Quantitative evaluation of hepatitis B virus mutations and hepatocellular carcinoma risk:a meta-analysis of prospective studies

Background： The temporal relationship between hepatitis B virus （HBV） mutations and hepatocellular carcinoma （HCC） remains unclear. Methods： We conducted a meta-analysis including cohort and nested case-control studies to prospectively examine the HCC risk associated with common variants of HBV in the PreS, Enhancer Ⅱ, basal core promoter （BCP） and precore regions. Pertinent studies were identified by searching PubMed, Web of Science and the Chinese Biological Medicine databases through to November 2014. Study-specific risk estimates were combined using fixed or random effects models depending on whether significant heterogeneity was detected. Results： Twenty prospective studies were identified, which included 8 cohort and 12 nested case-control studies. There was an increased risk of HCC associated with any PreS mutations with a pooled relative risk （RR） of 3.82 [95% confidence interval （CI）： 2.59-5.61]. The pooled-RR for PreS deletion was 3.98 （95% CI： 2.28-6.95）, which was higher than that of PreS2 start codon mutation （pooled-RR=2.63, 95% CI： 1.30-5.34）. C1653T in Enhancer Ⅱ was significantly associated with HCC risk （pooled-RR=l.83; 95% CI： 1.21-2.76）. For mutations in BCP, statistically significant pooled-RRs of HCC were obtained for T1753V （pooled- RR=2.09; 95% CI： 1.49-2.94） and AI762T/G1764A double mutations （pooled-RR=3.11; 95% CI： 2.08- 4.64）. No statistically significant association with HCC risk was observed for G1896A in the precore region （pooled-RR=0.77; 95% CI： 0.47-1.26）. Conclusions： This study demonstrated that PreS mutations, C1653T, T1753V, and A1762T/G1764A, were associated with an increased risk of HCC. Clinical practices concerning the HCC risk prediction and diagnosis may wish to focus on patients with these mutations.

A nested case-control study of maternal-neonatal transmission of hepatitis B virus in a Chinese population

AIM:To examine the determinants of maternal-neonatal transmission of hepatitis B virus(HBV) METHODS:A nested case-control study was conducted in Changsha,Hunan,People's Republic of China from January 1,2005 to September 31,2006 To avoid potential maternal blood contamination,we collected vein blood of newborns immediately after birth and before initial hepatitis B vaccination to determine the HBV infection status of the newborn For each HBsAg-positive infant,one HBsAg-negative infant born to an HBsAg-positive mother was matched by hospital at birth(same),gender(same),and date of birth(within 1 mo) A faceto-face interview was conducted to collect clinical and epidemiological data Conditional logistic regression analysis was used to estimate the independent effects of various determinants on maternal-neonatal transmission of HBV RESULTS:A total of 141 HBsAg-positive infants and 141 individually matched HBsAg-negative infants were included in the final analysis Maternal first-degree family history of HBV infection,intrahepatic cholestasis,and premature rupture of membranes were risk factors for perinatal transmission of HBV,whereas systematic treatment and HBV immunoglobulin injections for mothers with HBV infection were protective factors for maternal-neonatal transmission of HBV,after adjustment for potential confounding factors CONCLUSION:For HBsAg-positive mothers,systematic treatment,HBV immunoglobulin administration,and controlling intrahepatic cholestasis and pregnancy complications may reduce the incidence of perinatal transmission of HBV.

Postoperative adjuvant antiviral therapy for hepatitis B/C virus-related hepatocellular carcinoma:A meta-analysis

AIM:To investigate the impact of postoperative antiviral treatment on tumor recurrence and survival of patients with chronic hepatitis B virus(HBV) or hepatitis C virus(HCV) infection-related primary hepatocellular carcinoma(HCC) after curative therapy.METHODS:We performed a meta-analysis of randomized and non-randomized control trials from electronic search and manual search.The fixed effect model of Mantel-Haenszel method and the random effect model of Der Simonian and Laird method were used for homogeneous and heterogeneous studies,respectively.Seven HCV-related studies,three HBV-related studies and three studies on HBV or HCV-related HCC were identified.RESULTS:A total of 1224 patients were included in this analysis.The estimated odds ratios(OR) for the 1-,2-,3-and 5-year recurrence were 0.54 [15.4% vs 24.1%,95% confidence interval(CI):0.32-0.89,P=0.02],0.42(36.9% vs 58.0%,95% CI:0.19-0.90,P=0.03),0.37(47.9% vs 63.8%,95% CI:0.19-0.71,P=0.003),and 0.32(66.7% vs 74.3%,95% CI:0.15-0.66,P=0.002),respectively;and the OR for the 1-,2-,3-,5-and 7-year mortality were 0.23(1.2% vs 9.1%,95% CI:0.07-0.71,P=0.01),0.31(6.4% vs 22.1%,95% CI:0.12-0.79,P=0.01),0.43(12.7% vs 20.8%,95% CI:0.21-0.89,P=0.02),0.42(25.1% vs 42.0%,95% CI:0.27-0.66,P=0.0002) and 0.28(31.9% vs 52.2%,95% CI:0.13-0.59,P=0.0008).CONCLUSION:This meta-analysis indicates the postoperative antiviral therapy,interferon in particular,may serve as a favorable alternative to reduce recurrence and mortality in patients with HBV/HCV related HCCs.

Genomic change in hepatitis B virus associated with development of hepatocellular carcinoma

AIM: To determine the genomic changes in hepatitis B virus(HBV) and evaluate their role in the development of hepatocellular carcinoma(HCC) in patients chronically infected with genotype C HBV.METHODS: Two hundred and forty chronic hepatitis B(CHB) patients were subjected and followed for a median of 105 mo. HCC was diagnosed in accordance with AASLD guidelines. The whole X, S, basal core promoter(BCP), and precore regions of HBV were sequenced using the direct sequencing method.RESULTS: All of the subjects were infected with genotype C HBV. Out of 240 CHB patients, 25(10%) had C1653 T and 33(14%) had T1753 V mutation in X region; 157(65%) had A1762T/G1764 A mutations in BCP region, 50(21%) had G1896 A mutation in precore region and 67(28%) had pre-S deletions. HCC occurred in 6 patients(3%). The prevalence of T1753 V mutation was significantly higher in patients who developed HCC than in those without HCC. The cumulative occurrence rates of HCC were 5% and 19% at 10 and 15 years, respectively, in patients with T1753 V mutant, which were significantly higher than 1% and 1% in those with wild type HBV(P < 0.001).CONCLUSION: The presence of T1753 V mutation in HBV X-gene significantly increases the risk of HCC development in patients chronically infected with genotype C HBV.

Distinct expression patterns in hepatitis B virus-and hepatitis C virus-infected hepatocellular carcinoma

AIM: To identify biomarkers indicating virus-specific hepatocarcinogenic process,differential mRNA expres-sion in 32 patients with hepatitis B virus (HBV)-/hepa-titis C virus (HCV)-associated hepatocellular carcinoma (HCC) were investigated by means of cDNA microar-rays comprising of 886 genes. METHODS: Thirty two HCC patients were divided into two groups based on viral markers: hepatitis B virus positive and HCV positive. The expression profiles of 32 pairs of specimens (tumorous and surrounding non-tumorous liver tissues),consisting of 886 genes were analyzed. RESULTS: Seven up-regulated genes in HBV-associat-ed HCC comprised genes involved in protein synthesis (RPS5 ),cytoskeletal organization (KRT8 ),apoptosis related genes (CFLAR),transport (ATP5F1),cell mem-brane receptor related genes (IGFBP2),signal trans-duction or transcription related genes (MAP3K5),and metastasis-related genes (MMP9). The up-regulated genes in HCV-infected group included 4 genes: VIM (cell structure),ACTB (cell structure),GAPD (glycolysis) and CD58 (cell adhesion). The expression patterns of the 11 genes,identified by cDNA microarray,were con-firmed by quantitative RT-PCR in 32 specimens. CONCLUSION: The patterns of all identified genes were classified based on the viral factor involved in HBV-and HCV-associated HCC. Our results strongly suggest that the pattern of gene expression in HCC is closely associated with the etiologic factor. The pres-ent study indicates that HBV and HCV cause hepato-carcinogenesis by different mechanisms,and provide novel tools for the diagnosis and treatment of HBV-and HCV-associated HCC.

Occult hepatitis B virus infection and surgical outcomes in non-B, non-C patients with curative resection for hepatocellular carcinoma

AIM To investigate the prevalence, clinicopathological characteristics and surgical outcomes of occult hepatitis B virus(HBV) infection(OBI) in patients with non-B, non-C(NBNC) hepatocellular carcinoma(HCC).METHODS This study retrospectively examined the cases of 78 NBNC patients with curative resection for HCC for whom DNA could be extracted from formalin-fixed paraffin-embedded tissue. OBI was determined by the HBV-DNA amplification of at least two different sets of primers by TaqM an realtime polymerase chain reaction. Possibly carcinogenetic factors such as alcohol abuse, diabetes mellitus, obesity and non-alcoholic steatohepatitis(NASH) were examined. Surgical outcomes were evaluated according to diseasefree survival(DFS), overall survival(OS) and diseasespecific survival(DSS).RESULTS OBI was found in 27/78 patients(34.6%) with NBNC HCC. The OBI patients were significantly younger than the non-OBI cases at the time of surgery(average age 63.0 vs 68.1, P = 0.0334) and the OBI cases overlapped with other etiologies significantly more frequently compared to the non-OBI cases(P = 0.0057). OBI had no impact on the DFS, OS or DSS. Only tumorrelated factors affected these surgical outcomes.CONCLUSION Our findings indicate that OBI had no impact on surgical outcomes. The surgical outcomes of NBNC HCC depend on early tumor detection; this reconfirms the importance of a periodic medical examination for individuals who have NBNC HCC risk factors.

Significance of hepatitis B virus surface antigen, hepatitis C virus expression in hepatocellular carcinoma and pericarcinomatous tissues

AIM: To investigate the correlation between hepatitis B virus surface antigen (HBsAg), hepatitis C virus (HCV) expression in hepatocellular carcinoma (HCC), the HAI score of the noncancerous region of the liver and the serum Alpha fetoprotein (AFP) level.METHODS: The patterns of HBsAg and HCV in 100 cases of HCC and their surrounding liver tissues were studied on paraffin-embedded sections with immuno-histochemistry, the histological status was determined by one pathologist and one surgeon simultaneously using the hepatitis activity index (HAI) score, and AFP was detected by radioimmunity. The study included 100 consecutive patients who underwent curative resection for HCC. Based on HBsAg and HCV expression, the patients were classified into 4 groups: patients positive for HBsAg (HBsAg group), patients positive for HCV (HCV group), patients negative for both HCV and HBsAg (NBNC group) and patients positive for both HBsAg and HCV (BC group).RESULTS: The BC group had significantly higher HAI scores than the other three groups. (BC > HCV > HBsAg > NBNC). HBV and HCV virus infection was positively correlated with HAI (rs = 0.39, P = 0.0001). The positive rate of AFP (85.7%) and the value of AFP (541.2 ng/mL) in the group with HBV and HCV co-infection were the highest among the four groups. The positive rate (53.3%) of AFP and the value of AFP ( 53.3 ng/mL) in the group with none-infection of HBV and HCV were the lowest. HBV and HCV virus infection was positively correlated with AFP(rs = 0.38, P = 0.0001). CONCLUSION: The AFP increase in patients with liver cancer was positively correlated with the infection of HBV and HCV. The serum AFP elevation by the infection of HBV and HCV is one of mechanisms which lead to hepatocarcinogenesis, and the antivirus intervening treatment of hepatitis is significant for the prognosis of liver cancer. From our Spearman’s rank correlation analysis, we can conclude that the severity of virally induced inflammation is correlated with HBsAg and HCV expression in HCC tissues and noncancerous tissues. Prior co-infection of HBV in HCV patients may be an adverse risk factor for intrahepatic inflammation.

Difference in incidence of developing hepatocellular carcinoma between hepatitis B virus-and hepatitis C virus-infected patients

BACKGROUND It is generally accepted that the incidence of hepatocellular carcinoma(HCC)in hepatitis C virus(HCV)-associated patients is higher than that in hepatitis B virus(HBV)-associated patients.The reason why this difference in the incidence of HCC occurs in patients with HBV and HCV infections remains unclear.We report the possibility that the contributing power of inflammation,which is the main risk factor for developing HCC,may be different with HBV and HCV infections.AIM To investigate this,we surveyed the hazard ratio of inflammation for HCC development which was identified by serum alanine aminotransferase(ALT)levels between patients with HBV and HCV infections.METHODS The PubMed database was searched(2001-2021)for studies published in English regarding the incidence of HCC identifying 8924 HBV-and 7376 HCV-infected patients.From these studies,interferon-treated patients with both HBV and HCV infections were excluded.Furthermore,in HBV patients,those administered nucleos(t)ide analogues were excluded,and in HCV patients,those administered direct acting antivirals were also excluded.Studies citing hazard ratios of HCC regarding inflammation(serum elevated alanine aminotransferase levels)were selected.Finally,there were 14 studies of HBV-infected patients and 8 studies of HCV-infected patients.We calculated the hazard ratio in patients in an inflammatory state(serum ALT levels were above the normal range).RESULTS In the 14 studies of HBV patients,the average hazard ratio(HR)of elevated ALT for developing HCC was 2.74[1.98-3.77]and that in the 8 studies of HCV-infected patients was 5.51[3.08-9.83].The HR of inflammation for HCC development in HCV-associated liver diseases is about twice that in HBV-associated liver diseases.HR in HCV-infected patients was significantly(P=0.0391)higher than that in HBV-infected patients.In hepatitis B patients,the abnormal range adopted was 28-45 IU/L,and in hepatitis C patients,it was 20-50 IU/L.It was demonstrated that the abnormal ALT levels adopted in hepatitis B and C patients were very similar in this series.CONCLUSION The difference in the incidence of HCC development between HBV and HCV patients may depend on the difference in the hazard risk of ALT between HBV and HCV infections.

Pathological characterization of occult hepatitis B virus infection in hepatitis C virus-associated or non-alcoholic steatohepatitis-related hepatocellular carcinoma

Occult hepatitis B virus(HBV)infection,by definition,is a state in which infection with this virus does not manifest with the conventional diagnostic laboratory criteria reserved for the obvious form of HBV infection.As a result,occult HBV infection is commonly a surprise finding discovered accidently during the evaluation of other apparent liver diseases,such as hepatitis C virus(HCV)infection or non-alcoholic fatty liver disease and,more importantly,their evolution into life-threatening hepatocellular carcinoma.As infection with HCV and occult HBV is rarely considered when assessing these more obvious conditions,and in an attempt to offer a better understanding of this phenomenon,this study attempted to shed some light onto the uniqueness of occult HBV infection by addressing the natural history of HBV and HCV infections,as well as non-alcoholic fatty liver disease.This was carried out by taking into account the exclusive integration process undertaken by the HBV genome into infected host hepatocytes,with consideration given to conditions which afford reactivation of the occult infection and stress on the molecular mechanisms that underlie occult HBV infection.Finally,the clinical outcome of occult HBV infection and its relation to hepatocellular carcinoma is analyzed.

Significance of hepatitis virus infection in the oncogenicinitiation of hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is one of the most common causes of cancer-related death worldwide. Chronic infection of hepatitis B virus(HBV) and/or hepatitis C virus(HCV) is a major risk factor in the development of the HCC, independently from excessive alcohol abuse and metabolic disease. Since the biology of HBV and HCV is different, their oncogenic effect may go through different mechanisms, direct and/or indirect. Viral hepatitis infection is associated with cellular inflammation, oxidative stress, DNA damage, that may lead to subsequent hepatic injuries such as chronic hepatitis, fibrosis, cirrhosis, and finally HCC. Direct oncogenic properties of these viruses are related with their genotypic characteristics and the ability of viral proteins to interact with host proteins, thus altering the molecular pathways balance of the cells. In addition, the integration of HBV DNA, especially the gene S and X, in a particular site of the host genome can disrupt chromosomal stability and may activate various oncogenic mechanisms, including those in hematopoietic cells. Recently, several studies also had demonstrated that viral hepatitis could trigger the population of hepatic cancer stem cells. This review summarize available pre-clinical and clinical data in literature regarding oncogenic properties of HBV and HCV in the early initiation of HCC.

Hepatocellular carcinoma,human immunodeficiency virus and viral hepatitis in the HAART era

The incidence of hepatocellular carcinoma(HCC)in patients with human immunodeficiency virus(HIV) is rising.HCC in HIV almost invariably occurs in the context of hepatitis C virus(HCV)or hepatitis B virus (HBV)co-infection and,on account of shared modes of transmission,this occurs in more than 33% and 10% of patients with HIV worldwide respectively.It has yet to be clearly established whether HIV directly accelerates HCC pathogenesis or whether the rising incidence is an epiphenomenon of the highly active antiretroviral therapy(HAART)era,wherein the increased longevity of patients with HIV allows long-term complications of viral hepatitis and cirrhosis to develop.Answering this question will have implications for HCC surveillance and the timing of HCV/HBV therapy,which in HIV co-infection presents unique challenges.Once HCC develops,there is growing evidence that HIV co-infection should not preclude conventional therapeutic strategies,including liver transplantation.

Hepatitis B virus pre S1 deletion is related to viral replication increase and disease progression

AIM:To investigate the clinical implications of hepatitis B virus(HBV) pre S1 deletion.METHODS:We developed a fluorescence resonance energy transfer-based real-time polymerase chain reaction(RT-PCR) that can detect four genotypes(wild type, 15-bp, 18-bp and 21-bp deletion).The PCR method was used in two cohorts of Korean chronic HBV subjects with genotype C infections.Cohort Ⅰ included 292 chronic HBV subjects randomly selected from Cheju National University Hospital(Jeju, South Korea) or Seoul National University Hospital(Seoul, South Korea), and cohort Ⅱ included 90 consecutive chronic HBV carriers recruited from Konkuk University Hospital(Seoul, South Korea); the cohort Ⅱ patients did not have hepatocellular carcinoma or liver cirrhosis.RESULTS:The method proposed in this study identified 341 of 382 samples(89.3%).Deletion variants were identified in 100(29.3%) of the 341 detected samples.In both cohorts, the subjects with deletions had a significantly higher Hepatitis B virus e antigen(HBe Ag)-positive seroprevalence [cohort Ⅰ, wild(51.0%) vs deletion(75.0%), P < 0.001; cohort Ⅱ, wild(69.2%) vs deletion(92.9%), P = 0.002] and higher HBV DNA levels [cohort Ⅰ, wild(797.7 pg/m L) vs deletion(1678.9 pg/m L), P = 0.013; cohort Ⅱ, wild(8.3 × 108 copies/m L) vs deletion(2.2 × 109 copies/m L), P = 0.049], compared to subjects with wild type HBV.CONCLUSION:HBV genotype C pre S1 deletion may affect disease progression in chronic HBV subjects through an extended duration of HBe Ag seropositive status and increased HBV replications.

Hepatitis B virus and hepatitis C virus dual infection

Hepatitis B virus(HBV)and hepatitis C virus(HCV)share common mode of transmission and both are able to induce a chronic infection.Dual HBV/HCV chronic coinfection is a fairly frequent occurrence,especially in high endemic areas and among individuals at high risk of parenterally transmitted infections.The intracellular interplay between HBV and HCV has not yet been sufficiently clarified,also due to the lack of a proper in vitro cellular model.Longitudinal evaluation of serum HBV DNA and HCV RNA amounts has revealed that complex virological profiles may be present in coinfected patients.Dual HBV/HCV infection has been associated to a severe course of the liver disease and to a high risk of developing hepatocellular carcinoma.Despite the clinical importance,solid evidence and clear guidelines for treatment of this special population are still lacking.This review summarizes the available data on the virological and clinical features as well as the therapeutic options of the dual HBV/HCV infection,and highlights the aspects that need to be better clarified.

Biological impact of hepatitis B virus X-hepatitis C virus core fusion gene on human hepatocytes

AIM: To investigate the biological impact of hepatitis B virus X- hepatitis C virus core (HBV X-HCV C) fusion gene on hepatoma cells. METHODS: The recombinant adenoviruses Ad- XC, Ad-X and Ad-C expressing HBV X-HCV C fusion gene, HBV X gene and HCV C gene were constructed, respectively. Hepatoma cells were infected with different recombinant adenoviruses. MTT, colonyforming experiment, FCM, TUNEL assay were performed to observe the biological impact of the HBV X-HCV C fusion gene on liver cells. RESULTS: MTT showed that the Ad-XC group cells grew faster than the other group cells. Colony-forming experiment showed that the colony-forming rate for the Ad-XC group cells was significantly higher than that for the other group cells. FCM analysis showed that Ad-XC/Ad-X/Ad-C infection enhanced the progression of G1→S phase in the HepG2 cell cycle. The apoptosis index of the Ad-XC, Ad-X, Ad-C group cells was significantly lower than that of the Ad0 and control group cells. Semi-quantitative RT-PCR showed that the expression level of c-myc was the highest in Ad- XC infected cells. Tumor formation was found at the injected site of mice inoculated with Ad-XC-infected LO2 cells, but not in control mice. CONCLUSION: Ad-XC, Ad-X and Ad-C facilitate the proliferation activity of HepG2 cells and inhibit their apoptosis in vitro. The effect of Ad-XC is significantly stronger than that of Ad-X and Ad-C. Up-regulation of c-myc may be one of the mechanisms underlying the synergism of HBV X and HCV C genes on hepatocarcinogenesis in athymic nude mice.

Hepatitis C virus infection of human hepatoma cell line 7721 in vitro

AIM To establish a cell culture system with long-term replication of hepatitis C virus in vitro.``METHODS Human hepatoma cell line 7721 was tested for its susceptibility to HCV by incubating with a serum from a patient with chronic hepatitis C. Cells and supernatant were harvested at various phases during the culturing periods The presence of HCV RNA, the expression of HCV antigens in cells and/or supernatant were examined by RT-PCR, in situ hybridization and immunohistochemistry respectively.``RESULTS The intracellular HCV RNA was first detected on d 2 after infection and then could be intermittently detected in both cells and supernatant over a period of at least three months. The expression of HCV NS3, CP10antigens could be observed in cells. The fresh cells could be infected by supematant from cultured infected cells and the transmission of viral genome from HCV-infected 7721 cells to PBMCs was also observed.``CONCLUSION The hepatoma line 7721 is not only susceptible to HCV but also supports its long-term replication in vitro.

Vitamin D deficiency and hepatitis viruses-associated liver diseases:a literature review

The secosteroid hormone vitamin D has, in addition to its effects in bone metabolism also functions in the modulation of immune responses against infectious agents and in inhibiting tumorigenesis. Thus, deficiency of vitamin D is associated with several malignancies, but also with a plethora of infectious diseases. Among other communicable diseases, vitamin D deficiency is involved in the pathogenesis of chronic liver diseases caused by hepatitis B and C viruses(HBV, HCV) and high prevalence of vitamin D deficiency with serum levels below 20 mg/mL in patients with HBV and HCV infection are found worldwide. Several studies have assessed the effects of vitamin D supplementation on the sustained virological response(SVR) to interferon(IFN) plus ribavirin(RBV) therapy in HBV and HCV infection. In these studies, inconsistent results were reported. This review addresses general aspects of vitamin D deficiency and, in particular, the significance of vitamin D hypovitaminosis in the outcome of HBVand HCV-related chronic liver diseases. Furthermore,current literature was reviewed in order to understand the effects of vitamin D supplementation in combination with IFN-based therapy on the virological response in HBV and HCV infected patients.

Clinical cure and liver fibrosis reversal after postoperative antiviral combination therapy in hepatitis B-associated non-cirrhotic hepatocellular carcinoma: A case report

BACKGROUND The incidence of hepatocellular carcinoma(HCC)is high in China,and approximately 15%-20%of HCC cases occur in the absence of cirrhosis.Compared with patients with cirrhotic HCC,those with non-cirrhotic HCC have longer postoperative tumor-free survival.However,the overall survival time is not significantly increased,and the risk of postoperative recurrence remains.Strategies to improve the postoperative survival rate in these patients are currently required.CASE SUMMARY A 47-year-old man with a family history of HCC was found to have hepatitis B virus(HBV)infection 25 years ago.In 2000,he was administered lamivudine for 2 years,and entecavir(ETV 0.5 mg)was administered in 2006.In October 2016,magnetic resonance imaging revealed a tumor in the liver(5.3 cm×5 cm×5 cm);no intraoperative hepatic and portal vein and bile duct tumor thrombi were found;and postoperative pathological examination confirmed a grade II HCC with no nodular cirrhosis(G1S3).ETV was continued,and no significant changes were observed on imaging.After receiving pegylated interferon alfa-2b(PEG IFNα-2b)(180μg)+ETV in February 2019,the HBsAg titer decreased significantly within 12 wk.After receiving hepatitis B vaccine(60μg)in 12 wk,HBsAg serological conversion was realized at 48 wk.During the treatment,no obvious adverse reactions were observed,except for early alanine aminotransferase flares.The reexamination results of liver pathology were G2S1,and reversal of liver fibrosis was achieved.CONCLUSION The therapeutic regimen of ETV+PEG IFNα-2b+hepatitis B vaccine for patients with HBV-associated non-cirrhotic HCC following hepatectomy can achieve an HBV clinical cure and prolong the recurrence-free survival.

Extremely high titer of hepatitis B surface antigen antibodies in a primary hepatocellular carcinoma patient:A case report

BACKGROUND Hepatocellular carcinoma(HCC)may be caused by hepatitis B virus(HBV)infection.Post-infection recovery-associated changes of HBV indicators include decreased hepatitis B surface antigen(HBsAg)level and increased anti-HBsAg antibody titer.Testing to detect HBV DNA is conducted rarely but could detect latent HBV infection persisting after acute infection and prompt administration of treatments to clear HBV and prevent subsequent HBV-induced HCC deve-lopment.Here,we present an HCC case with an extremely high anti-HBsAg antibody titer and latent HBV infection.CASE SUMMARY A 57-year-old male patient with abdominal pain who was diagnosed with primary HCC presented with an extremely high level(over 2000 ng/mL)of serum alpha-fetoprotein.Abdominal B-ultrasonography and computed tomography scan results indicated focal liver lesion and mild splenomegaly.Assessments of serological markers revealed a high titer of antibodies against hepatitis B core antigen(anti-HBcAg antibodies),an extremely high titer(1000 mIU/mL)of hepatitis B surface antibodies(anti-HBsAg antibodies,anti-HBs)and absence of detectible HBsAg.Medical records indicated that the patient had reported no history of HBV vaccination,infection or hepatitis.Therefore,to rule out latent HBV infection in this patient,a serum sample was collected then tested to detect HBV DNA,yielding a positive result.Based on the aforementioned information,the final diagnosis was HCC associated with hepatitis B in a compensated stage of liver dysfunction and the patient was hospitalized for surgical treatment.CONCLUSION A rare HCC case with high serum anti-HBsAg antibody titer and detectable HBV DNA resulted from untreated latent HBV infection.

High level of serum cholesteryl ester transfer protein inactive hepatitis C virus infection

AIM: To determine the significance of cholesteryl ester transfer protein(CETP) in lipoprotein abnormalities in chronic hepatitis C virus(HCV) infection.METHODS: We evaluated the significance of the serum concentration of CETP in 110 Japanese patients with chronic HCV infection. Fifty-five patients had active HCV infection, and HCV eradication had been achieved in 55. The role of CETP in serum lipoprotein abnormalities, specifically, in triglyceride(TG) concentrations in the four major classes of lipoproteins, was investigated using Pearson correlations in conjunction with multiple regression analysis and compared them between those with active HCV infection and those in whom eradication had been achieved. RESULTS: The serum CETP levels of patients with active HCV infection were significantly higher than those of patients in whom HCV eradication was achieved(mean ± SD, 2.84 ± 0.69 μg/m L vs 2.40 ± 1.00 μg/m L, P = 0.008). In multiple regression analysis, HCV infection status(active or eradicated) was an independent factor significantly associated with the serum CETP level. TG concentrations in low-density lipoprotein(mean ± SD, 36.25 ± 15.28 μg/m L vs 28.14 ± 9.94 μg/m L, P = 0.001) and high-density lipoprotein(HDL)(mean ± SD, 25.9 ± 7.34 μg/m L vs 17.17 ± 4.82 μg/m L, P < 0.001) were significantly higher in patientswith active HCV infection than in those in whom HCV eradication was achieved. The CETP level was strongly correlated with HDL-TG in patients with active HCV infection(R = 0.557, P < 0.001), whereas CETP was not correlated with HDL-TG in patients in whom HCV eradication was achieved(R =-0.079, P = 0.56). CONCLUSION: Our results indicate that CETP plays a role in abnormalities of lipoprotein metabolism in patients with chronic HCV infection.

MicroRNAs as possible biomarkers for diagnosis and prognosis of hepatitis b- and c-related-hepatocellularcarcinoma

Aim of the present review is to summarize the current knowledge about the potential relationship between mi RNAs and hepatitis B virus(HBV)-hepatitis C virus(HCV) related liver diseases. A systematic computerbased search of published articles, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis Statement, was performed to identify relevant studies on usefulness of serum/plasma/urine mi RNAs, as noninvasive biomarkers for early detection of HBV and HCV-induced hepatocellular carcinoma(HCC) development, as well as for its prognostic evaluation. The used Medical Subject Headings terms and keywords were: "HBV", "HCV", "hepatocellular carcinoma", "micro RNAs", "mi RNAs", "diagnosis", "prognosis", "therapy", "treatment". Some serum/plasma mi RNAs, including mi R-21, mi R-122, mi-125a/b, mi R-199a/b, mi R-221, mi R-222, mi R-223, mi R-224 might serve as biomarkers for early diagnosis/prognosis of HCC, but, to date, not definitive results or well-defined panels of mi RNAs have been obtained. More well-designed studies, focusing on populations of different geographical areas and involving larger series of patients, should be carried out to improve our knowledge on the potential role of mi RNAs for HCC early detection and prognosis.