Complications of advanced liver disease including cirrhosis and hepatic decompensation have risen over the past decade among people with chronic hepatitis C, according to study findings presented at the 2016 AASLD Liver Meeting in November. However, in recent years the increase has slowed, especially among those at highest risk – black people and people aged 60 and over.
Over years or decades chronic hepatitis C virus (HCV) infection can lead to severe liver damage including cirrhosis (build-up of scar tissue), hepatocellular carcinoma (HCC, a type of liver cancer) and hepatic decompensation (when the liver can no longer perform its vital functions).
Successful hepatitis C treatment can slow or halt liver disease progression, but people who are treated too late, after they have already developed cirrhosis, remain at risk for HCC and end-stage liver disease.
An accumulation of fluid in the abdomen; may be caused by liver damage, especially cirrhosis.
- decompensated cirrhosis
The later stage of
cirrhosis, during which the liver cannot perform some vital functions and
complications occur. See also ‘cirrhosis’ and ‘compensated cirrhosis’.
- direct-acting antiviral (DAA)
A drug which prevents hepatitis C from reproducing by blocking certain steps in its lifecycle.
- sustained virological response (SVR)
Undetectable hepatitis C RNA after treatment has come to an end. Usually SVR refers to RNA remaining undetectable for 24 weeks (six months) after ending treatment and is considered to be a cure. SVR4 and SVR12 refer to RNA remaining undetectable for 4 and 12 weeks respectively.
Stretched veins which may burst and cause severe bleeding; a complication of cirrhosis.
Given the simplicity and effectiveness of interferon-free direct-acting antiviral (DAA) therapy, EASL guidelines and AASLD/IDSA guidelines recommend that everyone with hepatitis C should be treated regardless of fibrosis stage. But due to the high cost of the new drugs treatment is still often limited to those with more advanced liver disease.
Mei Lu and Stuart Gordon of the Henry Ford Health System and colleagues looked at trends in cirrhosis, decompensation and mortality among participants in the Chronic Hepatitis Cohort Study (CHeCS), a longitudinal observational study of people with hepatitis from four large and diverse US health systems.
"Previous estimates had suggested that the medical burden of chronic hepatitis C and its complications would increase in the US given the aging of the population, including the 'baby boomer' cohort born between 1945 and 1965, who are at the highest risk for [HCV] infection," Dr Gordon said in an AASLD press release.
As background, the researchers noted that a prior study of more than 47,000 US veterans with HCV found that the prevalence of cirrhosis and decompensated cirrhosis had doubled from 1996 to 2006, but these findings came mostly from men. A smaller study of 725 people in the US National Health and Nutrition Examination Survey (NHANES) found that cirrhosis among people with HCV tripled from 6.6% between 1988 and 1994 to 17.0% between 2007 and 2012.
The present analysis included data from 11,169 adults receiving 'real world' clinical care between 2006 and 2014 at the Henry Ford Health System in Detroit, Michigan; the Geisinger Heath System in Danville, Pennsylvania; and Kaiser-Permanente in Waipahu, Hawaii, and Portland, Oregon. A majority (60%) were men, most were white, 24% were black and 7% were Asian/Pacific Islander. Over time the proportion of people aged 60 and over increased from 15% to 49%. Most were seen prior to the DAA era and only 28 people had a known sustained virological response (SVR) to treatment.
Cirrhosis was determined based on diagnostic codes, liver biopsy results and fibrosis biomarkers. Decompensated cirrhosis was determined based on diagnostic codes for associated conditions: ascites (abdominal fluid accumulation), oesophageal varices (enlarged veins), HCC and liver transplantation.
The prevalence of cirrhosis increased from 20.5% in 2006 to 24.8% in 2010 to 28.8% in 2014. The researchers identified a 'join point' in 2007, after which the cirrhosis rate rose more slowly, with a 3.5% increase from 2007 through 2014. These findings are consistent with the veterans study, which saw 18.5% prevalence in 2006, but higher than the NHANES prevalence of 17% from 2007 and 2012.
Men and people age 50-60 or 60 and over had significantly higher cirrhosis prevalence than women and younger people. Asians had a higher prevalence than whites, but black people were considerably higher than either Asians or whites. However, trends in prevalence over time were statistically similar across groups.
The prevalence of decompensated cirrhosis rose less steeply, from 8.8% in 2006 to 9.0% in 2010 to 9.8% in 2014. Again, this was consistent with the 11% prevalence in 2006 seen in the veterans study.
Men had significantly higher decompensation prevalence than women, though both rose at a similar rate over time. People age 60 and over both had the highest prevalence and were the only age group with increasing prevalence over time, while rates for younger people fell or remained stable. There were no notable differences in decompensated cirrhosis by race.
All-cause mortality nearly doubled from 1.7% in 2006 to 3.2% in 2013. Black people, people age 60 and over, and men had higher death rates. Mortality rose steeply through 2010. After 2010 overall mortality levelled off, perhaps attributable in part to the introduction of pegylated interferon, the researchers suggested. Mortality actually decreased among black people and older people – that is, those with the highest prevalence saw the greatest improvement.
The researchers suggested that the steeper climb in cirrhosis compared to decompensation may be due to more and better hepatitis C treatment lowering the risk of liver disease progression. They added that older people with other co-morbidities may have been less likely to be successfully treated.
They noted that ongoing analysis of the CHeCS cohort would seek to determine whether highly effective DAA regimens may ultimately reverse the increasing prevalence of liver-related complications in this population.
"The proportion of hepatitis C patients with cirrhosis and its complications has grown significantly in the past decade, particularly among those over 60. The present analysis confirms the rising burden of chronic hepatitis C infection and its complications on the US health care system," Gordon said. "These rising rates may have levelled off in recent years, however, possibly related to better options for treating HCV infection. Future studies will help determine whether increased uptake of these newer medications can help stem the tide of HCV disease progression."