Dr Papatheodoridis and his team also looked at
survival of people with and without cirrhosis in this cohort of 1951 people
on long-term entecavir or tenofovir DF. All were treated for at least one year
(median six years). Follow-up continued to April 2016.
Over a median follow-up period of six years, 37 people without cirrhosis (2.7%) and 44 people with cirrhosis (8.4%) died from
any cause; 10 (0.7%) and 23 (4.4%) of these deaths were due to liver-related
causes. Thirty-seven people without cirrhosis (2.7%) and 80 people with cirrhosis
(15.2%) developed HCC, and eight (0.6%) and nine (1.7%), respectively, received
Cumulative survival probability for the whole patient
population at 1, 3, 5, 8 and 10 years was high: 99.7%, 97.8%, 95.9%, 94.1% and
94.1%, respectively. However, survival rates were significantly higher for
people without cirrhosis (100%, 98.5%, 97.3%, 96.2% and 96.2%) compared to those
with cirrhosis (99.1%, 95.9%, 92.8%, 89.3% and 89.3%).
Development of liver cancer was the major factor
affecting overall mortality – and was in fact the only factor affecting
liver-related mortality in this cohort, according to the researchers.
Among people with HCC, 45.9% of people without cirrhosis and 32.5% of those with cirrhosis either died from a liver-related
cause or got a liver transplant. In contrast, this occurred in just 0.01% of people without cirrhosis and 1.3% of people with cirrhosis without HCC. Having HCC gave a
hazard ratio of 5.47 – more than five times higher risk of all-cause death –
but after adjusting for HCC in a multivariate analysis, cirrhosis had a much
smaller though still significant effect (HR 1.08).
Finally, Kellie Young of the Santa Clara Valley
Medical Center in California,
Wong of the Alameda Health System and colleagues used data from the United
Network for Organ Sharing registry to evaluate trends in liver transplant wait-list
registrations, survival while wait-listed, and the likelihood of receiving
transplants among adults with chronic hepatitis B in the US.
This retrospective study looked at approximately
6700 people (about 80% men) waitlisted during three time periods:
- Era 1:
1992-1996, before treatment with nucleoside/nucleotide analogues
- Era 2:
1997-2004, lamivudine and adefovir (Hepsera)
- Era 3:
2005-2015, current therapies available (entecavir starting in 2005 and
tenofovir DF in 2008).
The number of waitlisted individuals more than doubled
from Era 1 (about 900) to Era 2 (about 2800), but then stabilised in Era 3 (about
3000). The proportion of white individuals fell over time (from nearly two-thirds
to a third) while the proportion of Asians rose (from about a quarter to about
half); black and Hispanic people accounted for a small proportion of
transplant candidates across time.
Overall, about a quarter of waitlisted individuals had
HCC. But the number of candidates with liver cancer rose steadily, from just 5%
in Era 1 to 15% in Era 2 and 39% in Era 3, although HCC dipped somewhat in the
last two years. The proportion of Asians with HCC reached two-thirds in Era 3. Dr
Wong suggested this might be because HBV genotypes found in Asia (B and C) may
be more likely to cause liver cancer.
During Era 1, 0.9% of waitlisted individuals died and
46.6% received transplants within a year; the average time to death on the
waitlist was 1432 days and the mean time to transplantation was 273 days.
During Era 2, 8.4% died and 40.3% got transplants within a year; the mean times
to death and transplantation were 569 and 311 days, respectively. And during
Era 3, 6.2% died while waiting and 47.5% got transplants; the mean times to
death and transplantation were 350 and 178 days.
The likelihood of dying while on the waitlist was
significantly higher in Era 1 compared to Era 2 (HR 4.55), but fell from Era 2
to Era 3 (HR 3.63 vs Era 1). Waitlist mortality was affected by both the
number of people who died and time to death on the transplant list. Era 1 had
both the smallest number of deaths and the longest mean time to death, which the
researchers said might be due to selection bias in favour of healthier individuals, as transplant outcomes were poor for people with hepatitis B prior to
The researchers noted that studies have shown that
MELD scores at the time of transplantation have increased in recent years,
suggesting people on the waitlist are now sicker. But the decline in the
likelihood of death on the waitlist from Era 2 to Era 3 may reflect the
improvement in hepatitis B treatment. A subgroup analysis of Era 3 showed that
survival increased from 2005-2007 to 2008-2011 (HR 0.77) and 2012-2015 (HR
0.61), even after controlling for disease severity.
The likelihood of receiving a transplant also fell
from 2005 to 2015. "These results we believe are a testament to the improved
HBV therapy as patients on the waitlist may have delayed progression of their
liver disease and thus a delayed need for transplant or longer time on the
transplant list," the researchers said. They also found that survival
after transplantation improved in each successive era, and also within Era 3.
"While current therapies are effective in
suppressing HBV and reducing risk of cirrhosis and hepatocellular carcinoma,
our current study demonstrates that HBV-related hepatocellular carcinoma is
still a major concern," Dr Wong said in an AASLD press release. "[W]ith the many potential HBV therapies
on the horizon, it will be interesting to understand what treatment endpoints
are most effective at reducing HBV disease progression and hepatocellular
carcinoma (e.g. viral suppression, normalization of alanine aminotransferases
and HBV surface antigen loss)."