The survival probability for those with HCC was low, with a median survival time of only 10.9 months, consistent with previously reported median survival times of 6-20 months [24]. Given that early diagnosis of HCC improves survival and increases the probability of cure [2], these findings highlight the importance of screening and early treatment of HBV and HCV, as well as screening for HCC in persons with HBV or HCV infection or cirrhosis of any etiology [8,25,26].
Unfortunately, HCC screening in the U.S. is not occurring according to recommendations. One study found that among non-cirrhotic patients with chronic HBV, only 6.7% were appropriately screened (one ultrasound every six months) and 33.7% did not receive HCC screening at all [27]. In another study ofthose with HCV and cirrhosis, fewer than 50% of patients received HCC surveillance in the first year following cirrhosis diagnosis and only 12% received ongoing surveillance as recommended [28]. In a retrospective study of patients diagnosed with cirrhosis, fewer than 20% of those who developed HCC had received regular screening [29]. To improve its use, HCC screening according to expert recommendations must be facilitated and covered by all health insurances.
HBV mono-infected individuals in this study had better survival than all other groups, a finding that persisted regardless of HCC stage at diagnosis. Even after adjusting for age at diagnosis, stage at diagnosis, and other factors, the hazard of death was lower for those with HBV compared with those with HCV or with neither infection. It is possible that persons with non-HBV HCC risk factors are more likely to have co-occurring advanced liver disease and/or cirrhosis before developing HCC. Unlike with HBV, virtually all cases of HCV-related HCC occur only after cirrhosis develops [30]. Non-viral HCC risk factors, including alcoholic liver disease and NAFLD, also increase the risk for cirrhosis [31]. The presence of cirrhosis has been found to limit HCC treatment options, potentially reducing survival rates [32]. Our study found that decedents with HCV had greater odds of dying from other liver diseases, whereas decedents with HBV had greater odds of dying from HCC.
There are several limitations to this study. First, the number of viral hepatitis cases in the study population might be underestimated due to undiagnosed infections [33], unreported infections, especially early in the study period before routine electronic laboratory reporting, under-matching of the viral hepatitis and cancer databases, and because some patients may have been diagnosed outside of NYC and thus not reported to DOHMH. Such misclassification would overestimate the number of non-infected persons, resulting in a dilution of the associations observed. Misclassification is also an issue when analyzing cause of death because death certificates can be unreliable [34]. This could affect the distributions of specific cause of death observed and emphasizes the need for improved death certificate accuracy. Additionally, many individuals had an unknown tumor stage at diagnosis, which may be relevant if lacking cancer stage information is related to other factors associated with survival. It is unknownwhether patients had other HCC risk factors, were screened for HCC, or received viral hepatitis and/or HCC treatment. Also unknown was patient HIV status, which influences both on the occurrence of HCC and survival among those with HCV infection [35,36]. Despite the above, this study provides a unique perspective on HCC in an urban setting with high viral hepatitis prevalence.
In this study, viral hepatitis was the largest contributor to HCC in NYC. Though important for those with HBV and cirrhosis from any cause, screening for HCC has its limitations. There is limited evidence for its use in persons with non-infectious risk factors (e.g. obesity, metabolic syndrome), a reduced ability of ultrasound to detect early stage HCC or detect HCC in obese patients, and logistical difficulties for providers in implementing screening procedures as recommended [37,38]. Therefore, efforts targeted at preventing and treating HBV and HCV infections and preventing and managing obesity, excess alcohol use, and metabolic syndrome will be key to reducing the morbidity and mortality associated with HCC. In particular, highly effective and curative HCV treatments may reduce liver damage and subsequent HCC in HCV-infected persons, and treatment for all those with HCV should be a priority.
To further these efforts, health department activities to increase screening, linkage to care, and treatment for those with HCV, both through outreach and direct service programs, should continue to be supported with city, state, and federal funds. Additionally, advocacy efforts to pressure drug manufacturers to make HCV medications affordable and for health insurers to cover the medications without restriction must continue if access to treatment is to become widespread. While in some ways more difficult, prevention of obesity and metabolic syndrome must also remain a priority. Luckily, extensive attention has been given to the obesity epidemic in the U.S., and DOHMH has been aggressive in implementing system-wide policies to address root causes of obesity in the city. Such policies and other innovative programs will be vital in reducing the burden of HCC.
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