Hepatocellular Carcinoma In Chronic Hepatitis Research Articles

Mean Platelet Volume and Mean Platelet Volume/Platelet Count Ratio as Diagnostic Markers for Hepatocellular Carcinoma in Chronic Hepatitis C Patients

Background and study aim: Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. AFP is the gold standard tumor marker for HCC, mean platelet volume (MPV) is a parameter obtained from complete blood count (CBC) by automated analyzers, shown to be increased in multiple malignancies and inflammatory conditions.This prospective study was designed to evaluate the diagnostic usefulness of MPV and MPV/ platelet count (PC) ratio in HCC patients due to chronic hepatitis C (CHC) infection. Materials and Methods: One hundred and twenty subjects enrolled in this study, they were divided into 4 equal groups: group I included 30 healthy subjects (control group), group II included 30 patients with chronic viral hepatitis without cirrhosis, group III included 30 cirrhotic patients without HCC and group IV included 30 cirrhotic patients with HCC.MPV, MPV/PC ratio & AFP were evaluated in all groups. Triphasic CT was done for patients of group IV to confirm the diagnosis of HCC. Liver biopsy was done for patients of group II to confirm the diagnosis of chronic hepatitis C. Results: MPV showed higher levels in HCC group compared to control, CHC, and cirrhotic groups with p value(<0.001) but there was no statistically significant difference between HCC group and cirrhotic group (p value=0.49), while MPV/platelet count ratio was higher in cirrhotic group (0.19±0.09 fL/ 109/L) than HCC group (0.14±0.08 fL/109/L) but also with no significant differences between both groups (p=0.06). There was insignificant positive correlation between MPV and AFP in HCC group ( Session [CurrentTestPartTermID];= 0.11 and p value =0.57). Also, there was insignificant negative correlation between MPV/PC and AFP in HCC group ( Session [CurrentTestPartTermID];= -0.17 and p value =0.37). In receiver operating characteristic (ROC) curve analysis, MPV had high sensitivity (73.33%), specificity (70 %), and area under curve (AUC) was 0.7, So it more better than MPV/platelet count ratio in diagnosis of HCC which had sensitivity (76.67%), low specificity (56.67%), and AUC was 0.63, while AFP had much higher sensitivity (90%), specificity (98.33%) than both studied parameters (MPV, MPV/PC ratio) with highly statistically difference when compared to MPV (p<0.001) and area under curve (AUC) was 0.9. Conclusion: MPV and MPV/PC ratio are less sensitive and specific than AFP in diagnosis of HCC. So AFP is still the gold standard marker in diagnosis of HCC and MPV and MPV/PC ratio may be used only in association with other markers like AFP to improve sensitivity of tumor detection.

Liver volume-based prediction model stratifies risks for hepatocellular carcinoma in chronic hepatitis B patients on surveillance.

Background and aimThe aim of this study was to determine whether dynamic computed tomography (CT)-measured liver volume predicts the risk of hepatocellular carcinoma (HCC) when the CT scans do not reveal evidence of HCC in chronic hepatitis B (CHB) patients on surveillance.MethodsThis retrospective multicentre cohort study included 1,246 patients who received entecavir and regular HCC surveillance in three tertiary referral centres in South Korea. Liver volumes were measured on portal venous phase CT images. A nomogram was developed based on Cox independent predictors and externally validated. Time-dependent receiver operating characteristic (ROC) analysis was performed for comparison with previous prediction models.ResultsPatients who received dynamic CT studies during surveillance had significantly higher risk for HCC compared to patients without CT studies (hazard ratio [HR] = 3.1; p < 0.001). Expected/measured liver volume ratio was an independent predictor of HCC (HR = 4.2; p = 0.002) in addition to age, sex and cirrhosis. The nomogram based on the four predictors discriminated risks for HCC (HR = 4.1 and 6.0 in derivation and validation cohort, respectively, for volume score > 150; p < 0.001). Time-dependent ROC analysis confirmed better performance of the volume score compared to HCC prediction models with conventional predictors (integrated area under curve = 0.758 vs. 0.661–0.712; p < 0.05).ConclusionsCT-measured liver volume is an independent predictor of future HCC, and nomogram-based liver volume score may stratify the risks of HCC in CHB patients who showed negative CT findings for HCC during surveillance.

Dynamic noninvasive markers predict hepatocellular carcinoma in chronic hepatitis C patients without sustained virological response after interferon-based therapy: Prioritize who needs urgent direct-acting antiviral agents.

Some patients with hepatitis C virus (HCV) infections who fail to achieve sustained virological responses (SVRs) after interferon (IFN) therapy do not develop hepatocellular carcinoma (HCC). Risk stratification of these patients may help identify those who would benefit most from treatment with direct-acting antivirals (DAAs).A total of 552 HCV-infected patients with non-SVR status were enrolled. Laboratory data before and after IFN treatment were analyzed to determine the relationship of changes in serum markers with development of HCC during the 7-year study period.HCC developed in 93 patients. The risk factors for HCC were pre-existing liver cirrhosis, low hemoglobin level at baseline, low pretreatment platelet count, high post-treatment alpha-fetoprotein (AFP) level (≥15 ng/mL), and high post-treatment Fibrosis 4 (FIB4) index (>3.25). For patients without pre-existing cirrhosis, those with high post-treatment AFP level and FIB4 index had the highest risk of HCC (1 year: 6.7%; 3 years: 10.9%; 5 years: 29.7%), followed by those with high post-treatment AFP level and low post-treatment FIB4 index (5 years: 25%), and those with low post-treatment AFP level and high post-treatment FIB4 index (1 year: 3.7%; 3 years: 5.2%; 5 years: 10.6%). The risk was even lower for patients with low post-treatment AFP level and FIB4 index (1 year: 0%; 3 years: 0.4%; 5 years: 2.5%). None of the patients with FIB4 indexes consistently below 1.45 developed HCC.The combined use of post-treatment AFP level and FIB4 index was useful for risk stratification of HCV-infected patients with non-SVR status after IFN therapy. These data may help clinicians to identify patients who most urgently need DAA treatment.

Prevalence of occult hepatitis B virus infection and Torque teno virus infection and their association with hepatocellular carcinoma in chronic hepatitis C patients

BackgroundThe role of occult hepatitis B virus (HBV) infection and Torque teno virus (TTV) infection in the development of hepatocellular carcinoma (HCC) in chronic hepatitis C patients is still uncertain. AimThe aim of the present study was to investigate the prevalence and significance of OBI and TTV infection, and to examine the genetic diversity of these viruses, in chronic hepatitis C patients with and without HCC. MethodsSera from 151 hepatitis C virus (HCV)-infected patients (49 patients with HCC and 102 without HCC) negative for HBV surface antigen (HBsAg) were tested for the presence of OBI and TTV infection by semi-nested and group-specific multiplex PCR assays, respectively. Nucleotide sequencing of HBV S region was further performed. ResultsOBI and TTV infection were detected in 5 (3.3%) and 68 (45%) patients, respectively. HBV isolates were classified into genotypes A (4/5, 80%) and D (1/5, 20%), and no HBsAg escape mutation was observed. TTV phylogenetic group 3 was the most prevalent among both HCC and non-HCC patients. OBI and TTV infection were significantly more frequent in patients with HCC than patients without HCC (p=0.003, and p=0.009, respectively). Moreover, TTV infection was associated with HCC (OR=2.23, 95%CI=1.04–4.80, p=0.040), independently of liver cirrhosis. ConclusionsA low prevalence of OBI was observed in patients with HCV-related chronic liver disease, and TTV infection was an independent factor associated with the occurrence of HCC. Whether TTV influences the progression of liver disease in chronic hepatitis C patients remains to be elucidated.

Antiplatelet therapy and the risk of hepatocellular carcinoma in chronic hepatitis B patients on antiviral treatment.

Antiplatelet therapy reduces the risk of HCC in chronic hepatitis B patients whose hepatitis B virus is effectively suppressed. However, antiplatelet therapy containing clopidogrel may increase the risk of bleeding. (Hepatology 2017;66:1556-1569).

Association of ACYP2 and MPHOSPH6 genetic polymorphisms with the risk of hepatocellular carcinoma in chronic hepatitis B virus carriers.

Hepatocellular carcinoma (HCC) is the dominant histologic type of primary liver cancer, and hepatitis B virus (HBV) infection is one of the major causes of HCC in the chronic HBV. Our study was investigated the association between the polymorphisms of ACYP2 and MPHOSPH6 genes and the risk of HCC induced by HBV infection. A total of 490 subjects were divided into two groups: 248 HBV patients with HCC (Case group), and 242 HBV patients without HCC (Control group). Unconditional logistic regression analysis was used to evaluate the association. The genetic association analysis revealed variant of rs12621038 in ACYP2 gene had a significant association with increasing the risk of HBV-induced HCC based on the genotype, dominant and additive model (P<0.05). Moreover, our results also showed that minor allele “C” of rs3751862 was prevalent in cases than controls (P<0.05), and rs3751862 significantly increased the risk of HCC in chronic HBV carriers under genotype and dominant model (P<0.05). In addition, the haplotype “T-G-G” in MPHOSPH6 showed a harmful factor for the HBV-induced HCC (P<0.05). The results suggested that ACYP2 and MPHOSPH6 as the plausible candidate genes may predict the risk of HCC after chronic HBV infection in Chinese Han population, and further investigations in studies with a larger sample size and other races are needed to validate our findings. These data provide a theoretical foundation for future studies of this correlation between the polymorphisms of ACYP2 and MPHOSPH6 genes and the HCC in chronic HBV carriers.

Association between the functional polymorphism Ile31Phe in the AURKA gene and susceptibility of hepatocellular carcinoma in chronic hepatitis B virus carriers.

Aurora kinase A (AURKA) is a serine threonine kinase which affects chromosomal separation and mitotic spindle stability through interaction with the centrosome during mitosis. Two functional nonsynonymous polymorphisms of the AURKA gene (Ile31Phe and Val57Ile) have been reported recently. We analyzed the association between the two polymorphisms and risk of the occurrence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in the Guangxi population consisting of 348 patients with HCC and 359 control subjects, and then validated the significant association in the Guangdong population consisting of 440 cases and 456 controls. All of the participants were of Chinese origin and HBV carriers. The two polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism assay or Sequenom MassARRAY iPLEX platform. In the Guangxi population, carriers of the AURKA 31Phe allele (Ile/Phe + Phe/Phe) were significantly associated with decreased susceptibility to HBV-related HCC when compared with noncarriers (Ile/Ile) (odds ratio [OR] = 0.63, 95% confidence interval [CI] = 0.46-0.86, P = 3.4 × 10-3). On the contrary, no significant association was found between Val57Ile and HBV-related HCC occurrence. The association of Ile31Phe with HBV-related HCC occurrence was confirmed in the Guangdong population (OR = 0.64, 95% CI = 0.49-0.83, P = 8.0 × 10-4). The pooled analysis gave a joint P value of 5.5 × 10-6 (joint OR = 0.63, 95% CI = 0.52-0.77). Our findings suggest that AURKA Ile31Phe may play a role in mediating the susceptibility to HBV-related HCC among Chinese.

Effect of interferon-based and -free therapy on early occurrence and recurrence of hepatocellular carcinoma in chronic hepatitis C

Although treatment for hepatitis C virus has been dramatically improved by the development of direct-acting antiviral agents (DAAs), whether interferon (IFN)-free therapy reduces hepatocarcinogenesis in an equivalent manner to IFN-based therapy remains controversial. The aims of this study were to evaluate the occurrence and recurrence of hepatocellular carcinoma (HCC) in chronic hepatitis C (CHC) patients treated with DAAs and to identify biomarkers of HCC development after antiviral treatment. A restrospective review of a prospective database of 1,897 CHC patients who were treated with IFN-based (1,145) or IFN-free therapies (752) was carried out. Cumulative HCC occurrence and recurrence rates were compared using propensity score-matched analysis. Predictors of HCC development after viral eradication were identified by multivariate analysis. Propensity score-matched analysis showed no significant difference in HCC occurrence (p=0.49) and recurrence rates (p=0.54) between groups treated with IFN-based or IFN-free therapies. In multivariate analysis, higher levels of post-treatment α-fetoprotein (AFP) or Wisteria floribunda agglutinin positive Mac-2 binding protein (WFA+M2BP) were independently associated with HCC occurrence and recurrence after viral eradication. Only post-treatment WFA+M2BP level was significantly associated with HCC occurrence and recurrence among patients without severe fibrosis. The area under the receiver operating characteristic (ROC) curve for WFA+M2BP levels was greater than that for AFP levels in ROC analysis. The risks of early HCC occurrence and recurrence after viral eradication were similar between IFN-based and IFN-free therapies. Post-treatment levels of WFA+M2BP may be helpful screening biomarkers for assessing the risk of HCC after IFN-free therapy. Patients with high WFA+M2BP levels after antiviral treatment, even without severe fibrosis, must be followed up carefully for HCC development. Lay summary: The risks of early HCC occurrence and recurrence after viral eradication were similar between IFN-based and IFN-free therapies. Post-treatment levels of WFA+M2BP may be helpful screening biomarkers for assessing the risk of HCC after IFN-free therapy.

Higher risk of hepatocellular carcinoma in chronic hepatitis B vs chronic hepatitis C after achievement of virologic response.

It is unclear whether the achievement of virologic response modifies the risk of hepatocellular carcinoma (HCC) differently in chronic hepatitis B (CHB) and chronic hepatitis C (CHC). Our aim was to compare the risk of HCC between patients with CHB and CHC who achieved virological response. We analysed data from patients with CHB treated with entecavir (n=2000) or CHC treated with peg-interferon and ribavirin (n=733) at a tertiary hospital from 2004 to 2011. Virological response was defined as serum HBV DNA<15IU/mL at 1year of treatment for CHB or the achievement of sustained virologic response for CHC. Virological response was achieved in 1520 patients with CHB (76.0%) and 475 patients with CHC (64.8%). During the median follow-up period of 6years, 228 patients with CHB (11.4%) and 59 patients with CHC (8.0%) developed HCC. Among patients with virological response, CHB was independently associated with a significantly higher incidence of HCC (hazard ratio, 2.17; 95% CI, 1.30-3.63; P=.003) than CHC. Among patients without virological response, there were no differences in HCC incidence between the two cohorts (P=.52). In patients with cirrhosis at baseline, the incidence of HCC did not differ between the two cohorts even after achieving virological response (P>.99). In conclusion, patients with CHB treated with entecavir were associated with a higher risk of HCC compared to patients with CHC treated with peg-interferon and ribavirin after achieving virological response. However, the risk of HCC did not differ between the two cohorts if the patients had cirrhosis at baseline, even if virological response was achieved.

Liver cirrhosis stages and the incidence of hepatocellular carcinoma in chronic hepatitis B patients receiving antiviral therapy

Objectives: Long-term antiviral therapy decreases the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB), however, it cannot eliminate the risk. We investigated the incidence of HCC at different stages of liver cirrhosis (LC) and identified clinical predictors for HCC development during antiviral therapy.Methods: The data from 356 treatment-naïve patients aged 40 to 69 years without a history of HCC who had received entecavir for ≥6 months were collected retrospectively. The incidence of HCC was evaluated in patients with CHB only, with LC without varices (stage 1), with varices (stage 2), and with ascites (stage 3).Results: The median follow-up period was 3.6 years. In total, 45 patients (12.6%) developed HCC. The annual incidence rates of HCC in patients with CHB only or LC in stages 1, 2, and 3 were 0.4%, 2.6%, 9.8%, and 6.7%, respectively. In multivariate analyzes, LC at stage 2 (hazard ratio [HR] 17.16, 95% confidence interval [C.I.] 3.93–75.01, p < .001), alcohol consumption (HR 3.84, 95% C.I. 1.99–7.39, p < .001), and older age (HR 1.06, 95% C.I. 1.01–1.11, p = .010) were significantly associated with HCC development. The risk decreased in those who stopped drinking after 2 years of abstinence (p = .0314).Conclusions: LC with significant portal hypertension (varices or ascites), alcohol consumption, and older age at the time of starting antiviral therapy are independent predictors for future HCC development.

Aflatoxin B1 exposure increases the risk of cirrhosis and hepatocellular carcinoma in chronic hepatitis B virus carriers.

The relation between aflatoxin B1 (AFB1 ) and cirrhosis in chronic carriers of hepatitis B virus (HBV) remains inconclusive. This case-control study nested in a large community-based cohort aimed to assess the effect of AFB1 exposure on cirrhosis and HCC in chronic HBV carriers. Serum AFB1 -albumin adduct levels at study entry were measured in 232 cirrhosis cases, 262 HCC cases and 577 controls. Multivariate-adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) were estimated using logistic regression. Among all chronic HBV carriers, the time intervals between study entry and diagnosis of HCC, cirrhosis, cirrhotic HCC, and non-cirrhotic HCC were all significantly (p < 0.0001) shorter in participants with high serum levels of AFB1 -albumin adducts than those with low/undetectable levels. There were significant dose-response relations with serum AFB1 -albumin adduct level at study entry for cirrhosis (p-trend = 0.0001) and cirrhotic HCC (p-trend < 0.0001) newly diagnosed within 9 years after entry as well as non-cirrhotic HCC (p-trend = 0.021) newly diagnosed within 4 years after entry. The aORs (95% CIs) for high versus undetectable serum AFB1 -albumin adduct levels were 2.45 (1.51-3.98) for cirrhosis (p = 0.0003), 5.47 (2.20-13.63) for cirrhotic HCC (p = 0.0003), and 5.39 (1.11-26.18) for non-cirrhotic (p = 0.0368) HCC, respectively. There remained a significant dose-response relation between serum AFB1 -albumin adduct level and HCC risk (p-trend = 0.0291) in cirrhosis patients, showing an aOR (95% CI) of 3.04 (1.11-8.30) for high versus undetectable serum levels (p = 0.0299). It is concluded that AFB1 exposure may increase the risk of cirrhosis and HCC in a dose-response manner among chronic HBV carriers.

Insulin resistance and the risk of hepatocellular carcinoma in chronic hepatitis B patients.

We analyzed whether insulin resistance (IR) assessed by homeostasis model assessment (HOMA2-IR) index can stratify hepatocellular carcinoma (HCC) risk in patients with chronic hepatitis B virus (HBV) infection. A retrospective cohort of 1696 chronic HBV-infected patients (age: 50.0±7.8years, men=964 [56.8%]) who underwent detailed health checkup program including C-peptide and fasting blood glucose measurement and followed up for more than a year were analyzed. During a median follow-up of 5.0years (range, 1.0-10.5years), 24 patients (1.4%) developed HCC. The HCC incidence rate was higher for patients with higher HOMA2-IR value than those with lower HOMA2-IR value (1.7% vs 0.5% for HOMA2-IR >1.200 vs ≤1.200, P=0.009). HOMA2-IR was a significant factor associated with HCC development in multivariable-adjusted model (HR [95% CI]: 3.25 [1.13-9.31], adjusted for age, sex, cirrhosis, and HBV DNA levels). The association between HOMA2-IR and HCC was markedly attenuated and became no longer statistically significant (HR [95% CI]: 1.93 [0.57-6.51]) when further adjusted for obesity, hypertension, and diabetes. In subgroup analysis, HOMA2-IR value was an independent factor associated with HCC in patients without overt metabolic abnormalities (hypertension, diabetes, and metabolic syndrome) but not for those with overt metabolic abnormalities. Insulin resistance assessed by HOMA2 was associated with the risk of HCC, indicating that HOMA2-IR can be a useful tool for stratifying the risk of HCC in chronic HBV-infected patients, particularly in patients without overt metabolic abnormalities.

Research advances in risk factors for hepatocellular carcinoma in chronic hepatitis C patients with sustained virologic response

Research advances in risk factors for hepatocellular carcinoma in chronic hepatitis C patients with sustained virologic response

Impact of direct-acting antiviral agents-induced SVR on the long-term burden of hepatocellular carcinoma in chronic hepatitis C cirrhosis.

230 Background: Sustained virological response (SVR) has been associated with decreased morbidity and mortality from hepatitis C virus (HCV) infection. Data are sparse, however, about the long-term benefits of direct-acting antiviral agents (DAAs) in terms of risk reduction for hepatocellular carcinoma (HCC). We estimate the impact of SVR on the HCC incidence in the DAA era when SVR is achieved nearly universally even in patients with advanced fibrosis and cirrhosis. Methods: We constructed a Markovian model of 50-year-old patients with compensated HCV cirrhosis (n=1,000) to model the incidence of HCC over 20-years of follow-up. We compared 2 cohorts: 1) SVR following DAA therapy and 2) no SVR (natural history). In the latter, HCC would develop at an annual rate of 4.2% and patients would die as a result of end stage liver disease (ESLD) according to their MELD (=6 at baseline). In the former, MELD score would not increase, the HCC risk would decrease and, in some patients, cirrhosis would regress. Results: The table summarizes the 20-year outcome in the two cohorts. In the cohort without SVR, HCC would occur in 33% and 63% would die of ESLD. In the SVR cohort, the proportion of HCC would increase to 37% as the number of subjects at HCC risk would increase, as a result of a dramatic reduction in deaths from ESLD. In the univariate sensitivity analyses, the cumulative HCC incidence was mainly influenced by the rate at which the risk of HCC is decreased after SVR, followed by the change in cirrhosis regression rate. Conclusions: Although HCC risk would decrease after SVR in a given individual patient with cirrhosis, on the population level, highly effective DAA therapy may lead to a paradoxical increase in the burden of HCC. These data underscore the important of (1) HCC surveillance in patients with cirrhosis even after SVR and (2) DAA intervention before cirrhosis develops. [Table: see text]

Increased hepatocellular carcinoma risk in chronic hepatitis B patients with persistently elevated serum total bile acid: a retrospective cohort study.

To investigate the association between long-term changes of serum total bile acid and hepatocellular carcinoma in chronic hepatitis B patients, we did a retrospective cohort study of 2262 chronic hepatitis B patients with regular antiviral treatment using data from the Hepatitis Biobank at Southwest Hospital Program from 2004 to 2014. Patients in the study were classified into 3 groups according to persistence of elevated serum total bile acid during follow-up: none-low, medium, and high persistence of elevated serum total bile acid. The association between persistence of elevated serum total bile acid and hepatocellular carcinoma was estimated using Cox proportional hazard models and Kaplan-Meier analysis including information about patients’ demographic and clinical characteristics. There were 62 hepatocellular carcinoma cases during a total follow-up of 14756.5 person-years in the retrospective study. Compared to patients with none-low persistence of elevated total bile acid, the multivariate adjusted hazard ratios (95% confidence interval) were 2.37 (1.16–4.84), and 2.57 (1.28–5.16) for patients with medium, and high persistence of elevated total bile acid. Our findings identified persistence of elevated serum total bile acid as an independent risk factor of hepatocellular carcinoma in chronic hepatitis B patients.

Development of hepatocellular carcinoma in chronic hepatitis B patients with advanced fibrosis is independent of viral genotype.

Hepatitis B is leading cause of liver related morbidity in Asia with predominant genotypes B and C in East-Asia. Data on Serum, intrahepatic viral-markers, and long-term follow-up of prevalent genotypes (GT) B and C in patients with biopsy proven advanced fibrosis are sparse. To compare serum, intrahepatic viral-markers and development of hepatocellular carcinoma (HCC) in GT-B and C in patients with advanced fibrosis (Ishak ≥ 4). Sixty-three treatment-naïve patients identified with advanced fibrosis on liver-biopsy performed between 1998 and 2000 at Singapore General Hospital. FFPE tissue was available for 59 patients and serum for 42 patients. HBV-DNA was quantified in serum and liver while qHBsAg quantified in serum. Patients were followed-up till December 2015. The median age was 47 ± 16 years, with 77.7% males. About 19 were GT-B, 43 patients were GT-C, and 1 had both GT-B and C. Mean follow-up was 13.5 years. The median serum HBV-DNA was 6.25 ± 2.17 and 6.58 ± 1.85 log IU/ml, serum HBsAg was 3.29 ± 0.80 and 3.45 ± 1.85 log IU/ml, and intrahepatic HBV-DNA was 0.52 ± 3.73 copies/cell and 0.4 ± 1.37 copies/cell in the GT-B and C, respectively (P > 0.1 in all). Complete cirrhosis (Ishak-6) was present in 47.6%, Ishak-5 fibrosis in 33.3%, and Ishak-4 fibrosis in 19% at recruitment. On follow-up HCC developed in 8/43 in GT-C and in 3/19 GT-B (P = 0.86). Advanced age and cirrhosis were significant factors for development of HCC. No difference in serum HBV-DNA, qHBsAg or intrahepatic HBV-DNA was seen in the two genotypes. HCC development seen over long-term follow-up was independent of genotypes in patients with advanced fibrosis. J. Med. Virol. 89:845-848, 2017. © 2016 Wiley Periodicals, Inc.

Circulating visfatin level is associated with hepatocellular carcinoma in chronic hepatitis B or C virus infection

Adipocytokines play an important role in adipose tissue homeostasis, especially in obesity-associated disorders such as non-alcoholic fatty liver and their complications including hepatocellular carcinoma (HCC). Although visfatin is an adipocytokine highly expressed in visceral fat that has been demonstrated to play a critical role in the progression of human malignancies, little is known about the role of visfatin in HCC associated with chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infection. In this study, we investigated whether plasma visfatin levels were altered in patients with HCC and the association between plasma visfatin levels and pretreatment hematologic profiles. Plasma visfatin levels were measured by enzyme-linked immunosorbent assays in 193 patients with different stages of HBV or HCV infection, and 92 healthy control subjects. The patients with HCC and chronic HCV or HBV infection had higher levels of visfatin than patients with HBV, HCV, and cirrhosis. In multivariate logistic regression analysis, levels of alpha-fetoprotein (AFP) (OR: 1.13, p=0.003), and plasma visfatin (OR: 1.17, p=0.046) were independently associated with HCC. Multiple stepwise regression analysis showed that plasma visfatin level was positively associated with age, aspartate aminotransferase to platelet ratio index (APRI), and AFP. Trend analyses confirmed that plasma visfatin concentration was associated with AFP>8ng/mL, cirrhosis, HCC, tumor size>5cm, and Barcelona Clinic Liver Cancer-C stage. These results suggested that the plasma visfatin level is associated with the presence of HCC, and that a higher plasma visfatin level may be important in the pathogenesis of HCC. Visfatin may act as both a protective and pro-inflammatory factor. Plasma visfatin concentration may serve as an additional tool to identify patients with more advanced necroinflammation.

The incidence and risk factors for the development of hepatocellular carcinoma after peginterferon plus ribavirin therapy for chronic hepatitis C.

Although the incidence of hepatocellular carcinoma (HCC) has been shown to be reduced after pegylated glycol-interferon plus ribavirin (Peg-IFN/RBV) therapy in patients with chronic hepatitis C, the risk factors for the development of HCC are not fully understood. The aim of this study was to clarify the incidence and the risk factors for the development of HCC after Peg-IFN/RBV therapy in patients with chronic hepatitis C. A total of 474 patients with chronic hepatitis C who received Peg-IFN/RBV therapy between December 2004 and August 2010 were enrolled and followed in a multicenter trial. The patients were assessed for HCC by either ultrasound or computed tomography every 6 months. The incidence and risk factors for the development of HCC were identified. Of the 474 patients, 23 developed HCC during a median follow-up of 4 years and 8 months (range 1-6 years and 3 months) after completion of Peg-IFN/RBV therapy. According to a univariate analysis, higher age, low platelet counts, a low level of serum albumin, a high level of alpha-fetoprotein (AFP) and a sustained viral response (SVR) to Peg-IFN/RBV therapy were independent factors associated with the occurrence of HCC. The multivariate analysis using the Cox proportional hazard model revealed the risk factors for HCC were the platelet count, AFP level and the outcome of Peg-IFN/RBV therapy. To reduce the incidence of HCC in chronic hepatitis C, attainment of a sustained response rate is an essential issue. For patients with low platelet counts and/or a high AFP level, strict surveillance should be continued even after eradication of HCV because the risk of HCC was found to be higher for these patients.

비만과 간세포암

Obesity is closely associated with hepatocellular carcinoma (HCC) as well as other malignancies. Obesity is an important risk factor for cancer development and overall mortality in HCC. Molecular mechanisms of hepatocarcinogenesis in obesity are adipose tissue remodeling, dysregulation of adipokines, increased reactive oxygen species, insulin resistance or hyperinsulinemia, alteration of gut microbiota, and dysregulation of microRNA. Obesity is the most common cause of non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH). NAFLD or NASH leads to HCC as well as liver cirrhosis. Hepatitis C virus regulates lipid homeostasis in liver. Obesity and its’ related factors (metabolic syndrome and diabetes mellitus) are significantly related to the risk of HCC development in chronic hepatitis C. However, it is not clear whether obesity is a risk factor for HCC in chronic hepatitis B. The relationship between obesity and HCC seems to be different according to etiology of background liver disease. Further studies are needed to clarify the effect of obesity on HCC in different etiologies of chronic liver disease.

Does obesity increase the risk of hepatocellular carcinoma in chronic hepatitis B patients?

Does obesity increase the risk of hepatocellular carcinoma in chronic hepatitis B patients?