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Turati et al. Hepatoma Res 2022;8:19 https://dx.doi.org/10.20517/2394-5079.2021.130 Page 9 of 15

Puerto Rico 1.29 1.14 5 -11.6 0.12 0.23 1 91.7 0.85 0.34 2 -60.0 0.20 0.00 0 -100.0
USA 2.08 2.31 1040 11.1 0.18 0.21 94 16.7 1.69 2.06 958 21.9 0.13 0.17 81 30.8

Australasian countries/regions
Hong Kong 3.72 3.31 41 -11.0 0.10 0.14 2 40.0 2.49 2.55 33 2.4 0.04 0.06 1 50.0
SAR
Israel 1.67 1.31 11 -21.6 0.05 0.09 1 80.0 1.63 1.51 13 -7.4 0.02 0.14 1 600.0
Japan 1.91 1.91 335 0.0 3.12 2.66 477 -14.7 0.96 0.93 163 -3.1 1.38 1.01 180 -26.8
Australia 2.49 2.79 87 12.0 0.08 0.03 1 -62.5 2.00 2.68 86 34.0 0.06 0.01 0 -83.3
New Zealand 1.98 2.42 15 22.2 0.50 0.32 2 -36.0 1.54 1.77 11 14.9 0.13 0.14 1 7.7

SAR: Special Administrative Region of the People’s Republic of China.

in Hungary to 3.9/100,000 in Portugal were found in Europe, from 0.4/100,000 in Argentina to 2.9/100,000 in Canada in Americas, and from 1.9/100,000 in

Japan to 3.3/100,000 in Hong Kong SAS in Australasia. Similar rates were observed in women, but with lower values than those in men. Variable patterns
emerged for ECC mortality rates, with rates below 1/100,000 for most countries. Among those, Hungary had the worst pattern in both sexes, with the highest
rate and the largest increase, from about 1.4/100,000 to 3.1/100,000 men and from about 1/100,000 to 2.1/100,000 women.

Figure 3 gives results from the joinpoint trends in major countries considered; joinpoint indices for separate calendar periods are given in Table 3. Considering
the nine major countries worldwide [Figure 3], we observed steady increases in the USA, the UK, and Australia over the entire studied period (APCs of 3.6%,
4.8%, and 4.3% in men and 4%, 5.5% and 4.8% in women, respectively). Japan showed stable trends since the early 2000s in both sexes. In contrast, increasing

trends have been slowing down over recent years in the other considered countries, i.e., Brazil, France, Germany, Italy, and Spain.

More favorable patterns emerged for ECC mortality in most countries as compared to those observed for ICC. Of note, we observed a leveling-off trend in the
USA in the most recent years (APC: +5.9% during 2013-2017 for men and +4.3% during 2010-2017 for women). Germany presented a decline in rates from
1998 to 2009 (APC: -3%) followed by a rapid but short increase during 2009-2013 (APC: +14.8%), which arrested thereafter.

DISCUSSION
The present global analysis, based on countries with acceptably reliable data, showed rising trends of ICC mortality for both sexes in most of the countries

considered, with some decelerations over the most recent years in selected countries; in the USA, the UK, and Australia, ICC mortality trends steadily
increased over the whole period. ECC mortality declined in most European and Australasian countries, while it tended to increase in American countries, with
the exception of Brazil.