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Fulltext Primary liver cancer in Malaysian children

Sinniah D, Sumithran E, Lin HP, Chan LL, Toh CK

Med J Malaysia, 1980 Mar;34(3):265-8.
PMID: 6251351

The high incidence of primary liver cancer in Malaysian males is not observed in childhood, where it constitutes 0.16 per 1000 paediatric hospital admissions and 3.20/0 of all childhood malignancies at the University Hospital, Kuala Lumpur. This frequency is comparable to that reported from several developed countries. The commonest liver tumour in children is the hepatoblastoma which is probably of embryonal origin and has a similar world wide "incidence. The relative infrequency of hepatocellular carcinoma in childhood and its association with cirrhosis, the hepatitis B antigen and its prevalence in the older age group helps to substantiate an acquired environmental aetiology.

Matched MeSH terms: Liver Neoplasms/epidemiology*
Hepatocellular carcinoma in the Malaysian Orang Asli

Sumithran E, Prathap K

Cancer, 1976 May;37(5):2263-6.
PMID: 177187

Necropsies were performed on 285 consecutively unclaimed Orang Asli bodies from Gombak Orang Asli Hospital during an eight-year period from May 1967 to April 1975. Of the 25 malignant neoplasms, hepatocellular carcinoma was by far the commonest (36%). The nine patients with this neoplasm had coexistant macronodular cirrhosis. There were 20 cases of cirrhosis; 45% of these had coexistant hepatocellular carcinoma. The 53,000 Orang Aslis living in West Malaysia comprise three tribes, the Negrito, Senoi, and Melayu Asli (Proto Malays). The Sinoi appear to have a high predilection for liver cancer, all our nine cases occurring in this group. These aboriginal people live in the jungles where they practice shifting cultivation and maintain their own dietary and social customs. Detailed studies of their dietary habits may provide a clue to the etiology of liver cancer in these people.

Matched MeSH terms: Liver Neoplasms/epidemiology*
Malignant tumours in west Malaysia

Kutty MK, Balasegaram M

J R Coll Surg Edinb, 1972 Mar;17(2):102-7.
PMID: 5021743
Matched MeSH terms: Liver Neoplasms/epidemiology
Fulltext Fruit and vegetable consumption in relation to hepatocellular carcinoma in a multi-centre, European cohort study

Bamia C, Lagiou P, Jenab M, Aleksandrova K, Fedirko V, Trichopoulos D, et al.

Br. J. Cancer, 2015 Mar 31;112(7):1273-82.
PMID: 25742480 DOI: 10.1038/bjc.2014.654

BACKGROUND: Vegetable and/or fruit intakes in association with hepatocellular carcinoma (HCC) risk have been investigated in case-control studies conducted in specific European countries and cohort studies conducted in Asia, with inconclusive results. No multi-centre European cohort has investigated the indicated associations.

METHODS: In 486,799 men/women from the European Prospective Investigation into Cancer and nutrition, we identified 201 HCC cases after 11 years median follow-up. We calculated adjusted hazard ratios (HRs) for HCC incidence for sex-specific quintiles and per 100 g d(-1) increments of vegetable/fruit intakes.

RESULTS: Higher vegetable intake was associated with a statistically significant, monotonic reduction of HCC risk: HR (100 g d(-1) increment): 0.83; 95% CI: 0.71-0.98. This association was consistent in sensitivity analyses with no apparent heterogeneity across strata of HCC risk factors. Fruit intake was not associated with HCC incidence: HR (100 g d(-1) increment): 1.01; 95% CI: 0.92-1.11.

CONCLUSIONS: Vegetable, but not fruit, intake is associated with lower HCC risk with no evidence for heterogeneity of this association in strata of important HCC risk factors. Mechanistic studies should clarify pathways underlying this association. Given that HCC prognosis is poor and that vegetables are practically universally accessible, our results may be important, especially for those at high risk for the disease.

Matched MeSH terms: Liver Neoplasms/epidemiology*
Epidemiology and survival of hepatocellular carcinoma in north-east Peninsular Malaysia

Norsa'adah B, Nurhazalini-Zayani CG

Asian Pac J Cancer Prev, 2013;14(11):6955-9.
PMID: 24377632

The incidence of hepatocellular carcinoma (HCC) is relatively high in Southeast Asia. Globally, HCC has a high fatality rate and short survival. The objectives of this retrospective cohort study were to review the epidemiology and survival of HCC patients at a tertiary centre in north-east of Peninsular Malaysia. Subjects were adult HCC patients diagnosed by histopathology or radio-imaging. Secondary liver carcinoma was excluded. Kaplan Meier and multiple Cox proportional hazard survival analyses were used. Only 210 HCC cases from years 1987-2008, were included in the final analysis. The number of cases was increasing annually. The mean age was 55.0 (SD 13.9) years with male:female ratio of 3.7:1. Approximately 57.6% had positive hepatitis B virus, 2.4% hepatitis C virus, 20% liver cirrhosis and 8.1% chronic liver disease. Only 2.9% had family history and 9.0% had frequently consumed alcohol. Most patients presented with abdominal pain or discomfort and had hepatomegaly, 47.9% had an elevated α-fetoprotein level of 800 IU/ml or more, 51.9% had multiple tumors and 44.8% involved multiple liver lobes. Approximately 63.3% were in stage 3 and 23.4% in stage 4, and 82.9% did not receive any treatment. The overall median survival time was 1.9 months (95% confidence interval (CI): 1.5, 2.3). The 1-month, 6-month, 1-year and 2-year survival rates were 71.8%, 23.3%, 13.0% and 7.3% respectively. Significant prognostic factors were Malay ethnicity [Adjusted hazard ratio (AHR) 1.6; 95%CI: 1.0, 2.5; p=0.030], no chemotherapy [AHR 1.7; 95%CI: 1.1, 2.5; p=0.017] and Child-Pugh class C [AHR 2.6; 95%CI: 1.4, 4.9; p=0.002]. HCC in our study affected a wide age range, mostly male, in advanced stage of disease, with no treatment and very low survival rates. Primary prevention should be advocated in view of late presentation and difficulty of treatment. Vaccination of hepatitis virus and avoidance of liver toxins are to be encouraged.

Matched MeSH terms: Liver Neoplasms/epidemiology*
Histopathological landmarks of hepatocellular carcinoma in Malaysians

Cheah PL, Looi LM, Nazarina AR, Goh KL, Rosmawati M, Vijeyasingam R

Malays J Pathol, 2003 Jun;25(1):37-43.
PMID: 16196376

A study was conducted at the Department of Pathology, University of Malaya Medical Centre, Kuala Lumpur into the histological type (WHO classification), grade (modified Edmondson and Steiner's grading system), mitotic rate, bile production, hyaline globule and Mallory hyaline formation of 52 cases of hepatocellular carcinoma (HCC) diagnosed during a 13-year period between 1st January 1990 to 31st December 2002. In addition, associated cirrhosis, dysplasia (large liver cell dysplasia: LLCD and small liver cell dysplasia: SLCD) and microvascular permeation were also looked for whenever the situation permitted. The patients' ages ranged from 21-years to 85-years (mean = 58.7 years) with a predilection for males and Chinese. Histologically, majority (73.1%) of the tumours demonstrated a trabecular pattern of growth. The bulk (73%) of the tumours were either of grade II or III differentiation. Mitotic activity ranged between 0-100/10 high power fields (hpf) with a mean of 22.2/10 hpf. Bile was noted in 25%, hyaline globules 17.3% and Mallory bodies in one case. Concomitant cirrhosis was present in 73.5%. 73.5% of the cases had associated LLCD. 5 with LLCD also showed SLCD. Microvascular permeation was shown in 76.2% of cases. On comparison with findings from other studies, no major difference seems to exist between the histological characteristics of our HCC cases and that of other populations.

Matched MeSH terms: Liver Neoplasms/epidemiology*
Incidence of primary liver cancer in Singapore, 1968-1982

Chia KS, Lee HP, Lee J

Ann Acad Med Singap, 1989 May;18(3):313-6.
PMID: 2549842

Based on data collected by the population-based Singapore Cancer Registry over the period 1968 to 1982, baseline epidemiological characteristics and incidence trends of primary liver cancer were described. This will facilitate the interpretation of future trends, especially in the light of new interventions such as hepatitis B immunisation. The primary liver cancer incidence is four times higher in males than in females, with the incidence peaked in the seventh decade. The incidence rate was higher in the Chinese than in Malays and Indians and marginally higher among foreign born than Singapore born Chinese. A general declining trend in liver cancer incidence was especially notable in the local born Chinese. Misclassification of metastatic carcinomas in the earlier years of cancer registration may have contributed to the initial higher incidence. Definitive decrease in incidence as a result of hepatitis immunisation will only be seen in another two to three decades.

Matched MeSH terms: Liver Neoplasms/epidemiology*
Epidemiology of non-alcoholic fatty liver disease in Asia

Wong SW, Chan WK

Indian J Gastroenterol, 2020 02;39(1):1-8.
PMID: 32152903 DOI: 10.1007/s12664-020-01018-x

The growing burden of non-alcoholic fatty liver disease (NAFLD) parallels the increasing prevalence of obesity in Asia. The overall prevalence of NAFLD in Asia is now estimated to be 29.6% and may have surpassed that in Western populations. NAFLD increases with increasing age and is closely associated with metabolic syndrome. Ethnic differences exist in the prevalence of NAFLD, but the underlying factors are unclear. There were initial concerns about lean NAFLD being associated with more severe liver disease and increased mortality, but subsequent studies suggested otherwise. Only some NAFLD patients progress to develop advanced liver fibrosis and cirrhosis, while the liver status remains unchanged in the majority; fibrosis stage is the most important predictor of disease-specific mortality in NAFLD. Surveillance for hepatocellular carcinoma (HCC) remains a challenge due to undiagnosed cirrhosis and the development of HCC in non-cirrhotic NAFLD patients. Diabetes mellitus shares a bidirectional relationship with NAFLD; NAFLD is highly prevalent among patients with diabetes mellitus, and diabetes mellitus is associated with more severe NAFLD. Chronic hepatitis B (CHB) is a major cause of chronic liver disease in Asia; NAFLD and CHB are increasingly observed together because of the increasing prevalence of NAFLD. Despite studies reporting favorable virologic outcome in CHB patients with NAFLD, NAFLD has been found to be independently associated with fibrosis progression and poorer prognosis in CHB patients. Therefore, NAFLD in CHB patients should be given more attention.

Matched MeSH terms: Liver Neoplasms/epidemiology
HBAg-positive chronic liver disease associated with cirrhosis and hepatocellular carcinoma in the Senoi

Sumithran E, Prathap K

Cancer, 1977 Oct;40(4):1618-20.
PMID: 198100

Necropsy and clinical data show that primary hepatocellular carcinoma (PHC) is the commonest cancer among the Senoi (a Malaysian aboringine group). The other aboringine tribes do not appear to have this high predilection for liver cancer. In the necropsy series, PHS was present in 10 out of 22 Senoi patients with cirrhosis. All the 22 livers contained hepatocytes that stained with Shikata's orcein stain and specific immunoperoxidase and immunofluorescent stains for hepatitis B antigen (HBAg). This observation raises the strong possibility that hepatitis B may be an important etiologic factor in the development of cirrhosis and PHC in the Senoi. The reason for the high susceptibility of the Senoi for HB virus infection is not clear, and the role of aflatoxin in the pathogenesis of PHC in the Senoi has yet to be determined. That the Senoi are a numerically small community, maintaining their own unique dietary and social customs and living in readily accessible areas in the Malaysian jungle, makes them an ideal population for the study of factors in the etiology of liver cancer.

Matched MeSH terms: Liver Neoplasms/epidemiology
Fulltext Circulating copper and zinc levels and risk of hepatobiliary cancers in Europeans

Stepien M, Hughes DJ, Hybsier S, Bamia C, Tjønneland A, Overvad K, et al.

Br J Cancer, 2017 Feb 28;116(5):688-696.
PMID: 28152549 DOI: 10.1038/bjc.2017.1

BACKGROUND: Copper and zinc are essential micronutrients and cofactors of many enzymatic reactions that may be involved in liver-cancer development. We aimed to assess pre-diagnostic circulating levels of copper, zinc and their ratio (Cu/Zn) in relation to hepatocellular carcinoma (HCC), intrahepatic bile duct (IHBD) and gall bladder and biliary tract (GBTC) cancers.
METHODS: A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort. Serum zinc and copper levels were measured in baseline blood samples by total reflection X-ray fluorescence in cancer cases (HCC n=106, IHDB n=34, GBTC n=96) and their matched controls (1:1). The Cu/Zn ratio, an indicator of the balance between the micronutrients, was computed. Multivariable adjusted odds ratios and 95% confidence intervals (OR; 95% CI) were used to estimate cancer risk.
RESULTS: For HCC, the highest vs lowest tertile showed a strong inverse association for zinc (OR=0.36; 95% CI: 0.13-0.98, Ptrend=0.0123), but no association for copper (OR=1.06; 95% CI: 0.45-2.46, Ptrend=0.8878) in multivariable models. The calculated Cu/Zn ratio showed a positive association for HCC (OR=4.63; 95% CI: 1.41-15.27, Ptrend=0.0135). For IHBC and GBTC, no significant associations were observed.
CONCLUSIONS: Zinc may have a role in preventing liver-cancer development, but this finding requires further investigation in other settings.

Matched MeSH terms: Liver Neoplasms/epidemiology*
HBV and liver cancer

Leung N

Med J Malaysia, 2005 Jul;60 Suppl B:63-6.
PMID: 16108176

The association of hepatitis B virus (HBV) infection and liver cancer is well documented in epidemiological study. Patients with chronic hepatitis B have increased risk of hepatocelluar carcinoma (HCC), in particular those with active liver disease and cirrhosis. The incidence of HCC increases with age and is more common among male patients. The introduction of universal HBV vaccination program for the newborn in endemic regions has started to show beneficial impact. Taiwan introduced this program two decades ago and the incidence of liver cancer among infants and young children have declined significantly. The carcinogenic events leading to HCC are under intense research. A number of hypotheses have been proposed. HBV is not directly hepatotoxic but its interaction with the host immune system creates opportunity for HBV DNA integration into the host genome. One of the main foci of research is the HBX-encoded X protein. Its integration and protein expression impose alteration in cell proliferation cycle and apoptosis process. Many other factors may be involved including viral-induced alterations in p53 and telemerase, HBV genotypes, co-infection with HCV or delta agents, patient's lifestyle such as smoking, alcohol excesses, and genetic factors of the host patient. The processes of necroinflammation, cell proliferation and fibrosis facilitate the initial carcinogenic development. HCC surveillance with tumor markers such as alpha-foetal protein, decarboxylated prothrombin, in conjunction with imaging techniques has identified early small HCC that is amenable to curative therapy. Viral load has been correlated with increase risk of HCC. The available anti-viral agents have demonstrated clinical benefit among those with maintained and sustained response. Interferon and lamivudine therapy have demonstrated reduction of HCC among responders. However, they only constitute a minority proportion of treated patients. The mainstay of prevention should lie in prevention of HBV infection and early effective therapy of chronic hepatitis B infection.

Matched MeSH terms: Liver Neoplasms/epidemiology*
An epidemiological study of cancers in the university hospital: a preliminary report

Huat LH

Med J Malaysia, 1979 Sep;34(1):32-7.
PMID: 542148
Matched MeSH terms: Liver Neoplasms/epidemiology
Fulltext Risk factors of hepatocellular carcinoma in type 2 diabetes patients: A two-centre study in a developing country

Azit NA, Sahran S, Voon Meng L, Subramaniam M, Mokhtar S, Mohammed Nawi A

PLoS One, 2021;16(12):e0260675.
PMID: 34882716 DOI: 10.1371/journal.pone.0260675

Type 2 diabetes mellitus (T2DM) is increasingly known as a risk factor of hepatocellular carcinoma (HCC). In this study, we determined the risk factors associated with HCC in T2DM patients. This was a matched case-control study conducted at two hepatobiliary referral centres in a developing country. Patients' sociodemographic, clinical, and biochemical characteristics between 1 January 2012 and 30 June 2018 were extracted from the electronic medical records and analysed using multivariate logistic regression analysis. A total of 212 case-control pairs were included. Significant risk factors included Chinese and Malay ethnicities that interacted with viral hepatitis (adjusted odds ratio [AOR] = 11.77, 95% confidence interval [CI]: 1.39-99.79) and (AOR = 37.94, 95% CI: 3.92-367.61) respectively, weight loss (AOR = 5.28, 95% CI: 2.29-12.19), abdominal pain/ discomfort (AOR = 6.73, 95% CI: 3.34-13.34), alcohol (AOR = 4.08, 95% CI: 1.81-9.22), fatty liver (AOR = 3.29, 95% CI: 1.40-7.76), low platelet (AOR = 4.03, 95% CI:1.90-8.55), raised alanine transaminase (AOR = 2.11, 95% CI: 1.16-3.86). and alkaline phosphatase (ALP) levels (AOR = 2.17, 95% CI: 1.17-4.00). Statins reduced the risk of HCC by 63% (AOR = 0.37, 95% CI: 0.21-0.65). The identification of these factors aids the risk stratification for HCC among T2DM patients for early detection and decision-making in patient management in the primary care setting.

Matched MeSH terms: Liver Neoplasms/epidemiology*
Hepatitis C virus prevalence and genotyping among hepatocellular carcinoma patients in Baghdad

Al-Kubaisy WA, Obaid KJ, Noor NA, Ibrahim NS, Al-Azawi AA

Asian Pac J Cancer Prev, 2014;15(18):7725-30.
PMID: 25292053

Hepatocellular carcinoma (HCC) is the third most common cause for cancer death in the world, now being especially linked to chronic hepatitis C virus (HCV) infection. This case-control study consisting of 65 HCC patients and 82 patients with other malignant tumours as controls was conducted to determine the association of HCV markers with HCC. Serum of each participant was obtained for detection of HCV Ab and RNA by DNA enzyme immunoassay (DEIA). Twenty six per cent (26.0%) of HCC patients had positive anti-HCV which was significantly greater than the control group (p=0.001). HCC patients significantly have a risk of exposure to HCV infection almost 3 times than the control group (OR=2.87, 95% C.I=1.1-7). Anti-HCV seropositive rate was significantly (p=0.03) higher among old age HCC patients and increases with age. Males with HCC significantly showed to have more than 9 times risk of exposure to HCV infection (OR=9.375, 95 % CI=1.299-67.647) than females. HCV-RNA seropositive rate was (70.8%) significantly higher among HCC patients compared to (22.2%) the control group (p=0.019). The most prevalent genotype (as a single or mixed pattern of infection) was HCV- 1b. This study detected a significantly higher HCV seropositive rate of antibodies and RNA in HCC patients.

Matched MeSH terms: Liver Neoplasms/epidemiology
Fulltext Dietary fat, fat subtypes and hepatocellular carcinoma in a large European cohort

Duarte-Salles T, Fedirko V, Stepien M, Aleksandrova K, Bamia C, Lagiou P, et al.

Int J Cancer, 2015 Dec 01;137(11):2715-28.
PMID: 26081477 DOI: 10.1002/ijc.29643

The role of amount and type of dietary fat consumption in the etiology of hepatocellular carcinoma (HCC) is poorly understood, despite suggestive biological plausibility. The associations of total fat, fat subtypes and fat sources with HCC incidence were investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which includes 191 incident HCC cases diagnosed between 1992 and 2010. Diet was assessed by country-specific, validated dietary questionnaires. A single 24-hr diet recall from a cohort subsample was used for measurement error calibration. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated from Cox proportional hazard models. Hepatitis B and C viruses (HBV/HCV) status and biomarkers of liver function were assessed separately in a nested case-control subset with available blood samples (HCC = 122). In multivariable calibrated models, there was a statistically significant inverse association between total fat intake and risk of HCC (per 10 g/day, HR = 0.80, 95% CI: 0.65-0.99), which was mainly driven by monounsaturated fats (per 5 g/day, HR = 0.71, 95% CI: 0.55-0.92) rather than polyunsaturated fats (per 5 g/day, HR = 0.92, 95% CI: 0.68-1.25). There was no association between saturated fats (HR = 1.08, 95% CI: 0.88-1.34) and HCC risk. The ratio of polyunsaturated/monounsaturated fats to saturated fats was not significantly associated with HCC risk (per 0.2 point, HR = 0.86, 95% CI: 0.73-1.01). Restriction of analyses to HBV/HCV free participants or adjustment for liver function did not substantially alter the findings. In this large prospective European cohort, higher consumption of monounsaturated fats is associated with lower HCC risk.

Matched MeSH terms: Liver Neoplasms/epidemiology*
Clinical and chemotherapeutic study of hepatocellular carcinoma in Malaysia: a comparison with African and American patients

Joishy SK, Bennett JM, Balasegaram M, MacIntyre JM, Falkson G, Moertel C, et al.

Cancer, 1982 Sep 15;50(6):1065-9.
PMID: 6286085

Twenty Malaysian patients with unresectable primary liver cell cancer were prospectively studied at the General Hospital, Kuala Lampur, and were compared for clinical features with an equal number each of African and American patients being studied by the Eastern Cooperative Oncology Group. The patients received intravenous 5-FU and oral MeCCNU which was used for the first time in an Asian country. Most of the Malaysian patients were Chinese, belonged to younger age groups, and presented with massive hepatomegaly, jaundice, and fever. Toxicity to MeCCNU invariably occurred in the form of leukopenia or thrombocytopenia, but none life threatening. Partial response was seen in 20% of Malaysians as compared to 16% in Americans and none in Africans. Malaysians achieved a median survival of 16 weeks compared to 28 weeks in Americans and only eight weeks in Africans. Malaysian Chinese patients were all HBc Ab + ve. Other factors which may have played an etiologic role in the induction of primary liver cancer included alcohol, Chinese herbal medicines, aflatoxin and habitual use of medicated rubbing oils.

Matched MeSH terms: Liver Neoplasms/epidemiology*
Fulltext Genetic diversity of hepatitis B co-infection with hepatitis C, D and E viruses among Malaysian chronic hepatitis B patients

Hudu SA, Niazlin MT, Nordin SA, Tan SS, Omar H, Shahar H, et al.

Afr Health Sci, 2018 Dec;18(4):1117-1133.
PMID: 30766578 DOI: 10.4314/ahs.v18i4.33

Background: Hepatitis B virus co-infection with other strains of viral hepatitis is associated with increased risk of liver cirrhosis and hepatic decompensation.
Objectives: This is a prevalence study that assessed the genetic diversity of chronic hepatitis B patients and coinfection.
Methods: Chronic hepatitis B patients enrolled in this study were tested for antibodies of other hepatitis viruses using ELISA kits. Patient clinical profiles were collected and partial genes of HBV, HCV, and HEV were amplified, sequenced, and analyzed using phylogenetic analysis. The associations between variables were determined using the chi-squared test.
Results: Of the 82 patients recruited for this study, 53.7% were non-cirrhotic, 22.0% cirrhotic, 20.7% acute flare and 3.7% hepatocellular carcinoma. Majority (58%) of patients had a high level of ALT (≥34 U/L). Sequence analysis showed HBV (63.9%) belonged to genotype B, HEV belonged to genotype 4 while HCV belonged to genotype 3a and the genotypes were found to be significantly associated with the clinical stage of the patients (χ2=56.632; p<0.01). Similarly, Hepatitis B e antigen was also found to be significantly associated with the clinical stage of infection (χ2=51.952; p<0.01).
Conclusion: This study revealed that genetic diversity was found to have a significant impact on the severity of infection.

Matched MeSH terms: Liver Neoplasms/epidemiology
Fulltext The association of coffee intake with liver cancer risk is mediated by biomarkers of inflammation and hepatocellular injury: data from the European Prospective Investigation into Cancer and Nutrition

Aleksandrova K, Bamia C, Drogan D, Lagiou P, Trichopoulou A, Jenab M, et al.

Am J Clin Nutr, 2015 Dec;102(6):1498-508.
PMID: 26561631 DOI: 10.3945/ajcn.115.116095

BACKGROUND: Higher coffee intake has been purportedly related to a lower risk of liver cancer. However, it remains unclear whether this association may be accounted for by specific biological mechanisms.
OBJECTIVE: We aimed to evaluate the potential mediating roles of inflammatory, metabolic, liver injury, and iron metabolism biomarkers on the association between coffee intake and the primary form of liver cancer-hepatocellular carcinoma (HCC).
DESIGN: We conducted a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition among 125 incident HCC cases matched to 250 controls using an incidence-density sampling procedure. The association of coffee intake with HCC risk was evaluated by using multivariable-adjusted conditional logistic regression that accounted for smoking, alcohol consumption, hepatitis infection, and other established liver cancer risk factors. The mediating effects of 21 biomarkers were evaluated on the basis of percentage changes and associated 95% CIs in the estimated regression coefficients of models with and without adjustment for biomarkers individually and in combination.
RESULTS: The multivariable-adjusted RR of having ≥4 cups (600 mL) coffee/d compared with <2 cups (300 mL)/d was 0.25 (95% CI: 0.11, 0.62; P-trend = 0.006). A statistically significant attenuation of the association between coffee intake and HCC risk and thereby suspected mediation was confirmed for the inflammatory biomarker IL-6 and for the biomarkers of hepatocellular injury glutamate dehydrogenase, alanine aminotransferase, aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), and total bilirubin, which-in combination-attenuated the regression coefficients by 72% (95% CI: 7%, 239%). Of the investigated biomarkers, IL-6, AST, and GGT produced the highest change in the regression coefficients: 40%, 56%, and 60%, respectively.
CONCLUSION: These data suggest that the inverse association of coffee intake with HCC risk was partly accounted for by biomarkers of inflammation and hepatocellular injury.

Matched MeSH terms: Liver Neoplasms/epidemiology
Fulltext Circulating Osteopontin and Prediction of Hepatocellular Carcinoma Development in a Large European Population

Duarte-Salles T, Misra S, Stepien M, Plymoth A, Muller D, Overvad K, et al.

Cancer Prev Res (Phila), 2016 Sep;9(9):758-65.
PMID: 27339170 DOI: 10.1158/1940-6207.CAPR-15-0434

We previously identified osteopontin (OPN) as a promising marker for the early detection of hepatocellular carcinoma (HCC). In this study, we investigated the association between prediagnostic circulating OPN levels and HCC incidence in a large population-based cohort. A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. During a mean follow-up of 4.8 years, 100 HCC cases were identified. Each case was matched to two controls and OPN levels were measured in baseline plasma samples. Viral hepatitis, liver function, and α-fetoprotein (AFP) tests were also conducted. Conditional logistic regression models were used to calculate multivariable odds ratio (OR) and 95% confidence intervals (95% CI) for OPN levels in relation to HCC. Receiver operating characteristics curves were constructed to determine the discriminatory accuracy of OPN alone or in combination with other liver biomarkers in the prediction of HCC. OPN levels were positively associated with HCC risk (per 10% increment, ORmultivariable = 1.30; 95% CI, 1.14-1.48). The association was stronger among cases diagnosed within 2 years of follow-up. Adding liver function tests to OPN improved the discriminatory performance for subjects who developed HCC (AUC = 0.86). For cases diagnosed within 2 years, the combination of OPN and AFP was best able to predict HCC risk (AUC = 0.88). The best predictive model for HCC in this low-risk population is OPN in combination with liver function tests. Within 2 years of diagnosis, the combination of OPN and AFP best predicted HCC development, suggesting that measuring OPN and AFP could identify high-risk groups independently of a liver disease diagnosis. Cancer Prev Res; 9(9); 758-65. ©2016 AACR.

Matched MeSH terms: Liver Neoplasms/epidemiology
Prospective association of liver function biomarkers with development of hepatobiliary cancers

Stepien M, Fedirko V, Duarte-Salles T, Ferrari P, Freisling H, Trepo E, et al.

Cancer Epidemiol, 2016 Feb;40:179-87.
PMID: 26773278 DOI: 10.1016/j.canep.2016.01.002

INTRODUCTION: Serum liver biomarkers (gamma-glutamyl transferase, GGT; alanine aminotransferase, ALT; aspartate aminotransferase, AST; alkaline phosphatase, ALP; total bilirubin) are used as indicators of liver disease, but there is currently little data on their prospective association with risk of hepatobiliary cancers.
METHODS: A nested-case control study was conducted within the prospective EPIC cohort (>520,000 participants, 10 European countries). After a mean 7.5 mean years of follow-up, 121 hepatocellular carcinoma (HCC), 34 intrahepatic bile duct (IHBC) and 131 gallbladder and biliary tract (GBTC) cases were identified and matched to 2 controls each. Circulating biomarkers were measured in serum taken at recruitment into the cohort, prior to cancer diagnosis. Multivariable adjusted conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI).
RESULTS: In multivariable models, 1SD increase of each log-transformed biomarker was positively associated with HCC risk (OR(GGT)=4.23, 95%CI:2.72-6.59; OR(ALP)=3.43, 95%CI:2.31-5.10;OR(AST)=3.00, 95%CI:2.04-4.42; OR(ALT)=2.69, 95%CI:1.89-3.84; OR(Bilirubin)=2.25, 95%CI:1.58-3.20). Each liver enzyme (OR(GGT)=4.98; 95%CI:1.75-14.17; OR(AST)=3.10, 95%CI:1.04-9.30; OR(ALT)=2.86, 95%CI:1.26-6.48, OR(ALP)=2.31, 95%CI:1.10-4.86) but not bilirubin (OR(Bilirubin)=1.46,95%CI:0.85-2.51) showed a significant association with IHBC. Only ALP was significantly associated with GBTC risk (OR(ALP)=1.59, 95%CI:1.20-2.09).
CONCLUSION: This study shows positive associations between circulating liver biomarkers in sera collected prior to cancer diagnoses and the risks of developing HCC or IHBC, but not GBTC.

Matched MeSH terms: Liver Neoplasms/epidemiology*

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