More than one-quarter of people with chronic hepatitis C at Kaiser-Permanente developed liver cirrhosis over 12 years and 40% of these experienced decompensation – higher rates than expected, according to a presentation at the recent Digestive Disease Week 2015 meeting in Washington, DC. The study also found that cirrhosis and decompensation were associated with comorbid conditions, supporting the idea of hepatitis C as a systemic disease.
Over years or decades, chronic hepatitis C virus (HCV) infection can lead to serious liver disease including advanced fibrosis, cirrhosis, liver cancer, decompensated liver failure and the need for a liver transplant. People with decompensation – which occurs when the liver can no longer carry out its vital functions – may develop ascites (abdominal fluid accumulation), bleeding varices (enlarged veins) in the oesophagus or stomach and hepatic encephalopathy (brain impairment).
Lisa Nyberg and colleagues analysed outcomes among people with hepatitis C who received care through Kaiser Permanente Southern California, a large, integrated health maintenance organisation with approximately 3.5 million members, between January 2002 and December 2013.
The projected public health burden of hepatitis C is based on old natural history studies that may not reflect the current patient population, the researchers noted as background. Hepatitis C is most common among ‘baby boomers’ born during 1945-1965. Compared with these earlier studies, the current cohort of people with hepatitis C is older and has a higher prevalence of obesity and other comorbid conditions that may affect the natural history of the disease.
This retrospective analysis included 54,383 people with a relevant diagnosis code or a positive HCV RNA lab test. Those who had liver cancer or had already had a liver transplant were excluded. Of these, 24,968 adults with HCV had been Kaiser-Permanente members for at least a year and met the inclusion criteria. About 60% were men, more than 40% were white, more than a quarter were Hispanic and the mean age was approximately 53 years.
Among these 24,968 eligible hepatitis C patients, 19% were found to have prevalent or pre-existing cirrhosis, 23% developed incident or new cirrhosis during follow-up and 58% did not have cirrhosis. Among people with pre-existing cirrhosis, 17% already had a decompensation diagnosis, 41% developed new decompensation and 42% did not experience decompensation.
Among 20,285 people without cirrhosis, 28% received a new diagnosis of cirrhosis over the entire 12-year study period, or an annual rate of 5.6%. Among people with new cirrhosis, 20% had decompensation when they were diagnosed with cirrhosis, 46% later developed decompensation and 34% did not have decompensation.
People who developed incident cirrhosis were significantly more likely than people without cirrhosis to have cardiovascular disease (18% vs 13%; crude hazard ratio [HR] 1.21) and diabetes (26% vs 20%; crude HR 1.18). People with cirrhosis were also more likely to have HIV, but this was not a significant difference (2.3% vs 1.9%; crude HR 1.14).
Among 7680 hepatitis C patients with initially compensated cirrhosis, 40% developed new decompensation over the 12-year study period, or an annual rate of 9.9%. Decompensation was significantly associated with cardiovascular disease, diabetes, chronic kidney disease and obesity.
People with cirrhosis who developed decompensation had a 19% likelihood of developing hepatocellular carcinoma, compared to 3.1% for people with compensated cirrhosis and 0.1% for people without cirrhosis (annual rates of 3.31%, 0.47% and 0.02%, respectively).
People with cirrhosis who had decompensation were much more likely to require liver transplants (14%) than either people with compensated cirrhosis (0.03%) or people without cirrhosis (0.03%). People with decompensated cirrhosis also were twice as likely to die as people with compensated cirrhosis (55% vs 21%), who in turn were more likely to die than people without cirrhosis (7.8%).
"Selected comorbid conditions are seen [at] higher prevalence in patients with HCV and cirrhosis and are associated with an increased risk of decompensation," the researchers concluded, "support[ing] the idea of HCV as a systemic illness."
"Our study lends support for early diagnosis and treatment of chronic hepatitis C to reduce morbidity and mortality," they added. The findings also support "aggressive management of comorbid conditions."
Nyberg LM et al. The natural history of chronic hepatitis C. An updated look at the rate of progression to cirrhosis and the incidence of decompensation in a large U.S. health maintenance organization. Digestive Disease Week 2015. Washington, DC, May 16-19, 2015. Abstract 809.