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Xie WY, Sun C, He H, Deng C, Sheng Y. Estimates of the prevalence of occult HBV infection in Asia: a systematic review and meta-analysis. Infect Dis (Lond) 2022; 54:881-896. [PMID: 36047593 DOI: 10.1080/23744235.2022.2115126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
PURPOSE Occult Hepatitis B virus infection (OBI) is of great significance to the transmission of Hepatitis B virus (HBV) and the evolution of the patient's clinical outcome. We conducted a systematic review and meta-analysis to estimate the prevalence of OBI in Asia. METHODS Literature search was conducted in PubMed, Cochrane Library database, Web of Science and Embase with the keywords of 'Hepatitis B virus', 'occult infection', 'prevalence'. 70 studies were included in the meta-analysis. Meta-analysis was performed using random-effects models to calculate the pooled prevalence of OBI and 95% confidence interval (CI). The data were analyzed in R 4.1.2. RESULTS The overall prevalence of OBI was 4% (95%CI: 0.03-0.06) in Asia. Subgroup analysis based on geographic region showed a prevalence of 3% (95%CI 0.02-0.06) in East Asia, 9% (95%CI 0.05-0.15) in West Asia, 3% (95%CI 0.01-0.11) in Southern Asia and 9% (95%CI 0.05-0.15) in Southeast Asia. Subgroup analysis demonstrated a prevalence of 1% (95%CI 0.00-0.02) in general population, 5% (95%CI: 0.03-0.08) in high-risk population, 9% (95%CI: 0.03-0.22) in the human immunodeficiency virus (HIV)-infected patient, 18% (95%CI: 0.09-0.32) in the hepatopathy patients. CONCLUSION Based on the meta-analysis of the prevalence of OBI in different populations, we concluded that the prevalence of OBI in the high-risk population, hepatopathy patients, and HIV-infected patients was higher than that in the general population. A systematic review showed that OBI was associated with disease progression and prognosis. Therefore, these populations should be routinely screened for OBI and promptly intervened to avoid promoting disease progression.
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Affiliation(s)
- Wen Yangyang Xie
- Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Changfeng Sun
- Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, China.,Infection & Immunity Laboratory, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Hongyan He
- Experimental Teaching Center, School of Public Health of Southwest Medical University, Luzhou, China
| | - Cunliang Deng
- Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Yunjian Sheng
- Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, China.,Infection & Immunity Laboratory, The Affiliated Hospital of Southwest Medical University, Luzhou, China
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Chang TS, Hsu NT, Chen SC, Hsu IL, Lee MH, Lu SN. Non-B, Non-C Hepatocellular Carcinoma in an HBV- and HCV-Endemic Area: A Community-Based Prospective Longitudinal Study. Viruses 2022; 14:v14050984. [PMID: 35632726 PMCID: PMC9145519 DOI: 10.3390/v14050984] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Revised: 04/30/2022] [Accepted: 05/04/2022] [Indexed: 02/04/2023] Open
Abstract
A large community cohort of adults who participated in a health screening program from 2003 to 2013 were prospectively analyzed for the risk factors of non-B, non-C (NBNC) hepatocellular carcinoma (HCC). The serostatus of hepatitis B and C of 52,642 participants was linked to the mortality and cancer registration data of the Health and Welfare Data Science Center, Ministry of Health and Welfare, Taiwan. During a median follow-up of 6 years, 35 of the 43,545 participants who were negative for both HBsAg and anti-HCV antibody developed HCC. Multivariate Cox regression analysis revealed that old age (hazard ratio, 95% CI: 1.058, 1.019−1.098, p = 0.003); male sex (2.446, 1.200−4.985, p = 0.014); high aspartate aminotransferase levels (6.816, 2.945−15.779, p < 0.001); fibrosis index based on four factor score (1.262, 1.154−1.381, p < 0.001); blood sugar (1.009, 1.002−1.015, p = 0.006); and alpha-fetoprotein ≥15 ng/mL (143.938, 43.094−480.760, p < 0.001) were independent risk factors for HCC. By contrast, triglyceride >150 mg/dL was associated with a decreased risk of HCC (0.216, 0.074−0.625, p = 0.005). This prospective community-based study provided insights into the potential HCC risk factors which may shed some light in HCC prevention and screening.
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Affiliation(s)
- Te-Sheng Chang
- Department of Gastroenterology and Hepatology, Division of Internal Medicine, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan;
- College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan
| | - Nien-Tzu Hsu
- Biostatistics Center of Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833253, Taiwan;
| | - Shu-Chuan Chen
- Public Health Bureau, Tainan City Government, Tainan 701017, Taiwan; (S.-C.C.); (I.-L.H.)
| | - I-Lin Hsu
- Public Health Bureau, Tainan City Government, Tainan 701017, Taiwan; (S.-C.C.); (I.-L.H.)
| | - Mei-Hsuan Lee
- School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
- Correspondence: (M.-H.L.); (S.-N.L.); Tel.: +886-2-28267248 (M.-H.L.); +886-7-7317123 (ext.6156) (S.-N.L.)
| | - Sheng-Nan Lu
- College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan
- Department of Gastroenterology and Hepatology, Division of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833401, Taiwan
- Correspondence: (M.-H.L.); (S.-N.L.); Tel.: +886-2-28267248 (M.-H.L.); +886-7-7317123 (ext.6156) (S.-N.L.)
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Koga H, Kai K, Aishima S, Kawaguchi A, Yamaji K, Ide T, Ueda J, Noshiro H. Occult hepatitis B virus infection and surgical outcomes in non-B, non-C patients with curative resection for hepatocellular carcinoma. World J Hepatol 2017; 9:1286-1295. [PMID: 29290910 PMCID: PMC5740092 DOI: 10.4254/wjh.v9.i35.1286] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2017] [Revised: 09/14/2017] [Accepted: 10/31/2017] [Indexed: 02/06/2023] Open
Abstract
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 TaqMan real-time 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 disease-free survival (DFS), overall survival (OS) and disease-specific 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 tumor-related 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.
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Affiliation(s)
- Hiroki Koga
- Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan
| | - Keita Kai
- Department of Pathology, Saga University Hospital, Saga 849-8501, Japan
| | - Shinichi Aishima
- Department of Pathology, Saga University Hospital, Saga 849-8501, Japan
- Department of Pathology and Microbiology, Saga University Faculty of Medicine, Saga 849-8501, Japan
| | - Atsushi Kawaguchi
- Center for Comprehensive Community Medicine, Saga University Faculty of Medicine, Saga 849-8501, Japan
| | - Koutaro Yamaji
- Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan
- Department of Pathology and Microbiology, Saga University Faculty of Medicine, Saga 849-8501, Japan
| | - Takao Ide
- Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan
| | - Junji Ueda
- Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan
| | - Hirokazu Noshiro
- Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan
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Shao L, Zhang A, Rong Z, Wang C, Jia X, Zhang K, Xiao R, Wang S. Fast and non-invasive serum detection technology based on surface-enhanced Raman spectroscopy and multivariate statistical analysis for liver disease. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2017; 14:451-459. [PMID: 29197594 DOI: 10.1016/j.nano.2017.11.022] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/08/2017] [Revised: 10/21/2017] [Accepted: 11/23/2017] [Indexed: 02/04/2023]
Abstract
This study explored a rapid and nondestructive liver disease detection technique based on surface-enhanced Raman spectroscopy (SERS) to realize the early diagnosis, prevention, and treatment of liver disease. SERS signals of serum were obtained from 304 normal individuals, 333 patients with hepatopathy, and 99 patients with esophageal cancer. The Raman spectra of different diseases were compared and diagnostic models of liver disease were established using orthogonal partial least squares discriminant analysis (OPLS-DA). The classification efficiencies of the different models were comprehensively evaluated through the receiver operating characteristic (ROC) curve and ten-fold cross validation. Area under the ROC curve is of greater than 0.97, indicating excellent classification of the groups. The accuracy rate of the test set reached 95.33%, and the lowest was 81.76% using the ten-fold cross validation. Thus, OPLS-DA combined with serum SERS is a rapid and non-invasive technique for the diagnosis of liver disease.
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Affiliation(s)
- Liting Shao
- Beijing Institute of Radiation Medicine, Beijing, PR China
| | - Aiying Zhang
- Beijing Institute of Hepatology, Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Zhen Rong
- Beijing Institute of Radiation Medicine, Beijing, PR China
| | - Chongwen Wang
- Beijing Institute of Radiation Medicine, Beijing, PR China
| | - Xiaofei Jia
- Beijing Institute of Radiation Medicine, Beijing, PR China
| | - Kehan Zhang
- Beijing Institute of Radiation Medicine, Beijing, PR China
| | - Rui Xiao
- Beijing Institute of Radiation Medicine, Beijing, PR China.
| | - Shengqi Wang
- Beijing Institute of Radiation Medicine, Beijing, PR China.
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Iida H, Aihara T, Ikuta S, Yamanaka N. Clinicopathological characteristics of hepatitis B surface antigen-negative and hepatitis C antibody-negative hepatocellular carcinoma. Oncol Lett 2015; 10:2233-2238. [PMID: 26622825 DOI: 10.3892/ol.2015.3562] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2014] [Accepted: 07/07/2015] [Indexed: 12/17/2022] Open
Abstract
The present study investigated the clinicopathological characteristics of resected hepatitis B virus surface antigen (HBs-Ag)-negative, hepatitis C virus antibody (HCV-Ab)-negative hepatocellular carcinoma (NBNC HCC). The clinicopathological characteristics of 164 patients with NBNC HCC, 144 patients with HBs-Ag-positive HCC (HBV group) and 550 patients with HCV-Ab-positive HCC (HCV group) were compared. In the NBCN HCC group, 61 patients succumbed after 2 years. Subsequently, NBCN HCC patients were compared according to survival time (<2 years, 39 patients vs. ≥2 years, 64 patients) to identify prognostic factors. Finally, the clinicopathological characteristics of NBNC HCC were compared according to history of alcohol abuse/pathological results: Non-alcoholic steatohepatitis HCC (NASH group, 40 patients), alcohol abuse HCC (AL group, 80 patients) and other HCCs (non-NASH/non-AL group, 44 patients). Age, diabetes prevalence and body mass index were significantly higher for NBNC HCC compared with virus-related HCC. Among stage II cases, the prognosis was significantly better for the NBNC compared with that for the HCV group. A high α-fetoprotein level, poorly differentiated HCC and advanced liver fibrosis were independent risk factors for the prognosis of NBNC HCC. The proportion of female patients was significantly higher among NASH compared with AL HCC patients. The cumulative survival rates following surgery were similar in the NASH, AL and non-NASH/non-AL groups. NBNC HCC is considered to be a lifestyle disease, with better prognosis for stage II patients. The prognostic factors for NBNC HCC patients undergoing hepatectomy were similar to those with virus-related HCC and did not differ according to alcohol abuse history or pathological results.
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Affiliation(s)
- Hiroya Iida
- Department of Surgery, Meiwa Hospital, Nishinomiya, Hyogo 663-8186, Japan
| | - Tsukasa Aihara
- Department of Surgery, Meiwa Hospital, Nishinomiya, Hyogo 663-8186, Japan
| | - Shinichi Ikuta
- Department of Surgery, Meiwa Hospital, Nishinomiya, Hyogo 663-8186, Japan
| | - Naoki Yamanaka
- Department of Surgery, Meiwa Hospital, Nishinomiya, Hyogo 663-8186, Japan
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Xiao L, Zhang RL, Zhang H, Tulahong A, Zhang YF, Wen H, Bao YX. Comparison of the clinical characteristics and survival between Uyghur patients with hepatitis virus-related and non-B, non-C hepatocellular carcinoma in Xinjiang, China. Chin J Cancer Res 2015; 27:279-87. [PMID: 26157324 DOI: 10.3978/j.issn.1000-9604.2015.01.04] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2014] [Accepted: 01/14/2015] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVE To compare the clinical characteristics and prognosis between hepatitis virus-related hepatocellular carcinoma (viral HCC) and non-B, non-C HCC (NBC-HCC) among Uyghur patients in Xinjiang province, China. METHODS Between 01/01/2000 and 31/12/2012, 319 Uyghur HCC patients were treated at the Cancer Centre of The First Affiliated Hospital of Xinjiang Medical University. The data for the patients were obtained from a retrospective review of the patients' medical records. A total of 18 patients were excluded from the study because of incomplete information. The patients were classified into two groups: viral HCC and NBC-HCC. The clinical characteristics and prognostic factors were statistically analysed. RESULTS For all 301 patients, gender (P=0.000), area of residence (P=0.002), diabetes mellitus (P=0.009), BMI (P=0.000), cirrhosis (P=0.000), tumour stage (P=0.004), Child-Pugh class (P=0.000), the TBIL level (P=0.000), and the alpha-fetoprotein (AFP) level (P=0.000) were significantly different between the NBC-HCC and viral HCC groups. The NBC-HCC patients tended to be diagnosed at advanced stages; however, the NBC-HCC patients exhibited lower Child-Pugh scores than the viral HCC patients. In all patients examined, the 0.5-, 1-, 3- and 5-year overall survival (OS) rates were 35.6%, 20.3%, 12.6% and 4.5%, respectively. No significant difference in OS was observed between the two groups (P=0.124). Cox multivariate analysis revealed that age (RR =1.539, P=0.001), TNM stage (RR =12.708, P=0.000), portal vein tumour thrombus (PVTT) (RR =2.003, P=0.000), Child-Pugh class (RR =1.715, P=0.000), and TACE + radiotherapy/RFA (RR =0.567, P=0.000) were significant independent prognostic factors for HCC patients. CONCLUSIONS The clinical characteristics differ between Uyghur patients with NBC-HCC and viral HCC. HCC in the Xinjiang region displays specific regional characteristics. Age, TNM stage, PVTT, Child-Pugh class and TACE + radiotherapy/RFA are significant risk factors that influence patient survival.
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Affiliation(s)
- Lei Xiao
- 1 Cancer Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China ; 2 Key Laboratory of Infection and Cancer, Urumqi 830054, China
| | - Rui-Li Zhang
- 1 Cancer Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China ; 2 Key Laboratory of Infection and Cancer, Urumqi 830054, China
| | - Hua Zhang
- 1 Cancer Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China ; 2 Key Laboratory of Infection and Cancer, Urumqi 830054, China
| | - Aisiker Tulahong
- 1 Cancer Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China ; 2 Key Laboratory of Infection and Cancer, Urumqi 830054, China
| | - Yue-Fen Zhang
- 1 Cancer Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China ; 2 Key Laboratory of Infection and Cancer, Urumqi 830054, China
| | - Hao Wen
- 1 Cancer Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China ; 2 Key Laboratory of Infection and Cancer, Urumqi 830054, China
| | - Yong-Xing Bao
- 1 Cancer Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China ; 2 Key Laboratory of Infection and Cancer, Urumqi 830054, China
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Sun L, Peng Q, Qu L, Gong L, Si J. Anticancer agent icaritin induces apoptosis through caspase-dependent pathways in human hepatocellular carcinoma cells. Mol Med Rep 2014; 11:3094-100. [PMID: 25434584 DOI: 10.3892/mmr.2014.3007] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2014] [Accepted: 10/31/2014] [Indexed: 11/06/2022] Open
Abstract
Icaritin is an active ingredient derived from the plant Herba epimedium, which exhibits various pharmacological and biological activities. However, the function, and the underlying mechanisms of icaritin on the growth of SMMC‑7721 human hepatoma cells have yet to be elucidated. The present study aimed to investigate the function and underlying mechanisms of icaritin in the growth of SMMC‑7721 cells. The cells were treated with varying concentrations of icaritin for 12, 24 and 48 h, respectively, prior to cytotoxic analysis. Apoptosis of SMMC‑7721 cells following treatment with icaritin was measured using flow cytometry. The gene expression of mitochondria‑ and Fas‑mediated caspase‑dependent pathways was detected by reverse transcription‑quantitative polymerase chain reaction and western blotting. Statistical analysis was performed by Student's t‑test and one‑way analysis or variance. The present study demonstrated that treatment with icaritin significantly inhibited growth, and induced apoptosis of SMMC‑7721 cells, in a time‑ and dose‑dependent manner. In addition, icaritin triggered the mitochondrial/caspase apoptotic pathway, by decreasing the Bcl‑2/Bax protein ratio and increasing activation of caspase‑3. Icaritin also activated the Fas‑mediated apoptosis pathway, as was evident by the increased expression levels of Fas and activation of caspase‑8. These data suggest that icaritin may be a potent growth inhibitor and induce apoptosis of SMMC‑7721 cells through the mitochondria‑ and Fas‑mediated caspase‑dependent pathways. The present study may provide experimental evidence for preclinical and clinical evaluations of icaritin for HCC therapy.
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Affiliation(s)
- Li Sun
- Department of Laboratory Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, P.R. China
| | - Qisong Peng
- Department of Laboratory Medicine, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, Jiangsu 211100, P.R. China
| | - Lili Qu
- Department of Laboratory Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, P.R. China
| | - Lailing Gong
- Department of Laboratory Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, P.R. China
| | - Jin Si
- Department of Laboratory Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, P.R. China
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Wu ZF, Xu Z, Li WS, Zhang HB, Yang N, Yao XQ, Liu FK, Yang GS. Impact of occult hepatitis B virus infection on outcome after resection for non-B non-C hepatocellular carcinoma. J Surg Res 2014; 193:153-60. [PMID: 25128925 DOI: 10.1016/j.jss.2014.07.021] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2014] [Revised: 06/01/2014] [Accepted: 07/10/2014] [Indexed: 01/02/2023]
Abstract
BACKGROUND To investigate the clinicopathologic characteristics of patients with both hepatitis B virus-surface antigen and hepatitis C virus antibody negative hepatocellular carcinoma (non-B non-C HCC [NBNC-HCC]) and examine the impact of occult hepatitis B virus infection (OBI) on patients' survival. METHODS All patients with OBI were identified from a database of patients with NBNC-HCC who underwent surgical resection between January 1, 2006, and December 31, 2008. Their clinicopathologic and survival characteristics were compared with NBNC-HCC patients without OBI. RESULTS Out of the 86 NBNC-HCC patients, 59 patients (68.6%) with OBI. A higher prevalence of hepatitis B core antigen positive rate, low platelet count, portal hypertension, and liver cirrhosis were observed in NBNC-HCC patients with OBI. The 1- and 3-y recurrence free survival rates were 66% and 25% in OBI group and 89% and 70% in the no OBI group, respectively (P < 0.001). The 1-, 3-, and 5-y overall survival rates were 86%, 55%, and 51% in OBI group and 93%, 85%, and 66% in no OBI group, respectively (P = 0.112). Multivariate analysis revealed that OBI (hazard ratio [HR] = 2.122; 95% confidence interval [CI], 1.086-4.149; P = 0.028), liver cirrhosis (HR = 2.411; 95% CI, 1.337-4.345; P = 0.003), and vascular invasion (HR = 5.858; 95% CI, 2.799-12.261; P < 0.001) were independent poor prognostic factors for recurrence free survival of patients with NBNC-HCC. CONCLUSIONS NBNC-HCC patients with OBI had a poorer prognosis. OBI can be a useful predictor for recurrence in patients with NBNC-HCC after surgery.
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Affiliation(s)
- Zhen-Feng Wu
- Department of Surgical Oncology, Jiangsu Province Hospital of Traditional Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Zhe Xu
- Department of Surgical Oncology, Jiangsu Province Hospital of Traditional Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Wei-Su Li
- Department of Surgical Oncology, Jiangsu Province Hospital of Traditional Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
| | - Hai-Bin Zhang
- Fifth Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
| | - Ning Yang
- Fifth Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Xue-Quan Yao
- Department of Surgical Oncology, Jiangsu Province Hospital of Traditional Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Fu-Kun Liu
- Department of Surgical Oncology, Jiangsu Province Hospital of Traditional Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Guang-Shun Yang
- Fifth Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
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9
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Lee JJ, Kwon OS. [Occult hepatitis B virus infection and hepatocellular carcinoma]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2014; 62:160-4. [PMID: 24077626 DOI: 10.4166/kjg.2013.62.3.160] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Many studies have suggested that occult HBV infection has a substantial clinical relevance to hepatocellular carcinoma (HCC). Occult HBV infection is an important risk factor for the development of cirrhosis and HCC in patients without HBsAg. As a matter of fact, occult HBV infection is one of the most common causes of crytogenic HCC in endemic areas of HBV. However, there still are controversial issues about the association between occult HBV infection and HCC according to the underlying liver disease. In alcoholic cirrhosis, occult HBV infection may exert synergistic effect on the development of HCC. However, there is insufficient evidence to relate occult HBV infection to hepatocarcinogenesis in non-alcoholic fatty liver disease. In cryptogenic HCC, occult HBV infection may play a direct role in the development of HCC. In order to elucidate the assocciation between occult HBV infection and HCC, underlying liver disease must be specified and larger number of cases must be included in future studies.
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Affiliation(s)
- Jong Joon Lee
- Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University School of Medicine, Incheon, Korea
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10
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Abou El Azm AR, Yousef M, Mansour N, Awad A, El Dardiry S, Abdel Aziz I. New Insights on Non-B non-C Hepatocellular Carcinoma in Mid Delta Region, Egypt. J Gastrointest Cancer 2014; 45:276-83. [DOI: 10.1007/s12029-013-9573-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Sun L, Chen W, Qu L, Wu J, Si J. Icaritin reverses multidrug resistance of HepG2/ADR human hepatoma cells via downregulation of MDR1 and P‑glycoprotein expression. Mol Med Rep 2013; 8:1883-7. [PMID: 24145579 DOI: 10.3892/mmr.2013.1742] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2013] [Accepted: 10/11/2013] [Indexed: 11/06/2022] Open
Abstract
Multidrug resistance (MDR) of tumor cells is a serious obstacle encountered in cancer treatment. In the current study a multiple drug‑resistant HepG2/adriamycin (HepG2/ADR) cell line was established and its MDR was characterized. Icaritin, an active ingredient isolated from the medical plant Herba Epimedium, was observed to reverse MDR in the present model. Icaritin significantly increased the intracellular accumulation of ADR and decreased the expression of the MDR1 gene in HepG2/ADR cells compared with drug‑sensitive HepG2 cells. In addition, the present results showed that icaritin may significantly downregulate the expression of P‑glycoprotein. These results indicate that icaritin is a novel and potent MDR reversal agent and may be a promising drug for tumor chemotherapy.
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Affiliation(s)
- Li Sun
- Department of Laboratory Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, P.R. China
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12
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Ueno M, Hayami S, Tani M, Kawai M, Hirono S, Yamaue H. Recent trends in hepatectomy for elderly patients with hepatocellular carcinoma. Surg Today 2013; 44:1651-9. [DOI: 10.1007/s00595-013-0739-6] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2013] [Accepted: 08/07/2013] [Indexed: 12/15/2022]
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13
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Nishikawa H, Osaki Y. Non-B, non-C hepatocellular carcinoma (Review). Int J Oncol 2013; 43:1333-42. [PMID: 23969900 DOI: 10.3892/ijo.2013.2061] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2013] [Accepted: 07/16/2013] [Indexed: 11/06/2022] Open
Abstract
Although most hepatocellular carcinoma (HCC) is related to viral infection, there is a substantial population of HCC patients (5-20%) who are negative for both markers of hepatitis B virus and hepatitis C virus infection [non-B, non-C (NBNC) hepatitis] in Japan and the incidence of NBNC-HCC has recently tended to increase. The most common cause of liver disease in developed countries is non‑alcoholic fatty liver disease (NAFLD), which includes non‑alcoholic steatohepatitis (NASH) and its related complications. Increased body mass index and diabetes mellitus are associated with developing NAFLD and NASH, which is a severe form of NAFLD. Furthermore, increasing clinical evidence supports the fact that NAFLD and NASH can progress to liver cirrhosis and even HCC. A detailed understanding of the epidemiology, etiology, molecular mechanism, clinical features and prognosis of NBNC-HCC could improve our screening and therapy of this disease. In this review, we primarily focus on clinical aspects of NBNC-HCC and refer to our current knowledge of this cancer.
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Affiliation(s)
- Hiroki Nishikawa
- Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Tennoji-ku, Osaka 543-0027, Japan
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Nishikawa H, Osaki Y. Clinical significance of occult hepatitis B infection in progression of liver disease and carcinogenesis. J Cancer 2013; 4:473-80. [PMID: 23901347 PMCID: PMC3726709 DOI: 10.7150/jca.6609] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2013] [Accepted: 07/05/2013] [Indexed: 01/04/2023] Open
Abstract
Occult hepatitis B infection (OBI) is defined as long-lasting persistence of hepatitis B virus (HBV) DNA in the liver of patients with hepatitis B surface antigen (HBsAg)-negative status, with or without serological markers of previous exposure (antibodies to HBsAg and/or to hepatitis B core antigen). Over the past two decades, significant progress has been made in understanding OBI and its clinical implications. OBI as a cause of chronic liver disease in patients with HBsAg-negative status is becoming an important disease entity. In conditions of immunocompetence, OBI is inoffensive in itself and detection of HBV DNA in the liver does not always indicate active hepatitis. However, when other factors that cause liver damage, such as hepatitis C virus infection, obesity and alcohol abuse are present, the minimal lesions produced by the immunological response to OBI might worsen the clinical course of the underlying liver disease. Several lines of evidence suggest that OBI is associated with progression of liver fibrosis and the development of hepatocellular carcinoma in patients with chronic liver disease. The major interest in OBI is primarily associated with the growing, widely discussed evidence of its clinical impact. The aim of this review is to highlight recent data for OBI, with a major focus on disease progression or carcinogenesis in patients with chronic liver disease.
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Affiliation(s)
- Hiroki Nishikawa
- Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Osaka, Japan
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El Azm ARA, Yousef M, Salah R, Mayah W, Tawfeek S, Ghorabah H, Mansour N. Serum anti-P53 antibodies and alpha-fetoprotein in patients with non-B non-C hepatocellular carcinoma. SPRINGERPLUS 2013; 2:69. [PMID: 23518665 PMCID: PMC3601255 DOI: 10.1186/2193-1801-2-69] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/24/2012] [Accepted: 02/04/2013] [Indexed: 01/21/2023]
Abstract
The rate of hepatocellular carcinoma (HCC) is increasing worldwide including Egypt. Non-B non-C HCC was reported in some countries. We aimed to investigate P53 antibodies and alpha-fetoprotein in patients with non-B non-C HCC in our region. In a case series study, included 281 patients with HCC and 20 patients with liver cirrhosis of matched age, sex and social factors were received for management at Tanta University Hospitals. Sera were tested for HCV and HBV markers by ELISA/PCR, alpha-fetoprotein (AFP) level and anti-p53 antibody were evaluated by ELISA. Antinuclear antibody, serum copper and iron were assessed in non-viral HCC. Liver scanning and biopsy were evaluated. Non-B non-C HCC patients were 13.87% of total. P53 antibody serum level in non-B non-C HCC patients showed insignificant difference (p>0.05) as compared to viral-associated HCC, while significant as compared to cirrhosis. They had significant decrease in serum AFP level (p<0.001) as compared to viral-associated HCC. Their tumors were mainly solitary, and have smaller-sizes. Sensitivity, specificity, PPV, NPV and accuracy test of anti P53 antibody positive patients were 91.52%, 84.63%, 90.34%, 80.2% and 74.8% respectively. It correlates positively with AFP, tumor size and staging, MELD score and Child-Pugh score. Non-B non-C HCC showed high serum prevalence of anti-p53 as viral-associated HCC suggesting an evidence of high onchogenecity. It appears of much benefit in diagnosis, follow up and differentiation from cirrhosis in presence of low levels of alpha-fetoprotein.
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Affiliation(s)
- Abdel Raouf Abou El Azm
- Faculty of Medicine, Egypt and president of the Egyptian Society of Liver and Environment, Tanta University, Tanta, Egypt
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Occult Hepatitis B (OBH) in Clinical Settings. HEPATITIS MONTHLY 2012. [DOI: 10.5812/hapatmon.6126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
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Alavian SM, Miri SM, Hollinger FB, Jazayeri SM. Occult Hepatitis B (OBH) in Clinical Settings. HEPATITIS MONTHLY 2012; 12:e6126. [PMID: 23087749 PMCID: PMC3475016 DOI: 10.5812/hepatmon.6126] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/20/2012] [Revised: 06/20/2012] [Accepted: 07/08/2012] [Indexed: 12/11/2022]
Abstract
CONTEXT Occult hepatitis B (OHB), or persistent HBV DNA in patients who are hepatitis B surface antigen (HBsAg) negative, is a recently recognized entity. In an attempt to summarize the issues, this review presents an overview of the current proposed hypothesis on the clinical relevance and also updates the knowledge on the classification of OHB in different clinical settings. EVIDENCE ACQUISITION OHB COULD BE FOUND IN DIFFERENT POPULATION AND CLINICAL BACKGROUNDS INCLUDING: viral co-infections (with either human immunodeficiency or hepatitis C viruses), HBV chronic carriers, dialysis patients, transplantation settings and certain clinical situations (named in here: special clinical settings) with no apparent distinguishable clinical parameters. RESULTS The exact magnitude, pathogenesis, and clinical relevance of OHB are unclear. Even the possible role exerted by this cryptic infection on liver disease outcome, and hepatocellular carcinoma development remains unknown. CONCLUSIONS Monitoring of Individuals with positive anti-HBc, mass immunization programs and improvement in diagnostic tools seem to be important to control the probability of transmission of HBV through cryptic HBV infection.
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Affiliation(s)
- Seyed Moayed Alavian
- Baqiyatallah Research Center for Gastroenterology and Liver Disease, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
| | - Seyed Mohammad Miri
- Baqiyatallah Research Center for Gastroenterology and Liver Disease, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
| | | | - Seyed Mohammad Jazayeri
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran
- Corresponding author: Seyed Mohammad Jazayeri, Department of Virology, School of Public Health, Tehran University of Medical Sciences, P.O. Box: 15155-6446, Tehran, IR Iran.Tel.: +98-2188992660, Fax: +98-2188992660, E-mail:
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Abstract
Chronic hepatitis B virus (HBV) infection is a complex clinical entity frequently associated with cirrhosis and hepatocellular carcinoma (HCC). The persistence of HBV genomes in the absence of detectable surface antigenemia is termed occult HBV infection. Mutations in the surface gene rendering HBsAg undetectable by commercial assays and inhibition of HBV by suppression of viral replication and viral proteins represent two fundamentally different mechanisms that lead to occult HBV infections. The molecular mechanisms underlying occult HBV infections, including recently identified mechanisms associated with the suppression of HBV replication and inhibition of HBV proteins, are reviewed in detail. The availability of highly sensitive molecular methods has led to increased detection of occult HBV infections in various clinical settings. The clinical relevance of occult HBV infection and the utility of appropriate diagnostic methods to detect occult HBV infection are discussed. The need for specific guidelines on the diagnosis and management of occult HBV infection is being increasingly recognized; the aspects of mechanistic studies that warrant further investigation are discussed in the final section.
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Abstract
Chronic hepatitis B virus (HBV) infection is a complex clinical entity frequently associated with cirrhosis and hepatocellular carcinoma (HCC). The persistence of HBV genomes in the absence of detectable surface antigenemia is termed occult HBV infection. Mutations in the surface gene rendering HBsAg undetectable by commercial assays and inhibition of HBV by suppression of viral replication and viral proteins represent two fundamentally different mechanisms that lead to occult HBV infections. The molecular mechanisms underlying occult HBV infections, including recently identified mechanisms associated with the suppression of HBV replication and inhibition of HBV proteins, are reviewed in detail. The availability of highly sensitive molecular methods has led to increased detection of occult HBV infections in various clinical settings. The clinical relevance of occult HBV infection and the utility of appropriate diagnostic methods to detect occult HBV infection are discussed. The need for specific guidelines on the diagnosis and management of occult HBV infection is being increasingly recognized; the aspects of mechanistic studies that warrant further investigation are discussed in the final section.
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Wang SH, Chen LM, Yang WK, Lee JD. Increased extrinsic apoptotic pathway activity in patients with hepatocellular carcinoma following transarterial embolization. World J Gastroenterol 2011; 17:4675-81. [PMID: 22180709 PMCID: PMC3233673 DOI: 10.3748/wjg.v17.i42.4675] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2011] [Revised: 06/10/2011] [Accepted: 06/17/2011] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the apoptosis pathway in residual viable hepatocellular carcinoma (HCC) tissues following transarterial embolization (TAE).
METHODS: Ten patients with HCC who received surgical resection after TAE were enrolled in the study group, and 24 patients with HCC who received surgical resection only served as the control group. In the study group, we measured the changes in tumor size and α fetoprotein (AFP) levels after TAE. All tissue samples were taken from the residual tumors. The expression of various apoptotic proteins was evaluated via immunoblotting procedures. The results were analyzed using a Student’s t test.
RESULTS: Tumor size and the AFP level decreased by 46.2% and 55.3% after TAE, respectively. There was no significant difference detected for the Bcl-2/Bax ratio or the cleaved caspase-9 expression levels in either group. However, extrinsic apoptopic pathway-related expression of Fas and cleaved caspase-8 expression were significantly higher in the study group than in the control group (P < 0.05). In addition, cleaved caspase-3 expression in the study group was higher (1.62-fold) than in control group (P < 0.05).
CONCLUSION: TAE is an effective palliative therapy that decreases tumor size and AFP levels via an increase in extrinsic apoptosis pathway in patients with unresectable HCC.
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Shirabe K, Toshima T, Taketomi A, Taguchi K, Yoshizumi T, Uchiyama H, Harimoto N, Kajiyama K, Egashira A, Maehara Y. Hepatic aflatoxin B1-DNA adducts and TP53 mutations in patients with hepatocellular carcinoma despite low exposure to aflatoxin B1 in southern Japan. Liver Int 2011; 31:1366-72. [PMID: 21745313 DOI: 10.1111/j.1478-3231.2011.02572.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND & AIMS Hepatitis B or C virus infection is considered to be the main cause of hepatocellular carcinoma (HCC) in Japan. Aflatoxin B1 (AFB1) is a carcinogen associated with HCC in regions with high exposure. Mutations in codon 249, exon 7 are a hallmark of AFB1 exposure. Therefore, to clarify the role of AFB1 in hepatocarcinogenesis, we examined AFB1-DNA in liver tissue and sequenced TP53 in Japanese patients with HCC. METHODS Hepatocyte AFB1-DNA adducts were determined immunohistochemically and direct sequencing of TP53 was done to determine mutations in 188 of 279 patients who underwent hepatic resection for HCC. We assessed hepatitis C virus antibodies (HCV Ab) and HBSAg expression; patients without either were defined as having non-B non-C hepatocellular carcinoma (NBNC HCC). RESULTS AFB1-DNA adducts were detected in hepatocyte nuclei in 18/279 patients (6%), including 13/83 patients (16%) with NBNC HCC and 5/51 patients (10%) expressing hepatitis B surface antigen. None of the patients with HCV Ab (n=136) were positive for AFB1-DNA. The incidence of the G-T transversion and mutations in exon 7 of TP53 in patients with AFB1-DNA adducts were significantly higher in patients with than in patients without AFB1-DNA adducts. All three patients with the codon 249 AGG-AGT mutation had AFB1-DNA adducts. CONCLUSION Although exposure to AFB1 is thought to be low in Japan, it is still associated with hepatocarcinogenesis, particularly in NBNC HCC and hepatitis B individuals.
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Affiliation(s)
- Ken Shirabe
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
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Utsunomiya T, Shimada M. Molecular characteristics of non-cancerous liver tissue in non-B non-C hepatocellular carcinoma. Hepatol Res 2011; 41:711-21. [PMID: 21682827 DOI: 10.1111/j.1872-034x.2011.00818.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Although chronic infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) are the most important risk factors for the development of hepatocellular carcinoma (HCC) worldwide, the proportion of HCC patients negative for the hepatitis B surface antigen and hepatitis C antibody, so-called "non-B non-C HCC", is rapidly increasing, especially in Japan. The background liver diseases of non-B non-C HCC patients can be multifactorial, including occult HBV infection and non-alcoholic steatohepatitis. It is reasonable to investigate the non-cancerous liver tissues to identify the potential molecular mechanisms responsible for the processes of hepatocarcinogenesis of non-B non-C HCC. However, to date, only a few studies have focused on this research concept based on the idea of "field cancerization". This review highlights the potential importance of the molecular analysis of non-cancerous liver tissues to clarify the molecular characteristics in patients with non-B non-C HCC. A better understanding of the molecular mechanisms underlying the individual predisposition to non-B non-C HCC will lead to improvements in the prevention, early diagnosis and treatment of this neoplastic disease.
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Affiliation(s)
- Tohru Utsunomiya
- Department of Surgery, The University of Tokushima, Tokushima, Japan
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Occult hepatitis B: clinical implications and treatment decisions. Dig Dis Sci 2010; 55:3328-35. [PMID: 20927592 PMCID: PMC3001399 DOI: 10.1007/s10620-010-1413-0] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2010] [Accepted: 08/26/2010] [Indexed: 01/27/2023]
Abstract
First reported in 1978, occult hepatitis B is a term used to describe the presence of hepatitis B virus (HBV) DNA without hepatitis B surface antigenemia. The prevalence of occult HBV is unclear and depends in part on the sensitivity of the hepatitis B surface antigen (HBsAg) and DNA assays used as well as the prevalence of HBV infection in the study population. The origin of occult HBV also remains in question. Several mechanisms have been hypothesized including mutations in the regulatory regions of the HBV genome, persistence of Ig-bound HBV immune complexes, viral interference, and blockage of free HBsAg secretion. Occult HBV has important clinical implications such as transmission through blood transfusion, reactivation in the setting of immunosuppression, and interference with hepatitis C treatment. To date, there is little data pertaining to the treatment of occult HBV outside of the setting of chemotherapy-induced HBV reactivation.
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Hayashi T, Hirai S, Shimatani A, Horita Y, Matsuda K, Hiramatsu K, Matsuda M, Ogino H, Shimizu K, Uchiyama A, Terahata S, Noda Y. Clinicopathological characteristics of surgically treated patients with non-B non-C type hepatocellular carcinoma. ACTA ACUST UNITED AC 2010. [DOI: 10.2957/kanzo.51.697] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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TATEIWA SHINPEI, YANO YOSHIHIKO, SEO YASUSHI, MIKI AKIRA, YUUKI KAWANO, AZUMA TAKESHI, HAYASHI YOSHITAKE. Clinical significance of hepatitis B virus-DNA in hepatocellular carcinoma negative for hepatitis B virus surface antigen. Exp Ther Med 2010. [DOI: 10.3892/etm_00000053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
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Obika M, Shinji T, Fujioka SI, Terada R, Ryuko H, Lwin AA, Shiraha H, Koide N. Hepatitis B virus DNA in liver tissue and risk for hepatocarcinogenesis in patients with hepatitis C virus-related chronic liver disease. A prospective study. Intervirology 2008; 51:59-68. [PMID: 18349544 DOI: 10.1159/000121363] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2007] [Accepted: 02/04/2008] [Indexed: 12/20/2022] Open
Abstract
AIMS To prospectively study whether occult hepatitis B virus (HBV) infection can promote the development of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related chronic liver disease. In addition, to evaluate the difference among HBV DNA-negative patients and patients with high and low HBV copy numbers. METHODS A total of 167 patients with HCV-related chronic liver disease without HBV surface antigen (HBsAg) were studied. HBV DNA in liver tissue was determined using polymerase chain reaction (PCR). RESULTS HBV DNA was detected in 9 of 167 patients (5.4%) by single PCR and in 25 patients (15.0%) by nested PCR. HCC developed in 12 of 167 patients (7.2%). Ten of 142 HBV DNA-negative patients (7.0%) and 2 of 9 patients with a high HBV copy number (22.2%) developed HCC, whereas none of 16 patients with a low HBV copy number developed HCC. The incidence rate of HCC in patients with a high HBV copy number was significantly higher than in HBV DNA-negative patients and patients with low HBV copy number. CONCLUSION A high amount of HBV DNA in liver tissue of HBsAg-negative patients with HCV-related liver disease might be associated with HCC development.
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Affiliation(s)
- Mikako Obika
- Department of Laboratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
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