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Moderate coffee consumption reduces the risk of hepatocellular carcinoma in hepatitis B chronic carriers: A case-control study

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Recent epidemiological studies have reported a dose-dependent protective effect of coffee on hepatocellular carcinoma (HCC) with risk reduction ranging from 30% to 80% in daily coffee drinkers compared with non-drinkers. This study examined whether coffee has a similar protective effect when consumed in moderate quantities in chronic hepatitis B virus (HBV) carriers, a group at high risk of developing liver cancer. A case-control design was employed. 234 HBV chronic carriers (109 cases and 125 controls) were recruited from the Prince of Wales Hospital in Hong Kong from December 2007 to May 2008. Data collection included review of medical records and face-to-face interview. Univariate and multivariate logistic regressions adjusting for age, gender, cigarette smoking, alcohol use, tea consumption and physical activity were conducted with dose-response analysis. Moderate coffee consumption significantly reduced the risk of HCC by almost half (OR 0.54, 95% CI 0.30 to 0.97) with a significant dose-response effect (χ²=5.41, df=1, p=0.02), reducing the risk for moderate drinkers by 59% (OR 0.41, 95% CI 0.19 to 0.89). The findings provided evidence to support the protective effect of coffee consumption in moderate quantities in HBV chronic carriers.
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Moderate coffee consumption reduces the risk of
hepatocellular carcinoma in hepatitis B chronic
carriers: a caseecontrol study
Winnie Wing-man Leung,
1
Suzanne C Ho,
1,2
Henry L Y Chan,
3
Vincent Wong,
3
Winnie Yeo,
4
Tony S K Mok
4
ABSTRACT
Background Recent epidemiological studies have
reported a dose-dependent protective effect of coffee on
hepatocellular carcinoma (HCC) with risk reduction
ranging from 30% to 80% in daily coffee drinkers
compared with non-drinkers. This study examined
whether coffee has a similar protective effect when
consumed in moderate quantities in chronic hepatitis B
virus (HBV) carriers, a group at high risk of developing
liver cancer.
Methods A caseecontrol design was employed. 234
HBV chronic carriers (109 cases and 125 controls) were
recruited from the Prince of Wales Hospital in Hong Kong
from December 2007 to May 2008. Data collection
included review of medical records and face-to-face
interview. Univariate and multivariate logistic regressions
adjusting for age, gender, cigarette smoking, alcohol use,
tea consumption and physical activity were conducted
with doseeresponse analysis.
Results Moderate coffee consumption significantly
reduced the risk of HCC by almost half (OR 0.54, 95% CI
0.30 to 0.97) with a significant doseeresponse effect
(
c
2
¼5.41, df¼1, p¼0.02), reducing the risk for
moderate drinkers by 59% (OR 0.41, 95% CI 0.19 to
0.89).
Conclusion The findings provided evidence to support
the protective effect of coffee consumption in moderate
quantities in HBV chronic carriers.
Liver cancer ranks fourth in incidence and third in
mortality among all cancers in Hong Kong.
1
Recent
epidemiological studies
2e14
in Japan and Europe
have suggested that coffee drinking lowers the risk
of hepatocellular carcinoma (HCC) by 76% in those
who consume ve or more cups per day,
9
with
consistent results from meta-analyses.
11 12
For
hepatitis B virus (HBV) and hepatitis virus C
chronic carriers, the protective effect of coffee
ranged from 46%
14
to 60%
4
in daily drinkers. These
studies were based on populations with heavy
coffee consumption, with per capita consumption
of 3.3, 5.3 and 5.5 kg, respectively, for Japanese,
Italian and Greek, compared with only 1.1 kg in
Hong Kong,
15
where only 12% of its residents
consume coffee habitually compared with the
global average of 55%.
16
The question of whether
lower coffee consumption would offer the same
protection against HCC was potentially important
for this population, especially as HBV chronic
carrier prevalence and liver cancer incidence rates
were high in Hong Kong compared with other parts
of the world. We hypothesised that HBV chronic
carriers with occasional or moderate coffee
consumption were at lower risk of HCC than those
with no coffee-drinking habit.
METHODS
A caseecontrol study design was employed. All
cases and controls were recruited from December
2007 to May 2008 during follow-up appointments
at the Special Outpatient Clinic (SOPD) of the
Prince of Wales Hospital in Hong Kong. Trained
research assistants, blind to the research hypoth-
esis, reviewed the medical record and administered
a 15-min face-to-face interview with each partici-
pant during follow-up at the SOPD. The study was
approved by the Joint CUHK-NTEC Clinical
Research Ethics Committee, with informed
consents from all participants.
Two hundred and thirty-four HBV carriers (109
cases, 125 controls) were entered into the study.
Cases and controls were frequency matched by age
group and gender distribution. Post-hoc analysis
indicated no signicant difference in alcohol use
(
c
2
¼1.66, df¼1, p¼0.44) and cigarette smoking
(
c
2
¼5.44, df¼1, p¼0.07) (table 1). HBV carrier
status was dened as the detection of hepatitis B
surface antigen in the blood samples of the partic-
ipant. HCC was dened as the topography code
C22.0 (ICD-O-3: C22.0, 817),
17
and diagnosis was
made based on the medical record for biopsy report,
radiological nding of a space-occupying lesion in
the liver and a raised
a
-fetoprotein $400
m
g/l, or
two coincidental radiological ndings of a space-
occupying lesion in the liver that has characteristic
features of HCC. All subjects in the SOPD docu-
mented seropositive on hepatitis B surface antigen
were eligible for inclusion; those under medication
for liver diseases and with a previous history of
cancer were excluded to control for confounding
due to liver medication and cancer relapse.
Exposure to coffee and potential confounders
including smoking, alcohol use, tea consumption
and physical activity (moderate intensity aerobic
exercise) were tapped in terms of intensity (days
per week of consumption; and amount per day)
and life-time exposure (years of consumption).
Univariate logistic regression was performed to
examine the crude OR of HCC risk in HBV chronic
carriers with a coffee consumption habit compared
with those without. Multivariate logistic regression
adjusting for potential confounders including age,
gender, tea consumption, cigarette smoking,
alcohol use and physical activity calculated as the
1
School of Public Health and
Primary Care, The Chinese
University of Hong Kong, Hong
Kong SAR, The People’s
Republic of China
2
Department of Community and
Family Medicine, The Chinese
University of Hong Kong, Hong
Kong SAR, The People’s
Republic of China
3
Department of Medicine and
Therapeutics, The Chinese
University of Hong Kong, Hong
Kong SAR, The People’s
Republic of China
4
Department of Clinical
Oncology, The Chinese
University of Hong Kong, Hong
Kong SAR, The People’s
Republic of China
Correspondence to
Ms Winnie W Leung, c/o Ms
Joyce Leung, 2/F PEC Building,
School of Public Health and
Primary Care, Prince of Wales
Hospital, Shatin, N.T., Hong
Kong;
winnieleung@cuhk.edu.hk
Accepted 2 June 2010
Published Online First
6 August 2010
556 J Epidemiol Community Health 2011;65:556e558. doi:10.1136/jech.2009.104125
Short report
product of intensity and life-time exposure was performed and
compared with the crude OR to examine for confounding. The
doseeresponse effect was tested using
c
2
test for trend, with
participants categorised into no coffee-drinking habit (<1 time/
week), occasional coffee-drinkers (1e3 times/week), and
moderate coffee-drinkers ($4 times/week) to yield OR for the
different dosages of coffee consumption.
RESULTS
Univariate logistic regression yielded a crude OR of 0.59 (95% CI
0.34 to 1.04), indicating a marginally non-signicant effect of
coffee consumption on HCC diagnosis. After controlling for age,
gender, tea and alcohol consumption, cigarette smoking and
physical activity, multivariate logistic regression indicated
a signicant protective effect of coffee against HCC (OR 0.54,
95% CI 0.30 to 0.97; table 2). The
c
2
test for trend suggested
a doseeresponse relationship (
c
2
¼5.41, df¼1, p¼0.02) with
occasional coffee drinkers of 3 days per week or less having an
OR of 0.57 (95% CI 0.24 to 1.36), and moderate coffee drinkers
of four or more days per week having an OR of 0.41 (95% CI
0.19 to 0.89), compared with HBV carriers with no
coffee-drinking habit.
DISCUSSION
The present study examined whether occasional and moderate
coffee drinking reduced the risk of HCC in chronic HBV carriers,
a population at elevated risk of developing liver cancer. Results
indicated that coffee drinking signicantly reduced the risk of
HCC by almost half in HBV chronic carriers, with moderate
drinkersrisk reduced by almost 60% compared with those with
no coffee-drinking habit. These results were consistent with
ndings from large-scale studies in Japan
35910
and Europe,
48
in
which daily coffee-drinking was found to protect against HCC
in the general population and HBV carriers.
214
Even at a much
lower dosage, the level of protection was comparable.
While the ndings are encouraging, the study was limited by
the relatively small sample size and the caseecontrol design,
which might have introduced recall bias. The use of prevalence
cases might also have introduced survivor effect. However, as
HCC participants in the present sample had a longer median
time from diagnosis of 31 months compared with reported
median survival rates,
18 19
any survivor effect might have
underestimated rather than overestimated the protective effect
of coffee. The lack of control on viral load, platelet count,
alanine aminotransferase level and other possible factors for
HCC is another limitation. Bearing these limitations in mind,
the results from the present study suggest that moderate coffee
consumption signicantly reduced the risk of HCC in HBV
carriers. Our converging evidence with previous studies calls for
clinical trials to study more rigorously the causal relationship
between coffee consumption and HCC risk. In itself, results
from this study suggest that coffee drinking, being a simple,
economical and easily modiable lifestyle factor, may have
important benets for HBV carriers and their families even in
moderate amounts for the large number of such individuals and
their families in Hong Kong.
Funding This study was funded by the Centre for Research and Promotion of
Women’s Health at The Chinese University of Hong Kong, Hong Kong SAR.
Table 1 Demographic characteristics of cases and controls (N¼234)
Cases
(N[109)
Controls
(N[125)
c
2
* df p ValueN (%) N (%)
Sex
Male 86 (78.9) 102 (81.6) 0.27 1 0.60
Female 23 (21.1) 23 (18.4)
Age group, years
#39 5 (4.6) 5 (4.0) 0.36 1 0.95
40e49 24 (22.0) 31 (24.8)
50e59 55 (50.5) 63 (50.4)
$60 25 (22.9) 26 (20.8)
Cigarette smoking
Never smoker 67 (61.5) 88 (70.4) 5.44 1 0.07
Ever smoker 11 (10.1) 17 (13.6)
Current smoker 31 (28.4) 20 (16.0)
Alcohol use
Never user 69 (63.3) 89 (71.2) 1.66 1 0.44
Ever user 11 (10.1) 10 (8.0)
Current user 29 (26.6) 26 (20.8)
*
c
2
test for trend for age group, cigarette smoking and alcohol use.
Table 2 Logistic regression analyses of coffee consumption on HCC
risk with OR, 95% CI and doseeresponse effect
Outcome
OR 95% CI
Case
(N[109)
Control
(N[125)
n (%) n (%)
Univariate analysis*
No 81 (74.3%) 79 (63.2%) 1 e
Yes 28 (25.7%) 46 (36.8%) 0.59 0.34 to 1.04
Multivariate analysisy
No 81 (74.3%) 79 (63.2%) 1 e
Yes 28 (25.7%) 46 (36.8%) 0.54 0.30 to 0.97
Doseeresponse analysisz
No coffee habit (<1 time/week) 86 (78.9%) 82 (65.6%) 1 e
Occasional (1e3 times/week) 11 (10.1%) 17 (13.6%) 0.58 0.24 to 1.36
Moderate ($4 times/week) 12 (11.0%) 26 (20.8%) 0.41 0.19 to 0.89
*Univariate logistic regression with coffee consumption (yes, no) predicting hepatocellular
carcinoma (HCC) diagnosis, giving the crude OR.
yMultivariate logistic regression with coffee consumption (yes, no) predicting HCC
diagnosis, adjusting for age, gender, cigarette smoking, alcohol use, tea consumption and
physical activity.
z
c
2
test for trend:
c
2
¼5.41, df¼1, p¼0.02.
What is already known on this subject
Recent epidemiological studies reported a dose-dependent
protective effect of coffee on HCC with risk reduction ranging
from 30% to 80% in daily coffee drinkers compared with non-
drinkers.
What this study adds
Even at a much lower dosage of occasional to moderate coffee
consumption, the level of protection from HCC was comparable
at 60%.
J Epidemiol Community Health 2011;65:556e558. doi:10.1136/jech.2009.104125 557
Short report
Competing interests None.
Patient consent Obtained.
Ethics approval This study was conducted with the approval of the Joint
CUHK-NTEC Clinical Research Ethics Committee.
Provenance and peer review Not commissioned; externally peer reviewed.
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558 J Epidemiol Community Health 2011;65:556e558. doi:10.1136/jech.2009.104125
Short report
... [5][6][7][8] Over more recent years, there have been a growing number of publications reporting that coffee intake not only improves liver biochemistry, but also slows progression to cirrhosis [9][10][11][12][13] and is associated with a reduced risk of death from liver disease. [14][15][16][17][18] The reported magnitude of the protection that coffee offers from liver death in cohort studies is impressive, though the impact on hepatitis B-related mortality is less certain. In one of the largest high quality prospective cohort studies to date, Setiawan and colleagues 14 demonstrated a 46% reduction in death from liver cirrhosis for people assessed at study entry as drinking 2-3 cups/day; and a 71% reduction in death from cirrhosis in those consuming 4 or more cups daily, after adjusting for key confounders including age, BMI, diabetes, gender, race, education level and alcohol intake. ...
... Making this assumption, the estimated number of liver-related Some published data suggest that hepatitis B infected people derive less mortality benefit from coffee consumption compared with other aetiologies of chronic liver disease. 14,15,17 To account for this, we performed an additional sensitivity analysis to determine the impact of excluding all hepatitis B-related liver deaths (Table S4). ...
... Collectively, these data have been considered compelling enough However, the paper by Goh and colleagues 15 raises the important point that it is not clear if the benefits of coffee on liver mortality risk reduction are uniformly spread between all aetiologies of liver disease. 15,17 In this paper, the positive impact of coffee on liver related mortality was exclusively in those with nonviral hepatitis related liver disease. However, only two of 63,257 subjects had hepatitis C-related liver mortality and these were excluded from the analysis, therefore the majority of those with viral hepatitis were hepatitis B infected, suggesting that coffee may not have a benefit in those with hepatitis B. However, other papers have not supported this finding. ...
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Background Epidemiological data suggest that coffee has a dose‐dependent protective effect on liver‐related mortality. Aim To estimate the potential impact of increased per capita coffee consumption on global liver‐related mortality. Methods Using the Global Burden of Disease 2016 dataset (adults > 15 years), we modelled the impact of increased per capita coffee consumption on liver‐related mortality in 2016 for 194 countries using published risk ratios for >2 cups coffee/ day (RR 0.54, 95% CI 0.42‐0.69) and ≥4 cups/ day (RR 0.29, 95% CI 0.17‐0.50), adjusted for confounders and tested model assumptions using sensitivity analyses. Results Worldwide, there were an estimated 1,240,201 (95% CI 118 4300‐1 354 410) adult liver‐related deaths in 2016. Median global liver mortality rate in 2016 was 15 deaths/ 100 000 population/ year (all ages, both genders; IQR 11‐21 deaths per 100 000). If all countries with per capita coffee intake ≤2 cups/ day increased to >2 cups/ day, the predicted total number of liver‐related deaths would have been 630 947 in 2016 (95% CI 629 693‐631 861) with 452 861 (95% CI 451 948‐454 116) deaths averted (PPR 7.8 liver‐related deaths/ 100 000/ year). If per capita consumptions was ≥ 4 cups/ day, the predicted number of liver‐related deaths in 2016 would have been 360 523 (95% CI 359 825‐361 992) with 723 287 (95% CI 721 817‐723 984) deaths averted (PPR 12.1 liver‐related deaths/100 000/year). Conclusion Increasing per capita coffee consumption to > 2 cups per day on a population level has the potential to avert hundreds of thousands of liver‐related deaths annually if the impact of coffee on liver‐related mortality is confirmed in clinical trials.
... Ohfuji et al. [60] 2006 Japan Case-control 73 253 ...
... while, despite the OR below unit for daily coffee drinkers, the statistical significance was not obtained in HCVnegative group. This study supported the previous findings by Gelatti et al. [23] , Ohfuji et al. [60] , and Inoue et al. [25] who demonstrated an inverse association between coffee drinking and HCC risk in HCV-positive patients. However, not all studies are concordant on that point [51] . ...
... The reverse causation bias could not be excluded in observational studies, even though obviously it is higher in retrospective case-control [22,23,51,52,[59][60][61]68] than prospective cohort studies, which evaluate the exposure of interest years before the liver cancer occurrence [24][25][26][27][53][54][55][56]58] . Several attempts have been made to minimize this bias. ...
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Coffee is one of the most widely consumed beverages worldwide. It is a complex chemical mixture composed of thousands of physiologically active compounds, including caffeine, chlorogenic acid, and diterpenes (cafestol and kahweol). Recently, coffee has emerged as a beverage with various health benefits, in particular in liver disease. Several epidemiological and observational studies demonstrated an inverse association between coffee consumption and primary liver cancer risk. The biological mechanisms underlying the hepatoprotective effect of coffee are still not completely understood. This article reviews the current available literature about the association between coffee consumption and hepatocellular carcinoma risk and the proposed mechanisms by which coffee exerts its chemopreventive properties.
... Epidemiological reporting on the association between coffee drinking and liver cancer began in the 1980s, mainly from case-control studies, followed from 2000 by a gradual increase in reports from cohort studies. To date, a total of 14 cohort studies [16][17][18][19][20][21][22][23][24][25][26][27][28][29] and 10 case-control studies [30][31][32][33][34][35][36][37][38][39] have examined the association between coffee intake and liver cancer risk. While case-control studies were conducted in various countries, more than half (8 studies) of the cohort studies were from Japan. ...
... Although some results conflicted, these observational studies generally reported a consistent risk reduction in regular coffee drinkers. Many studies, mostly with case-control or nested casecontrol designs, took account of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, the established cause of liver cancer, by adjustment, stratification, or subset analysis [20,21,24,25,27,30,32,[34][35][36][37][38][39]. These studies consistently observed an inverse association between coffee intake and liver cancer risk regardless of history of hepatitis or liver disease. ...
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Purpose of Review We reviewed the available literature on observational studies, meta-analyses, expert reports, and umbrella reviews. Here, we summarize the latest findings on the association between coffee intake and liver cancer risk. Recent Findings Most observational studies and meta-analyses show a protective effect of coffee intake on liver cancer risk, with dose-responsiveness and across different populations, and regardless of hepatitis virus infection status. Risk reduction by coffee consumption has also been observed for chronic liver diseases. Potential mechanisms include the effect of a number of bioactive compounds such as caffeine, chlorogenic acids, phenolic compounds and diterpenes; antioxidant properties; induction of defense mechanisms; and anti-inflammatory properties. Other potential mechanisms include improvement in insulin sensitivity and prevention of metabolic syndrome and diabetes. Summary Accumulated evidence, with consistency across study designs and populations, suggests that coffee intake probably reduces the risk of liver cancer. Future research should aim to elucidate the mechanism of this preventive effect with establishing the causality of an association.
... Concerning to histopathologically, heavy coffee ingestion was associated with extent of liver fibrosis and cirrhosis (Leung et al., 2011). Also, it was demonstrated that liver is specific targeted for caffeine, thus obviously resulted in hepatotoxicity and loss of integrity (Manne and Saab, 2015). ...
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... Although coffee and caffeine can increase the risk of cardiovascular disease, numerous studies have demonstrated that coffee and caffeine have hepatoprotective effects against chronic liver diseases (14). Epidemiological and clinical investigations have suggested that the consumption of coffee could reduce the risk of alcoholic liver cirrhosis (15), type-2 diabetes (16), NAFLD (17), and HCC (18,19), and reduce the progression of NASH, the severity of fibrosis (20), and alanine aminotransferase (ALT) activity in patients with liver injury (21). The recent meta-analysis results of Stefano et al. show that coffee consumption may play a protective role in fibrosis. ...
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... and p for trend <0.001 for occasional use, 1-2 cups/day, and 3 or more cups/day. This study formed the overture to other investigations involving Asian subjects, namely, a case-control study by Leung et al. [33] and cohort studies by Inoue [34] and Johnson et al. [35] which confirmed the beneficial effect of coffee. Also an Italian case-based study by Montella et al. [36] supported this evidence. ...
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A significant number of studies suggests that coffee consumption reduces cancer risk. This beneficial effect is usually ascribed to the presence of polyphenolic antioxidants and anti- inflammatory agents, including caffeine, cafestol, kahweol and chlorogenic acids. To summarize recent literature on this subject we performed a bibliographic search in PubMed and Embase over the period January 2005 to December 2020 to identify cohort studies and meta-analysis (with data collection ensuring quality of selected reports) that could provide quantitative data on the relationship between coffee consumption and common cancers. The totality of eligible scientific papers support the evidence that coffee intake is inversely associated with hepatocellular cancer risk and to a - slight extent- breast cancer risk among postmenopausal women. As to the association with other organs, including esophagus, pancreas, colorectum, kidneys, bladder, ovaries and prostate, the results are less clear as reports reveal conflicting results or statistically non- significant data. Therefore this overview does not allow broad- based conclusions. Important uncertainties include general study design, inhomogeneous patient sampling, different statistical analysis, (deliberate) misreporting of socio- economic status, education, coffee brewing methods, consumption caffeinated or decaffeinated coffee, smoking habits and alcohol intake. Obviously, more epidemiological research needs to be conducted before solid science- based recommendations can be made with regard to coffee consumption.
... Moreover, daily coffee intake reduces the risk of several chronic diseases, such as hepatocellular diseases, Parkinson's disease, type 2 diabetes mellitus and several types of cancer [15,17]. Green Coffee (GC) extracts produce an antihypertensive effect in rats and humans [18,19], improve human vaso-reactivity [20], inhibit fat accumulation in mice and humans [21,22] and modulate glucose metabolism in humans [23]. ...
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Background Vitamin C (VC) is believed to enhance immunity and is regularly integrated as a supplementary agent during several treatments. Objective The green (GC) and roasted (RC) Coffee (Coffea arabica) aqueous extracts (0, 125, 250 and 500 μg/ml) combined with VC (50 μg/ml) were examined on the cancerous MCF-7 cell line and normal human lymphocytes. Methods Neutral red uptake assay, comet assay, immunocytochemical reactivity for protein expression and mRNA expression of apoptosis-related genes were done. Results A significant (P 7<0.05) concentration-dependent increase of apoptotic features, such as morphological changes, abundant nuclear condensation, altered expression of p53 and caspase-3 mRNA, down-regulation of Bcl-2 protein as well as the acidic autophagosomal vacuolization in treated cells. The oxidative stress and DNA single strand breaks were noticed too. Conclusion These results suggest that coffee in combination with VC undergo apoptotic anticancer pathway. This supports the integration of coffee and vitamin C as a valuable candidate for anticancer research and treatments.
... After removal of duplicate publications, 172 studies remained for title and abstract screening, of which 22 were potentially relevant for full-text review. Among the 22 reviewed publications, studies (with possible overlap) were excluded from the primary meta-analysis on physical activity and liver cancer if the exposure variable was not physical activity (n ¼ 6) (36-41), or if the outcome was not liver cancer (n ¼ 1) (19), or the effect estimates for physical activity were not shown (n ¼ 4) (36,37,41,42). Additionally, studies were excluded if the study design was not prospective (n ¼ 5) (43)(44)(45)(46)(47) or if the article had a shorter follow-up or fewer events than another publication from the same study (n ¼ 5) (16,41,(48)(49)(50). ...
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Three hundred and forty cases of hepatocellular carcinoma in Hong Kong were studied for their clinical features, and various factors were analysed for their prognostic values. The clinical presentation was often vague and rather non-specific and a majority of patients were presented late and often unresectable. The overall median survival was 8 weeks. The Karnofsky performance scale and bilirubin level were the most important prognostic factors. The treated group survived longer than the untreated group.
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We analysed the relation between coffee consumption and hepatocellular carcinoma in two case-control studies conducted between 1984 and 1998 in Italy and Greece, including 834 cases and 1912 controls. Compared to non coffee drinkers, the multivariate odds ratio was 0.7 for drinkers of three or more cups per day. British Journal of Cancer (2002) 87, 956–959. doi:10.1038/sj.bjc.6600582 www.bjcancer.com © 2002 Cancer Research UK
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An association between coffee drinking and reduced risk of liver cancer has been suggested by animal studies, but epidemiologic evidence of such an association in a high-risk population is lacking. We conducted a large-scale population-based cohort study of the association between coffee drinking and hepatocellular carcinoma (HCC) in a Japanese population. Newly diagnosed case patients (250 men and 84 women) with HCC were identified from a 10-year follow-up of the Japan Public Health Center-based Prospective Study, which consists of 90,452 middle-aged and elderly Japanese subjects (43,109 men and 47,343 women). Case patients were grouped according to coffee intake and were stratified by hepatitis virus infection, sex, age, diet, lifestyle factors, and previous history of liver disease. Multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CIs) for HCC were calculated with Cox proportional-hazards modeling. All statistical tests were two-sided. Subjects (men and women combined) who consumed coffee on a daily or almost daily basis had a lower HCC risk than those who almost never drank coffee (HR = 0.49 [95% CI = 0.36 to 0.66]); risk decreased with the amount of coffee consumed (compared with nondrinkers, the HR for 1-2 cups per day = 0.52 [95% CI = 0.38 to 0.73]; for 3-4 cups per day = 0.48 [95% CI = 0.28 to 0.83]; for > or =5 cups per day = 0.24 [95% CI = 0.08 to 0.77], P(trend) < .001). The risk of liver cancer in almost never drinkers in this population was 547.2 cases per 100,000 people over 10 years, but it was 214.6 cases per 100 000 people with drinking coffee on a daily basis. The inverse association persisted when the participants were stratified by lifestyle factors. Similar associations were observed when the analysis was restricted to hepatitis C virus-positive patients (all daily drinkers compared with nondrinkers: HR =0.57 [95% CI = 0.37 to 0.86]), to hepatitis B virus-positive patients (HR = 0.60 [95% CI = 0.31 to 1.18]) and to subjects with no past history of chronic liver disease (HR = 0.45 [95% CI = 0.30 to 0.67]). In the Japanese population, habitual coffee drinking may be associated with reduced risk of HCC.
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Although case-control studies suggested that coffee consumption is associated with a decreased risk of liver cancer, no prospective cohort study has been carried out. To examine the association between coffee consumption and the risk of liver cancer, we conducted a pooled analysis of data available from 2 cohort studies in Japan. A self-administered questionnaire about the frequency of coffee consumption and other health habits was distributed to 22,404 subjects (10,588 men and 11,816 women) in Cohort 1 and 38,703 subjects (18,869 men and 19,834 women) in Cohort 2, aged 40 years or more, with no previous history of cancer. We identified 70 and 47 cases of liver cancer among the subjects in Cohort 1 (9 years of follow-up with 170,640 person-years) and Cohort 2 (7 years of follow-up with 284,948 person-years), respectively. We used Cox proportional hazards regression analysis to estimate the relative risk (RR) and 95% confidence interval (CI) of liver cancer incidence. After adjustment for potential confounders, the pooled RR (95% CI) of drinking coffee never, occasionally and 1 or more cups/day were 1.00 (Reference), 0.71 (0.46-1.09) and 0.58 (0.36-0.96), respectively (p for trend = 0.024). In the subgroup of subjects with a history of liver disease, we found a significant inverse association between coffee consumption and the risk of liver cancer. Our findings support the hypothesis that coffee consumption decreases the risk of liver cancer. Further studies to investigate the role of coffee in prevention of liver cancer among the high-risk population are needed.
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We examined the relation between coffee drinking and hepatocellular carcinoma (HCC) mortality in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study). In total, 110,688 cohort members (46,399 male and 64,289 female subjects) aged 40-79 years were grouped by coffee intake into three categories: one or more cups per day, less than one cup per day and non-coffee drinkers. Cox proportional hazards model by SAS was used to obtain hazard ratio of HCC mortality for each coffee consumption categories. The hazard ratios were adjusted for age, gender, educational status, history of diabetes and liver diseases, smoking habits and alcohol. The hazard ratio of death due to HCC for drinkers of one and more cups of coffee per day, compared with non-coffee drinkers, was 0.50 (95% confidence interval 0.31-0.79), and the ratio for drinkers of less than one cup per day was 0.83 (95% confidence interval 0.54-1.25). Our data confirmed an inverse association between coffee consumption and HCC mortality.