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Does hepatitis B virus (HBV) genotype influence the clinical outcome of HBV infection?

Between 5 and 10% of adults infected with the hepatitis B virus (HBV) develop a chronic infection lasting longer than 6 months, which may lead to advanced liver disease. HBV can be classified into six genotypic families: A, B, C, D, E and F, but only genotypes A and D are significantly represented in western Europe, where they account for some 90% of cases of infection with HBV. In the present study, we investigated a possible association between HBV genotype A or D and clinical outcome of the infection. We compared the prevalence of these genotypes in a group of patients with chronic active hepatitis to that of a group with acute resolving hepatitis. In patients with chronic active hepatitis, genotype A was found in 28 of 35 patients and genotype D in only four. The remaining three patients were infected with genotype non-A, non-D. In contrast, genotype D was found in 24 of 30 patients with acute hepatitis, whilst genotype A was found in only three patients of this group. Three were infected with genotype non-A, non-D. Our results show a clear association between genotype A and chronic outcome (Ficher's exact test: two-sided P-value, P < 0.0001). They suggest that HBV genotypes may play a role in the virus-host relationship. Possible mechanisms for such a role are discussed.

Acute Disease↗

Influence of different hepatitis C virus genotypes on the course of asymptomatic hepatitis C virus infection.

BACKGROUND & AIMS: The association of liver disease with hepatitis C virus (HCV) genotypes mainly refers to patients with serious liver damage; little information is available on symptomless carriers. The aim of this study was to investigate the correlation of genotypes with clinical course, risk factors for infection, and antibody to HCV reactivity in asymptomatic subjects. METHODS: One hundred nine viremic blood donors with at least 1 year of follow-up were studied; 41 underwent liver biopsy. Genotypes were determined by line-probe assay. RESULTS: Genotype 1 was found in 47 (43.1%), genotype 2 in 48 (44%), genotype 3 in 8 (7.3%), genotype 4 in 2 (1.8%), and coinfections in 4 (3.7%). The relative risk (RR) for a raised pattern of alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltranspeptidase was 2.1 (confidence interval [CI], 1.4-3.2), 1.7 (CI, 1.2-2.4), and 2.8 (CI, 1.6-4.9) in subjects with genotype 1 vs. 0.4 (CI, 0.2-0.7), 0.4 (CI, 0.3-0.7), and 0.4 (CI, 0.2-0.8) in subjects with genotype 2. Chronic hepatitis was found in 68%; the RR of chronic hepatitis was similar for genotypes 1 and 2 (RR, 1.1 [CI, 0.8-1.7] vs. RR, 1.0 [CI, 0.7-1.6]). Reactivity to NS4-derived antigens was infrequent in type 2-infected subjects. CONCLUSIONS: Genotype 2 was as frequent as genotype 1 but associated with less liver function impairment. The high prevalence of chronic hepatitis should be considered in counseling viremic asymptomatic donors.

Adult↗

The natural course of chronic hepatitis C: a comparison between patients with genotypes 1 and 2 hepatitis C viruses.

This study was conducted to clarify if the long-term histological outcome among patients with chronic hepatitis C differs according to whether they are infected with genotype 1 or 2 hepatitis C virus (HCV). We examined 140 patients with chronic hepatitis C. The HCV genotype was determined by the enzyme-linked immunosorbent assay (ELISA) based on genotypes 1 and 2 specific recombinant proteins; genotype 1 was found in 100 patients (96 were 1b and 4 were indeterminate) and genotype 2 in 36. The two groups showed no significant difference for any clinical background features. Deterioration of the grade of liver histology during the follow-up period was seen in 68.0 percent of the patients with genotype 1 as compared with 41.7 percent of those with genotype 2 (P < .01). Similarly, the deterioration of the stage of liver histology was more common in the former group than in the latter (63.0 percent and 38.9 percent respectively; P < .05). The mean serum HCV-RNA titer was significantly higher in the patients with genotype 1 than in those with genotype 2 (P < .001), and multivariate analysis showed the titer was one of the independent factors of the deterioration of the stage (P = .0044). This phenomenon may be related in part to the difference in pathogenicity between the two HCV genotypes. In conclusion, our results suggest that more severe progression of chronic hepatitis C is seen in patients showing genotype 1b compared with those with genotype 2.

Adolescent↗

[Significance of genotypes in chronic hepatitis C virus infection and hepatitis C virus induced liver cirrhosis in Germany].

INTRODUCTION AND OBJECTIVE: Hepatitis C virus (HCV) infection is characterized by a high chronicity rate. Several HCV genotypes have been described. As their distribution pattern in Germany had been unknown it was the aim of this study to determine it in a sizeable group of patients and to find out whether the genotypes differ in the severity of the disease caused by them. PATIENTS AND METHODS: 115 consecutive patients were studied prospectively, 62 (40 men, 22 women) with chronic HCV infection (group 1) and 53 (36 men, 17 women) with liver cirrhosis caused by HCV (group 2). The genotypes were determined by line probe assay. RESULTS: The mean age of the patients in group 1 was significantly lower than that in group 2 (40.4 +/- 13.7 vs 57.1 +/- 12.1 years; P < 0.0001). In group 1, genotype 1b was most frequent (53%; 1a: 21%, 3a: 21%, 2b: 3%, 2a: 2%). Genotype 1b also predominated in group 2 (78%; 1a: 17%, 2a: 4%, 3a: 2%). The differences in frequency between the two groups were significant regarding genotypes 1b (P = 0.01) and 3a (P = 0.005). Genotype 3a was found only in the younger patients. Mean age of patients with genotype 3a and chronic hepatitis C was significantly lower than that of the other patients in this group (34.2 +/- 4.6 vs 42.0 +/- 14.8 years; P < 0.002). CONCLUSIONS: The results show that in Germany genotype 1b predominates and seems to be associated more often with the advanced stages of liver disease. The fact that genotype 3a occurs exclusively in younger patients points to a change in genotype spectrum: infection with this genotype may take a less aggressive course since fewer cases of liver cirrhosis have been observed.

Adult↗

The clinical utility of fetal cell sorting to determine prenatally fetal E/e or e/e Rh genotype from peripheral maternal blood.

OBJECTIVE: This study was undertaken to determine the fetal E/e or e/e Rh genotype prenatally from peripheral maternal blood by examining sorted fetal cells from alloimmunized and nonalloimmunized pregnancies. STUDY DESIGN: Eighteen maternal peripheral venous blood samples were obtained before amniocentesis from 15 pregnant women who were homozygous for the e allele. Five were not alloimmunized and 10 were alloimmunized. The mononuclear cell layer was isolated from the maternal blood and enriched for fetal nucleated red blood cells by flow cytometry with monoclonal antibodies to CD36 or CD71 and to glycophorin A. Eight samples were treated with CD45 monoclonal antibody-coated magnetic beads before they were sorted to deplete the maternal sample of leukocytes (CD45(+) cells). We defined the positive fetal cell fractions as the monoclonal antibody positive-sorted cells derived from the maternal samples. These included sorted cells that were CD36(+)/glycophorin A(+), CD71(+)/glycophorin A(+) and CD45(-) cells that were sorted to become CD45(-)/CD36(+)/glycophorin A(+) or CD45(-)/CD71(+)/glycophorin A(+). The negative fractions were the cells that were negative for either CD36/glycophorin A or CD71/glycophorin A or were the CD45(+) cells. Deoxyribonucleic acid was isolated from all fractions and amplified by polymerase chain reaction with allele-specific primers for the E or e Rh genes. Gel electrophoresis was performed to detect fetal E/e or e/e Rh genotype. The fetal E/e or e/e Rh genotype was confirmed by serologic and deoxyribonucleic acid testing. The accuracy of E/e or e/e Rh genotype determination from the positive cell fractions was compared with that of E/e or e/e Rh genotype determination from the negative fractions. RESULTS: Fetal E/e or e/e Rh genotype was determined correctly in 17 of 18 of the fetal cell enriched positive fractions (94%). Fetal E/e or e/e Rh genotype was determined correctly in 11 of 14 of the maternal samples in the negative unselected cell fractions (79%). Fetal E/e or e/e Rh genotype was determined correctly in 15 of 16 sample fractions that underwent magnetic bead separation with CD45 and were subsequently sorted into positive and negative fractions (94%). Fetal E/e or e/e Rh genotype was determined correctly in 13 of 13 of the samples obtained from the alloimmunized pregnancies (100%). CONCLUSIONS: The use of monoclonal antibodies for cell sorting or for magnetic separation predicted fetal E/e or e/e Rh genotype from peripheral maternal blood correctly in as many as 100% of alloimmunized pregnancies. Thus noninvasive fetal E/e or e/e Rh genotyping can be performed by polymerase chain reaction amplification of the rare fetal cells in maternal blood. The correct prediction of fetal E/e or e/e Rh genotype from the cell population not selected by the monoclonal antibodies suggests that there are fetal cell types other than fetal nucleated erythrocytes that can also be used as a source of fetal deoxyribonucleic acid for noninvasive genetic diagnosis. Improved technology may provide methods less laborious than cell sorting to accurately determine fetal Rh type from different fetal cell types that circulate in maternal blood.

Antibodies, Monoclonal↗

Prevalence and clinical implications of hepatitis B virus genotypes in southern Taiwan.

BACKGROUND: Hepatitis B virus (HBV) infection is a major health problem. HBV genotypes may be associated with progression of liver disease. The distribution and clinical implications of HBV genotypes in southern Taiwan are evaluated. METHODS: We used a polymerase chain reaction-restriction fragment length polymorphism genotyping method to determine HBV genotypes. RESULTS: The genotype distribution for 265 patients with chronic HBV infection was as follows: A, 3 (1%); B, 158 (60%); C, 90 (34%); D, 7 (2.5%); E, 0: F, 0; and unclassified, 7 (2.5%). Compared with genotype B patients, genotype C patients had a higher hepatitis B e antigen positive rate and higher fibrosis score. There was no significant difference in the mean age between genotype B and genotype C patients with hepatocellular carcinoma (HCC). However, when patients were stratified by age, the prevalence of genotype C was significantly higher in young HCC patients (<50 years of age) than in age-matched asymptomatic carriers (40% versus 10%, P < 0.001). Using multivariate analysis, the significant risk factors for advanced liver disease (cirrhosis or HCC) for patients with chronic HBV infection were old age, male gender and genotype C. CONCLUSIONS: These results suggest that genotype C is associated with more severe liver diseases than the B variant.

Adolescent↗

Hepatocellular carcinoma in Sweden: its association with viral hepatitis, especially with hepatitis C viral genotypes.

Viral markers of chronic hepatitis were tested for in 95 frozen serum samples from 299 patients from Malmö, Sweden, with hepatocellular carcinoma (HCC), diagnosed between 1977 and 1994. Hepatitis B analysis included anti-HBc, HBsAg and, if anti-HBc positive, HBV DNA. Hepatitis C infection analysis included anti-HCV screening, RIBA, HCV RNA and HCV genotyping. HCV genotyping was also carried out in 9 HCV-viraemic HCC-patients from Gothenburg. HCV genotype distribution in HCC cases was compared with Swedish HCV-infected blood donors. Among the 95 patients from Malmö, 28 (29%) had anti-HBc, but only 5 (5%) were chronic HBV carriers, compared with 16 (17%) with chronic hepatitis C (p = 0.021). HCV-related HCC was more common among immigrants (8/16 vs. 8/79; p < 0.001). Genotyping of 25 HCV-infected cases showed genotype 1a in 6 (24%), genotype 1b in 13 (52%), genotype 2b in 4 (16%), and genotype 3a in 2 (8.0%) patients. Genotype 1b was more common among HCC patients than among blood donors (p < 0.001), but 8 of 13 genotype 1b-infected patients were from countries where genotype 1b is predominant. Among native Swedes there was no difference between the HCV genotypes infecting blood donors and those found in HCC patients.

Blood Donors↗

Response to changes in antiretroviral therapy after genotyping in human immunodeficiency virus-infected children.

BACKGROUND: HIV genotyping has been beneficial when choosing salvage regimens in adults failing highly active antiretroviral therapy (HAART). Our objectives were to evaluate the usefulness of genotyping in HIVinfected children failing HAART and to determine whether the presence of resistance mutations was associated with previous antiretroviral therapy. METHODS: We followed the progress of pediatric patients who had HIV genotyping performed after HAART failure. Charts were reviewed at 3-month intervals for 1 year after genotyping for changes in viral load and CD4+ cell percentage. Patients whose antiretroviral therapy was changed after genotyping were compared with those whose medications were not changed. We also compared the proportion of patients with genotypic mutations according to antiretroviral exposure at time of genotyping. RESULTS: Eighteen pediatric patients were eligible for inclusion. None of 10 patients who had antiretroviral therapy changed after genotyping had a decrease in viral load atmonths after genotyping. One of 8 patients who had no changes in antiretroviral therapy had a sustained decrease in viral load at 12 months. Two-thirds of patients had resistance mutations to antiretrovirals without prior exposure to that drug. CONCLUSIONS: This study did not demonstrate substantial clinical benefit to HIV genotyping in antiretroviral agent-experienced pediatric patients with high viral loads. These results contrast with favorable short term clinical and virologic responses to therapeutic changes after genotyping in HIV-infected adults. However, medication history alone does not appear to be an adequate alternative to genotyping in choosing salvage regimens in antiretroviral agent-experienced children.

Adolescent↗

Outcome of liver disease in a large cohort of histologically proven chronic hepatitis C: influence of HCV genotype.

OBJECTIVE: To assess the influence of hepatitis C virus (HCV) genotypes on the clinical outcome of liver disease, we analysed 2,307 patients. RESULTS: The most frequently represented genotypes were 1b (40%) and 2 (28.1%). Patients with these genotypes had a median age higher than patients with other genotypes (P< 0.01). The overall survival of subjects with genotype 1b was poorer than the survival of patients with other genotypes (P< 0.01). Liver cirrhosis was found in 280 patients (12.1%), and type 1b was the most represented isolate among them (P< 0.01). Sixty-two patients (22%) developed hepatocellular carcinoma (HCC) during a follow-up of 1481.8 cumulative years (estimated crude incidence rate, 4.1 cases per 100 person-years for all cirrhotics; 5.9 cases for genotype 1a; 4.5 cases for genotype 1b; and 2.8 cases for genotypes non-1). Considering the whole population of 2,307 patients, only genotype 1b was associated significantly with both cirrhosis and the development of HCC. One hundred and nineteen cirrhotic patients underwent treatment with interferon in uncontrolled studies. Interferon therapy was associated with both better survival (P< 0.01) and a lower cumulative hazard for HCC (P< 0.01). CONCLUSIONS: Genotype 1b was associated with a poorer prognosis, probably because it leads to cirrhosis and consequently to HCC development. However, our data did not confirm genotype 1b as an independent risk factor for HCC in liver cirrhosis, which plays a major role in carcinogenesis. Interferon should be considered as a useful strategy in cirrhosis for improvement of survival and reduction of HCC risk.

Adolescent↗

Relationship between viral load and genotypes of hepatitis B virus in children with chronic hepatitis B.

OBJECTIVE: We evaluated the prevalence and clinical significance of hepatitis B virus (HBV) genotypes in children with chronic hepatitis B. METHODS: Hepatitis B virus genomes of 249 hepatitis Be antigen-positive chronic hepatitis B surface antigen carriers were genotyped based on restriction fragment length polymorphism. Genotypes were correlated with corresponding values for alanine aminotransferase levels, quantitative HBV DNA and histological findings. RESULTS: One hundred and sixty-two boys and 87 girls (mean age, 7.2 years) were studied. Ninety-six percent were attributed to HBV genotypes A (32.5%) or D (63.5%). The remaining were classified as genotypes B, C, E and F. There was no significant difference in both alanine aminotransferase levels and histological findings among different genotypes. However, there was a clear association between very high HBV DNA levels and individuals with genotype D (P = 0.006). Mean time follow-up of 3.6 years showed later anti-HBe seroconversion in patients with genotype D than in those with genotype A (58% vs 37%). CONCLUSIONS: Compared with children with genotype A, children with genotype D showed a significantly higher viral load. Inasmuch as a relationship exists between viral load and response to treatment in children infected through vertical transmission, children with genotype D have to be carefully monitored. Long-term studies are needed to determine whether these patients are at risk of a poorer outcome.

Adolescent↗

Enrichment and genotypic diversity of phlD-containing fluorescent Pseudomonas spp. in two soils after a century of wheat and flax monoculture.

Fluorescent Pseudomonas spp. producing the antibiotic 2,4-diacetylphloroglucinol (2,4-DAPG) play a key role in the suppressiveness of some soils to take-all of wheat and other diseases caused by soilborne pathogens. Soils from side-by-side fields on the campus of North Dakota State University, Fargo, USA, which have undergone continuous wheat, continuous flax or crop rotation for over 100 years, were assayed for the presence of 2,4-DAPG producers. Flax and wheat monoculture, but not crop rotation, enriched for 2,4-DAPG producers, and population sizes of log 5.0 CFU g root(-1) or higher were detected in the rhizospheres of wheat and flax grown in the two monoculture soils. The composition of the genotypes enriched by the two crops differed. Four BOX-PCR genotypes (D, F, G, and J) and a new genotype (T) were detected among the 2,4-DAPG producers in the continuous flax soil, with F- and J-genotype isolates dominating (41 and 39% of the total, respectively). In contrast, two genotypes (D and I) were detected in the soil with continuous wheat, with D-genotype isolates comprising 77% of the total. In the crop-rotation soil, populations of 2,4-DAPG producers generally were below the detection limit, and only one genotype (J) was detected. Under growth-chamber and field conditions, D and I genotypes (enriched by wheat monoculture) colonized the wheat rhizosphere significantly better than isolates of other genotypes, while a J-genotype isolate colonized wheat and flax rhizospheres to the same extent. This study suggests that, over many years of monoculture, the crop species grown in a field enriches for genotypes of 2,4-DAPG producers from the reservoir of genotypes naturally present in the soil that are especially adapted to colonizing the rhizosphere of the crop grown.

Bacterial Proteins↗

Genotyping of measles virus in clinical specimens on the basis of oligonucleotide microarray hybridization patterns.

An oligonucleotide microarray hybridization method for identification of most known measles virus (MV) genotypes was developed. Like the conventional genotyping method, the microarray relied on detecting sequence differences in the 450-nucleotide region coding for the COOH-terminal 150 amino acids of the nucleoprotein (N). This region was amplified using PCR primers binding to all known MV genotypes. The microarray included 71 pairs of oligonucleotide probes (oligoprobes) immobilized on glass slides. Each pair consisted of a genotype-specific oligoprobe, which matched the sequence of only one target genotype, and a control oligoprobe, which contained mismatches at the nucleotide positions unique to this genotype. A pattern recognition algorithm based on cluster analysis of the ratios of hybridization signals from specific and control oligoprobes was used to identify the specific MV genotype. Following the initial validation, the method was used for rapid genotyping of two panels of coded samples. The results of this study showed good sensitivity (90.7%), specificity (100%), and genotype agreement (91.8%) for the new method compared to the results of genotyping conducted using phylogenetic analysis of viral sequences of the C terminus of the N gene. In addition, the microarray demonstrated the ability to identify potential new genotypes of MV based on the similarity of their hybridization patterns with those of known MV genotypes.

Genotype↗

Greater diversity of hepatitis C virus genotypes found in Hong Kong than in mainland China.

A hepatitis C virus (HCV) genotyping PCR assay based on type-specific primers was expanded to include genotype 6a as well as genotypes 1a, 1b, 2a, and 3a. The nucleotide sequences of a 194-bp fragment in the center of the HCV core gene showed that the homologies between genotype 6a and genotypes 1a, 1b, 2a, 2b, 3a, and 5 were 81.2, 82.1, 73.8, 77.3, 81.4, and 78.9%, respectively. A high degree of homology (99.6%) was seen in the amplified core region among eight clinically unrelated genotype 6a isolates. Although the Hong Kong Chinese patients had predominantly genotype 1b (70%), it was noteworthy that genotype 6a was the second most common genotype (14%). Four other HCV genotypes--1a, 1b, 2a, and 2b--were also present. In contrast, HCV infection by mainland China was confined to genotypes 1b and 2a. Thus, we found a greater diversity of HCV genotypes in Hong Kong than in mainland China.

Base Sequence↗

Genotypes and clinical phenotypes of hepatitis B virus in patients with chronic hepatitis B virus infection.

Genotype C of hepatitis B virus (HBV) has been shown to be associated with a poor clinical outcome, compared to genotype B. To explore the clinical phenotypes, with special reference to the seroconversion of hepatitis B e antigen (HBeAg) and frequency of acute exacerbation between patients infected with HBV genotypes B and C, a cohort of 272 Taiwanese patients with chronic HBV infection was analyzed. According to the status of HBeAg at enrollment and frequency of acute exacerbation during the follow-up period, five groups of patients with distinct clinical phenotypes were categorized. Of the 272 HBV carriers, 185 (68%) were infected with HBV genotype B and the remaining 87 (32%) were infected with genotype C. Among them, 150 (55%) were positive for HBeAg and patients with genotype C infection tended to have a higher positive rate of HBeAg than those with genotype B infection (63 versus 51%). Genotype B was more prevalent than genotype C in different groups of HBV carriers. However, the prevalence of genotype C in patients with multiple episodes of acute exacerbation who failed to have HBeAg seroconversion was significantly higher than in all 272 patients (50 versus 32%, P = 0.025), in those with HBeAg seroconversion after only one episode of acute exacerbation (50 versus 12%, P = 0.01), or in those negative for HBeAg at enrollment and without acute exacerbations (50 versus 23%, P = 0.002). In conclusion, patients with genotype C infection have a more aggressive clinical phenotype than do those with genotype B infection, which contributes to the former group's progressive liver disease and poor clinical outcomes.

Adult↗

Clinical and serological variation between patients infected with different Hepatitis B virus genotypes.

Hepatitis B virus (HBV) has eight genotypes which have distinct geographical distributions. Studies comparing differences in the clinical outcomes of infections caused by strains with genotype-related variations in the HBV genome have largely compared genotypes B and C and genotypes A and D but not all four genotypes. The present study included 196 HBV-infected patients attending an infectious diseases outpatient clinic in Sweden. The age and geographic origin, liver function, HBeAg and anti-HBe status, and the presence or absence of HBV DNA were analyzed for each patient. HBV DNA was detected in 144 patients, and the HBV genotype and the core promoter and precore sequences were determined for the isolates from 101 of these patients. Among the patients who might be considered most likely to be nonviremic, namely, anti-HBe-positive HBV carriers with normal alanine aminotransferase (ALT) levels, 65% had detectable HBV DNA and were thus viremic. Among the viremic patients, HBeAg-positive patients were more likely to have elevated ALT levels than anti-HBe-positive patients. HBV genotypes A to F were represented in the study, and their distributions coincided accurately with the origin of the patient. A significantly higher number of genotype D-infected patients were anti-HBe positive and had elevated ALT levels (42% of genotype D-infected patients but 0% of patients infected with genotypes B and C). Genotype D strains with mutations in the core promoter and precore regions were significantly correlated with elevated ALT levels in the patients. The differences were not age related. Therefore, in this large-scale cross-sectional study, genotype D appears to be associated with more active disease.

Adult↗

Interaction and replication activation of genotype I and II hepatitis delta antigens.

The nucleotide sequences of hepatitis D viruses (HDV) vary 5 to 14% among isolates of the same genotype and 23 to 34% among different genotypes. The only viral-genome-encoded antigen, hepatitis delta antigen (HDAg), has two forms that differ in size. The small HDAg (HDAg-S) trans-activates viral replication, while the large form (HDAg-L) is essential for viral assembly. Previously, it has been shown that the packaging efficiency of HDAg-L is higher for genotype I than for genotype II. In this study, the question of whether other functional properties of the HDAgs are affected by genotype differences is addressed. By coexpression of the two antigens in HuH-7 cells followed by specific antibody precipitation, it was found that HDAgs of different origins interacted without genotypic discrimination. Moreover, in the presence of hepatitis B virus surface antigen, HDAg-S was incorporated into virion-like particles through interaction with HDAg-L without genotype restriction. As to the differences in replication activation of genotype I HDV RNA, all HDAg-S clones tested had some trans-activation activity, and this activity varied greatly among isolates. As to the support of HDV genotype II replication, only clones of HDAg-S from genotype II showed trans-activation activity, and this activity also varied among isolates. In conclusion, genotype has no effect on HDAg interaction and genotype per se only partly predicts how much the HDAg-S of an HDV isolate affects the replication of a second HDV isolate.

Amino Acid Sequence↗

Effect of antiviral treatment on evolution of liver steatosis in patients with chronic hepatitis C: indirect evidence of a role of hepatitis C virus genotype 3 in steatosis.

BACKGROUND AND AIM: Recent studies suggest that liver steatosis in chronic hepatitis C may be the expression of a direct cytopathic effect of hepatitis C virus (HCV), particularly in patients infected with genotype 3. To investigate this hypothesis, we studied the relationship between steatosis evolution and HCV clearance after antiviral treatment in patients with chronic hepatitis C and paired liver biopsies. METHODS: A total of 151 patients (37 with HCV genotype 3; 114 with HCV non-3 genotypes) were selected according to the following criteria: presence of steatosis at initial biopsy; no antiviral treatment prior to the first biopsy; antiviral treatment received between the two biopsies; body mass index (BMI) <28 kg/m(2); absence of excessive alcohol intake; no serum hepatitis B surface antigen or human immunodeficiency virus antibodies; and absence of diabetes mellitus. Evolution of steatosis was examined by comparing steatosis grades between the two biopsies. RESULTS: Twenty five patients (16.5%) were sustained virological responders (SVR) to antiviral treatment. Steatosis evolution after antiviral treatment was as follows: improvement in 36% of cases; stability in 51%; and worsening in 13%. Steatosis improvement was significantly more frequent in SVR than in non-responders (NR) (64% v 31%; p<0.004). This significant difference occurred in patients infected with genotype 3 (91% v 19%; p<0.0001) but not in those infected with non-3 genotypes (43% v 34%; NS). Among the 25 SVR, improvement in steatosis was significantly more frequent in patients infected with genotype 3 than in those infected with non-3 genotypes (91% v 43%; p<0.04) whereas in NR, improvement in steatosis did not differ between those infected with genotype 3 and non-3 genotypes (19% v 34%; NS). In multivariate analysis, four factors were independently associated with steatosis improvement: sustained virological response to antiviral therapy (odds ratio (OR) 6.06 (95% confidence interval (CI) 1.61-22.9); p = 0.01), severe steatosis (OR 5.50 (95% CI 1.54-19.6); p = 0.01), HCV genotype 3 (OR 2.90 (95% CI 0.85-10.0); p = 0.07), and BMI >25 kg/m(2) (OR 0.24 (95% CI 0.08-0.73); p = 0.02). CONCLUSIONS: Our results showed significant improvement in steatosis in patients infected with HCV genotype 3, who achieved sustained viral clearance. This provides further evidence for direct involvement of HCV genotype 3 in the pathogenesis of hepatic steatosis.

Adult↗

Genotypes of mutans streptococci tend to persist in their host for several years.

The aim of this study was to evaluate the consistency of the prevalence of mutans streptococci in a group of Swedish families. Eleven families, which had previously been examined for genotypes of mutans streptococci, were re-examined after 2-5 years. The families consisted of mother, father and a child (mean age 7.2 years at the follow-up examination). One father did not participate. Pooled plaque samples were obtained from buccal and occlusal surfaces. Isolates of mutans streptococci were genotyped using chromosomal DNA digested with restriction endonuclease HaeIII, separated by gel electrophoresis and visualised through UV illumination after ethidium bromide staining. Comparing the DNA fingerprints of mutans streptococci found at baseline and follow-up, 9 children harboured one or two genotypes which were similar on the two sampling occasions. Two of these children had also gained a genotype. The remaining 2 children had lost a genotype each and 1 of them had gained two new genotypes. All 21 adults showed one or two genotypes identical to those found at baseline. Nine of these 21 adults had also lost one genotype. Four of these 9 and additionally 4 of the remaining adults showed one or two new genotypes. Six mother-child pairs shared a genotype at baseline and this pattern remained for five pairs at the end of the study. The results suggest that genotypes of mutans streptococci have a fairly high degree of consistency in children between 3 and 8 years of age as well as in adults, indicating persistence of the strains. However, the results also indicate that some subjects may gain and/or lose genotypes.

Adult↗