The number of deaths due to hepatitis C is at an all-time high in the US and exceeds those attributable to 60 other infectious diseases including HIV and tuberculosis, according to new surveillance data released this week by the Centers for Disease Control and Prevention (CDC). However, a related Italian study found that hepatitis C patients who are successfully treated have a life expectancy similar to that of the general population.
An estimated 3.5 million people in the US are living with hepatitis C. Over years or decades chronic hepatitis C virus (HCV) infection can lead to severe liver disease including cirrhosis, liver cancer and end-stage liver failure; many people infected years ago are now developing serious complications. New direct-acting antiviral (DAA) therapies can cure hepatitis C more than 90% of the time, but if treatment is started too late liver damage may not be reversible.
The new preliminary CDC surveillance data show that there were 19,659 deaths associated with hepatitis C in 2014, up from 11,051 in 2003 – a 78% increase over the past decade. The hepatitis C death rate was especially high among people age 55 to 64 years.
Hepatitis C prevalence in the US is highest among 'Baby Boomers' (people born between 1945 and 1965), many of whom were infected decades ago. But cases of acute HCV infection have more than doubled since 2010 – reaching 2194 in 2014 – and these are largely occurring among younger people who inject drugs in rural and suburban areas of the Midwest and Eastern US.
"Because hepatitis C often has few noticeable symptoms, the number of new cases is likely much higher than what is reported," said Dr John Ward, director of CDC's Division of Viral Hepatitis. "Due to limited screening and underreporting, we estimate the number of new infections is closer to 30,000 per year. We must act now to diagnose and treat hidden infections before they become deadly and to prevent new infections."
The CDC recommends comprehensive prevention programmes to reduce HCV infections among drug users, including regular hepatitis C testing (along with hepatitis B and HIV testing), rapid linkage to medical care for those who test positive and access to substance use treatment, sterile injection equipment, and other services.
Hepatitis C vs other infectious diseases
In a related analysis described in the May 15 edition of Clinical Infectious Diseases, Kathleen Ly and colleagues from the Division of Viral Hepatitis looked at trends in hepatitis C-related mortality in the US compared to trends for 60 other nationally notifiable infections routinely reported to the CDC.
The researchers used death certificate information from the National Center for Health Statistics to analyse multiple-cause-of-death data from 2003 to 2013. To calculate mortality rates, the number of deaths associated with HCV infection and other notifiable infections were divided by the total US census population for each year and adjusted for the age distribution of the population.
From 2003 to 2013 the number of deaths associated with hepatitis C rose from 11,051 to 19,368, for an average annual increase of 865 deaths per year or +6.2%. The hepatitis C mortality rate increased from 3.72 to 5.03 deaths per 100,000 persons. Just over half of these deaths occurred among people age 55 to 64.
In contrast, the number of deaths associated with 60 other notifiable infectious diseases fell from 24,745 in 2003 to 17,915 in 2013, an average annual decrease of 718 deaths per year or -3.4%. The mortality rate for these other infections decreased from 8.51 to 5.25 deaths per 100,000 persons. Thus, since 2012 the number of hepatitis C-related deaths surpassed that of the 60 other notifiable infections.
The decline in deaths due to other infectious diseases was mostly attributable to decreasing HIV-related mortality (from 15,168 to 8831 deaths; -41.8%), as well as declines in deaths due to pneuomococcal disease (from 1283 to 885 deaths; -31.0%) and tuberculosis (from 1382 to 992 deaths; -28.2%).
"One explanation for the increasing HCV-related mortality could be that many HCV-infected persons are not receiving antiviral therapy and achieving a sustained virologic response indicative of a cure," the authors wrote. One study found that only 19% of people with hepatitis C and 16% of HIV/HCV co-infected patients were eligible for and received treatment; 13% and 11%, respectively, completed therapy; and 3% and 6%, respectively, were cured.
Furthermore, they noted that in one analysis only 19% of hepatitis C patients who died had HCV listed anywhere on their death certificate – although 75% had indications of substantial or extensive liver disease at time of death – leading them to believe that "these data greatly underestimate the true hepatitis C mortality burden."
They suggested that "underappreciation of the seriousness of HCV infection" may be due in part to "the lack of cohesive and vocal advocacy groups as many patients were former injection drug users" and "a new therapeutic nihilism not about the efficacy of antivirals but about their perceived cost, despite evident cost-effectiveness."
"The unabated increasing trend in the number of hepatitis C-related deaths documented from 1999 to 2013, predominantly among middle-aged persons, underscores the urgency in finding, evaluating, and treating patients in the largest infectious disease epidemic in the United States," the authors concluded.
Treatment improves survival
Another recent study published in the June 2016 advance edition of the Journal of Hepatology underscores the importance of timely hepatitis C treatment.
Savino Bruno of Humanitas University and colleagues looked at life expectancy among hepatitis C patients with compensated liver cirrhosis in three Italian cohorts who achieved sustained virological response (SVR) to interferon-based therapy, comparing it to survival among people who were untreated, treated but not cured, or had decompensated liver disease. A total of 795 patients with HCV-related cirrhosis received interferon-based treatment.
Overall, 28 out of 181 patients who achieved SVR died during a median follow-up period of 9.6 years, with 10-year and 20-year survival rates of 90.9% and 62.9%, respectively – the same as the expected number of deaths in the age- and sex-matched general population.
Patients who did not achieve SVR had a standardised mortality ratio of 3.85, or a nearly fourfold greater risk of death, while those with decompensated liver disease had a standardised mortality ratio of 6.70, or nearly sevenfold greater mortality.
Interferon-free therapy using direct-acting antivirals has only been available for a few years, so it is not yet possible to see long-term survival trends, but the new DAA drugs with their high cure rates are expected to have an even greater impact on hepatitis C related complications and death.
"Patients with compensated HCV cirrhosis achieving SVR by [interferon] obtain a main benefit levelling their survival curve to that of the general population," the researchers concluded. "Wider applicability of [interferon]-free regimens will possibly make this achievement more generalizable."
They added that hepatitis C patients with compensated cirrhosis should be treated as early as possible for maximum benefit. New DAAs will allow sicker patients who are ineligible for, cannot tolerate or do not benefit from interferon and ribavirin to be successfully treated.
This recommendation is supported by a study presented at the recent International Liver Congress, which showed that people with advanced cirrhosis have a lower cure rate, experience more adverse events and are less likely to experience post-treatment improvement in liver function than those treated sooner.
CDC. Surveillance for Viral Hepatitis - United States, 2014. May 4, 2016.
Ly KN et al. Rising mortality associated with hepatitis C virus in the United States, 2003-2013. Clinical Infectious Diseases 62(10):1287-1288. May 15, 2016.
Bruno S et al. Survival of patients with HCV cirrhosis and sustained virologic response is similar to the general population. Journal of Hepatology 64(6). June 2016.