HCV HBV感染与肝细胞性肝癌

调查了肝癌高发地区不同肝病患者中丙型肝炎病毒(HCV)感染率。慢性肝病患者绝大多数已被乙型肝炎病毒(HBV)感染。HCV第二代抗体阳性率,肝癌7.3％,肝硬化6.6％,慢性肝炎6.6％和急性肝炎3.4％。两种病毒的复合感染率,肝癌5.1％,肝硬化1.7％,慢性肝炎3.9％和急性肝炎1.1％。在38例HCV抗体阳性的慢性肝病患者中,ALT异常84.2％,有输血史者占57.9％,HCV-RNA阳性率为71.1％。本研究的资料分析提示,在肝癌高发地区尽管HCV抗体阳性率较低,但HCV感染也是肝癌发生的重要病因之一。     

Hepatitis B viral load affects prognosis of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a complex disease that is dually challenging to treat due to underlying chronic liver disease in addition to the cancer itself.The prognosis of patients with HCC is determined by intrahepatic tumor status and reserved hepatic function.Hepatitis B virus(HBV)is an established major risk factor of HCC development,and HBV viral load is being increasingly recognized as a prognostic factor in the presence of established HCC.High HBV viral load may affect the prognosis of HBV-related HCC patients in several ways.First,it is associated with more frequent recurrence of HBV-related HCC after treatment.Second,it is associated with more occurrence and severity of potentially life-threatening HBV reactivation.Last,it is associated with more worsened liver function,which limits the therapeutic options for HBV-related HCC.HBV,directly or indirectly,can induce hepatocarcinogenesis.In patients with a high HBV DNA level and subsequent active hepatitis,adhesion molecules expressed on the sinusoidal cells are up-regulated and may increase intrahepatic metastasis.HCC progression after treatment can lead to a poor prognosis by reducing number of normal functioning hepatocytes.Thus,high HBV viral load can affect the prognosis of patientswith HCC by frequent recurrence after treatment for HCC and deterioration of hepatic function associated with HCC progression.Recent meta-analysis showed that antiviral treatment reduces HCC recurrence and liver-related mortality after curative therapy of HCC.Given the strong relationship between high HBV DNA load and poor survival outcome of HCC patients due to cancer progression,it is expected that long-term antiviral therapy results in the sustained HBV suppression,control of inflammation,reduction in HCC progression,and eventually in improved overall survival.     

Prevention of hepatocellular carcinoma: progress and challenges

Hepatocellular carcinoma (HCC) is a lethal cancer for both men and women and is caused by multiple risk factors. Most patients with HCC have an underlying liver disease caused by either chronic viral infection due to hepatitis B or hepatitis C virus or non-viral etiologic risk factors such as alcohol, fatty liver disease, dietary aflatoxin exposure, smoking and diabetes mellitus. While these risk factors are progressively and persistently damaging the liver, the majority of patients show very few symptoms of HCC. By the time symptoms appear the cancer is typically at a very advanced stage with limited options for treatment. In order to prevent death from HCC, it is therefore critically important to reduce the prevalence of the major risk factors, identify and treat those at high risk for development of HCC, and institute effective surveillance strategies for early diagnosis and treatment of HCC. This article reviews the recent progress and current challenges to the prevention of HCC.     

Nucleos(t)ide analogs in the prevention of hepatitis B virus related hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is among the most common cancer types and causes of cancer related mortality worldwide.Almost 50% of all HCC cases globally are attributable to chronic hepatitis B virus(HBV) infection.The incidence rates of HCC in untreated Asian subjects with HBV infection was estimated to be 0.2% in inactive carriers,0.6% for those with chronic hepatitis without cirrhosis,and 3.7% for those with compensated cirrhosis.In Western populations,HCC incidences are reported to be 0.02% in inactive carriers,0.3% in subjects with chronic hepatitis without cirrhosis,and 2.2% in subjects with compensated cirrhosis.Despite effective antiviral treatment options which are able to transform chronic hepatitis into an inactive carrier state,the risk of HCC cannot be fully ruled out to exclude those patients from surveillance.Newer nucleos(t)ide analogues(NAs) as entecavir and tenofovir are very potent in terms of sustained virological suppression which leads to improved liver histology.However,they do not have any influence on the ccc DNA or integrated DNA of HBV in the liver.Nonetheless,viral replication is the only modifiable component among the established risk factors for HBV-related HCC with the current treatment options.In this review,it was aimed to summarize cumulative evidence behind the concept of prevention of HBV related HCC by NAs,and to discuss remaining obstacles to eliminate the risk of HCC.     

Molecular mechanisms of viral hepatitis induced hepatocellular carcinoma

Chronic infection with viral hepatitis affects half a billion individuals worldwide and can lead to cirrhosis, cancer, and liver failure. Liver cancer is the third leading cause of cancer-associated mortality, of which hepatocellular carcinoma (HCC)represents 90%of all primary liver cancers. Solid tumors like HCC are complex and have heterogeneous tumor genomic profiles contributing to complexity in diagnosis and management. Chronic infection with hepatitis B virus (HBV),hepatitis delta virus (HDV), and hepatitis C virus (HCV) are the greatest etiological risk factors for HCC. Due to the significant role of chronic viral infection in HCC development, it is important to investigate direct (viral associated) and indirect (immune-associated) mechanisms involved in the pathogenesis of HCC. Common mechanisms used by HBV, HCV, and HDV that drive hepatocarcinogenesis include persistent liver inflammation with an impaired antiviral immune response, immune and viral protein-mediated oxidative stress, and deregulation of cellular signaling pathways by viral proteins.DNA integration to promote genome instability is a feature of HBV infection, and metabolic reprogramming leading to steatosis is driven by HCV infection. The current review aims to provide a brief overview of HBV, HCV and HDV molecular biology, and highlight specific viral-associated oncogenic mechanisms and common molecular pathways deregulated in HCC, and current as well as emerging treatments for HCC.     

Significance of viral status on occurrence of hepatitis B-related hepatocellular carcinoma

Hepatitis B virus (HBV) infection remains a challenging global health problem, with more than 350 million people chronically infected and at risk of developing hepatocellular carcinoma (HCC). Interactions that occur among host, environmental, and viral factors determine the natural course and predict the prognosis of patients with chronic HBV infection. In the past decades, several important viral factors of predictive of HCC have been identified, such as high hepatitis B surface antigen level, seropositivity of hepatitis B e antigen, high viral load, viral genotype, and specific viral sequence mutations. Identification of certain viral risk factors for HCC development and stratification of patient risk are very important to perform future surveillance programs. In this article, we thus reviewed the risk of viral factors involved in hepatocarcinogenesis.     

Occult hepatitis B virus infection is not associated with disease progression of chronic hepatitis C virus infection

AIM To clarify the prevalence of occult hepatitis B virus(HBV) infection(OBI) and the association between OBI and liver disease progression, defined as development of liver cirrhosis or hepatocellular carcinoma(HCC), worsening of Child-Pugh class, or mortality in cases of chronic hepatitis C virus(HCV) infection. METHODS This prospective cohort study enrolled 174 patients with chronic HCV infection(chronic hepatitis, n = 83; cirrhosis, n = 47; HCC, n = 44), and evaluated disease progression during a mean follow-up of 38.7 mo. OBI was defined as HBV DNA positivity in 2 or moredifferent viral genomic regions by nested polymerase chain reaction using 4 sets of primers in the S, C, P and X open reading frame of the HBV genome. RESULTS The overall OBI prevalence in chronic HCV patients at enrollment was 18.4%, with 16.9%, 25.5% and 13.6% in the chronic hepatitis C, liver cirrhosis and HCC groups, respectively(P = 0.845). During follow-up, 52 patients showed disease progression, which was independently associated with aspartate aminotransferase 40 IU/L, Child-Pugh score and sustained virologic response(SVR), but not with OBI positivity. In 136 patients who were not in the SVR state during the study period, OBI positivity was associated with neither disease progression, nor HCC development. CONCLUSION The prevalence of OBI in chronic HCV patients was 18.4%, and OBI was not associated with disease progression in South Koreans.     

High serum adiponectin correlates with advanced liver disease in patients with chronic hepatitis B virus infection

Purpose  Adiponectin possesses anti-inflammatory and insulin-sensitizing properties. Little is known about the role of adiponectin in hepatitis B-related liver disease. Methods  Serum adiponectin and hepatitis B viral factors were cross-sectionally assayed in 280 patients with chronic hepatitis B virus (HBV) infection including 120 patients with chronic HBV infection, 40 patients with cirrhosis, and 120 patients with hepatocellular carcinoma (HCC); 116 healthy adults were used as controls. The dynamics of serum adiponectin level was also studied longitudinally in 25 patients with hepatitis B e antigen (HBeAg) seroconversion (SC). Results  We found that serum adiponectin level in patients with chronic HBV infection was similar to that in healthy controls and was significantly lower than patients with cirrhosis and HCC. In univariate analysis, high serum adiponectin level significantly correlated with the presence of HBV-related cirrhosis or HCC, abnormal serum ALT level, and HBV genotype C. Multivariate analysis revealed that high serum adiponectin level significantly correlated with the development of HCC. Serum adiponectin levels remained stationary in patients experiencing HBeAg SC. Conclusions  Our findings suggest that HBV infection itself does not affect adiponectin levels. Serum adiponectin level correlates with the progression of HBV-related liver diseases but not with the development of HBeAg SC.     

Genotypes, mutations, and viral load of hepatitis B virus and the risk of hepatocellular carcinoma: HBV properties and hepatocarcinogenesis

Chronic infection with hepatitis B virus (HBV) is the major risk factor for hepatocellular carcinoma (HCC) worldwide. Ten HBV genotypes (A-J) have been discovered so far. Genotypes B and C are endemic in East and Southeast Asia. Genotype C HBV is associated with increased risks of cirrhosis and HCC. Genotype B (B2) is associated with the development of HCC in non-cirrhotic patients younger than 50 years and with relapse of HCC after surgical treatment. It is also associated with earlier hepatitis B e antigen seroconversion than genotype C. High HBV load is independently associated with the occurrence and post-treatment recurrence of HCC. Different genotypes have distinct patterns of mutations. Viral mutations in the core promoter region and in the preS region are frequently found to be significantly associated with an increased risk of HCC. These mutations often occur before the onset of HCC and accumulate during the progression of chronic HBV infection. Multiple such mutations are more frequent in patients with HCC and are specific for HCC. HBV subgenotypes, viral mutations, and viral load can be used for the prediction of HCC. Early identification of HBV-infected individuals who will eventually develop HCC will help to develop active prophylactic protocols to reduce or delay the occurrence of HCC.     

Human genes involved in hepatitis B virus infection

Persistent hepatitis B virus(HBV)infection is a significant public health problem because it is a major cause of chronic liver disease,cirrhosis,and hepatocellular carcinoma(HCC).Roughly one-third of the world population has been infected with HBV and there are about350 million(5%-6%)persistent carriers.HBV causes80%of all liver cancer cases and is the second most important carcinogen,after smoking tobacco.There is an approximate 90%risk of becoming a persistent carrier following perinatal infection in infants born to e antigen positive carrier mothers and a 30%risk in pre-school children.Only 5%-10%of adults become persistent carriers following infection.Of individuals persistently infected with HBV,10%-30%will develop liver cirrhosis and HCC.These highly variable outcomes in both clearance rates and disease outcomes in persistently infected individuals cannot be fully explained by differences in immunological,viral or environmental factors.Thus,differences in host genetic factors may affect the natural history of hepatitis B.     

Current impact of viral hepatitis on liver cancer development: The challenge remains

Chronic infections due to hepatitis B and hepatitis C viruses are responsible for most cases of hepatocellular carcinoma (HCC) worldwide, and this association is likely to remain during the next decade. Moreover, viral hepatitis-related HCC imposes an important burden on public health in terms of disability-adjusted life years. In order to reduce such a burden, some major challenges must be faced. Universal vaccination against hepatitis B virus, especially in the neonatal period, is probably the most relevant primary preventive measure against the development of HCC. Moreover, considering the large adult population already infected with hepatitis B and C viruses, it is also imperative to identify these individuals to ensure their access to treatment. Both hepatitis B and C currently have highly effective therapies, which are able to diminish the risk of development of liver cancer. Finally, it is essential for individuals at high-risk of HCC to be included in surveillance programs, so that tumors are detected at an early stage. Patients with hepatitis B or C and advanced liver fibrosis or cirrhosis benefit from being followed in a surveillance program. As hepatitis B virus is oncogenic and capable of leading to liver cancer even in individuals with early stages of liver fibrosis, other high-risk groups of patients with hepatitis B are also candidates for surveillance. Considerable effort is required concerning these strategies in order to decrease the incidence and the mortality of viral hepatitis-related 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.     

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.     

中国北方地区321例乙型肝炎病毒相关肝细胞癌患者的流行病学和临床特征分析

背景:我国是肝细胞癌(HCC)高发区,其中大部分HCC与乙型肝炎病毒(HBV)感染相关,有必要对其自然史和临床进程作大样本调查研究。目的:了解中国北方地区HBV相关HCC患者的流行病学和临床特征。方法:对中国北方地区321例HBV相关HCC患者作流行病学问卷调查,行肝功能、甲胎蛋白(AFP)、HBV血清标志物和HBV DNA水平检测,并进行统计分析。结果:321例HBV相关HCC患者中,仅7.2%接受过抗病毒治疗;46.4%和25.5%分别有肝硬化和肝癌家族史;38.3%有饮酒史。21.0%的患者乙型肝炎e抗原(HBeAg)阳性,62.3%乙型肝炎e抗体(HBeAb)阳性,HBeAg阳性者合并肝硬化的比例和HBV DNA水平较高。84.5%的患者HBV DNA阳性,但其中仅42.6%HBV DNA≥5.0log10,HBV DNA高水平者合并肝硬化的比例显著高于HBV DNA低水平者。无症状HBV感染、慢性乙型肝炎、代偿性和失代偿性肝硬化患者分别占4.1%、24.1%、39.0%和32.9%。71.0%的患者AFP升高,但其中仅33.8?P≥400ng/ml。结论:本组HBV相关HCC患者中,HBeAg阳性和高HBV DNA水平者不多,但病情常较重。肝硬化是HCC的重要危险因素,饮酒和肝癌家族史对HCC的发生有一定影响。血清AFP筛查有助于HCC的诊断。     

Anti-viral therapy to reduce recurrence and improve survival in hepatitis B virus-related hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is the most common malignancy and the third leading cause of cancer death worldwide.Chronic infection with hepatitis B virus(HBV)and hepatitis C virus accounts for approximately75%-80%of HCC cases worldwide.In particular,chronic HBV infection is a predominant risk factor for HCC in Asia and Africa.Hepatic resection and radiofrequency ablation are increasingly used for the curative treatment of HCC,and good local control can be achieved.However,the high rate of recurrence is a major obstacle to improving prognosis.A high viral load of HBV DNA is the most important correctable risk factor for recurrence.Furthermore,interferon and/or nucleotide analogues may decrease HBV DNA.Therefore,these drugs may decrease recurrence.In this article,treatment strategies for HBV-related HCC are described in order to reduce recurrence and improve survival.     

Chronic hepatitis B and metabolic risk factors:A call for rigorous longitudinal studies

Long-term nucleos(t)ide analogue therapy in chronic hepatitis B virus(HBV)infection is effective in suppressing viral replication and reducing liver-related complications. However, HBV-related liver events can still occur in different patient sub-groups. There is emerging evidence that, similar to chronic hepatitis C virus infection, metabolic risk factors may play a role in the disease process of chronic HBV. While the mechanistic nature of metabolic-HBV interactions remains uncertain, studies in different HBV-infected populations have demonstrated that hepatic steatosis, increased body-mass index, diabetes, or a combination of different metabolic risk factors are associated with an increased risk of hepatocellular carcinoma and cirrhosis. The impact of metabolic risk factors is especially prominent in patients with quiescent virological activity,including on-treatment patients with effective viral suppression. As the proportion of on-treatment chronic HBV patients increases worldwide,longitudinal studies determining the relative risks of different metabolic parameters with respect to clinical outcomes are needed. Future studies should also determine if metabolic-directed interventions can improve disease outcomes in chronic HBV.     

Epidemiology of viral hepatitis in Somalia: Systematic review and meta-analysis study

AIM To provide a clear understanding of viral hepatitis epidemiology and their clinical burdens in Somalia.METHODS A systematic review and meta-analysis was conducted as Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive literature search of published studies on viral hepatitis was performed from 1977-2016 in Pub Med, Google Scholar, Science Direct, World Health Organization African Index Medicus and the Africa Journals Online databases, as well as on the Ministry of Health website. We also captured unpublished articles that were not available on online systems.RESULTS Twenty-nine studies from Somalia and Somali immigrants(United Kingdom,United States,Italy,Libya)with a combined sample size for each type of viral hepatitis[hepatitis A virus(HAV):1564,hepatitis B virus(HBV):8756,hepatitis C virus(HCV):6257,hepatitis D virus(HDV):375 and hepatitis E virus(HEV):278]were analyzed.The overall pooled prevalence rate of HAV was 90.2%(95%CI:77.8%to 96%).The HAV prevalence among different age groups was as follows:1 year old,61.54%(95%CI:40.14%to79.24%);1-10 years old,91.91%(95%CI:87.76%to94.73%);11-19 years old,96.31%(95%CI:92.84%to 98.14%);20-39 years old,91.3%(95%CI:83.07%to 95.73%);and40 years old,86.96%(95%CI:75.68%to 93.47%).The overall pooled prevalence of HBV was 18.9%(95%CI:14%to 29%).The overall pooled prevalence among subgroups of HBV was20.5%(95%CI:5.1%to 55.4%)in pregnant women;5.7%(95%CI:2.7%to 11.5%)in children;39.2%(95%CI:33.4%to 45.4%)in patients with chronic liver disease,including hepatocellular carcinoma(HCC);7.7%(95%CI:4.2%to 13.6%),12.4%(95%CI:6.3%to 23.0%)and 11.8%(95%CI:5.3%to 24.5%)in age groups20 years old,20-39 years old and40years old,respectively.The HBV prevalence among risk groups was 20%(95%CI:7.19%to 44.64%)in female prostitutes,21.28%(95%CI:7.15%to48.69%)in hospitalized adults,5.56%(95%CI:0.99%to 25.62%)in hospitalized children,60%(95%CI:31.66%to 82.92%)in patients with acute hepatitis,33.55%(95%CI:14.44%to 60.16%)in patients with ancylostomiasis,12.34%(95%CI:7.24%to 20.26%)in patients with leprosy and 20.19%(95%CI:11.28%to33.49%)in schistosomiasis patients.The overall pooled prevalence of HCV was estimated as 4.84%(95%CI:3.02%to 7.67%).The prevalence rates among blood donors,risk groups,children and patients chronic liver disease(including HCC)was 0.87%(95%CI:0.33%to 2.30%),2.43%(95%CI:1.21%to 4.8%),1.37%(95%CI:0.76%to 2.46%)and 29.82%(95%CI:15.84%to 48.98%),respectively.The prevalence among genotypes of HCV was 21.9%(95%CI:15.36%to 30.23%)in genotype 1,0.87%(95%CI:0.12%to 5.9%)in genotype 2,25.21%(95%CI:18.23%to 33.77%)in genotype 3,46.24%(95%CI:37.48%to 55.25%)in genotype 4,2.52%(95%CI:0.82%to7.53%)in genotype 5,and 1.19%(95%CI:0.07%to16.38%)in genotype 6.The overall pooled prevalence of HDV was 28.99%(95%CI:16.38%to 45.96%).The HDV prevalence rate among patients with chronic liver disease,including HCC,was 43.77%(95%CI:35.09%to 52.84%).The overall pooled prevalence of HEV was46.86%(95%CI:5.31%to 93.28%).CONCLUSION Our study demonstrates a high prevalence of all forms of viral hepatitis in Somalia and it also indicates that chronic HBV was the commonest cause of chronic liver disease.This highlights needs for urgent public health interventions and strategic policy directions to controlling the burden of the disease.     

Direct antiviral agents in hepatitis C virus related liver disease: Don’t count the chickens before they’re hatched

Since molecules with direct-acting antiviral (DAA) became available, the landscape of the treatment of hepatitis C virus (HCV) infection has completely changed. The new drugs are extremely effective in eradicating infection, and treatment is very well tolerated with a duration of 8-12 wk. This review aims to report the outstanding clinical benefits of DAA and to highlight their critical disadvantages, identifying some clinically relevant hot topics. First, do the rates of virological response remain as high when patients with more advanced cirrhosis are considered? Large studies have shown slightly lower but still satisfactory rates of response in these patients. Nevertheless, modified schedules with an extended treatment duration and use of ribavirin may be necessary. Second, does the treatment of HCV infection affect the risk of occurrence and recurrence of liver cancer? Incidence is reduced after viral eradication but remains high enough to warrant periodic surveillance for an early diagnosis. In contrast, the risk of recurrence seems to be unaffected by viral clearance; however, DAA treatment improves survival because of the reduced risk of progression of liver disease. Third, can HCV treatment also have favorable effects on major comorbidities? HCV eradication is associated with a reduced incidence of diabetes, an improvement in glycemic control and a decreased risk of cardiovascular events; nevertheless, a risk of hypoglycemia during DAA treatment has been reported. Finally, is it safe to treat patients with HCV/ hepatitis B virus (HBV) coinfection? In this setting, HCV is usually the main driver of viral activity, while HBV replication is suppressed. Because various studies have described HBV reactivation after HCV clearance, a baseline evaluation for HBV coinfection and a specific follow-up is mandatory.     

Natural history: The importance of viral load, liver damage and HCC

Viral hepatitis is the main cause of liver disease. Progression of viral hepatitis leading to liver cirrhosis and hepatocellular carcinoma occurs frequently in chronic HBV- and HCV-infected patients. Viral and host-related factors and modifiable and non-modifiable factors associated with advanced liver disease can be distinguished. For hepatitis B, viral factors include HBeAg status, HBV genotype, naturally occurring mutations, and viral load. The level of serum HBV DNA, reflecting the concentration of intrahepatic HBV DNA, is positively correlated with the risk for liver cirrhosis and HCC. The continued presence of intracellular hepatitis B virus and the resulting immune response might be the driving force for the progression of HBV-related liver disease and HBV reactivation. However, little is known about the natural course of intrahepatic HBV DNA, and further studies are needed. Patients with HCV and/or HDV and/or HIV coinfections are at an increased risk for an adverse outcome of their liver disease. For hepatitis C, courses of the disease are variable. Viral factors seem to be less significant for disease progression, while host-related effects play a more important role. Among these are modifiable cofactors such as hepatic steatosis and insulin resistance which lead to a more severe disease and lower response to antiviral therapy with chronic hepatitis C. The precise interactions between HCV and host metabolic factors need further elucidation, especially as the rate of metabolic diseases is on the increase.     

Current therapy for hepatitis C or D or immunodeficiency virus concurrent infection with chronic hepatitis B

Concurrent hepatitis C virus (HCV), hepatitis delta virus (HDV), or human immunodeficiency virus (HIV) infection with chronic hepatitis B virus (HBV) appears to increase the risk of progressive liver disease including liver cirrhosis and hepatocellular carcinoma. There is a 10% prevalence of HCV infection in chronic HBV or HDV infection. Serological evidence of previous exposure to HBV is found in more than 80% of HIV-positive patients in the high risk group. Notably, the most recently acquired virus tends to suppress the pre-existing virus. In chronic HBV infection acquired perinatally or in early childhood, usually HCV is dominant and may suppress or even displace HBV and HDV. Less frequently, HBV or HDV suppresses HCV. It is generally agreed that the dominant virus should be identified in order to make appropriate treatment decisions. Studies with standard interferon (IFN) to treat patients with HCV dominantly dual HBV/HCV infection have showed only limited virological response. But high dose of IFN has been demonstrated with better response rate. Combined ribavirin with standard or pegylated IFN therapy could achieve a sustained HCV clearance rate comparable with those infected with HCV alone. On the contrary, patients with HBV dominantly dual viral infection might indicate more appropriate addition of lamivudine to IFN than ribavirin. Additionally, patients with concurrent infection of HBV and HDV, IFN seems to be the only effective agent. However, the efficacy of IFN is related to the dose. High dose of IFN [9 MU tiw (thrice per week)] and longer treatment duration (at least 2 years) have been shown to achieve adequate virological response. In patients with concurrently infected HBV and HIV, anti-HBV therapy should be considered for all patients with evidence of liver disease, irrespective of the CD4 cell count. In patients not requiring antiretroviral therapy, HBV therapy should be preferentially based on IFN, adefovir, or telbivudine. In contrast, in patients with CD4 cell counts <350 cells/μl or those already on antiretroviral therapy, agents with double anti-HBV and anti-HIV activity are preferred. At present, the evidence of therapeutic efficacy is not sufficient to make a recommendation in treating patients with dual HBV/HCV or HBV/HDV or HBV/HIV infection. Further studies of the well-designed, larger scale are needed to elucidate the role of different regimens or combination in the treatment of dual viral infection.