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Abstract

  1. Top of page
  2. Abstract
  3. Materials and Methods
  4. Results
  5. Discussion
  6. Acknowledgements
  7. References

Upward trends in mortality from hepatocellular carcinoma (HCC) were recently reported in the United States and Japan. Comprehensive analyses of most recent data for European countries are not available. Age-standardized (world standard) HCC rates per 100,000 (at all ages, at age 20-44, and age 45-59 years) were computed for 23 European countries over the period 1980-2004 using data from the World Health Organization. Joinpoint regression analysis was used to identify significant changes in trends, and annual percent change were computed. Male overall mortality from HCC increased in Austria, Germany, Switzerland, and other western countries, while it significantly decreased over recent years in countries such as France and Italy, which had large upward trends until the mid-1990s. In the early 2000s, among countries allowing distinction between HCC and other liver cancers, the highest HCC rates in men were in France (6.8/100,000), Italy (6.7), and Switzerland (5.9), whereas the lowest ones were in Norway (1.0), Ireland (0.8), and Sweden (0.7). In women, a slight increase in overall HCC mortality was observed in Spain and Switzerland, while mortality decreased in several other European countries, particularly since the mid-1990s. In the early 2000s, female HCC mortality rates were highest in Italy (1.9/100,000), Switzerland (1.8), and Spain (1.5) and lowest in Greece, Ireland, and Sweden (0.3). In most countries, trends at age 45-59 years were consistent with overall ones, whereas they were more favorable at age 20-44 years in both sexes. Conclusion: HCC mortality remains largely variable across Europe. Favorable trends were observed in several European countries mainly over the last decade, particularly in women and in young adults. (HEPATOLOGY 2008.)

Trends in liver cancer incidence and mortality are extremely difficult to understand and interpret, because the liver is one of the most common sites of secondaries, and the distinction between primary and metastatic liver cancer is variable across countries and calendar periods.1, 2 Still, the upward trends in mortality from hepatocellular carcinoma (HCC) recently reported from the United States,3, 4 Japan,5, 6 and a few major European countries such as France, Germany, or Italy (until the mid-1990s)7 were so large to be considered at least in part real.

Further, over the last few decades, diverging trends were observed in the two sexes from the 15 countries of European Union (EU) as a whole, being upward in men, but downward or approximately stable in women,2 while in both sexes trends for all ages and truncated at 35-64 years (when deaths certification is more reliable) were similar. Thus, these patterns probably reflect some real underlying trend, which has to be related to different exposure to the major recognized causes of HCC, that is chronic infection with hepatitis B (HBV) and C (HCV) viruses and alcohol consumption.8–11

To provide an updated analysis of HCC mortality in Europe, we considered rates in major European countries between 1980 and 2004, and analyzed changes over time using joinpoint regression analysis.

Materials and Methods

  1. Top of page
  2. Abstract
  3. Materials and Methods
  4. Results
  5. Discussion
  6. Acknowledgements
  7. References

Official death certification numbers from HCC for 23 European countries for the period 1980-2004 were derived from the World Health Organization (WHO) database, as available on electronic support.12 We considered the 25 EU member states as of 2004, excluding Cyprus, Luxembourg, and Malta (which have instable rates); Belgium (which has data only up to 1997); and Slovakia and Slovenia (for lack of data before partition of former Czechoslovakia and Yugoslavia, respectively). We also included in the analysis the following non-EU countries: Croatia, Norway, the Russian Federation, and Switzerland.

For each country, only the years since the introduction of the Ninth Revision of the International Classification of Diseases (ICD) were considered,13 because on the WHO data based on the Eighth revision of the ICD it was not possible to distinguish HCC from bile duct carcinoma. For most countries, for which the coding and classification of HCC did not meaningfully change between the Ninth13 and the Tenth Revision14 of the ICD, HCC deaths were recoded according to the Ninth Revision. Thus, we considered ICD-IX code 155.0 and ICD-X codes C22.0, C22.2, C22.3, C22.4, and C22.7. For a few eastern European countries, including Estonia, Hungary, Latvia, Poland, and the Russian Federation, data did not allow distinction between HCC and other liver cancers (including in particular intrahepatic bile duct carcinoma and unspecified liver cancers). These entries have therefore been listed separately. For Greece, only data since 1985 were included, while for Finland and Spain, only data since 1990 were included.

Estimates of the resident population, based on official censuses, were obtained from the same WHO database.12 From the matrices of certified deaths and resident populations, age-specific rates for each 5-year age group and calendar year were computed. Age-standardized rates per 100,000 persons—at all ages and at ages 20-44 and 45-59 years—were computed using the direct method, and based on the world standard population.15

Joinpoint regression analysis was used to identify years when a significant change in the linear slope (on a log scale) of the temporal trend occurred.16 This analysis chooses the best fitting point(s), called joinpoint(s), at which the trend changes significantly. The analysis starts with the minimum number of joinpoints (for example, 0 joinpoints, which is a straight line), and tests whether one or more joinpoints (up to three) are significant and must be added to the model. The estimated annual percent change (APC) is then computed for each of the identified trends by fitting a regression line to the natural logarithm of the rates using calendar year as a regressor variable (that is, given y = a + bx, where y = ln(rate) and x = calendar year, the APC is estimated as 100*(eb − 1)). Joinpoint analysis was performed using the “Joinpoint” software from the Surveillance Research Program of the US National Cancer Institute.17

Results

  1. Top of page
  2. Abstract
  3. Materials and Methods
  4. Results
  5. Discussion
  6. Acknowledgements
  7. References

Table 1 gives the overall age-standardized mortality rates from HCC per 100,000 men and women from selected European countries in the years 1980-1984, 1990-1994 and 2000-2004, and the corresponding percent changes. Among countries allowing distinction between HCC and other liver cancers, in 1980-1984 the highest male mortality rates were in Italy (5.6) and Switzerland (4.6), while the lowest ones were in Ireland (0.7) and Portugal (0.9). HCC mortality in men increased between 1980-1984 and 2000-2004 in Austria, Germany, Portugal, Switzerland and the United Kingdom, and between 1990-1994 and 2000-2004 in Greece, Croatia, Denmark, Ireland, Lithuania, Norway and Spain. Mortality decreased between 1980-1984 and 2000-2004 in the Czech Republic and the Netherlands, and between 1990-1994 and 2000-2004—after upward trends between 1980-1984 and 1990-1994—in Finland, France, Italy, and Sweden. In the early 2000s, the highest male rates were in France (6.8), Italy (6.7), and Switzerland (5.9), while the lowest ones were in Norway (1.0), Ireland (0.8), and Sweden (0.7). Liver cancer rates were comparatively high and stable in Estonia, Hungary, and Russia and downward in Poland. Data from these countries are, however, difficult to interpret, because no reliable distinction was possible between primary and unspecified liver cancers. In women in the early 1980s, the highest HCC mortality rates were in Italy (2.5) and the Czech Republic (1.6), while the lowest ones were in Ireland (0.3) and Portugal (0.4). Mortality from HCC in women increased between 1980-1984 and 2000-2004 in Portugal and Switzerland, and between 1990-1994 and 2000-2004 in Croatia, Greece, Ireland, Norway, and Spain. Mortality decreased between 1980-1984 and 2000-2004 in the Czech Republic, the Netherlands, and the United Kingdom, and between 1990-1994 and 2000-2004 in Denmark, Finland, France, Germany, Italy, Lithuania, and Sweden. In the early 2000s, female mortality rates were highest in Italy (1.9), Switzerland (1.8), and Spain (1.5) and lowest in Greece, Ireland, and Sweden (0.3). As for men, liver cancer mortality was comparably high in Hungary, Russia, and other eastern European countries.

Table 1. Overall Age-Adjusted (World Population) Mortality Rates from HCC per 100,000 Men and Women in Selected European Countries in 1980-1984, 1990-1994, and 2000-2004 (Unless Mentioned in Parentheses), and the Corresponding Change in Rates
CountryMenWomen
1980-19841990-19942000-2004Number of Deaths*% Change% Change1980-19841990-19942000-2004Number of Deaths*% Change% Change
1990-1994/1980-19842000-2004/1990-19941990-1994/1980-19842000-2004/1990-1994
  • *

    Number of deaths in the more recent year available.

Austria3.533.714.243015.114.31.30.850.9288−34.68.2
Croatia (1995-1999)0.881.244740.90.290.372527.6
Czech Republic (1986-1989)4.173.452.76222−17.3−20.01.591.450.99106−8.8−31.7
Denmark (1994/2000-2001)0.881.497269.30.580.4119−29.3
Finland3.672.69121−26.72.240.9154−59.4
France (2000-2003)3.576.916.79331393.6−1.70.691.020.9670447.8−5.9
Germany1.672.492.89238549.116.10.650.920.7589241.5−18.5
Greece0.771.55162101.30.170.304976.5
Ireland0.710.610.7826−14.127.90.320.160.3011−50.087.5
Italy (2000-2002)5.608.146.72360145.4−17.42.482.491.9216500.4−22.9
Lithuania (1998-1999)1.321.40236.10.440.3923−11.4
The Netherlands1.221.091.05118−10.7−3.70.520.440.3351−15.4−25.0
Norway (1986-1989)1.360.760.9623−44.126.30.690.370.4313−46.316.2
Portugal (2000-2003)0.942.122.71236125.527.80.400.640.687260.06.3
Spain4.424.92213011.31.281.5385319.5
Sweden (1987-1989/2000-2002)2.122.260.68676.6−69.91.241.310.27375.6−79.4
UK1.171.171.387910.017.90.480.380.36244−20.8−5.3
Countries Whose Data Did Not Allow Distinction Between HCC and Other Liver Cancers
Estonia (1997-1999)4.885.36499.82.162.26344.6
Hungary (2000-2003)7.798.217.726265.4−6.03.803.772.92361−0.8−22.5
Latvia (1996-1999)4.105.099724.12.111.8742−11.4
Poland7.686.224.151027−19.0−33.36.834.472.65970−34.6−40.7
Russian Federation5.565.6645751.82.432.5235953.7
Switzerland4.585.605.9337422.35.91.121.501.7517633.916.7

Table 2 gives the corresponding rates for men and women aged 45-59 years. The trends of HCC mortality in this age group were similar, although more marked, to overall ones for both men and women from most European countries, with the exception of an increased mortality between 1990-1994 and 2000-2004 in middle-aged men from the Netherlands, and in middle-aged women from Portugal, and for a decreased mortality over the same period in middle-aged men from Ireland, Lithuania, and Norway, and in middle-aged women from Croatia and Greece.

Table 2. Age-Adjusted (World Population) Mortality Rates from Hepatocellular Carcinoma (HCC) per 100,000 Men and Women Aged 45-59 Years in Selected European Countries in 1980-1984, 1990-1994, and 2000-2004 (Unless Mentioned in Parentheses), and Corresponding Change in Rates
CountryMenWomen
1980-19841990-19942000-2004Number of Deaths*% Change% Change1980-19841990-19942000-2004Number of Deaths*% Change% Change
1990-1994/1980-19842000-2004/1990-19941990-1994/1980-19842000-2004/1990-1994
  • *

    Number of deaths in the more recent year available.

Austria5.005.065.73561.213.21.770.911.064−48.616.5
Croatia (1995-1999)1.152.4711114.80.590.553−6.8
Czech Republic (1986-1989)5.795.244.4152−9.5−15.82.132.021.3614−5.2−32.7
Denmark (1994/2000-2001)0.782.6417238.50.790.684−13.9
Finland4.082.3616−42.22.640.702−73.5
France (2000-2003)5.789.449.0460463.3−4.21.171.291.207010.3−7.0
Germany2.443.203.7632531.117.50.891.080.998221.3−8.3
Greece1.252.8034124.00.270.262−3.7
Ireland1.620.980.914−39.5−7.10.410.200.633−51.2215.0
Italy (2000-2002)9.4011.238.2541719.5−26.53.252.441.4889−24.9−39.3
Lithuania (1998-1999)2.202.046−7.30.490.452−8.2
The Netherlands1.731.471.6523−15.012.20.750.490.478−34.7−4.1
Norway (1986-1989)1.281.170.891−8.6−23.90.930.410.353−55.9−14.6
Portugal (2000-2003)1.813.434.684789.536.40.860.850.9112−1.27.1
Spain6.188.0933830.91.271.31533.1
Sweden (1987-1989/2000-2002)1.993.001.061350.8−64.71.782.080.29516.9−86.1
UK1.861.762.12132−5.420.50.800.620.4831−22.5−22.6
Countries Whose Data Did Not Allow Distinction Between HCC and Other Liver Cancers
Estonia (1997-1999)7.367.097−3.73.812.592−32.0
Hungary (2000-2003)11.4811.6313.451571.315.65.325.014.0049−5.8−20.2
Latvia (1996-1999)6.177.672024.32.963.0984.4
Poland11.818.865.44233−25.0−38.69.435.923.56136−37.2−39.9
Russian Federation10.349.731210−5.93.934.156315.6
Switzerland6.187.337.556818.63.01.231.932.021056.94.7

HCC mortality in major European countries was also given for adults aged 20-44 years, where absolute numbers are small, but death certification reliability is more satisfactory (Table 3). Trends in mortality rates for young adults were consistent with those for the overall population, although somewhat more favorable, particularly in women. Only in France and Spain HCC mortality in young men was increasing in the last decade.

Table 3. Age-Adjusted (World Population) Mortality Rates from Hepatocellular Carcinoma (HCC) per 100,000 Men and Women Aged 20-44 Years in Major European Countries in 1980-1984, 1990-1994, and 2000-2004 (Unless Mentioned in Parentheses), and Corresponding Change in Rates
CountryMenWomen
1980-19841990-19942000-2004Number of Deaths*% Change% Change1980-19841990-19942000-2004Number of Deaths*% Change% Change
1990-1994/1980-19842000-2004/1990-19941990-1994/1980-19842000-2004/1990-1994
  • *

    Number of deaths in the more recent year available.

France (2000-2003)0.450.490.54598.910.20.160.140.1116−12.5−21.4
Germany0.220.220.20360.0−9.10.110.150.091436.4−40.0
Italy (2000-2002)0.540.410.3637−24.1−12.20.290.210.0911−27.6−57.1
Spain0.350.565060.00.140.14120.0
UK (2000-2002,2004)0.220.210.2324−4.59.50.160.120.064−25.0−50.0
Countries Whose Data Did Not Allow Distinction Between HCC and Other Liver Cancers
Hungary (2000-2003)0.781.151.031347.4−10.40.510.690.41735.3−40.6
Poland0.910.680.5232−25.3−23.50.690.490.2916−29.0−40.8
Russian Federation0.750.772382.70.450.481496.7

The findings from joinpoint regression analysis for HCC mortality over the period 1980-2004 in selected European countries are given in Fig. 1 and Table 4 for men at all ages and at age 45-59 years. During the period considered, overall male mortality from HCC increased in Austria (APC = +1.1%), Germany (+4.2% in 1980-1995 and −0.1% in 1995-2004), Greece since the mid-1980s (+4.3%), Spain (+1.8%), Switzerland (+20.4% in 1980-1982 and +0.5% in 1996-2002), and the United Kingdom (+4.4% in 1994-2004), while it decreased in the Czech Republic (+0.7% in 1986-1991, −13.4% 1990-2004 and +0.4% in 1994-2004) and the Netherlands (−0.6%). Mortality also decreased since the mid-1990s after increases in the previous years in Finland (−2.6%), France (−6.2%), Italy (−3.0%), and Portugal (−4.2%). The results of joinpoint analyses were similar for men aged 45-59 years (Fig. 1 and Table 4).

thumbnail image

Figure 1. Joinpoint analysis for HCC mortality in men all ages, and aged 45-59 years in selected European countries, 1970-2002. Men, all ages (filled circles); Men 45-59 years (open circles).

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Table 4. Joinpoint Regression Analysis for Hepatocellular Carcinoma Mortality at all Ages and at Age 45-59 Years for Selected European Countries, 1970-2004
CountryMenWomen
Trend 1Trend 2Trend 3Trend 1Trend 2Trend 3
YearsAPCYearsAPCYearsAPCYearsAPCYearsAPCYearsAPC
  • APC: Annual percent of change.

  • *

    Significantly different from 0 (P < 0.05).

All ages            
Austria1980-20041.1*    1980-1992−3.9*1992-20040.7  
Czech Republic1986-19910.71991-1994−13.41994-20040.41986-2004−3.6*    
Finland1990-2004−2.6*    1990-2004−8.8*    
France1980-198611.5*1986-19983.9*1998-2003−6.2*1980-19983.9*1998-2003−7.4*  
Germany1980-19954.2*1995-2004−0.1  1980-19944.0*1994-2004−3.7*  
Greece1985-20044.3*    1985-20041.3    
Italy1980-19934.1*1993-2002−3.0*  1980-2002−1.1*    
Netherlands1980-2004−0.6    1980-2004−2.0*    
Portugal1980-19861.91986-199613.5*1996-2003−4.2*1980-1987−3.71987-199613.2*1996-2003−7.6*
Spain1990-20041.8    1990-20041.6*    
Switzerland1980-198220.41982-20040.5  1980-20041.6*    
UK1980-19911.4*1991-1994−9.91994-20044.4*1980-1991−0.31991-1994−14.91994-20043.0*
45-59 years            
Austria1980-20040.9    1980-2004−2.4*    
Czech Republic1986-2004−1.8*    1986-2004−3.5*    
Finland1990-2004−5.0*    1990-2004−12.6*    
France1980-19869.6*1986-19972.5*1997-2003−3.2*1980-19982.0*1998-2003−6.5  
Germany1980-20042.1*    1980-19942.4*1994-2004−2.0  
Greece1985-20045.0*    1985-2004−1.0    
Italy1980-19932.1*1993-2002−4.2*  1980-2002−3.7*    
Netherlands1980-2004−0.1    1980-2004−2.0*    
Portugal1980-20035.7*    1980-20031.5    
Spain1990-20042.8*    1990-20040.3    
Switzerland1980-20041.2*    1980-20041.9*    
UK1980-20040.3    1980-19900.61990-1994−14.41994-20040.8

Corresponding figures for women are given in Fig. 2 and Table 4. A slight increase in overall female HCC mortality was observed between the 1980s and the 2000s in Spain and Switzerland (APC = +1.6%), and between 1994 and 2004 in the United Kingdom (+3.0%). Between the 1980s and the 2000s, mortality decreased in Austria (−3.9% in 1980-1992 and +0.7% in 1992-2004), the Czech Republic (−3.6%), Italy (−1.1%), and the Netherlands (−2.0%). Mortality also decreased since the mid-1990s in Finland (−8.8%), France (−7.4%), and Germany (−3.7%). The results of joinpoint analyses were similar for women aged 45-59 years (Fig. 2 and Table 4).

thumbnail image

Figure 2. Joinpoint analysis for HCC mortality in women all ages, and aged 45-59 years in selected European countries, 1970-2002. Women, all ages (filled circles); Women 45-59 years (open circles).

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Discussion

  1. Top of page
  2. Abstract
  3. Materials and Methods
  4. Results
  5. Discussion
  6. Acknowledgements
  7. References

This updated analysis of mortality from HCC in Europe confirms a large variability across European countries, with high rates in France and Italy and some eastern countries and low rates in northern countries1 such as Ireland, the Netherlands, Norway, and the United Kingdom throughout the study period.

The patterns of HCC mortality in the last 20 years were also variable, with slight upward trends in Austria, Germany, Switzerland, and other northern countries and significant declines over the last years in a few countries such as France and Italy, which had large upward trends previously. In most European countries, somewhat more favorable trends were observed in women and in young populations.

Thus, the trends of HCC mortality appear to be more favorable in European countries than in the United States, where mortality rates have been rising in the last years particularly in men aged 45-65 years.3, 4 This was explained by a high exposure to HCV during the 1960s and 1970s, through contact with contaminated blood and use of injection drugs in young U.S. men.4, 18, 19 Still, recent rates in middle-aged U.S. men are comparable to those for France, Italy, and Spain and lower than those for several eastern European countries, though higher than those for most northern European ones.

This article has essentially descriptive value, because it provides an extensive picture of HCC trends in Europe. Comments on such a large amount of data remain open to various interpretations and have therefore been related to a few major determinants common to various areas.

In any case, in the interpretation of HCC mortality trends, great caution is required given the substantial problems of reliability and validity of certification data for liver cancer, mainly due to the difficulty in distinguishing primary and secondary liver neoplasms.1, 2 Thus, the high rates observed in Hungary, Poland, the Russian Federation, and a few other eastern European countries are partly due to difficulties in separate classification of HCC. Moreover, it is possible that changes in HCC cancer rates are due to artefacts of liver cancer coding procedures. For instance, the drop in the United Kingdom in the 1990s is due to the coding and death certificate changes of 1993.20 Similarly, the sharp drop in rates observed in Sweden in the mid-1990s may reflect changes in coding practices more than real variation in mortality. However, the consistency of mortality trends at all ages and in young and middle-aged populations (when death certifications are more accurate1), and the differences observed between sexes, weigh against the possibility that problems in diagnostic practices explain a large part of the trends observed. Changes in mortality from primary liver cancer other than HCC may also explain the increase in liver cancer mortality reported in the United Kingdom21 that was partly due to an increase in the mortality from intrahepatic cholangiocarcinoma.20, 22

Notwithstanding the difficulties in the interpretation of the geographical patterns and temporal trends for HCC mortality in various European countries, they can be related to changes in the main recognized causes of HCC, that is, HBV and HCV infection23, 24 and alcohol drinking.10

There is inadequate information on the prevalence and trends of HBV and HCV in various populations, and consequently their contribution to liver mortality trends cannot be reliably quantified. However, the extending coverage of HBV vaccination,25 and the reduction in the prevalence of the infection reported in young populations from southern Europe,26 may at least in part explain the reduced mortality observed during recent years in France and Italy. HCV control has been less effective, due to the absence of a vaccine. Although the prevalence of HCV is low in most northern European countries, the contribution of HCV to HCC in southern and eastern Europe appear to be substantial,18, 27, 28 and HCC mortality across European countries is at least in part related to HCV prevalence.29 Incidence data for European countries, with higher rates in southern countries and lower and stable ones in northern and eastern countries, are also consistent with the variable distribution of HCV.30 In Italy, a higher seroprevalence of HCV has been reported in the elderly, indicating that HCV infection may have been more frequent in the distant past as a consequence of widespread unsafe injection practices.18 This may explain the increase in liver cancer mortality up to the early 1990s and the subsequent decrease. Variable patterns in HCV prevalence in European countries may also explain the difference with recent U.S. trends, which have been upward particularly in middle-aged men, following a rise in HCC infection acquired from injection drug use and possibly during the Vietnam War.4, 18, 19

Alcohol drinking is another well recognized risk factor for HCC in European populations, because it increases the alcoholic-cirrhosis risk, alone or in combination with HBV and HCV infections.10, 11 The reduction in per capita alcohol consumption observed since the 1970s in various countries mainly of southern Europe12 has likely contributed to the decrease in cirrhosis incidence and mortality in those countries during the last decade,31 with a consequent impact on HCC mortality, too.

Tobacco smoking is another recognized risk factor for HCC, though the strength of the association is much lower than that of HBV/HCV and alcohol.11, 32 The recent declines in male smoking prevalence33 may thus have contributed to some of the recent favorable trends in men, although the potential impact of smoking on HCC mortality rates remains difficult to evaluate with precision.

Diabetes is also related to the excess of HCC,11, 34 and the increased prevalence of overweight and obesity, with consequent increase of diabetes, in some western and northern European countries may have had some role on the increases reported in these areas of the continent. However, as for tobacco smoking, the impact of diabetes on HCC rates on a population level remains inadequately quantified.

Changes in the incidence and mortality rates from cirrhosis may also have affected HCC rates, because a large proportion of HCCs develop from cirrhotic liver.35 The improved survival and reduced mortality from cirrhosis, due to improvements in the prevention and treatment of this condition,31 have in fact increased the possibility of developing HCC in patients with cirrhosis, although the increased management and treatment of these patients may have also helped prevent the development of HCC. Of some importance are also the improvements in diagnosis, mainly due to widespread use of ultrasound and measurement of α-fetoprotein since the early 1980s, which led to more frequent detection of neoplastic liver in patients with cirrhosis. Rates from cirrhosis are much higher than those from HCC in several countries, and consequently even a limited diagnostic shift may have had an appreciable influence on HCC death certification, and hence on mortality rates.

Significant improvements in the management in HCC have occurred in recent years, through increased surveillance of patients at high risk for HCC, earlier diagnosis and adoption of treatments such as liver transplantation, hepatic resection, or local ablation, with consequent improved survival in carefully selected patients.36, 37 However, the impact on survival and HCC mortality at the population level is still unclear. European cancer registries have in fact showed only modest improvements in survival from primary liver cancer over the last few decades, that is, from 5% for cancers diagnosed in the mid-1970s to 8% in those diagnosed in the mid-1990s in Vaud cancer registry,38 and from about 3% to about 7% from EUROCARE data.30

In conclusion, HCC mortality remains largely variable across Europe. Favorable trends were observed in various European countries over the last decades, particularly in women and in young adults. Widespread use of HBV vaccination, continuous screening of blood and blood products for HBV and HCV infection, and control of alcohol drinking and tobacco smoking should contribute to further reduce the mortality from this neoplasm in Europe.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Materials and Methods
  4. Results
  5. Discussion
  6. Acknowledgements
  7. References

The authors thank Dr. Robert E. Tarone from the International Epidemiology Institute, Rockville, MD, USA for his thoughtful comments and Mrs I. Garimoldi for editorial assistance. C.L.V. was a Senior Fellow of the International Agency for Research on Cancer, Lyon, France.

References

  1. Top of page
  2. Abstract
  3. Materials and Methods
  4. Results
  5. Discussion
  6. Acknowledgements
  7. References
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