Risk Of Primary Hepatocellular Carcinoma Research Articles

Study on the risk of hepatitis B-related cirrhosis combined with type 2 diabetes mellitus for the occurrence of primary hepatocellular carcinoma

Objective: To investigate whether type 2 diabetes mellitus increases the risk of hepatitis B-related cirrhosis combined with type 2 diabetes mellitus for the occurrence of primary hepatocellular carcinoma, and to compare the effects of different nature of diabetes duration on the risk of different anti-diabetic drugs. Methods: A retrospective case-control study was conducted. (1) 325 cases with hepatitis B-related cirrhosis complicated with primary hepatocellular carcinoma were selected as the study group and 601 patients with hepatitis B cirrhosis as the control group. The relationship between diabetes mellitus and the risk of primary liver cancer was analyzed by multivariate logistic regression analysis. (2) Selected the study group and control group combined with type 2 diabetes mellitus, and used multivariate logistic regression analysis to study the relationship between diabetes-related factors and the risk of primary liver cancer. Results: The incidence of diabetes was 14.2% in the study group and 6.0% in the control group, and the difference was statistically significant between the two groups (P < 0.05). Multivariate logistic regression analysis showed that type 2 diabetes was one of the independent risk factors for primary hepatocellular carcinoma, which had increased the risk of primary hepatocellular carcinoma (adjusted odds ratio (AOR): 1.982, 95% CI: 1.224-3.210). Patients with diabetes > 10 years (adjusted ratio: AOR value 6.011, 95% CI: 1.659-21.777) were at significantly higher risk for primary hepatocellular carcinoma than that of patients with diabetes < 10 years. Metformin (adjusted odds ratio: AOR 0.188, 95% CI: 0.052-0.688) had reduced the risk, while insulin (adjusted odds ratio: AOR 6.682, 95% CI: 1.899-23.510) had increased the risk. Conclusion: Type 2 diabetes mellitus is one of the independent risk factors for primary HCC, which can increase the risk of hepatocellular carcinoma in hepatitis B cirrhosis in relation to the duration of diabetes mellitus. The risk of hepatocellular carcinoma is higher in patients with duration of diabetes > 10 years and metformin reduces the risk.

A Prospective Study of Nut Consumption and Risk of Primary Hepatocellular Carcinoma in the U.S. Women and Men.

Although increasing evidence suggests a potential beneficial effect of nut consumption on various diseases, no epidemiologic study has yet examined the association between nut consumption and risk of hepatocellular carcinoma (HCC). We prospectively examined this association in 88,783 women from the Nurses' Health Study and 51,492 men from the Health Professionals Follow-up Study. Nut consumption was assessed every 4 years using validated food frequency questionnaires. Multivariable HRs and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards regression models after adjusting for HCC risk factors. After an average of 27.9 years of follow-up, we identified a total of 162 incident HCC cases. Higher total nut consumption was not significantly associated with HCC risk (the highest vs. lowest tertile intake, HR, 0.84; 95% CI, 0.56-1.26). For the same comparison, higher tree nut consumption was associated with a lower HCC risk (HR, 0.64; 95% CI, 0.43-0.95). We found nonsignificant inverse associations with consumption of walnuts, peanuts, and peanut butter. Overall, nut consumption was not strongly associated with HCC risk. There was a suggestive inverse association with tree nut consumption. Future studies should carefully consider hepatitis B or C virus infections and examine these associations in other racial/ethnic groups.

Role of Insulin Resistance and Cytokeratin 18 on the Recurrence of Hepatocellular Carcinoma after Radiofrequency Ablation

Background and study aim : Many studies have reported that insulin resistance raises the risk of primary hepatocellular carcinoma (HCC). Caspase-generated cytokeratin-18 (CK-18) fragments are produced during apoptosis of hepatic cells. The present study aims to evaluate the value of serum CK-18 and the impact of insulin resistance on recurrence of HCV related HCC in patients treated with radiofrequency ablation (RFA). . Patients and Methods: The present study was conducted on 60 HCV patients. Group I: 30 patients with HCC treated by RFA and group II: 30 non HCC cirrhotic patients. Insulin resistance was estimated by the homeostatic model assessment of insulin resistance (HOMA-IR) and CK-18 level was measured for all patients using ELISA. Results: HOMA-IR and CK-18 levels were significantly elevated in HCC patients when compared to non HCC cirrhotic patients. There was a significant increase in CK-18 and HOMA-IR levels in patients with local recurrence versus those with no recurrence (p<0.001). Univariate analysis revealed that HOMA-IR (p=<0.001) and CK-18 (p=<0.001) were significant predictors of recurrence of HCC. Conclusion: CK-18 and HOMA-IR are potential prognostic markers as they can predict the recurrence of HCC.

Correlation between polymorphisms in DNA mismatch repair genes and the risk of primary hepatocellular carcinoma for the Han population in northern China

Purpose: This study investigated correlations between polymorphisms in DNA mismatch repair (MMR) genes and the risk of primary hepatocellular carcinoma (PHC). Methods. Single nucleotide polymorphisms (SNPs) in the DNA MMR genes MLH3 (rs175080), PMS1 (rs5742933), PMS2 (rs1059060), MSH3 (rs26279), MSH5 (rs1150793, rs2075789) and MSH6 (rs1042821) were detected using the SNaPshot method in 250 PHC cases and in 308 patients without PHC in the Han population in northern China. Results. The AA genotype in MLH3 (rs175080) increased the risk of PHC (odds ratio [OR] = 3.424; 95% confidence interval [CI]: 1.097–10.689). The AG and GG genotypes in MSH3 (rs26279) increased the risk of PHC (OR: 1.644 and 3.300; 95% CI: 1.112–2.428 and 1.765–6.168, respectively). The AA genotype in MSH5 (rs2075789) increased the risk of PHC (OR: 9.229; 95% CI: 1.174–72.535). The CT genotype in MSH6 (rs1042821) reduced the risk of PHC (OR: 0.629; 95% CI: 0.428–0.924). Conclusions. Our study suggests that polymorphisms in MLH3 (rs175080), MSH3 (rs26279), MSH5 (rs2075789) and MSH6 (rs1042821) may be independent risk factors for PHC.

Alpha-1 Antitrypsin Deficiency and the Risk of Hepatocellular Carcinoma in Patients With End-Stage Liver Disease

Introduction: Based on limited studies, it has been proposed that alpha-1 antitrypsin deficiency (A1ATD) is associated with a risk of primary hepatocellular carcinoma (HCC) that exceeds that attributable to cirrhosis alone. Moreover, recent data suggest that PI*Z heterozygotes (e.g., PI*MZ) had an increased risk of HCC. The aim of this study was to evaluate the association between A1ATD/ Z allele and HCC in a cohort of patients with end stage liver disease (ESLD). Methods: Patients evaluated for orthotopic liver transplant at the Cleveland clinic between 2003 and 2014 were included in this retrospective study. Complete data was collected on 696 subjects. The diagnosis of A1ATD was based on phenotype abnormalities (ZZ or MZ), the presence of PAS-positive diastaseresistant (PAS+) globules on liver biopsy, or both. The diagnosis of HCC was based on imaging, biopsy, or examination of the explanted liver. All patients with A1ATD were identified and the prevalence of HCC in this population was calculated. Time-to-event analysis for interval censored data was performed to assess occurrence of HCC in patients with other causes of cirrhosis such as alcoholic liver disease, hepatitis C (HCV), or non-alcoholic steatohepatitis (NASH). Results: A total of 696 subjects were included in the analysis. Seven percent of these had A1ATD. Of subjects without A1ATD, 45% had HCV, 18% had alcoholic liver disease, 18% had NASH, and 18% had other primary diagnosis. Median follow-up time was 3.2 years (25th, 75th percentiles: 1, 5.2), during which time 29% of subjects developed HCC. Crude percentage of HCC was 8.5% in the A1ATD group compared to 30% in the no A1ATD group (p=0.004). Figure 1 presents the cumulative incidence plot for HCC. Subjects with A1ATD were found to have significantly lower HCC rates compared to subjects without A1ATD (p=0.002).Figure 1: Cumulative incidence of HCC in ESLD patients with and without A1ATD.Conclusion: A1ATD was not associated with an increased risk of HCC in a group of patients with ESLD. In fact, patients with cirrhosis and A1ATD were less likely to develop HCC compared to patients with other causes of cirrhosis.

Green tea consumption, inflammation and the risk of primary hepatocellular carcinoma in a Chinese population

Objective: Green tea has been found to possess anti-inflammatory, anti-oxidative and anti-carcinogenic properties. The present study examines the association between green tea drinking and hepatocellular carcinoma (HCC) and its interactions with other risk or protective factors and single nucleotide polymorphisms (SNP) of inflammation and oxidative stress related genes. Methods: A population-based case-control study with 204 primary HCC cases and 415 healthy controls was conducted in Taixing, China. Epidemiological data were collected using a standard questionnaire. SNPs of genes of the inflammation and metabolic pathways were genotyped at the UCLA Molecular Epidemiology Laboratory. Logistic regression was performed to estimate adjusted odds ratios and 95% confidence intervals. Results: Longer duration and larger quantities of green tea consumption were inversely associated with primary HCC. Individuals who drank green tea longer than 30 years were at lowest risk (adjusted OR = 0.44, 95% CI: 0.19–0.96) compared with non-drinkers. A strong interaction was observed between green tea drinking and alcohol consumption (adjusted OR for interaction = 3.40, 95% CI: 1.26–9.16). Green tea drinking was also observed to have a potential effect modification on HBV/HCV infection, smoking and polymorphisms of inflammation related cytokines, especially for IL-10. Conclusion: Green tea consumption may protect against development of primary HCC. Potential effect modifications of green tea on associations between primary HCC and alcohol drinking, HBV/HCV infection, and inflammation-related SNPs were suggested.

A potentially functional polymorphism in the promoter region of miR‐34b/c is associated with an increased risk for primary hepatocellular carcinoma

The miR-34 family members are direct transcriptional targets of tumor suppressor p53, and loss of miR-34 function can impair p53-mediated cell cycle arrest and apoptosis. A potentially functional SNP rs4938723 (T > C) was found in the promoter region of pri-miR-34b/c (423 bp from the transcription start site), located in the CpG island and might affect transcription factor GATA binding and therefore pri-miR-34b/c expression. In our study, we hypothesized that SNPs miR-34b/c rs4938723 and TP53 Arg72Pro may independently or jointly contribute to primary hepatocellular carcinoma (HCC) susceptibility. We then genotyped the 2 SNPs in a case-control study of 501 patients with primary HCC and 548 cancer-free controls in a Chinese population. We observed that the variant genotypes of miR-34b/c rs4938723 were associated with significantly increased HCC risks compared with the wild-type TT genotype (adjusted OR = 1.37, 95% CI =1.06-1.78 for TC; OR = 1.53, 95% CI = 1.02-2.31 for CC and OR = 1.40, 95% CI = 1.10-1.80 for TC/CC). Furthermore, we found a significant interaction between alcohol drinking and SNP rs4938723 on HCC risk (p = 0.05 for multiplicative and p = 0.01 for additive interaction). However, we did not find any main effect of TP53 Arg72Pro on HCC risk in this population. These findings indicate that the potentially functional SNP rs4938723 in the promoter region of pri-miR-34b/c may contribute to the susceptibility of HCC in this Chinese population.

Insulin resistance raises the risk for recurrence of stage I hepatocellular carcinoma after curative radiofrequency ablation in hepatitis C virus‐positive patients: A prospective, case series study

Several studies have reported that insulin resistance raises the risk of primary hepatocellular carcinoma (HCC). We conducted a prospective, case series study to test the impact of insulin resistance on the recurrence after curative radiofrequency ablation (RFA) of stage I HCC in HCV-positive patients. From January 2006 to December 2007, 226 consecutive patients underwent treatment for primary HCC at our institutions, including 37 stage I cases. Among them, 33 were HCV-positive, and three, six and 24 received curative surgery, transarterial chemoembolization or RFA, respectively. In the 24 patients treated with RFA, recurrence-free survival was analyzed using the Kaplan-Meier method. The factors contributing to recurrence of HCC were subjected to univariate and multivariate analyses using the Cox proportional hazards model. Insulin resistance was estimated by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Kaplan-Meier analysis showed that the recurrence-free survival was lower in patients with higher HOMA-IR (>2.3, P = 0.0252) or with lower serum albumin level (<3.3 g/dL, P = 0.0004). In the univariate analysis, HOMA-IR (P = 0.0420) and albumin (P = 0.0036) were significantly associated with recurrence of HCC. Multivariate analysis revealed albumin (odds ratio = 0.01, 95% confidence interval = 0.0002-0.015, P = 0.0001) and HOMA-IR (odds ratio = 3.85, 95% confidence interval = 1.57-14.2, P = 0.0015) to be independent predictors for recurrence of HCC. Serum albumin level and HOMA-IR were independent risk factors for recurrence of stage I HCC after curative RFA in HCV-positive patients. Patients with these factors require closer surveillance.

Cyclooxygenase-2 gene -1195G/A genotype is associated with the risk of HBV-induced HCC: A case-control study in Han Chinese people

This study aimed to identify functional single nucleotide polymorphisms in the cyclooxygenase-2 gene promoter and evaluate their effects on the risk of primary hepatocellular carcinoma (HCC) with hepatitis B virus (HBV) infection. We conducted a population-based, case-control study enrolling 630 Han Chinese people in Hubei province. Subjects included primary HCC patients with HBV infection (n = 210), chronic hepatitis B cases (n = 210) and healthy Han Chinese (n = 210). −1195G/A polymorphism was analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing analysis. We found -1195A allele carriers had a higher risk of HCC with HBVinfection (OR, 0.72; 95% CI, 0.548–0.946). The −1195A allele might be used as a marker in screening individuals at high risk of HCC with HBV infection.

A 1:1 matched case-control study on the interaction between HBV, HCV infection and DNA repair gene XPC Ala499Val, Lys939Gln for primary hepatocellular carcinoma

To evaluate the interaction between environmental factors, HBV/HCV infections and DNA repair gene XPC exon 8 Ala499Val, exon 15 Lys939Gln on related risks to primary hepatocellular carcinoma (PHC). A 1:1 matched case-control study was conducted in Shunde city, Guangdong province. The genotypes of Ala499Val and Lys939Gln were detected by polymerase chain reaction restrictive fragment length polymorphism (PCR-RFLP) analysis, and gene-environment interactions were analyzed by conditional logistic regression. Among people infected by HBV with non- or at least one mutant gene of Ala499Val carriers, the risk of PHC significantly increased, with ORs as 3.768 (95%CI: 1.137 - 12.485) and 3.667(95%CI: 1.122 - 11.981) respectively. With non- or at least one mutant gene of Lys939Gln, the risk was increasing with ORs as 6.778 (95%CI: 2.025 - 22.688) and 3.152 (95%CI: 1.062 - 9.351) respectively. In those with HCV infection, non- or at least one mutant gene of Ala499Val might increase the risk with ORs as 2.955 (95%CI: 0.587 - 14.869), 1.085(95%CI: 0.307 - 3.839) respectively. However, when compared to the ones with no mutant gene of Lys939Gln among the same research subjects, those carrying at least one gene may decrease the risk, with OR lowered from 4.197 (95%CI: 0.870 - 20.243) to 0.887 (95%CI: 0.228 - 3.448). But the interactions between HBV infection, HCV infection and XPC genes were not statistically significant. Among people infected by HCV, the mutant gene of Ala499Val had the tendency to lower the risk of PHC, and the mutant gene of Lys939Gln also appeared the same in the population with either HBV infection or HCV infection in Shunde, Guangdong. Another study with large samples should be performed to analyze the interactions among environments-genes.

Etiologic fraction and interaction of risk factors for primary hepatic carcinoma in Guangxi, China

To explore etiologic fraction (EF) and interaction of hepatitis B virus (HBV) infection and other risk factors for primary hepatocellular carcinoma (PHC) in Guangxi, China. A hospital-based case-control study including 500 PHC patients and 500 nontumorous patients was carried out in Guangxi. EF and interactions of HBV infection and other risk factors for PHC were analyzed by crossover analysis and nonconditional multiple logistic regression. HBV infection, family history of PHC, diabetes mellitus, eating raw fish, heavy alcohol consumption, frequently used drug, low income, mental oppression and blood type B all were risk factors for PHC. With EFs of 0.725, 0.186, 0.119, 0.486, 0.385, 0.438, 0.277, 0.607, 0.299, respectively and with etiologic fractions attributable to interaction [EF(A xB)] of 0.736, 0.643, 0.849, 0.551, 0.592, 0.618, 0.902, 0.577; and indices of interaction of 0.743, 0.651, 0.853, 0.560, 0.600, 0.626, 0.907, 0.586, respectively. Main risk factors for PHC might include HBV infection, family history of PHC, diabetes mellitus, eating raw fish, heavy alcohol consumption, frequently used drug, low income, mental oppression and blood type B. HBV infection with other risk factors might exert synergistic action on developing PHC and increase the risk of PHC.

Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and the risk of primary Hepatocellular Carcinoma (HCC) in a Chinese population

Methylenetetrahydrofolate reductase (MTHFR), which is expressed in the liver, may be involved in both DNA methylation and DNA synthesis. It is also indicated as a potential risk factor of liver cancer in patients with chronic liver disease. To date, no study has been conducted on MTHFR and hepatocellular carcinoma (HCC) using a population-based design. The objective of this study was to evaluate the effects of polymorphisms of the MTHFR gene on the risk of primary liver cancer and their possible effect modifications on various environmental risk factors. A population-based case-control study was conducted in Taixing, China. MTHFR C677T and A1298C were assayed by PCR-RFLP techniques. The frequency of MTHFR 677 C/C wild homozygotes genotype was 25.8% in cases, which was lower than that in controls (34.5%). The adjusted odds ratios (ORs) for the MTHFR 677 C/T and T/T genotype were 1.66(95% CI: 1.06-2.61), 1.21(95% CI: 0.65-2.28) respectively when compared with the MTHFR 677 C/C genotype. Subjects carrying any T genotype have the increased risk of 1.55(95% CI: 1.01-2.40) for development of primary hepatocellular carcinoma. A high degree of linkage disequilibrium was observed between the C677T and A1298C polymorphisms, with the D' of 0.887 and p < 0.01. The MTHFR 677 any T genotype was suggested to have potentially more than multiplicative interactions with raw water drinking with p-value for adjusted interaction of 0.03. We observed that the MTHFR 677 C/T genotype was associated with an increased risk of primary liver cancer in a Chinese population. The polymorphism of MTHFR 677 might modify the effects of raw water drinking on the risk of primary hepatocellular carcinoma.

Asymptomatic Liver Mass

Asymptomatic Liver Mass

Blue green algal (cyanobacterial) toxins, surface drinking water, and liver cancer in Florida

The blue green algae or cyanobacteria represent a diverse group of organisms that produce potent natural toxins. There have been case reports of severe morbidity and mortality in domestic animals through drinking water contaminated by these toxins. Microcystins, in particular, have been associated with acute liver damage and possibly liver cancer in laboratory animals. Although, there has been little epidemiologic research on toxin effects in humans, a study by Yu (1995) found an association between primary liver cancer and surface water. Surface water drinking supplies are particularly vulnerable to the growth of these organisms; current US drinking water treatment practices do not monitor or actively treat for blue green algal toxins including the microcystins. After a monitoring survey in Florida found organisms and microcystins (among other cyanobacterial toxins) in surface water drinking sources, a pilot ecological study was performed using a Geographic Information System (GIS) to evaluate the risk of primary hepatocellular carcinoma (HCC) and proximity to a surface water treatment plant at cancer diagnosis. The study linked all HCC cancers diagnosed in Florida from 1981 to 1998 with environmental databases. A significantly increased risk for HCC with residence within the service area of a surface water treatment plant was found compared to persons living in areas contiguous to the surface water treatment plants. However, this increased risk was not seen in comparison to persons living in randomly selected ground water treatment service areas or compared to the Florida cumulative incidence rate for the study period, using various comparison and GIS methodologies. Furthermore, these findings must be interpreted in light of significant issues of latency, high population mobility, and the lack of individual exposure information. Nevertheless, the issue of acute and chronic human health effects associated with the consumption of surface waters possibly contaminated by blue green algal toxins merits further investigation.

Induction of oxidative single- and double-strand breaks in DNA by ferric citrate

The relative risk of primary hepatocellular carcinoma in genetic hemochromatosis (GH) is estimated at over 200 times as that of control populations. Recently, ferric ion chelated to citrate (Fe-citrate) was identified as the major non-transferrin-bound iron in the serum of GH patients. We investigated whether low concentration of Fe-citrate plus reductant could damage supercoiled plasmid DNA under physiological pH and ionic strength. Incubation of Fe-citrate with either H 2O 2, l-ascorbate, or l-cysteine induced single- and double-strand breaksin supercoiled plasmid pZ189 in a concentration- and time-dependent fashion. DNA strand breaks produced by Fe-citrate plus H 2O 2 increased at reduced pH (≤ 6.9). Catalase and free radical scavengers inhibited the DNA breakage produced by Fe-citrate in combination with each reductant, suggesting that H 2O 2 and finally .OH are responsible DNA damaging species. The catalytic ability of Fe-citrate to induce DNA strand breaks, particularly double-strand breaks (DSBs), may contribute to the carcinogenic processes observed in GH.

Serum α-fetoprotein levels and microheterogeneity in patients with different liver diseases

Serum alpha-fetoprotein levels were determined in patients (268) with liver disease. Markedly elevated concentrations (greater than 100 micrograms/l) were found in twelve patients with malignant tumours and two with cirrhosis. Molecular variants of alpha-fetoprotein were distinguished by lectin affinity chromatography of these sera. Reversible binding to concanavalin A (86 +/- 5%) and to lentil agglutinin (61 +/- 19%) conformed to expected values for primary hepatocellular carcinoma except in one patient with a metastatic carcinoma whose alpha-fetoprotein binding to concanavalin A was similar to non-liver alpha-fetoprotein (44 +/- 13%), and the two patients with cirrhosis in whom binding to lentil agglutinin was typical for benign liver disorders (less than 20%). Since low levels of serum alpha-fetoprotein and non-characteristic alpha-fetoprotein binding patterns assisted in the regrouping of eleven out of 24 patients initially thought to have primary hepatocellular carcinoma, it was concluded that alpha-fetoprotein determination and lectin affinity chromatography are helpful in distinguishing primary hepatocellular carcinoma from metastatic and benign liver diseases. Slight increases in the alpha-fetoprotein level in the presence of serum hepatitis B surface antigen indicated seven patients at risk for primary hepatocellular carcinoma who should be monitored frequently.

Serum Ferritin Levels and Hepatocellular Carcinoma: the Cart or the Horse?

Previous studies from this laboratory support the view that increased serum ferritin levels are associated with an increased risk of primary hepatocellular carcinoma (PHC). We have tested this hypothesis in a population of Korean patients with chronic liver disease followed for development of PHC. Serum ferritin levels were measured over time in 249 patients with liver diseases (mostly chronic) followed for 2 to 17 years in Seoul, Korea. Most of the patients were chronically infected with hepatitis B virus. During the first 8 months of follow–up, there were no cases of PHC and no deaths. During this same period, no patient had a serum ferritin level initially below 300 ng/ml and rising above 300 ng/ml, but some patients with ferritin levels above 300 ng/ml experienced decreases to below 300 ng/ml. Therefore, patients were grouped by ferritin level during the first 8 months of follow–up into 3 categories according to the above criteria. Multivariate analysis showed that consistently elevated ferritin levels (category 3) were significantly associated with the development of PHC. Men were more likely to have elevated ferritin levels than women and were at higher risk of developing PHC. Men who were chronically infected with HBV and had ferritin levels above 300 ng/ml had a 50% chance of developing PHC during the follow–up period, compared with a 20% risk of PHC for men with lower ferritin levels (categories 1 and 2). This elevated risk of PHC in men with elevated ferritin levels was confined to the first 3 years of follow–up.

Hepatitis B virus and primary hepatocellular carcinoma: treatment of HBV carriers with Phyllanthus amarus

A viricide capable of eliminating hepatitis B virus (HBV) from chronic carriers should, theoretically, decrease the risk of primary hepatocellular carcinoma. Extracts of Phyllanthus amarus have been shown to inhibit the DNA polymerase of HBV and woodchuck hepatitis virus (WHV) in vitro. Three of four recently infected WHV carriers treated i.p. with P. amarus extract lost WHV, animals infected for greater than or equal to 3 months showed a decrease in virus levels. Preliminary results in human carriers treated orally with P. amarus for 1 month indicated that approximately 60% of the carriers lost HBV during the observation period.

Increased serum ferritin in chronic liver disease: A risk factor for primary hepatocellular carcinoma

Previous studies from this laboratory support the view that increased serum ferritin levels are associated with an increased risk of primary hepatocellular carcinoma (PHC). We have tested this hypothesis in a population of Korean patients with chronic liver disease followed for development of PHC. Serum ferritin levels were measured over time in 249 patients with liver diseases (mostly chronic) followed for 2 to 17 years in Seoul, Korea. Most of the patients were chronically infected with hepatitis B virus. During the first 8 months of follow-up, there were no cases of PHC and no deaths. During this same period, no patient had a serum ferritin level initially below 300 ng/ml and rising above 300 ng/ml, but some patients with ferritin levels above 300 ng/ml experienced decreases to below 300 ng/ml. Therefore, patients were grouped by ferritin level during the first 8 months of follow-up into 3 categories according to the above criteria. Multivariate analysis showed that consistently elevated ferritin levels (category 3) were significantly associated with the development of PHC. Men were more likely to have elevated ferritin levels than women and were at higher risk of developing PHC. Men who were chronically infected with HBV and had ferritin levels above 300 ng/ml had a 50% chance of developing PHC during the follow-up period, compared with a 20% risk of PHC for men with lower ferritin levels (categories 1 and 2). This elevated risk of PHC in men with elevated ferritin levels was confined to the first 3 years of follow-up.

Virus-Associated Cancers in Greenland: Frequent Hepatitis B Virus Infection But Low Primary Hepatocellular Carcinoma Incidence&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;

The incidence of primary hepatocellular carcinoma (PHC) in Greenland between 1960 and 1981 was determined and compared with the rate of this disease in Denmark. The annual age and sex rate (per 100,000) was not significantly different (overall, 1.9 vs. 2.2) despite a large difference in the prevalence of hepatitis B surface antigen (HBsAg) and anti-HBs markers of hepatitis. On the basis of a recent report of a very strong risk of PHC among male HBsAg carriers, 4.0 cases of PHC per year were expected in male Eskimos, but only 0.2 cases per year were observed. The incidence rates of other cancers suggested to be virally associated, including nasopharyngeal carcinoma, salivary gland cancer, and carcinoma of the cervix, were all high in Greenland compared to rates for the Danish population, and these high incidence rates are in accord with the markedly higher prevalences in Greenland Eskimos of viruses with which these other cancers have been associated. Thus Greenland Eskimos do not have a high incidence of PHC despite a high prevalence of HBsAg carriers, which suggests that other carcinogenic factors in this environment may be absent or that protective factors are present.