Overt and hidden coinfection with hepatitis B and C viruses in chronic liver disease and porphyria cutanea tarda

The aim of this study was to assess the rate of hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection ("the coinfection") in chronic liver disease (CLD) and to reveal overt and hidden HBV infection in patients with antibodies to HCV (anti-HCV). A total of 209 untreated patients (64 with chronic hepatitis B, 79 with chronic hepatitis C and 66 with porphyria cutanea tarda (PCT)) were screened for serological markers of HBV and HCV infection in serum by third generation enzyme-linked immunosorbent assay (ELISA) methods and for HBV DNA and HCV RNA in serum by polymerase chain reaction (PCR). The rate of the overt coinfection in chronic hepatitis B was very low (2/64, 3%). However, in chronic hepatitis C, the rate of the hidden coinfection with HBV was relatively high (19/79, 24%); these patients had higher alanine transaminase (ALT) and asparagine transaminase (AST) levels in serum and a more advanced liver disease. In PCT patients, the rates of HBV and HCV infections were the same, 21% (14/66). In the PCT patients infected with HBV or HCV, the rate of the coinfection was 33% (7/21). The PCT patients with the coinfection had a high serum ALT level and the worst histological picture in the liver. The hidden HBV infection was more frequent than the overt one. The possibility of the overt or hidden coinfection in CLD renders a detailed analysis of all serum samples for both viruses mandatory. Vaccination against HBV infection should be offered to anti-HCV-positive individuals as well as to PCT patients not showing antibodies to HBV (anti-HBV).     

Viral replication in patients with concomitant hepatitis B and C virus infections

The aim of this study was to assess the implications of dual infection with hepatitis B virus (HBV) and hepatitis C virus (HCV). The HBV and HCV status in 100 patients with chronic hepatitis was analysed. HBV DNA was studied using liquid hybridization and the polymerase chain reaction (PCR). HCV viremia was measured using qualitative and quantitative PCR. The HCV genotype was determined by PCR. Patients were divided into three groups according to their HCV-RNA and HBsAg status: group I consisted of 40 patients with chronic hepatitis caused by HBV; group II, 40 patients with chronic hepatitis caused by HCV; and group III, 20 patients infected with both viruses. The HBV-DNA level was higher in group I than in group III (66.4 vs. 11.5 pg/ml; p<0.05). Quantification of HCV viremia revealed mean values of 36.9 copies × 10⁵/ml in group II and 5.5 copies/ml × 10⁵ in group III (p<0.05). The mean aminotransferase level and histological activity were higher in group III. HCV genotype 1b was the predominant type. The data suggest that there is reciprocal inhibition of viral replication in patients with dual HBV and HCV infection. Liver disease appears to be more severe in patients with chronic hepatitis B and C.     

Co-infection by serologically-silent hepatitis B virus may contribute to poor interferon response in patients with chronic hepatitis C by down-regulation of type-I interferon receptor gene expression in the liver

Intrahepatic mRNA levels of type-I interferon (IFN) receptor genes have been shown to correlate with the clinical efficacy of IFN therapy in patients with chronic hepatitis C. Recently, co-infection by serologically-silent hepatitis B virus (HBV) has been assumed to be associated with the poor IFN response in patients with chronic hepatitis C. The aim of this study was to investigate the relationship between the co-infection of serologically-silent HBV and type-I IFN receptor gene expression in the liver of patients with chronic hepatitis C. The intrahepatic mRNA levels of IFNAR2, one of the two subunits of the type-I IFN receptor, were quantified and compared with both the prevalence of HBV DNA and the hepatitis C virus (HCV) genotype in 45 patients with chronic hepatitis C, who were negative for hepatitis B surface antigen. Co-infection, as evaluated by a nested polymerase chain reaction, was present in 22 patients (48.9%), with dominance of the HCV genotype 1b (65.2%) over genotype 2a (31.8%). Co-infection was associated with lower IFNAR2 mRNA levels, higher levels of serum HCV RNA, and a poor IFN response, regardless of the HCV genotype. The findings suggest the possibility that co-infection by serologically-silent HBV is one of the factors that can lead to an unfavorable IFN response in chronic hepatitis C by down-regulation of IFN receptor gene expression in the liver.     

Impaired response to alpha interferon in patients with an inapparent hepatitis B and hepatitis C virus coinfection

Summary.  The possibility of hepatitis B virus (HBV) infection in HBsAg-negative patients has been shown. However, an “inapparent” coinfection by HBV in hepatitis C virus (HCV)-positive patients generally is not taken into account in clinical practice. Mechanisms responsible for resistance to interferon (IFN) have not been completely clarified. The aim of this study was to investigate whether an “inapparent” coinfection by HBV in anti-HCV-positive chronic liver disease patients may influence IFN response. Fourteen anti-HCV positive, HBsAg-negative but serum HBV DNA-positive patients by PCR and 111 anti-HCV-positive, HBsAg-negative and HBV DNA (PCR)-negative patients with chronic hepatitis were treated with 3 MU of recombinant α-2a IFN 3 times weekly for 12 months. Serum HBV DNA and HCV RNA were determined before treatment, after 6–12 months and in coincidence with ALT flare-up by PCR. HBV PCR was performed using primers specific for the S region of the HBV genome and HCV PCR with primers localised in the 5′NC region of HCV genome. IgM anti-HBc was tested using IMx Core-M Abbott assay. By the end of treatment, ALT values had become normal in 4/14 HBV DNA-positive patients (28%), but all “responders” (4/4) relapsed between 2 and 5 months after therapy. All but one patient were HCV RNA-positive before treatment, 6 were also both HBV DNA and HCV RNA-positive during ALT flare-ups. In 5 patients, only HBV DNA and in 3 patients, only HCV RNA was detected when transaminase values increased. All patients remained HBsAg-negative and anti-HCV-positive. IgM anti-HBc was detected both before treatment and during ALT elevation in 3 patients and only during ALT relapse in 3 others. Of the 111 anti-HCV positive, HBsAg-negative and HBV DNA (PCR)-negative patients with chronic hepatitis, a biochemical response to IFN treatment was observed in 54% of the cases. Relapse of ALT values was observed in 47% of the cases during a follow-up of 1 year after treatment. “Inapparent” HBV/HCV coinfection may be implicated in cases of resistance to IFN treatment. In addition, HBV replication may persist in patients in whom HCV replication was inhibited by IFN treatment. The pathogenic role of HBV in liver disease was confirmed by detection of IgM anti-HBc in some cases; the appearance of these antibodies only after IFN treatment suggests that IFN may exert a selective role in favour of HBV. Further studies will show the effect of different treatment schedules. HBV DNA and/or IgM anti-HBc detection with very sensitive methods may be important both as a prognostic factor and as a tool for better understanding interviral relationships and mechanisms involved in multiple hepatitis virus infections.     

High prevalence of dual or triple infection of hepatitis B, C, and delta viruses among patients with chronic liver disease in Mongolia

Mongolia is known for its high endemicity for hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis delta virus (HDV) infections among apparently healthy individuals. However, there are little or no data on the prevalence and genotype distribution of HBV, HCV, and HDV among patients with chronic liver disease in Mongolia. Therefore, serum samples obtained in 2004 from 207 patients (age, mean+/-standard deviation, 51.0+/-11.9 years) including those with chronic hepatitis (n=90), liver cirrhosis (n=41), and hepatocellular carcinoma (n=76) were tested for serological and molecular markers of HBV, HCV, and HDV infections. Of the 207 patients, 144 (69.6%), 106 (51.2%), and 117 (56.5%) tested positive for hepatitis B surface antigen (HBsAg) and/or HBV DNA, HCV RNA, and HDV RNA, respectively. Collectively, 172 patients (83.1%) were viremic for one or more of these viruses, including dual viremia of HBV/HDV (26.6%) or HBV/HCV (7.7%) and triple HBV/HCV/HDV viremia (30.0%). Of note, triple ongoing infection was significantly more frequent among patients with hepatocellular carcinoma than among those with chronic hepatitis (63.2% vs. 14.4%, P<0.0001). One hundred sixty patients (77.3%) had a history of blood transfusion and/or surgery. The distribution of HBV genotypes among the 116 HBV-viremic patients was: A (0.9%), B (0.9%), C (6.0%), D (88.8%), and C plus D (3.4%). All 117 HDV isolates were classified into genotype I. The 106 HCV RNA-positive samples were typed as genotype 1b (92.5%), 2a (0.9%), or 1b plus 2a (6.6%); mixed infection of two distinct HCV genotypes was found exclusively in the patients with hepatocellular carcinoma.     

Anti-envelope 1 and 2 immune response in chronic hepatitis C patients: effects of hepatitis B virus co-infection and interferon treatment

Antibodies against envelope glycoprotein 1 and 2 (anti-E1/E2) have been suggested to influence HCV replication levels. Hepatitis B virus (HBV) may interfere with hepatitis C virus (HCV) replication. At present there are no data on anti-E1/E2 antibody responses or on the effect of interferon (IFN) treatment in HBV-HCV co-infection. Accordingly, we evaluated serum anti-E1/E2 antibodies in 50 patients (median age, 26.5; males, 30) with chronic hepatitis, 38 with HCV and 12 with HBV-HCV co-infection, who had undergone alpha-IFN treatment. Before starting IFN, the HCV group showed higher HCV-RNA levels (bDNA assay) than the HBV-HCV group (median 3.75 vs. 0.64 x 10(6) Eq/ml, respectively; P < 0.05). Similarly, the anti-E2 levels (EIA assay) were higher in the HCV group than in the HBV-HCV (mean +/- SD, 53.8 +/- 54.58 vs. 24.5 +/- 41.50 U/ml, respectively; P < 0.02), and the prevalence of anti-E2 was also higher in the HCV group (94 vs. 58%, respectively; P < 0.007). No correlation was found between anti-E1/E2 antibodies and the HCV-RNA levels. The prevalence of E1/E2 antibodies was similar in the different HCV genotypes. Higher baseline levels of anti-E2 antibodies and a decrease or disappearance of anti-E2 antibodies during IFN were associated with IFN sustained response in both groups, whereas no reduction in the anti-E1/E2 levels was observed in non-responders. The data show that HBV co-infection influences both HCV replication and the anti-E1/E2 antibody production. High pre-treatment levels of anti-E2 antibodies and their decrease or disappearance during interferon treatment are often associated with HCV clearance in sustained responders, irrespective of the HCV genotype.     

Prevalence and clinical implications of occult hepatitis B viral infection in hemophilia patients in Japan

The prevalence and clinical implications of occult hepatitis B virus (HBV) infection were investigated in the Japanese patients with hemophilia in whom a high prevalence of infection with transfusion-transmissible viruses has been reported. HBV DNA was detected in the sera of 22 of 43 (51.2%) patients with hemophilia who were negative for HBV surface antigen (HBs), indicating that these patients had occult HBV infection. No factor, including age, type or severity of hemophilia, presence of HBs or HBV core (HBc) antibody, or coinfection with hepatitis C virus (HCV) or human immunodeficiency virus (HIV) was associated with occult HBV infection, except for high anti-HBc titer and/or coinfection with HCV genotype 1 (1a or 1b). In general, occult HBV infection did not appear to have significant clinical implications. However, in patients in whom HBV was detected by PCR specific for the surface (S)-region, higher alanine aminotransferase levels were observed. The genotype of the occult HBV in the present study was exclusively the domestic type indigenous to Japan (genotype C), suggesting a different route of transmission for HBV in comparison to HCV and HIV in this population.     

Low rates of active hepatitis B and C infections among adults and children living with HIV and taking antiretroviral therapy: A multicenter screening study in Lesotho

Lesotho presents the second-highest adult human immunodeficiency virus (HIV) prevalence globally. Among people living with HIV, data on hepatitis B virus (HBV) or hepatitis C virus (HCV) coinfection are limited. We report HBV and HCV coinfection data from a multicentre cross-sectional study among adult and pediatric patients taking antiretroviral therapy in 10 health facilities in Lesotho. Among 1318 adults screened (68% female; median age, 44 years), 262 (20%) had immunologically controlled HBV infection, 99 (7.6%) tested anti-HBs positive and anti-HBc negative, indicating vaccination, and 57 (4.3%) had chronic HBV infection. Among the patients with chronic HBV infection, 15 tested hepatitis B envelope antigen (HBeAg) positive and eight had detectable HBV viremia (median, 2 477 400 copies/mL; interquartile range, 205-34 400 000) with a mean aspartate aminotransferase-to-platelet ratio index of 0.48 (SD, 0.40). Prevalence of HCV coinfection was 1.7% (22 of 1318), and only one patient had detectable HCV viremia. Among 162 pediatric patients screened, three (1.9%) had chronic HBV infection, whereby two also tested HBeAg-positive, and one had detectable HBV viral load (210 copies/mL). Six of 162 (3.7%) had anti-HCV antibodies, all with undetectable HCV viral loads. Overall prevalence of chronic HBV/HIV and HCV/HIV coinfection among adults and children was relatively low, comparable to earlier reports from the same region. But prevalence of immunologically controlled HBV infection among adults was high. Of those patients with chronic HBV infection, a minority had detectable HBV-DNA.     

Epidemiological and clinical evaluation of hepatitis B, hepatitis C, and delta hepatitis viruses in Tajikistan

The implication of genotypes is recognized increasingly in the clinical course of hepatitis B virus (HBV) and in response to anti-viral drugs of hepatitis C virus (HCV). Genotypic prevalence of both etiological agents varies geographically and no data are available for Tajikistan. To investigate the epidemiology and clinical significance of HBV and HCV genotypes in chronic hepatitis (group 1) and liver cirrhosis/hepatocellular carcinoma (HCC) (group 2) patients in Tajikistan, 124 patients with chronic liver disease (group 1 = 84 and group 2 = 40) were enrolled. Genotypes of HBV, HCV, and delta hepatitis virus (HDV) were determined by sequencing. The overall prevalence of anti-HCV, HCV core antigen (HCVcAg) and HBsAg was 46% (57/124) and 41.1% (51/124), respectively. Coinfection of HCV/HBV, HBV/HDV, and HCV/HBV/HDV was found in 4.8% (6/124), 11.2% (12/124), and 0.8% (1/124) of cases, respectively. HDV genotype 1 was found in 19.6% (10/51) of HBsAg-positive patients. The HBV/HDV coinfection was relatively high in group 2 compared to group 1 (15% vs. 7.1%). HCV/1b detected in 84.6% (44/52) of HCV RNA-positive patients, followed by 3a (7.6%), 2a (5.7%), and 2c (1.9%). HBV/D was detected in 94.1% (48/51) of HBsAg-positive patients, followed by HBV/A [5.8% (3/51)]. T1762/A1764 double mutation was associated with liver cirrhosis/HCC in HBV-infected patients (P = 0.0004). This is the first study on the molecular epidemiology of hepatitis viruses among chronic liver diseases patients in Tajikistan. Among HBV-infected patients, the T1762/A1764 mutation was associated with liver cirrhosis/HCC.     

Infection with hepatitis A, B, C, and delta viruses among patients with acute hepatitis in Mongolia

One hundred ten consecutive patients (60 males and 50 females; age, mean +/- standard deviation [SD], 22.6 +/- 6.4 years; range 16-48 years) who were clinically diagnosed with sporadic acute hepatitis between December 2004 and January 2005 in Ulaanbaatar, Mongolia, were studied. IgM antibodies to hepatitis A virus were detected in 18 patients (16.4%), IgM antibodies to hepatitis B core (anti-HBc IgM) in 38 patients (34.5%) including two patients with concurrent hepatitis delta virus (HDV) infection, and hepatitis C virus RNA in nine patients (8.2%). There were 30 hepatitis B virus (HBV) carriers who had detectable hepatitis B surface antigen and antibodies to HDV but were negative for anti-HBc IgM, suggesting that they acquired type D acute hepatitis due to superinfection of HDV on a background of chronic HBV infection. None had IgM antibodies to hepatitis E virus (HEV). Consequently, 16.4, 32.7, 6.4, 1.8, and 27.3% of the patients were diagnosed as having acute hepatitis of type A, B, C, type B + D (HBV/HDV coinfection), and type D (superinfection of HDV), respectively. The cause of hepatitis was not known in the remaining 17 patients (15.5%). All 18 HAV isolates were genotyped as IA, all 9 HCV isolates were genotyped as 1b, and all 32 HDV isolates were classified into genotype I. The distribution of HBV genotypes among the 67 HBV isolates was A (1.5%, n = 1) and D (98.5%, n = 66). The present study indicates that de novo infections of HAV, HBV, HCV, and HDV are prevalent among young adults in Mongolia.     

Relevance of inapparent coinfection by hepatitis B virus in alpha interferon-treated patients with hepatitis C virus chronic hepatitis

The aim of the study was to investigate whether an “inapparent” coinfection by hepatitis B virus (HBV) in anti-HCV-positive chronic liver disease patients may influence interferon (IFN) response. Fourteen anti-HCV-positive, hepatitis B surface antigen (HBsAg)-negative but serum HBV-DNA-positive patients and 111 anti-HCV-positive, HBsAg-negative, and HBV-DNA-negative patients with chronic hepatitis were treated with 3 MU of recombinant α-2a IFN 3/week for 1.2 months. Serum HBV-DNA and HCV-RNA were determined before treatment, after 6–12 months, and at the time of alanine aminotransferase (ALT) flare-up by HBV polymerase chain reaction (PCR) and HCV PCR, respectively. IgM anti-HBc were tested using the IMx Core-M assay (Abbott Laboratories, North Chigago, IL). By the end of treatment, ALT values had become normal in 4/14 HBV-DNA-positive patients (28%), but all “responders” (4/4) relapsed. IgM anti-HBc was detected both before treatment and during ALT elevation in three patients and only during ALT relapse in another three. In the remaining 111 patients, a biochemical response to IFN treatment was observed in 54% and relapse of ALT values in 47%. “Inapparent” HBV/HCV coinfection may be implicated in cases of resistance to IFN. HBV replication and HBV-related liver damage may persist in patients in whom HCV replication was inhibited by current doses of IFN, as suggested also by the presence of IgM anti-HBc in some cases. Further studies will show the effect of different treatment schedules. HBV-DNA and/or IgM anti-HBc detection with very sensitive methods may be important both as a prognostic factor and as a tool for better understanding of intervirus relationships and mechanisms involved in multiple hepatitis virus infections. J. Med. Virol. 51:313–318, 1997. © 1997 Wiley-Liss, Inc.     

乙型肝炎病毒基因分型及临床应用研究

目的了解常州地区乙型肝炎病毒基因型分布特征,探讨其基因型与肝功能损伤、病毒复制水平及对拉米夫定疗效的关系. 方法采用巢式聚合酶链反应 (nest-PCR), 扩增乙型肝炎病毒S基因区, 用末端标记方法对PCR产物标记并直接测序, 测序结果和GenBank中登录的标准基因型序列相比较. 结果对该地区146份不同HBV感染者血清HBV DNA进行了基因分型,B型51份 (34.9%),C型95份(65.1%),未发现B、C以外其他基因型;丙氨酸转氨酶(ALT)水平分别为383.8±335.7IU和364.3±333.7 IU,(t=0.335,P>0.05)、HBV DNA含量分别为107.795±1.22和107.69±1.19拷贝/毫升(t=0.138,P>0.05)、HBeAg 阳性数分别为36/51和64/95,(χ2=0.159,P>0.05);104例慢性乙型肝炎中B型为43例、C型为61例,28例肝硬化和肝癌患者检出B型4例、C型24例,二组比较χ2=7.65,P<0.01;23例B基因型患者和45例C基因型患者接受48周以上拉米夫定治疗,48周后反跳者B型为18例,C型为14例,χ2=13.49,P<0.001.结论本地区HBV DNA基因型为B型和C型;二种基因型丙氨酸转氨酶水平、病毒复制水平和HBeAg表达水平差异均无显著性;C基因型与肝硬化和肝癌关系密切;拉米夫定对C基因型患者的疗效强于B型.     

Hepatitis C virus is frequently coinfected with serum marker-negative hepatitis B virus: Probable replication promotion of the former by the latter as demonstrated by in vitro cotransfection

Patients with hepatitis C have been reported occasionally to be coinfected with serum marker-negative (silent) hepatitis B virus (HBV). The frequency and significance of such coinfection were investigated. Thirty patients with hepatitis C virus (HCV) infections (10 acute, 10 chronic, 10 cirrhotic) were selected randomly; the acute cases were without serum hepatitis B surface antigen (HBsAg) and anti-hepatitis B core IgM, and the chronic cases were without HBsAg. A nested polymerase chain reaction for the X open reading frame was used to amplify HBV DNA in serum, and immunoperoxidase staining was carried out on liver biopsy specimens. Nucleotide sequencing was carried out to characterize the amplified HBV DNAs. In order to clarify the possibility that the silent HBV mutant promotes HCV replication in the liver, the full-length HCV RNA and the cloned silent HBV DNA dimer were cotransfected into an established cell line, HuH-7, and the amount of secreted HCV RNA was quantified serially. The target HBV DNA was amplified in 26 (86.7%) of the 30 patients. Subsequent direct nucleotide sequencing in 9 selected patients revealed an 8-nucleotide deletion, characteristic of a silent HBV mutant. Immunostaining revealed hepatitis B surface antigen in 15 (50.0%). Cotransfected silent HBV DNA augmented the secretion of HCV RNA by up to 5-fold in comparison with HCV RNA transfection alone. In conclusion, HCV is coinfected frequently with the silent HBV mutant and the latter probably promotes the replication of the former in the liver. J. Med. Virol. 52:399–405, 1997. © 1997 Wiley-Liss, Inc.     

Kinetics of HBV DNA and HBsAg in acute hepatitis B patients with and without coinfection by other hepatitis viruses

The kinetics of hepatitis B virus (HBV) and its surface antigen (HBsAg) during acute hepatitis has not yet been studied accurately in a representative number of patients. The influence of coinfecting hepatitis viruses during the acute phase of infection is not known. Three to four serum samples from 21 patients with acute HBV monoinfection and 27 with coinfection were taken at intervals of 6-10 days and analyzed for the number of HBV genome equivalents (ge) by real time polymerase chain reaction (PCR) and for HBsAg quantity using Laurell electrophoresis. Log HBV ge/ml decreased during the follow-up from 6.8 +/- 1.1 to 5.1 +/- 1.0 to 4.2 +/- 0.8 to 3.3 +/- 1.1 (mean +/- SD). The half-life times of HBV ge increased from 1.6 days at the beginning to 4 days at the end. HBsAg decreased much slower: from 38 to 23 to 12 to 3.8 microg/ml. Half-life time was around 8 days at the beginning and 5.7 days at the end, but 11 patients showed a rapid elimination of HBsAg and HBV DNA. Hepatitis C virus (HCV) coinfection did not change the kinetics of HBV ge and HBsAg significantly. A moderate but significant suppression of HBV ge levels was observed in hepatitis D virus (HDV) coinfected patients. HBsAg levels were, however, enhanced in this cohort. In conclusion, the data suggest that expression and elimination of HBV is in most patients with acute hepatitis B not altered by coinfecting hepatitis viruses. The initial decrease of HBV ge and HBsAg in serum appears to be caused by decay or non-specific removal in the absence of replacement.     

Direct-acting antiviral treatment in adults infected with hepatitis C virus: Reactivation of hepatitis B virus coinfection as a further challenge

Use of direct-acting antiviral drugs (DAAs) greatly improves management of adults infected with hepatitis C virus (HCV) whether patients are treatment-naive or unsuccessfully pre-treated. Several inhibitors of viral nonstructural proteins (NS3/4A protease, NS5A and NS5B polymerase) allow a rapid HCV clearance and increase rates of sustained virological response. Both the EASL and AASLD guidelines have recently published up-to-date recommendations for their use, addressing each HCV genotype and particular situations. However, management of patients coinfected with hepatitis B virus (HBV) has been developed by these guidelines with reference to cases of HBV reactivation reported during previous anti-HCV regimens containing interferon known active against both HBV and HCV. In the setting of the interferon-free HCV therapies with DAAs only, the possibility of HBV reactivation during treatment of hepatitis C is raised due to viral interferences in HCV/HBV coinfected persons. Herein, we report a case of early HBV reactivation during DAAs-based anti-HCV treatment (ledipasvir/sofosbuvir) in a patient having a resolved HBV infection and chronically infected with HCV genotype 4 and HIV. Moreover, we review similar recent cases of HBV reactivation in patients infected with HBV and HCV genotype 1 during treatment of hepatitis C by regimen incorporating other combination of DAAs (sofosbuvir/simeprevir or daclatasvir/asunaprevir). Due to the potential risk of early HBV reactivation in HCV/HBV-coinfected patients during interferon-free DAAs-based HCV therapies, altogether these cases highlight the necessity to closely monitor HBV coinfection, regardless its stage (chronic, occult, resolved), whatever HCV genotype or class of DAAs used.     

慢性乙型肝炎病毒基因型与临床病理相关性分析

目的 了解慢性乙型肝炎病毒基因型与临床及病理表现的相互关系.方法对92例慢性乙型肝炎患者进行HBV基因分型,并与其临床生化结果、病毒定量和肝组织病理进行相关性分析.结果 B基因型16例(17.4%),C基因型71例(77.2%),B+C混合型3例(3.2%),未分出型2例(2.2%),其中B和C基因型在丙氮酸转氨酶水平分别为(82.6±82)U/L和(84.7±71.5)U/L,病毒复制水平Log值分别为(5.8±1.4)和(5.9±1.5),C型患者中有8例病理诊断为肝炎肝硬化,但均无统计学意义.结论 B型和C型慢性肝炎患者在丙氨酸转氨酶、病毒复制、HBeAg表达水平及肝脏病理炎症和纤维化程度间差异无统计学意义.     

慢性丙型肝炎患者HCV基因型调查

目的 研究丙型肝炎病毒（ＨＣＶ）基因型的流行病学特点。方法 采用ＩＮＮＯ－ＬＩＰＡ反向线形探针杂交法，对来自我国南方（上海，武汉，徐州）、北方（北京、天津）和东北（大连、沈阳）７市的１０７例慢性丙型肝炎患者进行了ＨＣＶ基因型调查。结果（１）地域性，ＨＣＶ１ｂ是主要的基因型，其检出率达８３．１７％，其中东北２市（７２．２２％）低于北方２市（８７．６５％，Ｐ〈０．０１）；２型的检出率较低，仅占６．８６     

Clinical features and treatment efficacy of peginterferon alfa plus ribavirin in chronic hepatitis C patients coinfected with hepatitis B virus

Background/Aims

Cross-sectional studies have documented that 2-10% of patients who are chronically infected with hepatitis C virus (HCV) are also positive for hepatitis B virus (HBV) surface antigen (HBsAg). Data related to HCV-HBV coinfection are lacking in Korea. This study evaluated the clinical characteristics, the treatment efficacy of peginterferon alfa plus ribavirin, and the changes induced by such treatment in HBV status in chronic hepatitis C (CHC) patients coinfected with HBV.

Methods

Eighteen (2.37%) HBsAg-positive CHC patients were selected from among the 758 subjects from the K(G)yeonggi-Incheon Peginterferon alfa and ribavirin in chronic hepatitis C Treatment (KIPECT) study, which evaluated the treatment efficacy and safety of peginterferon alfa plus ribavirin in CHC patients. Data on changes in the status of HBV infections were obtained.

Results

HCV genotype 1b was the most common (44%). The overall sustained virologic response rate was 72% in all patients, and 60% and 87.5% in genotypes 1 and 2, respectively. Two of the 18 patients were positive for HBeAg, and 15 had baseline HBV DNA level of less than 2,000 IU/mL. Two of the three whose levels exceeded this threshold showed no detectable DNA after treatment. After the completion of treatment, serum HBV DNA levels were increased in the two patients whose baseline HBV DNA levels were less than 2,000 IU/mL.

Conclusions

The prevalence of HBV coinfection in CHC patients was 2.37% and most of the patients were inactive carriers. The treatment efficacy was similar to that of HCV mono-infection. Reactivation of HBV replication was observed in some patients after CHC treatment.     

Selection of more pathogenic hepatitis C virus genotype II during long-term follow-up of interferon-treated patients

The behavior of hepatitis C virus (HCV) infection with regards to type and number of HCV genotypes (tested with genotype-specific nested polymerase chain reaction) was evaluated in 60 patients with anti-HCV-positive chronic active hepatitis without cirrhosis [17 untreated and 43 subjects undergoing single or repeat courses of interferon (IFN) therapy] during a mean follow-up period of 76±18 months. In untreated patients (2 genotype I, 6 genotype II, 9 mixed infections) 4 out of 9 mixed infections selected for genotype II at the end of follow-up. Of the 43 treated patients 10 were long-term responders with histological remission, 6 were shortterm responders, and 22 did not respond. Fifteen of the latter patients received another course of IFN therapy, and only 3 patients responded. Eight of the 10 responders had infection with a single genotype (4 gt I, 3 gt II, 3 gt III). After IFN therapy, all but 2 patients cleared the HCV infection. The responders to the second IFN course (1 gt I, 1 gt II, 1 gt III) remained viremic. Of the shortterm responders, 2/6 patients had genotype II and 4 had a mixed infection (3 gt II±I and 1 gt II±III); gt III became prevalent in the latter in all but one patient. Of the nonresponders 18/24 had more than one genoytpe, 5 were genotype II at baseline and one had genotype I. At the end of the follow-up period 15/18 with mixed infection had selected for gt II (P<0.01 vs. untreated patient). Thirteen of 18 nonresponders who selected genotype II during follow-up developed cirrhosis, compared with none among the four untreated which also selected for genotype II (P<0.01) and with none of the patients maintaining their baseline genotype (P<0.01). In conclusion, patients with single HCV genotype, other than gt II, respond better to IFN, which seems to easily suppress HCV genotypes other than II. Genotype II is scarcely inhibited and becomes predominant during follow-up. In the patients selecting for genotype II, cirrhosis develops more rapidly than in untreated patients, where the selection for genotype II occurs at much slower rate.Abbreviations ALT Alanine aminotransferase - HAI Histological activity index - HCV Hepatitis C virus - IFN Interferon - PCR Polymerase chain reaction     

Liver histopathology in patients with concurrent chronic hepatitis C and HIV infection

To investigate the influence of human immunodeficiency virus (HIV) coinfection on preexisting long-term chronic C hepatitis (HCV) 68 liver biopsies from 22 HIV/HCV-coinfected, 13 HIV and 33 HCV-monoinfected patients and 71 livers obtained at autopsy from 26 HIV/HCV-coinfected and 45 HIV-monoinfected patients were studied by histo- and immunohistochemistry. All HIV patients had reached the advanced stage of immunodeficiency (stage III CDC), except for 3 haemophiliacs (stage II CDC). HCV infection was associated with a higher degree of portal, periportal and lobular inflammation — regardless of whether there was concurrent HIV infection. HIV/HCV coinfection was associated with a significantly higher rate of granulocytic cholangiolitis than HCV and HIV monoinfection (P < 0.05), a histological feature uncommon in C hepatitis. In HIV/HCV coinfection cholestasis was a predominant histological feature. HCV monoinfection and HCV/HIV coinfection were associated with the highest fibrosis index. In HIV/HCV coinfection centrilobular fibrosis was significantly more marked than in HCV monoinfection (P < 0.05), suggesting an HIV associated fibrogenic effect. Patients with chronic C hepatitis showed a significantly increased rate of posthepatitic cirrhosis compared with the patients without HCV infection (P < 0.05). At autopsy, 10 of the 20 HIV/HCV-coinfected haemophiliacs had developed cirrhosis because of chronic C hepatitis, whereas cirrhosis was found in only 2 of 6 HIV/HCV-coinfected non-haemophiliacs (1 case of chronic B and C hepatitis, and 1 case of chronic alcohol abuse). No cirrhosis was observed in the 45 autopsy patients with HIV monoinfection. The findings suggest that HIV coinfection aggravates the course of preceding long-term chronic C hepatitis by a more marked (centrilobular) fibrosis. HIV/HCV-coinfected patients are threatened by a higher rate of posthepatitic cirrhosis —particularly in multitransfused haemophiliacs — and cholestatic hepatopathy.