Serological reactivity and viral genotypes in hepatitis C virus infection.

Patients infected with hepatitis C virus (HCV) were examined with four commercial HCV immunoblotting assays and for anti-GOR antibody to ascertain whether serological findings varied with the genotype of the infecting virus. The results indicate that patients infected with different HCV genotypes tend to show different immunoblotting profiles, mainly due to a low prevalence of antibodies to the viral region NS4 in patients infected with genotypes III and IV. Differences were more evident with second- than with third-generation assays. Patients infected with genotype IV exhibited a lower prevalence of anti-GOR antibody than patients infected with other genotypes.     

Hepatitis C viral genotype influences the clinical outcome of patients with acute posttransfusion hepatitis C

Most patients with an acute infection of hepatitis C virus (HCV) will develop chronic hepatitis, and only about 15-20% of the cases will resolve spontaneously. The mechanism for the different outcomes in patients with acute HCV infection remains unclear. HCV genotype has been recognized as an important factor affecting the clinical course and outcome of chronic hepatitis C patients. In order to evaluate the role of HCV genotype in the clinical course and outcome of acute posttransfusion hepatitis C, 67 patients with acute posttransfusion hepatitis C from a prospective study of posttransfusion non-A, non-B hepatitis were enrolled. Thirty-nine patients (58.2%) were HCV genotype 1b. Among the 67 patients with acute posttransfusion hepatitis C, 53 (79.1%) progressed to chronic hepatitis. Significantly more patients with genotype 1b than non-1b genotypes developed chronic hepatitis (89.7% vs. 64.3%; P = 0.019). There was no significant difference in gender, mean age, amount of transfused blood, hepatitis symptoms, jaundice, incubation period, peak serum alanine transaminase, or serum HCV RNA titer between patients with HCV genotype 1b and non-1b infections. Patients who developed chronic hepatitis had a significantly greater incidence of genotype 1b infection (66.0% vs. 28.6%; P = 0.013) and a longer incubation period (7.3 weeks vs. 5.4 weeks; P = 0.052) than patients whose infection was resolved. Patients with a genotype 1b infection that resolved itself spontaneously all had an incubation period of less than 6 weeks. Multivariate logistic regression analysis revealed that genotype 1b and an incubation period > or = 6 weeks were significant predictive factors for the development of chronic hepatitis. Therefore, the HCV genotype can influence the outcome of patients with acute HCV infection.     

输血后乙型肝炎病毒感染的前瞻性研究

目的　了解输血后所致乙型肝炎病毒 (HBV)感染现状 ,以及通过检测乙型肝炎病毒表面抗原筛选献血员的效果。方法　用酶联免疫吸附测定 (ELISA)和聚合酶链反应 (PCR)分别检测了受血者和供血者血清中HBV M和HBVDNA。结果　在 5 83份供血者血中HBV M阳性 32 6份 ,HBVDNA阳性 5 7份。 136份受血者输血后 39份血清HBV M阳转 ,阳转率为 2 8 6 8% ;2 3份HBVDNA阳性 ,阳性率为 16 9%。结论　经检测乙型肝炎病毒表面抗原筛选献血员后仍有输血后乙型肝炎病毒感染的可能。     

Serological and molecular genetic markers of hepatitis C virus in infected donors

The frequency of hepatitis C virus (HCV) markers was determined in donors; the spectrum and activity of specific antibodies (anti-HCV), the distribution of virus genotypes, and HCV RNA concentrations were studied in virus carrier donors. The activity of antibodies in HCV RNA-negative donors was significantly lower than that in HCV RNA-positive donors (p < or = 0.001). There was a statistically significant difference in antibody activities in donors infected with genotype 1b as compared with those infected with genotype 3a (p < 0.001). However, no correlation was found between the concentration of a virus genome and the activity of specific antibodies. The risk for obtaining infected blood donations was determined during plasma screening by enzyme immunoassay (EIA). Our investigations have indicated that the frequency of serological window period donations is one case per 74750 test plasma units and that of HCV RNA-positive donations with low antibody positivity coefficients, which are frequently detectable as seronegative during screening for laboratory errors, is one case per 37375 test units. A combination of EIA and polymerase chain reaction has shown to minimize the risk of contamination of donor plasma with HCV markers.     

Differential diagnosis of viral hepatitis based on hepatitis viral markers

192 patients of acute viral hepatitis (AVH) from three different hospitals of Madras metropolitan area during November 1985 to January 1986 were investigated for serologic markers of hepatitis A virus (anti HAVIgM) and hepatitis B virus (HBsAg, HBeAg, anti HBcIgM and anti HBs) by Enzyme linked immunosorbent assay (ELISA). While the overall pattern of AVH in Madras as revealed from the study showed Hepatitis A to be 36.4%, Hepatitis B 34.4% and Non-A Non-B 29.1%, the pattern differed significantly when areawise categorisation was done. The major AVH type in Government General Hospital was Hepatitis B (48.9%). While it was hepatitis A (46.9%) in Government Stanley Hospital and Non-A Non-B (40.0%) in Military Hospital. Using anti HBcIgM marker of Hepatitis B Virus and anti HAVIgM it was possible to make out that 13.5% of the cases, currently suffering from hepatitis A were either HBV carriers (8.3%) or cases convalescing from a previous Hepatitis B attack (5.3%). Various combinations of HBV markers positivity were observed and their diagnostic significance inferred.     

Recombinant immunoblot assay for hepatitis C antibody in patients with posttransfusion non-A, non-B hepatitis.

In a prospective study of 287 patients who received blood transfusion, 26 who were found positive for hepatitis C antibody (anti-HCV) by an enzyme-linked immunosorbent assay (ELISA) were studied by a recombinant immunoblot assay (RIBA). Nineteen of the 26 patients had posttransfusion non-A, non-B (NANB) hepatitis. Sixteen (84.2%) of the 19 patients with hepatitis had positive results by RIBA, 2 had indeterminate results, and 1 was negative. By contrast, five of the 7 recipients without hepatitis were negative, 1 indeterminate, and 1 positive by RIBA. Those with negative RIBA results had significantly lower optical density (OD) readings by ELISA than those with positive RIBA tests. Therefore, patients without hepatitis or lower OD value have a higher false-positive rate in anti-HCV ELISA than did those with a high OD value or with evidence of hepatitis.     

How to interpret viral markers in the management of chronic hepatitis B infection

BackgroundHepatitis B virus (HBV) infection is a global public health issue with several unsolved clinical challenges. As multiple new drugs are under development, HBV markers are gaining importance for both diagnostic and prognostic purposes.ObjectivesThis review summarizes the most important data on the usefulness of HBV markers in the natural history of this infection, and in predicting clinical and treatment outcomes.SourcesSelected peer-reviewed publications on HBV markers published between January 2009 and July 2021.ContentIn addition to the classical markers (e.g. HBV-DNA), newer ones, such as quantitative HBsAg, HBcrAg, HBV-RNA and quantitative anti-HBc, have proven useful for predicting events within the natural history of HBV infection, the development of complications (e.g. hepatocellular carcinoma) and the response to antiviral therapy. Most data regarding the response to treatment have been related to nucleos(t)ide analogues, whereas evidence on new therapeutic agents, such as capsid assembly modulators or small interference RNAs, is promising, but still scarce.ImplicationsKnowledge on the use of viral markers is a key factor for optimizing the clinical appraisal of HBV infection. The new markers have an enhanced ability to predict clinical outcomes. Further studies should expand the current evidence on the use of markers in relation to antiviral agents currently under evaluation. Wide availability of these markers in regions with a high incidence of HBV infection is of paramount importance.     

Serological diagnostics of hepatitis E virus infection

Development of accurate diagnostic assays for the detection of serological markers of hepatitis E virus (HEV) infection remains challenging. In the course of nearly 20 years after the discovery of HEV, significant progress has been made in characterizing the antigenic structure of HEV proteins, engineering highly immunoreactive diagnostic antigens, and devising efficient serological assays. However, many outstanding issues related to sensitivity and specificity of these assays in clinical and epidemiological settings remain to be resolved. Complexity of antigenic composition, viral genetic heterogeneity and varying epidemiological patterns of hepatitis E in different parts of the world present challenges to the refinement of HEV serological diagnostic assays. Development of antigens specially designed for the identification of serological markers specific to acute infection and of IgG anti-HEV specific to the convalescent phase of infection would greatly facilitate accurate identification of active, recent and past HEV infections.     

New assays for quantitative determination of viral markers in management of chronic hepatitis B virus infection.

We performed a quantitative study of serum hepatitis B virus (HBV) markers, including new parameters such as pre-S1 antigen (Ag), pre-S2 Ag, and anti-HBx, in 88 chronic hepatitis B surface antigen (HBsAg) carriers. New IMx assays for HBsAg and immunoglobulin M (IgM) anti-HBc detection were also used. The population studied was composed of 65 chronic hepatitis cases (40 positive for hepatitis B antigen [HBeAg] and 25 positive for anti-HBe) and 23 anti-HBe-positive, asymptomatic HBsAg carriers. Serum HBsAg levels detected by IMx were higher in HBeAg-positive than in anti-HBe-positive HBsAg carriers (all patient subgroups included) and correlated with the serum HBV DNA level (P = 0.0001). Both pre-S1 and pre-S2 Ags were detected by enzyme immunoassays in almost all HBsAg carriers. Both pre-S1 and pre-S2 Ag titers correlated positively with the serum HBsAg concentration (P = 0.0001), but only the pre-S1 Ag titer correlated with the level of serum HBV DNA (P = 0.02). The detection of low levels of IgM anti-hepatitis B core (anti-HBc) antibodies by IMx was associated with the presence of liver disease (P = 0.05) but not with the level of viral replication. The prevalence of anti-HBx antibodies detected by the enzyme immunoassay was slightly, although not significantly, higher in patients with high levels of HBV DNA (greater than 100 pg/ml) than in patients without detectable HBV DNA (P = 0.16). In anti-HBe-positive chronic HBsAg carriers, the quantitative detection of serum HBV DNA, pre-S Ag titers, and IgM anti HBc allowed us to predict which patients suffered from chronic liver disease and/or supported viral replication (P < 0.05). In a follow-up study of eight patients undergoing antiviral therapy, the clearance of both pre-S1 Ag and HBV DNA was associated with a subsequent clearance of HBV. Therefore, the quantitative determination of HBV DNA, pre-S Ags, IgM anti-HBc may prove useful for the decision to use and the monitoring of antiviral therapy, especially in anti-HBe-positive HBsAg carriers.     

Predictors of spontaneous viral clearance and outcomes of acute hepatitis C infection

Background/Aims

This study evaluated the predictors of spontaneous viral clearance (SVC), as defined by two consecutive undetectable hepatitis C virus (HCV) RNA tests performed ≥12 weeks apart, and the outcomes of acute hepatitis C (AHC) demonstrating SVC or treatment-induced viral clearance.

Methods

Thirty-two patients with AHC were followed for 12-16 weeks without administering antiviral therapy.

Results

HCV RNA was undetectable at least once in 14 of the 32 patients. SVC occurred in 12 patients (37.5%), among whom relapse occurred in 4. SVC was exhibited in 8 of the 11 patients exhibiting undetectable HCV RNA within 12 weeks. HCV RNA reappeared in three patients (including two patients with SVC) exhibiting undetectable HCV RNA after 12 weeks. SVC was more frequent in patients with low viremia than in those with high viremia (55.6% vs. 14.3%; P=0.02), and in patients with HCV genotype non-1b than in those with HCV genotype 1b (57.1% vs. 22.2%; P=0.04). SVC was more common in patients with a ≥2 log reduction of HCV RNA at 4 weeks than in those with a smaller reduction (90% vs. 9.1%, P<0.001). A sustained viral response was achieved in all patients (n=18) receiving antiviral therapy.

Conclusions

Baseline levels of HCV RNA and genotype non-1b were independent predictors for SVC. A ≥2 log reduction of HCV RNA at 4 weeks was a follow-up predictor for SVC. Undetectable HCV RNA occurring after 12 weeks was not sustained. All patients receiving antiviral therapy achieved a sustained viral response. Antiviral therapy should be initiated in patients with detectable HCV RNA at 12 weeks after the diagnosis.     

Serological analysis of duck hepatitis B virus infection

A radioimmunoassay was developed to detect duck hepatitis B virus surface antigen and antibody; viraemia (DHBV DNA or DHBsAg) was detected in all ducks inoculated within 3 weeks post-hatch, and persistent infection developed in 93% of birds in this group. In contrast, only 80% and 60% of ducks inoculated 4- and 6-weeks post-hatch respectively developed viraemia, and approximately 70% of the viraemic ducks became carriers. Markers of viraemia were undetected in ducks inoculated 8 weeks post-hatch and in uninfected controls. A typical anti-DHBs seroconversion developed subsequently in 2 of 4 birds that showed transient viraemia, and antibody also developed in 3 of 7 ducks inoculated 4-8 weeks post-hatch that showed no viraemia. However, gene amplification by the polymerase chain reaction demonstrated DHBV DNA in ducks from the latter group suggesting that the antibody did not result from passive vaccination. Thus, increased resistance to infection develops with increasing age that may be related to several factors including host immunity. This model may help elucidate similar age-related features of human hepatitis B virus infections.     

乙型肝炎病毒感染时的C基因热点变异

为了解乙型肝炎病毒感染在不同病变时的Ｃ基因热点变异，对９１名感染者以限制片段长度多态性技术检测前Ｃ终２８和Ｃ区Ｌ９７点突变。在急性乙型肝炎和慢性无症状携带者几无突变、在慢性持续性肝炎中罕见，而在慢性活动性肝炎和活动性肝硬变中分别达８０％和７８％，肝细胞癌中为６１％。ＨＢｅＡｇ（＋）的慢性活动性肝炎和活动性肝硬变１６例中，混合有终２８变异１１例，抗－ＨＢｅ（＋）病例中亦有野毒株混合。Ｃ区密码９７亮氨酸变异（Ｌ９７）亦见混合。野毒株和变异株在病程中有消长，Ｃ基因的热点变异与病变活动性密切相关。第一军医大学南方医院     

Patterns of serological markers in transfusion-transmitted hepatitis C virus infection using second-generation HCV assays.

A semiautomated dot blot assay and cDNA polymerase chain reaction (PCR) were used to study longitudinal anti-hepatitis C virus (HCV) recognition patterns in relation to presence of HCV-RNA in transfusion recipients and their infectious donors. In 9 recipients, 4 different patterns of HCV infection were observed: (A) persistent HCV carriage accompanied by chronic hepatitis in 6, (B) acute resolved hepatitis, but persistent HCV replication in one, and (C) continuous HCV replication without hepatitis in one and (D) acute resolved hepatitis with clearance of infection in one. This last self-limited infection was characterized by the disappearance of HCV-RNA as well as anti-HCV reactivity. In contrast, antibody reactivity persisted in 7 of 8 patients with chronic HCV infection who could be followed until 1990. Seven of the 9 recipients developed antibodies to all recombinant peptides in dot blot assay; one became positive for anti-C33 and anti-core and one developed anti-core only. The sequence of appearance of antibodies differed among individual patients. In 7 patients with full anti-HCV recognition patterns, the sequence of events was (mean and limits in days after transfusion): onset of hepatitis at day 50 (22-74), seroconversion of anti-C33 at day 91 (59-129), anti-core at day 133 (54-203), and anti-C100 at day 143 (59-365). The incorporation of C33 and core proteins, in addition to C100, in the second generation anti-HCV ELISA enhanced the detection rate in the HCV-infected transfusion recipients from 7/9 (78%) to 9/9 (100%).(ABSTRACT TRUNCATED AT 250 WORDS)