乙型肝炎肝硬化患者外周血骨桥蛋白与IL-18水平变化的临床意义

目的：探讨慢性乙型肝炎、肝硬化患者外周血细胞因子骨桥蛋白与IL-18水平变化的临床意义。方法：应用ELISA法对102例慢性乙型肝炎、34例乙型肝炎肝硬化、95例HBV携带者及20名健康献血者（对照组）外周血细胞因子骨桥蛋白与IL-18表达水平进行了测定。结果：慢性乙型肝炎、肝硬化患者组外周血骨桥蛋白及IL-18表达水平明显高于对照组（P〈0.05）;肝硬化患者组骨桥蛋白、IL-18水平明显高于慢性乙型肝炎组（P〈0.05）;慢性乙型肝炎重型组骨桥蛋白、IL-18水平明显高于慢性乙型肝炎轻型组（P〈0.05）;慢性乙型肝炎患者血清总胆红素水平与骨桥蛋白和IL-18表达水平呈正相关关系（r=0.71,P〈0.05;r=0.78,P〈0.05）。结论：乙肝病毒感染性慢性肝脏疾病发生发展与细胞因子骨桥蛋白及IL-18水平变化相关,慢性乙型肝炎、肝炎后肝硬化患者外周血骨桥蛋白与IL-18表达水平呈正相关关系（r=0.74,P〈0.05）。     

PI3K/Akt信号通路及内质网应激在肝纤维化大鼠肝细胞凋亡中的作用

目的观察磷脂酰肌醇-3激酶/蛋白激酶(PI3K/Akt)信号通路及葡萄糖调节蛋白78(GRP78)、生长停滞及DNA损伤基因(CHOP/GADD153)在四氯化碳(CCl4)诱导的肝纤维化中的表达并探讨其可能的作用。方法将30只SD大鼠随机分为正常组、肝纤维化模型(皮下注射40%CCl4橄榄油溶液)4及8周组。HE染色法观察肝组织病理形态学;用real-time PCR技术检测肝脏内GRP78及CHOP mRNA的表达;用Western blot检测肝脏内PI3K/Akt信号通路中Akt1、磷酸化Akt1及内质网应激相关蛋白GRP78及CHOP的表达;用原位末端转移酶标记(TUNEL)检测细胞凋亡。结果与正常组大鼠比较,肝纤维化模型4及8周组大鼠肝脏内GRP78及CHOP mRNA和蛋白表达均明显升高(P0.05),而肝脏内Akt1和磷酸化Akt1蛋白的表达则较正常大鼠显著降低(P0.05);与正常组大鼠比较,肝纤维化模型4及8周组大鼠肝细胞凋亡显著升高(P0.05)。结论 PI3K/Akt信号通路及内质网应激可能在肝纤维化大鼠肝细胞凋亡中发挥了重要作用。     

全肝容积CT灌注成像对乙型肝炎、乙型肝炎肝硬化肝储备功能评价的研究

目的 探讨全肝容积CT灌注成像(VCTP)中乙型肝炎、乙型肝炎肝硬化肝脏左叶、右叶及全肝灌注参数在评价肝脏储备功能中的价值。方法 前瞻性纳入泰安市中心医院影像科2012年11月—2014年2月间,经临床、其它检查证实为乙型肝炎的患者26例(肝炎组)、代偿期乙型肝炎肝硬化的患者24例(代偿组)、失代偿期乙型肝炎肝硬化的患者22例(失代偿组)和对照组(肝功能正常)30例。采用西门子SOMATON Definition AS+128螺旋CT行全肝容积灌注成像,对每组病例的血流量(BF)、血容量(BV)、肝动脉灌注量(ALP)、门静脉灌注量(PVP)及肝动脉灌注指数(HPI)共5个灌注指标进行分析。各组肝脏不同CT灌注参数值的比较采用单因素方差分析,以P<0.05为差异有统计学意义。结果 对照组、肝炎组、代偿组及失代偿组单因素方差分析结果显示,随着肝脏病变程度的加重,肝右叶、肝左叶及全肝灌注参数中的BF、BV、PVP值均逐渐减小,HPI却逐渐增加,4组间总体比较,差异具有统计学意义(P值均＜0.05)。肝脏右叶、左叶及全肝灌注参数对肝功能的评价是一致的,肝脏右叶、左叶灌注参数的走势无明显差异。全肝、肝右叶、肝左叶的灌注参数ALP组间比较差异无统计学意义(P值均＞0.05)。结论 全肝VCTP能反映乙型肝炎、乙型肝炎肝硬化的血流动力学变化,肝脏右叶、左叶灌注参数BF、BV、PVP都是随病变程度的加重而减小,肝脏右叶、左叶及全肝灌注参数对肝功能的评价是一致的。     

角蛋白18磷酸化增加结肠癌HCT116细胞自噬并提高其对奥沙利铂的敏感性

目的研究奥沙利铂(OXA)作用下角蛋白18(K18)磷酸化与结肠癌HCT116细胞自噬和凋亡的关系并分析其可能机制。方法 HCT116细胞分别转染空载质粒、野生型K18和33、52磷酸化位点突变的K18质粒(Ser33/52A),用60μmol/L的OXA处理细胞,加入自噬抑制剂3-甲基腺嘌呤(3-MA)或细胞自噬诱导剂雷帕霉素处理细胞。异硫氰酸荧光素标记的膜联素Ⅴ/碘化丙啶(annexinⅤ-FITC/PI)双标记结合流式细胞术以及钙黄绿素乙酰甲酯/碘化丙啶(calcein-AM/PI)染色法分析K18及其突变体对细胞凋亡的影响;Western blot法检测K18的磷酸化水平、自噬相关蛋白微管相关蛋白1轻链3(LC3)、beclin-1的表达。结果 Ser33/52A质粒的转染可以明显降低K18的磷酸化水平,经过OXA处理后,转染K18质粒组的HCT116细胞的凋亡率显著高于空载质粒转染对照组,而Ser33/52A质粒转染的HCT116细胞的凋亡率明显低于空载体和K18质粒转染的细胞凋亡率,K18质粒转染组细胞自噬明显高于空载转染对照组,而Ser33/52A质粒转染组自噬水平明显降低。结论 K18过表达促进HCT116细胞自噬及其对OXA的敏感性,而K18 Ser33和Ser52磷酸化水平的降低则抑制自噬并降低HCT116细胞的凋亡率。     

肝衰竭肝脏的组织病理学变化及其干细胞活化情况

目的探讨肝移植病例中重型肝炎肝衰竭的病理组织学变化与其肝脏干细胞活化状态的关系。方法收集肝移植病例中重型肝炎肝衰竭33例,以相应供肝组织作为正常对照,以免疫组织化学EnVision法检测肝组织中c-kit、Ki-67、HBsAg及HBcAg表达情况,并选择10例c-kit明显阳性病例进行了甲苯胺蓝组织化学染色做为对比染色,分析肝衰竭病例肝脏病理组织学、病毒抗原表达、有无人工肝治疗史,c—kit阳性肝脏干细胞活化数量。结果33例中男性25例,女性8例,年龄分布为21～64岁。符合急性肝衰竭6例,其中2例与乙型肝炎病毒感染有关,3例为药物中毒所致,1例为急性妊娠脂肪肝;亚急性肝衰竭5例,均为乙型肝炎病毒感染所致;慢性急性发作性肝衰竭22例,均为乙型肝炎病毒感染所致。肝移植手术前有人工肝治疗史13例。肝脏活化的干细胞被c-kit单克隆抗体所标记,但不能被甲苯胺蓝染料染色。正常供肝内无或偶见c-kit阳性细胞;急性肝衰竭组c-kit阳性细胞为3．50±2．66（0～8）个／mm^2。;亚急性肝衰竭组为11．47±8．85（3～30）个／mm^2;慢性急性发作性重型肝炎组为15．50±10．95（5～45）个／mm^2,各组之间c-kit阳性细胞数差异有统计学意义。有无人工肝治疗史对c-kit阳性细胞计数无明显影响。供体肝脏组织Ki-67染色阴性,而肝衰竭病例在汇管区或旁汇管区可以检测到数量不等的Ki-67阳性细胞,但并不与c-kil阳性前体细胞呈平行关系。结论急性肝衰竭时肝细胞大片坏死但内源性干细胞活化不足是预后差的原因之一。而病程迁延较长的亚急性或慢性肝衰竭,肝脏干细胞活化水平逐渐升高,提示积极治疗肝衰竭使其设法渡过急性期,可以不同程度调动肝脏自身再生重建机制。     

慢性乙型肝炎患者外周血单个核细胞中IL—18表达水平

目的探讨白细胞介素 18(IL- 18)在乙型肝炎病毒感染中的作用。方法应用流式细胞免疫学方法 ,对 30例慢性乙型肝炎活动期、缓解期 ,15例 HBS Ag阳性无症状携带者 ,10例正常对照外周血单个核细胞 (PBMC) IL- 18的表达进行检测。结果无症状携带者表达最低 ,慢性乙型肝炎缓解期低于正常对照 (P<0 .0 1) ,活动期与正常对照无显著差异 (P=0 .2 5 )。活动期 IL- 18的表达与肝组织炎症活动度有关 (P<0 .0 1) ,与血清 AL T水平呈正相关 (r=0 .6 3,P<0 .0 1)。结论 IL- 18与慢性乙型肝炎病情的活动相关 ,与肝组织炎症程度相关     

肝源性糖尿病临床分析

目的探讨肝源性糖尿病与慢性肝病临床类型的关系。方法对肝源性糖尿病61例临床资料进行回顾性分析。结果肝源性糖尿病的发生率在乙型肝炎患者中为9.8%(61/623),其中慢性肝炎患者中为7.1%(28/396),慢性重型肝炎中为6.4%(5/78);肝硬化中为22.1%(33/149),与慢性肝炎、慢性重型肝炎相比,差异显着(P<0.01)。肝源性糖尿病患者中血糖重度升高的比率,肝硬化与慢性肝炎、慢性重型肝炎相比,差异显着(P<0.01)。结论糖尿病是慢性肝病的常见并发症,多发生于肝硬化患者,糖尿病轻重与肝损害程度成正比。在控制饮食、保肝、抗病毒和胰岛素治疗后,效果较好。     

HSP70在慢性乙型肝炎患者肝组织中的表达及意义

目的探讨热休克蛋白 70 ( HSP70 )在慢性乙型肝炎肝组织中的表达及意义。方法采用免疫组化技术对 3 6例慢性乙型肝炎和 2 0例正常肝组织中 HSP70的表达进行检测。结果慢性乙型肝炎和正常肝组织中肝细胞 HSP70表达阳性率分别为 4 5 %和 15 % ,两者相比差异显著 ( χ2 =6.3 ,P<0 .0 5 ) ;中度和重度肝炎 HSP70阳性率明显高于轻度肝炎 (阳性率分别为 62 .5 %和 3 0 % ,χ2 =3 .9,P<0 .0 5 ) ;HSP70阳性细胞多位于灶性和碎屑样坏死区。结论肝细胞 HSP70的异常表达在慢性乙型肝炎免疫保护中起重要作用 ,可作为肝组织损伤的一种标志。     

癌基因STAT5在肝细胞肝癌中的表达和意义

目的 检测STAT5在人肝癌组织中的表达并探讨其在肝癌发生发病中的意义.方法 采用免疫组织化学技术,分析58例肝癌标本,27例肝硬化组织标本,18例肝脏血管瘤标本,12例正常肝组织标本中STAT5蛋白的表达并进行统计学分析比较.结果 STATS在58例肝癌标本中有49例阳性表达(84.48%),27例肝硬化标本中4例阳性表达(14.81%),30例肝血管瘤和正常肝组织中无阳性表达(P＜0.01).结论 STAT5在肝癌组织中表达率高,可能在肝脏恶性肿瘤的发病中有重要意义.     

重型乙型肝炎患者单核细胞HLA-DR分子表达及临床意义

目的:探讨重型乙型肝炎患者外周血单核细胞功能变化的特点及其意义.方法:应用流式细胞术(FCM)和酶联免疫吸附法对重型肝炎患者单核细胞HLA-DR分子的表达及外周血中白细胞介素.10(IL-10)的水平进行检测,并结合临床资料加以分析.结果:与正常对照组比较,慢性乙型肝炎、肝炎肝硬化、慢性重型肝炎患者外周血单核细胞HLA-DR的表达水平逐渐下降,尤其以慢性重型肝炎患者下降最为明显;而慢性重型肝炎患者外周血中IL-10的水平则明显升高,差异均具有统计学意义(P＜0.01).相关分析表明,HLA-DR的表达水平与凝血酶原活动度呈正相关(rs=0.61,P＜0.01).慢性重型肝炎患者死亡与存活组比较,前者HLA-DR水平明显降低;而IL-10水平明显升高,差异具有统计学意义(P＜0.01).结论:外周血单核细胞HLA-DR的表达水平与慢性重型肝炎患者病情严重程度以及预后密切相关,检测外周血单核细胞HLA-DR分子水平有助于评价重型肝炎患者的免疫功能状态以及判断预后.     

乙型肝炎病毒对超敏C反应蛋白表达的影响及其临床意义

目的 探讨乙型肝炎病毒( HBV)对超敏C反应蛋白(hs-CRP)表达的影响及其临床意义.方法 采用RT-PCR检测人肝癌细胞系HepG2和HepG2.2.15中hs-CRP mRNA的表达,通过Olympus5400全自动生化分析仪检测HBV患者和健康对照者hs-CRP血清学水平,分析hs-CRP在慢性乙型肝炎、肝硬化和肝癌患者中hs-CRP表达水平的差异.结果 HepG2.2.15细胞中hs-CRPmRNA的表达水平较HepG2高;hs-CRP在乙肝感染者血清学水平显著升高(P＜0.05);hs-CRP在肝硬化患者和肝癌患者明显高于慢性肝炎患者.结论 HBV能够上调hs-CRP的表达,其血清学水平与疾病进程相关.     

c－erbB－2蛋白和表皮生长因子受体在肝脏病变中的表达

对１８４例乙型肝炎、肝硬变和肝细胞癌（ＨＣＣ）及２９例正常肝组织的标本作了ＡＢＣ法染色，观察其ｃ－ｅｒｂＢ－２蛋白和表皮生长因子受体（ＥＧＦＲ）的表达情况。３６％（４８／１３４）的慢性肝炎、肝硬变和ＨＣＣ组织中有ＥＧＦＲ表达，主要定位于血窦内皮。良、恶性病变肝组织之间在ＥＧＦＲ表达强度上无显著差别，提示ＥＧＦＲ可能与慢性肝脏病变中血窦内皮的增生有关。在正常肝，仅少数标本（５／２９）中见到ｃ－ｅｒｂＢ－２微弱表达；在ＨＢＶ相关的慢性肝脏病变，所有标本中均检测到ｃ－ｅｒｂＢ－２蛋白，主要定位于肝小多角细胞（ＳＰＬＣ）、小细胞性不典型增生（ＳＣＤ）及小管状化生（ＤＭ）的肝细胞；ＨＣＣ细胞中ｃ－ｅｒｂＢ－２蛋白阳性较弱。这提示ｃ－ｅｒｂＢ－２基因的活化与人ＨＣＣ发生有关。其作用机制可能是促进ＳＰＬＣ向ＳＣＤ的转化及促进ＳＣＤ的进展。ｃ－ｅｒｂＢ－２与ＨＢｘＡｇ表达的密切关联提示这种原癌基因的活化可能也与ＨＢＶＸ基因有关。     

Molecular and clinical characteristics of hepatitis B virus in Korea

Korea is an endemic area of hepatitis B virus (HBV) infection but very little is known about the molecular characteristics of HBV isolates from Korean patients or the association with disease progression. The complete HBV genome sequences from 53 Korean patients with chronic hepatitis B, advanced cirrhosis, or hepatocellular carcinoma (HCC) were analyzed to identify (i) subgenotype distribution and genetic diversity and (ii) signature mutations associated with liver disease progression. With the exception of 1 patient infected with HBV/B, all 52 patients (98.1%) were infected with HBV/C, subgenotype C2. These strains were 98.4% identical and the frequency of amino acid substitutions occurring within key immunological epitopes increased with disease severity. A number of amino acid/nucleotide substitutions were associated with HCC, namely sR24K (HBsAg), SI126T (HBsAg), and pcA1846T (precore gene) mutations (P = 0.029, 0.001, and 0.008, respectively). HBV harboring deletions in the pre‐S region were also associated with increased liver disease severity (chronic hepatitis B vs. cirrhosis, P = 0.040; chronic hepatitis B vs. HCC, P = 0.040). Despite the high degree of sequence conservation, several key HBV mutations were associated with disease progression. Prospective studies with larger cohorts of patients are required to evaluate further the clinical manifestation of HBV/C2 in Korea. J. Med. Virol. 82: 1126–1134, 2010. © 2010 Wiley‐Liss, Inc.     

Reversible phospho‐Smad3 signalling between tumour suppression and fibrocarcinogenesis in chronic hepatitis B infection

Transforming growth factor (TGF)‐β, type I receptor (TβRI) and c‐Jun N‐terminal kinases (JNK) phosphorylate Smad3 differentially to create 2 isoforms phosphorylated (p) at the COOH‐terminus (C) or at the linker region (L) and regulate hepatocytic fibrocarcinogenesis. This study aimed to compare the differences between how hepatitis B virus (HBV) infection affected hepatocytic Smad3 phosphorylated isoforms before and after anti‐viral therapy. To clarify the relationship between Smad3 phosphorylation and liver disease progression, we studied 10 random patients in each stage of HBV‐related fibrotic liver disease (F1–4) and also 10 patients with HBV‐associated HCC. To examine changes in phosphorylated Smad3 signalling before and after anti‐HBV therapies, we chose 27 patients with chronic hepatitis B who underwent baseline and follow‐up biopsies at 52 weeks from the start of nucleoside analogue treatments (Lamivudine 100 mg daily or Telbivudine 600 mg daily). Fibrosis stage, inflammatory activity and phosphorylated Smad3 positivity in the paired biopsy samples were compared. Hepatocytic pSmad3C signalling shifted to fibrocarcinogenic pSmad3L signalling as the livers progressed from chronic hepatitis B infection to HCC. After nucleoside analogue treatment, serum alanine aminotransferase (ALT) and HBV‐DNA levels in 27 patients with HBV‐related chronic liver diseases were decreased dramatically. Decrease in HBV‐DNA restored pSmad3C signalling in hepatocytes, while eliminating prior fibrocarcinogenic pSmad3L signalling. Oral nucleoside analogue therapies can suppress fibrosis and reduce HCC incidence by successfully reversing phosphorylated Smad3 signalling; even liver disease progressed to cirrhosis in chronic hepatitis B patients.     

乙型肝炎病毒对载脂蛋白B表达的影响及其机制探讨

目的 探讨乙型肝炎病毒(HBV)对载脂蛋白B(ApoB)表达的影响,并探讨其调节机制.方法 采用RT-PCR和Western blot法检测HepG2和HepG2.2.15中ApoB mRNA和蛋白的表达,全自动生化分析仪Olympus 5400检测HBV患者和健康对照者ApoB血清学水平,分析健康对照者、慢性乙型肝炎、肝纤维化和肝癌患者中ApoB表达水平的差异,将HBV感染性克隆pHBV1.3转染HepG2细胞,RT-PCR和Western blot法检测ApoB和微粒体甘油三酯转移蛋白(MTP)表达水平的变化.结果 HepG2.2.15细胞中ApoB mRNA和蛋白的表达水平较HepG2低;ApoB在慢性乙型肝炎患者和肝纤维化患者的血清学水平明显低于健康对照者(P＜0.05);HBV能够在mRNA和蛋白水平抑制ApoB和MTP的表达.结论 HBV可能通过抑制MTP的表达抑制ApoB的合成和分泌.

Abstract：

Objective To explore the effect of hepatitis B virus(HBV) on the expression of apolipoprotein B(ApoB) and its regulatory mechanism. Methods mRNA and protein expression of ApoB in HepG2 and HepG2.2.15 cells was measured by RT-PCR and Western blot, serum ApoB levels in patients with HBV infection and in healthy individuals were measured by biochemical analyzer Olympus 5400, the expression of ApoB difference among healthy individuals, patients with chronic hepatitis B, liver cirrhosis, and hepatocellular carcinoma were analyzed, HBV infectious clone pHBV1.3 was tranfected into HepG2 cells,and expression of ApoB and microsomal triglyceride transfer protein(MTP) was measured by RT-PCR and Western blot. Results Expression of ApoB mRNA and protein was lower in HepG2.2.15 cells than in HepG2 cells, serum apoB levels was much lower in patients with chronic hepatitis B and liver cirrhosis as compared to healthy individuals( P ＜0.05 ), HBV could inhibit the expression of ApoB and MTP at mRNA and protein levels. Conclusion HBV may downregulate the synthesis and secretion of ApoB via inhibits the expression of MTP.     

Hepatitis B virus DNA in leukocytes of patients with hepatitis B virus-associated liver diseases

In order to determine the relationship between hepatitis B virus (HBV) infection of human white blood cells and different forms of HBV-associated liver diseases, we tested for HBV DNA in the sera and leukocytes of 11 healthy individuals without any serological markers of HBV infection and 91 patients with HBV infection and other gastrointestinal and urinary diseases by dot and Southern blot hybridization. HBV DNA was found in leukocytes of chronic HBV carriers, in acute and chronic hepatitis, and in patients with liver cirrhosis and hepatocellular carcinoma. Between 27 and 50% of individuals in different categories of patients examined were positive for leukocyte HBV DNA. HBV DNA was also detected in the sera of some of these patients but was absent in others. Serum HBV DNA-positive rates seemed to be highest in hepatitis B e antigen-positive asymptomatic carriers (8/10, 80%), and tended to drop to lower levels as the disease progressed to liver cirrhosis (0/8) while leukocyte HBV DNA-positive rates were highest in patients with cirrhosis (4/8, 50%). The results also show that in individuals who were serologically negative for hepatitis B surface antigen (HBsAg) and positive for antibodies to HBsAg and/or HBcAg, HBV DNA was absent in most of the sera (27/28, 96%) but it was present in leukocytes of some of these patients (7/28, 25%). In control experiments with 11 healthy individual, HBV DNA was not detected in either sera or leukocytes. In all the cases with leukocyte HBV DNA, the HBV DNA molecules were present in free forms with discrete sizes. The exceptions were a case of liver cirrhosis and a case of chronic hepatitis with possible HBV sequence integration into high molecular weight cellular DNA. Since HBV does infect human leukocytes, it may perhaps interfere with the immunological functions of the white blood cells, and thus play an important role in the pathogenesis of HBV-induced liver disease.     

Occult hepatitis B virus infection in patients with chronic hepatitis C liver disease.

BACKGROUND: Hepatitis B virus (HBV) infections in patients who lack detectable hepatitis B surface antigen (HBsAg) are called occult infections. Although such infections have been identified in patients with chronic hepatitis C liver disease, their prevalence and clinical significance are not known. METHODS: With the polymerase chain reaction, we searched for HBV DNA in liver and serum samples from 200 HBsAg-negative patients with hepatitis C virus (HCV)-related liver disease (147 with chronic hepatitis, 48 with cirrhosis, and 5 with minimal histologic changes). One hundred of the patients had detectable antibodies to the HBV core antigen (anti-HBc); 100 were negative for all HBV markers. Eighty-three were treated with interferon alfa. We also studied 50 patients with liver disease who were negative both for HBsAg and for HCV markers. In six patients found to have occult HBV infection, we evaluated possible genomic rearrangements through cloning or direct sequencing procedures. RESULTS: Sixty-six of the 200 patients with chronic hepatitis C liver disease (33 percent) had HBV sequences, as did 7 of the 50 patients with liver disease unrelated to hepatitis C (14 percent, P=0.01). Among the 66 patients, 46 were anti-HBc-positive and 20 were negative for all HBV markers (P<0.001). Twenty-two of these 66 patients (33 percent) had cirrhosis, as compared with 26 of the 134 patients with hepatitis C infection but no HBV sequences (19 percent, P=0.04). HBV sequences were detected in 26 of the 55 patients in whom interferon therapy was ineffective and 7 of the 28 patients in whom interferon therapy was effective (P=0.06). None of the sequenced HBV genomes had changes known to interfere with viral activity and gene expression. CONCLUSIONS: Occult hepatitis B infection occurs frequently in patients with chronic hepatitis C liver disease and may have clinical significance.     

Hepatitis B and C: natural course of disease

Significant progress in the understanding of the natural history of hepatitis B and C has been made in recent years due to molecular diagnosis techniques. The most important biologic feature of hepatitis B and C viruses (HBV, HCV) is their ability to cause chronic hepatitis. The natural course of HBV infection is variable, ranging from inactive HBsAg carrier state to progressive chronic hepatitis that can evolve into liver cirrhosis and hepatocellular carcinoma. HBeAg-negative chronic hepatitis is due to a naturally occurring HBV variant with mutations in the precore or basic core promoter regions. It accounts for the majority of cases in many European countries and is generally associated with a more severe liver disease. The morbidity and mortality in chronic hepatitis B are linked to the evolution to cirrhosis and hepatocellular carcinoma. The progression of fibrosis is strongly associated with persistent active viral replication When the diagnosis is made, the 5-year cumulative incidence of developing cirrhosis ranges from 8% to 20%. The 5-year cumulative incidence of hepatic decompensation is 20%. Hepatocellular carcinoma is one of the most common cancers worldwide, 75% of which are related to chronic HBV infection. Coinfection with hepatitis D virus can lead to a more progressive liver disease in a shorter period of time. Hepatitis C virus infection becomes chronic in 80% of infected persons resulting in different stages of chronic hepatitis, with 20%-30% progressing to cirrhosis within 20 years period. The progression of fibrosis determines the ultimate prognosis. The major factors known to be associated with fibrosis progression are older age, male gender and alcohol consumption. Viral load and genotype do not play a role in the disease progression. Progression to fibrosis is more rapid in immunocompromised patients.