Coexistence of low levels of HBsAg and high levels of anti-HBs may increase risk of hepatocellular carcinoma in chronic hepatitis B patients with high HBV load

ObjectiveThe clinical significance of coexistence of HBsAg/anti-HBs in chronic hepatitis B (CHB) patients remains controversial. This study was aimed to assess the association of this serological pattern with hepatocellular carcinoma (HCC) in patients with CHB.MethodsIn this cross-section study, 206 CHB patients with coexistence of HBsAg/anti-HBs and 206 CHB patients with HBsAg alone were included to evaluate the risk of HCC development by logistic regression analysis. In addition, a retrospective cohort of 260 patients with CHB was recruited to estimate the cumulative incidence of HCC by Kaplan–Meier analysis.ResultsThe serological pattern of coexistence of HBsAg/anti-HBs, with high levels of (“High”) HBsAg/low levels of (“Low”) anti-HBs, were considered as independent risk factors for HCC. In particular, patients with “High” HBsAg/“High” anti-HBs [odds ratio (OR), 4.295; 95% confidence interval (CI), 1.104–16.699; p = 0.035] and “Low” HBsAg/ “High” anti-HBs (OR, 3.207; 95%CI, 1.299–7.919; p = 0.012) exhibited significantly higher risk for HCC development. However, only “Low” HBsAg /“High” anti-HBs might increase risk of HCC in CHB patients with high HBV load (logrank p < 0.001) in our cohort study.ConclusionThe coexistence of “Low” HBsAg /“High” anti-HBs might increase the risk of HCC development in CHB patients with high HBV load, which reflected that the long-term interaction between immune response and virus might lead to the development of HCC. The identification of the patients with poor prognosis will help clinicians to refine the therapeutic decisions and individualize follow-up strategies.     

Coexistence of BCL1/CCND1 and CMYC aberrations in blastoid mantle cell lymphoma: a rare finding associated with very poor outcome

A patient with mantle cell lymphoma (MCL) of the pleomorphic blastoid subtype is reported. The disease was clinically aggressive and refractory to chemotherapy, and the patient survived only 2 months. Cytogenetically, a t(11;19;14)(q13;q13;q32) was found. Fluorescent in situ hybridization (FISH) and molecular analyses demonstrated involvement of the BCL1/CCND1 locus in a three-way translocation. In addition, subclonal abnormalities of the region 8q24 manifested either as a t(8;22)(q24;q11)/CMYC rearrangement or trisomy 8 were identified. The pathogenetic impact of this very uncommon association of BCL1/CCND1 and CMYC rearrangements in MCL is discussed and the literature is reviewed.     

Clinical features of hepatitis B virus-related hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a major cause of cancer death,and chronic hepatitis B is a serious worldwide problem.The epidemiology of HCC is distinctive.Hepatitis B virus (HBV) plays a major role in hepatocarcinogenesis.Prevention of HBV-related HCC is a key issue in current hepatology.This paper describes the prevention and clinical features of HBVrelated HCC,along with a short review of the disease.     

Expression of B7-H4 and hepatitis B virus X in hepatitis B virus-related hepatocellular carcinoma

AIM: To investigate the expression and clinical significance of B7-H4 and hepatitis B virus X(HBx) protein in hepatitis B virus-related hepatocellular carcinoma(HBV-HCC).METHODS: The expression of B7-H4 in the human HCC cell lines Hep G2 and Hep G2.2.15 were detected by western blot, flow cytometry, and immunofluorescence. The expression of B7-H4 and HBx in 83 HBV-HCC was detected by immunohistochemistry, and the relationship with clinicopathological features was analyzed. Paraffin sections were generated from 83 HBV-HCC patients(22 females and 61 males) enrolled in this study. The age of these patients ranged from 35 to 77 years, with an average of 52.5 ± 11.3 years. All experiments were approved by the Ethics Committees of the Second Affiliated Hospital, Zhejiang University School of Medicine.RESULTS: B7-H4 was significantly upregulated in Hep G2.2.15 cells compared to Hep G2 cells. Specifically, the protein expression of B7-H4 in the lysates of Hep G2 cells was more than that in Hep G2.2.15 cells. In addition, HBx was expressed only in Hep G2.2.15 cells. Similar data were obtained by flow cytometry. The positive rates of B7-H4 and HBx in the tissues of 83 HBV-HCC patients were 68.67%(57/83) and 59.04%(49/83), respectively. The expression of HBx was correlated with tumor node metastases(TNM) stage, and the expression of B7-H4 was positively correlated with HBx(rs = 0.388; p 0.01). The expression level of B7-H4 in HBx-positive HBV-HCC tissues was substantially higher than that in HBx-negative HBV-HCC tissues. The expression level of B7H4 was negatively related to tumor TNM stage.CONCLUSION: Higher expression of HBx and B7-H4 was correlated with tumor progression of HBV-HCC, suggesting that B7-H4 may be involved in facilitating HBV-related hepatocarcinogenesis.     

恶性淋巴瘤患者乙型肝炎病毒感染状况分析

目的了解本院初诊非霍奇金淋巴瘤(NHL)患者中乙型肝炎病毒(HBV)的感染状况。方法对163例NHL患者临床资料进行回顾性分析,分析HBV表面抗原(HBsAg)阳性患者的比率。结果本组NHL患者HBsAg阳性率为20.86%,明显高于该地区普通人群(13.28%);20~50岁组患者HBsAg阳性率高于低年龄组。结论NHL患者HBsAg阳性率高于普通人群,HBV感染可能对恶性淋巴瘤的发病有一定的作用。     

Molecular mechanism of hepatitis B virus X protein function in hepatocarcinogenesis

Many factors are considered to contribute to hepatitis B virus(HBV)-associated hepatocellular carcinoma(HCC),including products of HBV,HBV integration and mutation,and host susceptibility. HBV X protein(HBx) can interfere with several signaling pathways associated with cell proliferation and invasion,and HBx C-terminal truncation has been suggested to impact the development of HCC. This review focuses on the pathological functions of HBx in HBV-induced hepatocarcinogenesis. As a transactivator,HBx can affect regulatory non-coding RNAs(nc RNAs),including micro RNAs and long nc RNAs. HBx is also involved in epigenetic modification and DNA repair. HBx interacts with various signal-transduction pathways,such as the p53,Wnt,and nuclear factor-κB pathways. We conclude that HBx hastens the development of hepatoma.     

Evolving treatment strategies in mantle cell lymphoma

Mantle cell lymphoma is an incurable, moderately aggressive B cell lymphoma. While a small proportion of patients with indolent disease can be managed expectantly, most patients require treatment. The therapeutic approach is driven by physician recommendation, patient choice, age, fitness and comorbidities. Young, fit patients often receive combination chemoimmunotherapy, including high dose cytarabine, with autologous stem cell transplant. Recent data has indicated benefit from maintenance rituximab following autologous stem cell transplant. Ongoing trials are investigating combinations of chemotherapy and targeted agents as well as the role of minimal residual disease guided therapy. Older, less fit patients often receive bendamustine and rituximab or anthracycline based regimens. Maintenance rituximab is typically administered in older MCL patients after anthracycline based chemotherapy although its use after bendamustine based therapy is not supported by current data. Current trials focus on refining this regimen with the addition of targeted agents. In the relapsed and refractory setting, novel agents have demonstrated activity although durability of responses remains unsatisfactory.     

BCL6 rearrangement in a patient with mantle cell lymphoma

 We describe a patient with mantle cell lymphoma (MCL) associated with BCL6 gene rearrangement. MCL is a distinct subtype of non-Hodgkin's lymphoma characterized by CD5+, CD10–, CD20+, t(11;14)(q13;q32) and PRAD1/cyclin D1 overexpression. Although rearrangement of the BCL6 gene is the most frequent genetic change among diffuse lymphomas and some follicular lymphomas this is the first report of a patient with MCL associated with BCL6 rearrangement. Received: 6 January 1997 / Accepted: 17 February 1997     

乙型肝炎和肝癌患者乙型肝炎病毒前C区1896位点突变的研究

为探索乙型肝炎病毒前Ｃ区突变是否与肝损程度及肝癌发生有关，对１３９例ＨＢｓＡｇ、ＨＢＶＤＮＡ和抗－ＨＢｅ阳性，ＨＢｅＡｇ阴性的慢性ＨＢＶ感染者和肝癌患者的血清标本，采用３＇碱基特异性聚合酶反应进行了第１８９６位核苷酸突变的检测分析。     

Dermatomyositis associated with hepatitis B virus-related hepatocellular carcinoma

Dermatomyositis (DM) is an idiopathic inflammatory myopathy (IIM) with typical cutaneous manifestations. It has been proposed that DM may be caused by autoimmune responses to viral infections, and previous studies have also shown that an association between DM and malignancy. However, chronic hepatitis B virus (HBV) infection associated with DM and hepatocellular carcinoma (HCC) is rarely encountered. The authors report a case of DM and HCC in a patient with a HBV infection. A 58-year-old man presented erythematous skin rashes on a sun-exposed area of 2 year’s duration, and recent proximal muscle weakness. His medical history revealed that he had a chronic HBV infection. A diagnosis of DM relies on proximal muscle weakness, elevated muscle enzymes, myopathic changes (demonstrated by electromyography), muscle biopsy evidence of myositis, and its characteristic cutaneous findings. A Liver mass in the left lobe visualized by abdominal computed tomography was confirmed histologically as HCC. This case suggests that DM associated with HCC might be caused by a HBV infection.     

The STAT4 and not the IFNL3 variant is associated with hepatitis B virus clearance in a population from the Khyber Pakhtunkhwa region of Pakistan

Background and study aimsHost genetic modifiers of the risk and persistence of hepatitis B virus (HBV) infection in the Pakistani population have not been clearly elucidated. Recently, two genome-wide association studies described that STAT4 and IFNL3 variants are associated with different aspects of the course of HBV infection. However, the roles of these variants in the persistence of HBV infection have not been investigated in the HBV-infected population of Pakistan. Therefore, we examined the roles of the STAT4 and IFNL3 variants in a chronic HBV-infected population from the Khyber Pakhtunkhwa (KPK) region of Pakistan.Patients and methodsSTAT4 rs7574865 and IFNL3 rs12979860 genotyping were performed in 297 subjects (240 infected with HBV and 57 controls). Statistical analyses were performed using the chi-squared test, Student’s t-test, Hardy–Weinberg equilibrium tests and logistic regression models.ResultsAmong the 297 subjects, compared with the IFNL3 rs12979860 genotype [odds ratio (OR) = 0.7, 95% confidence interval (CI) = 0.39–1.29, p = 0.2), the STAT4 rs7574865 genotype was independently associated with the risk of developing chronic HBV infection [OR = 1.9, 95% CI = 1.09–3.50, p = 0.02].ConclusionThe STAT4 rs7574865 and not the IFNL3 rs12979860 variant is associated with persistence of HBV infection in a Pakistani population from the KPK region.     

Surgical treatment of HCC in a patient with lamivudine-resistant hepatitis B cirrhosis with adefovir dipivoxil

We describe a 77-year-old woman with chronic hepatitis B who became resistant to lamivudine. She was started on adefovir (10 mg daily) while still continuing lamivudine therapy. Four mo later her liver function improved and serum Hepatitis B virus (HBV)-DNA level became undetectable. Three years after the start of additional adefovir treatment, hepatocellular carcinoma (HCC) was detected and the patient underwent a successful hepatectomy. Our findings suggest that the addition of adefovir to ongoing lamivudine therapy cannot completely suppress hepatocarcinogenesis, but is useful for improving liver function in patients with lamivudine-resistant HBV-related cirrhosis, allowing HCC surgery.     

Key role of hepatitis B virus mutation in chronic hepatitis B development to hepatocellular carcinoma

Chronic hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). The HBV mutations, which include point mutation, deletion, insertion and truncation mutation of HBV gene in 4 open reading frames (S, C, P, X), are closely associated with HCC pathogenesis. Some mutations accumulated during chronic HBV infection could be regarded as a biomarker to predict the occurrence of HCC. The detection of the mutations in clinical practice could be helpful for defining better preventive and therapeutic strategies and, moreover, predicting the progression of liver disease.     

Latent hepatitis B is a risk factor for hepatocellular carcinoma in patients with chronic hepatitis C

AIM:To study the potential association between hepatocellular carcinoma(HCC)in patients with chronic hepatitis C(CHC),cirrhosis and latent hepatitis B(LHB)infection,defined as the absence of detectable serum hepatitis B surface antigen(HBsAg)and the presence of hepatitis B core antibody(HBcAb).METHODS:This retrospective analysis is comprised of 185 cirrhotic patients with HCC who were hepatitis C virus antibody(HCV Ab)(+)and HBsAg(-)at Wayne State University between 1999 and 2008.From these,108 patients had HCV polymerase chain reaction confirmation of viremia while the remaining(77)were considered to have CHC on the basis of a positive HCV Ab and the absence of any other cause of liver disease.Controls were drawn from our institutional database from the same time period and consisted of 356 HBsAg(-)age,race and gender matched patients with HCV RNA-confirmed CHC and without evidence of HCC.A subgroup of controls included 118matched patients with liver cirrhosis.χ2test and t test were used for data analysis.RESULTS:Seventy-seven percent of patients in all3 groups were African Americans.Patients with HCC had a significantly higher body mass index(P=0.03),a higher rate of co-infection with human immunodeficiency virus(HIV)(P=0.05)and a higher prevalence of alcohol abuse(P=0.03)than the controls.More patients with HCC had LHB than controls(78%vs39%,P=0.01).Sixty three percent of patients with HCC were both hepatitis B surface antigen(HBsAb)(-)and HBcAb(+)compared to 23%of controls(P<0.01).When compared to cirrhotic controls,the frequency of HBcAb(+)remained higher in patients with HCC(78%vs 45%,P=0.02).Patients with HCC were more likely to be both HBsAb(-)and HBcAb(+)than the cirrhotic controls(63%vs 28%,P=0.01).Although not statistically significant,100%of CHC and HIV coinfected patients with HCC(n=11)were HBcAb(+)when compared to controls(44%;n=9).CONCLUSION:These data suggest that LHB occurs at a significantly increased frequency in patients with CHC and HCC than in patients with CHC without HCC.     

Spontaneous splenic rupture in two patients with a blastoid variant of mantle cell lymphoma

 Spontaneous rupture of the spleen is a rare complication of hematological malignancies, occurring most commonly in patients with acute leukemia, but it has been documented in chronic leukemias and also in lymphomas. We report two patients with histologically and immunohistochemically confirmed mantle cell lymphoma (MCL) who experienced a spontaneous splenic rupture. An 80-year-old woman and a 51-year-old man had a blastoid variant of MCL and responded poorly to conventional treatment. Both patients recovered after splenectomy. The woman died of progressive lymphoma 2 months later. An allogeneic bone marrow transplantation was performed in the man with a good initial result, but an aggressive relapse was seen only 6 months later and he died of progressive lymphoma. In view of our data, we suggest special caution when MCL is complicated by rapid progression and severe splenomegaly. Although it is a rare phenomenon, the risk of splenic rupture should be kept in mind. Received: 2 September 1996 / Accepted: 16 October 1996     

Challenge of hepatitis C in Egypt and hepatitis B in Mauritania

Egypt has one of the highest prevalence rates of hepatitis C virus(HCV) in the world,mostly with genotype 4 that is highly associated with severe fibrosis. As a consequence,hepatocellular carcinoma has become the leading cause of cancer in this country. Mauritania is a highly endemic area for hepatitis B virus(HBV). HBV and HCV could both be iatrogenically transmitted through infected blood products,infected needles,and medical equipment improperly sterilized. Adequate and efficient healthcare and public health measures with good surveillance programs,access for screening,prevention strategies,and successful treatment are needed to halt the spread of these diseases. Herein,we have reviewed the epidemiology,modes of transmission,predisposing factors,and novel treatment modalities of these viruses. We have proposed practices and interventions to decrease the risk of transmission of HCV and HBV in the affected countries,including strict adherence to standard precautions in the healthcare setting,rigorous education and training of patients and healthcare providers,universal screening of blood donors,use of safetyengineered devices,proper sterilization of medical equipment,hepatitis B vaccination,as well as effective direct-acting antiviral agents for the treatment of HCV.     

Prevention of hepatocellular carcinoma in chronic viral hepatitis B and C infection

Hepatocellular carcinoma(HCC)is a leading cause of cancer-related mortality worldwide,with the majority of cases associated with persistent infection from hepatitis B virus(HBV)or hepatitis C virus(HCV).Natural history studies have identified risk factors associated with HCC development among chronic HBV and HCV infection.High-risk infected individuals can now be identified by the usage of risk predictive scores.Vaccination plays a central role in the prevention of HBV-related HCC.Treatment of chronic HBV infection,especially by nucleoside analogue therapy,could also reduce the risk of HBV-related HCC.Concerning HCV infection,besides the advocation of universal precautions to reduce the rate of infection,pegylated interferon and ribavirin could also reduce the risk of HCV-related HCC among those achieving a sustained virologic response.Recently there has been mounting evidence on the role of chemopreventive agents in reducing HBV-and HCV-related HCC.The continued advances in the understanding of the molecular pathogenesis of HCC would hold promise in preventing this highly lethal cancer.