Genotype distribution in Nagoya and new genotype (genotype 3a) in Japanese patients with hepatitis C virus

We evaluated hepatitis C virus (HCV) genotype distribution among Japanese patients in the city of Nagoya and the possible existence of any other genotype not determined by Okamoto's method. Eighty-five of 93 (91.4%) anti-HCV-positive patients had detectable HCV RNA. The genotype of the HCV isolate was determined in 84 of 85 (98.8%) of these HCV RNA-positive patients by Okamoto's method but determination was not possible in one (1.2%). Genotype 1b was detected in 58 of the 85 patients (68.2%), genotype 2a in 20 (23.5%), genotype 2b in 3 (3.5%), and genotype 1b+2a in 3 (3.5%). In the remaining 1 patient in whom the genotype could not be determined, we determined the nucleotide sequence of the core region in HCV RNA extracted from this patient and evaluated it by molecular evolutionary analysis. This HCV isolate was then classified as genotype 3a. These results suggest that genotype 3a is rare among Japanese patients with HCV; thus, when classifying Japaneses isolates, we should take more care because genotype 3a is not determined by current typing systems.     

Epidemiological changes in hepatitis C virus genotypes in France: evidence in intravenous drug users

Hepatitis C virus (HCV) genotypes are distributed differently depending on geography and route of infection. We characterized the distribution of genotypes in a large cohort of patients with chronic hepatitis C in the South-east of France and evaluated the relative prevalence according to time of acquisition. One thousand, one hundred-and-eighty-three patients who were anti-HCV-positive were studied. HCV genotype distribution has changed significantly from the 1960s to 2000. The prevalence of genotype 1b decreased from 47% before 1978 to 18.8% in the 1990s while the prevalence of genotype 1a and 3a increased during the same period from 18% and 15.3% to 28.8% and 26.3%, respectively. The logistic regression model showed that genotype 1a was significantly more common in patients infected through intravenous drug injection odds ratio ((OR): 2.08, P  < 0.01) and after 1990 (OR: 1.98, P  < 0.05). Genotype 1b was significantly less frequent in patients infected through intravenous drug injection (OR: 0.17, P  < 0.001) and has decreased since 1978 (OR: 0.27, P  < 0.001). Genotype 3a was independently associated with intravenous drug injection (OR: 6.1, P  < 0.001) and tattooing (OR: 8.01, P  < 0.001) and was more frequent in the 1979–90 period (OR: 2.05 and 1.74, P  < 0.001 and P  < 0.05). Our results show a modification of HCV genotypes distribution over the last four decades due to an increase of intravenous drug use (IVDU) contamination and an evolution of HCV genotypes distribution only in IVDU population characterized by a decrease of genotype 1b, an increase of genotype 3a from 1970 to 1990 and a higher increase of genotype 1a which is currently the predominant genotype in our population.     

Changes in epidemiological patterns of HCV infection and their impact on liver disease over the last 20 years in Greece

SUMMARY: The aim of this study was to investigate the relative frequency of hepatitis C virus (HCV) genotypes in Greek patients with chronic infection as well as possible secular changes in their distribution in relation to modes of transmission, age and time at acquisition of the infection and other variables. We evaluated 434 unselected patients, 241 males and 193 females with a median age of 46.2 years (18-75), with chronic HCV infection presenting during the period 1996-2000. HCV infection was confirmed by the detection of HCV-RNA by polymerase chain reaction (PCR), while HCV genotyping was performed by the Inno-LiPA assay. Liver biopsies were evaluated according to Ishak's scoring system. Of 434 patients, 167 had a history of blood transfusion [post-transfusion hepatitis (PTH)], 80 were i.v. drug users and in 187 the route of infection remained unknown. The overall distribution of HCV genotypes 1, 2, 3 and 4 was 47, 8.3, 27 and 15.2%, respectively. Genotype 3 was common in younger adults and i.v. drug users, whereas genotype 1 predominated in older people and PTH patients (P < 0.001 for both). Infection acquired before 1981 (group A) was related to transfusion and genotype 1, while after 1981 (group B) with i.v. drug use and genotype 3 (P < 0.01). Biopsy was available in 369 (85%) patients, of whom 22.5% had cirrhosis; 29.8% in group A and 9.9% in group B. In a multivariate analysis, cirrhosis was strongly associated with the duration of infection (P = 0.013). Our study revealed a change of HCV genotype distribution in the last 20 years among Greek patients with chronic HCV infection as a result of epidemiological changes in HCV transmission. The presence of cirrhosis was associated only with the duration of infection. These observations have impact both on prevention and treatment.     

Replacement of hepatitis C virus genotype 1b by genotype 2 over a 10-year period in Venezuela

BACKGROUND: Changes in hepatitis C virus (HCV) genotype distribution with time have been reported in several countries. GOALS: To explore eventual changes in HCV genotype distribution in Venezuela over a 10 years period. STUDY: HCV genotype was determined by direct sequencing of the 5' noncoding region, in 236 isolates circulating in patients treated during years 2005 to 2006. Genotype distribution was compared with the one observed in 43 patients followed during years 1994 to 1996. RESULTS: The prevalence HCV genotype 1 and 2 was 70% and 26%, respectively, in patients followed during years 1994 to 1996. The frequency of genotype 2 was significantly increased to 41% (P=0.04) in patients treated during years 2005 to 2006. A significant reduction in HCV genotype 1b prevalence (48% to 27%, P=0.01) was also observed after this 10 years period, whereas the prevalence of HCV genotype 1a did not change over time (22% vs. 27%, NS). Transfusion was more significantly associated with infection with HCV genotype 1b than with other genotypes (52% vs. 20%, P=0.002). CONCLUSIONS: HCV subtype 1b seems to have been displaced by HCV genotype 2 in a relatively short period, without increase in the frequency of genotype 3. The low frequency of HCV genotype 3 in Venezuela might be due to the fact that intravenous drug use in Venezuela is less common than in other countries. The implementation of anti-HCV testing in blood banks since 1994 in Venezuela, might have contributed to the reduction in the frequency HCV genotype 1b infection.     

Treatment of advanced hepatitis C with a low accelerating dosage regimen of antiviral therapy

Patients with advanced hepatitis C virus (HCV) are at risk of death and are candidates for liver transplantation. After transplantation, HCV recurs and may rapidly progress to cirrhosis and graft loss. Treatment is needed to prevent progression of disease and minimize recurrence after liver transplantation. We evaluated the effectiveness, tolerability, and outcome of a low accelerating dose regimen (LADR) of antiviral therapy in the treatment of patients with advanced HCV. One hundred twenty-four patients (male/female ratio 81:43; age range 37-71 years; 70% genotype 1) were treated with LADR. Sixty-three percent had clinical complications of cirrhosis (ascites, spontaneous bacterial peritonitis, varices, variceal hemorrhage, encephalopathy). The mean Child-Turcotte-Pugh (CTP) score was 7.4 +/- 2.3, and the mean MELD score was 11.0 +/- 3.7. Fifty-six patients were CTP class A, 45 were class B, and 23 were class C. Forty-six percent were HCV RNA-negative at end of treatment, and 24% were HCV RNA-negative at last follow-up. Sustained virological response (SVR) was 13% in patients infected with genotype 1 HCV and 50% in patients infected with non-1 genotypes (P < .0001). Non-1 genotype, CTP class A (genotype 1 only), and ability to tolerate full dose and duration of treatment (P < .0001) were predictors of SVR. Twelve of 15 patients who were HCV RNA-negative before transplantation remained HCV RNA-negative 6 months or more after transplantation. In conclusion, in a sizeable proportion of patients with advanced HCV, LADR may render blood free of HCV RNA, stabilize clinical course, and prevent posttransplantation recurrence.     

Prevalencia de los marcadores de infección de los virus de las hepatitis en pacientes portadores del VIH en el sur de España

Objectives

To determine: (a) The prevalence of active infection by the hepatitis C virus (HCV) and hepatitis B virus (HBV) in HIV-infected patients, as well as previous exposure to hepatitis A virus (HAV), HBV and HCV. (b) The proportion of patients who have been vaccinated against HAV and/or HBV. (c) The HCV genotype distribution and the percentage of patients who have started treatment against HCV infection.

Methods

All HIV-infected patients who attended the Infectious Diseases Unit of a tertiary care hospital in Southern Spain between September 2008 and February 2009 were included in a prospective cross-sectional study.

Results

A total of 520 patients were included. Three hundred and fifty-eight (69%) patients had positive HCV antibody, while 71% of them showed detectable HCV-RNA. The HCV genotype distribution was: 153 (62%) genotype 1, 49 (20%) genotype 3, and 45 (18%) genotype 4. One hundred and thirteen (36.5%) subjects had received treatment against HCV. The prevalence of active HBV infection was 4.4%, while the exposure to HBV was 54.8%. Four hundred and thirty-seven (84%) patients had positive markers of infection of HAV. Of the patients eligible to be vaccinated, 25.6% and 22.3% patients were vaccinated against HAV and HBV, respectively.

Conclusions

The current prevalence of active HCV infection remains high in our area. There were no changes in the HCV genotype distribution. The number of patients with indication for HBV and HAV vaccination and receive these vaccines is low.     

Hepatitis C virus genotypes in a non-cirrhotic Italian population with chronic hepatitis C: correlation with clinical, virological and histological parameters. Results of a prospective multicentre study

To identify correlations between the distribution of hepatitis C virus (HCV) genotypes and demographic, pathological and virological parameters of HCV-infected patients, we prospectively recruited 650 patients with biopsy-proven chronic hepatitis C without histological aspects of cirrhosis; none had been treated with antiviral therapy. Data regarding gender, age, mode of HCV transmission, alanine aminotransferase (ALT) and HCV RNA levels, immunoglobulin M (IgM) anticore values, liver histology and histological activity were obtained from each patient and correlated on multivariate analysis with infecting HCV genotype. Fifty-five per cent of the patients were infected with HCV genotype 1, 20% with HCV genotype 2, 18% with HCV genotype 3 and 7% with HCV genotype 4. Non-transfusional HCV transmission, low ALT levels, IgM anticore reactivity and a low histological grading score were independent variables associated with HCV genotype 1. Older age, female gender, post-transfusional transmission and a high histological grading score were related to HCV genotype 2, whilst younger age, history of current/previous drug abuse, high ALT values, low IgM anticore reactivity and high viraemic levels were associated with HCV genotype 3. History of illicit use of intravenous drugs and low HCV RNA levels were the only independent variables correlated with HCV genotype 4. Genotype 1 remains predominant in Italy but the prevalence of HCV genotypes is changing in relation to age and mode of transmission: Italian patients with HCV genotype 3 are younger and exhibit higher levels of ALT and HCV RNA than patients with other genotypes.     

Hepatitis C genotypes in Australian haemophilia patients

Background: Differences in the hepatitis C virus (HCV) genotype influence the severity of HCV related liver disease and response to interferon therapy. HCV infection is frequent in Australian haemophilia patients who have been exposed repeatedly to multiple HCV genotypes through non HCV virally inactivated clotting factor concentrates. The distribution of the various HCV genotypes in Australian haemophilia patients is unknown. Aim: To examine the HCV genotype distribution and clinical features of HCV associated liver disease in Australian haemophilia patients. Methods: Forty patients with bleeding disorders who were known to be both HCV antibody and polymerase chain reaction (PCR) positive were evaluated by direct sequencing of the PCR products for the HCV genotype. Results: Genotype 1 was found in 65% of patients (26/40), type 2 in 5% (2/40) and type 3 in 30% (12/40). No genotypes 4 to 6 were found. There was no association between the HCV genotype and the severity of haemophilia, alanine transaminase levels, or the presence of portal hypertension. Unlike European, Asian and American studies where the majority of type 1 infection is subclass lb, in Australian haemophilia patients it is subclass la (73% - 19/26) which may have a better prognosis and response to interferon. Conclusions: Despite patients with haemophilia being exposed to multiple HCV genotypes, it appears that there is no selection advantage of one genotype over another. Australian haemophilia patients with HCV have a different genotype distribution to that reported in other countries and care should be observed in interpreting non Australian studies concerning HCV.     

我国丙型肝炎病毒基因1型与非基因1型的临床特征分析

目的初步明确我国HCV基因1型与非基因1型的基本临床特征。方法通过全国多中心、大样本的流行病学调查,经具备国际认证资质的第三方检测机构,采用国际通用的测序法进行病毒基因型分析,并进一步对HCV基因1型与非基因1型的临床特征进行了分析。结果共采集来自全国东西南北中的18个研究中心的764例患者血浆标本,男性384例,女性380例,平均年龄(44.9±14.3)岁,平均病程(7.7±7.3)年。通过临床特征分析发现,基因1型患者年龄分布偏大,病程较长;将横断面调查时患者的ALT水平进行比较,基因1型中有54.9%的患者ALT处于异常,非基因1型中有56.9%的患者ALT处于异常,两者差异无统计学意义(P>0.05);将横断面调查时患者的身体质量指数(BMI)水平进行比较,基因1型中有39.6%的患者BMI异常,非基因1型中有31.6%的患者BMI异常,两者差异无统计学意义(P>0.05);将感染途径分为输血感染与非输血感染,在输血感染患者中,66.1%的输血感染患者为基因1型,在非输血感染患者中,非基因1型占51.1%,两者差异有统计学意义(P<0.05)。结论与非基因1型相比,慢性丙型肝炎基因1型患者年龄分布偏大,病程较长,多为输血感染。     

Prevalence and characterization of hepatitis C virus genotype 4 in Japanese hepatitis C carriers

Hepatitis C virus (HCV) can be classified into six major genotypes, the prevalences of which differ around the world. In Japan, the main genotypes are HCV 1 and HCV 2; others are found only rarely. Little is known about the prevalence in Japan of HCV genotype 4 which, is found frequently in North and Central Africa and the Middle East. Thus, we conducted a study to clarify distribution of HCV genotype 4 and the clinical demographics of patients with HCV genotype 4 in Japan. We examined HCV genotypes in 899 Japanese individuals with HCV viremia living in Aichi Prefecture, including 63 hemophiliacs. Four patients (0.4%) were infected with HCV genotype 4. All four of these patients were male hemophiliacs who had received clotting factors from foreign countries. Three patients were co-infected with human immunodeficiency virus (HIV); none were co-infected with GB virus-C/hepatitis G virus. Phylogenetic analysis of the El region indicated that all four patients were infected with subtype 4a. This subtype is related genetically to a subtype previously reported in Japanese and Italian hemophiliacs. HCV genotype 4 is indeed rare in Japan and may be detected only among hemophiliacs who have received inactivated clotting factor concentrates from foreign countries.     

Distribution of HCV genotypes and HCV RNA viral load in different regions of Mexico

Background and aim. To identify the geographic distribution of hepatitis C virus (HCV) genotypes and HCV RNA viral load in a large number of HCV-infected carriers in Mexico.Methods. Patients with chronic hepatitis C (n = 8,802) were studied to identify HCV genotype using an immune line probe assay in samples shown previously to be positive for viral RNA by an RT-PCR test. Baseline HCV RNA was also evaluated.Results. Genotype 1 accounted for 70.3%, genotype 2 for 21.8%, genotype 3 for 7.2%, genotype 4 for 0.3%, and genotype 5 for 0.1% of all cases; coinfection was present in 0.3%. Overall, Genotype 1 was the most prevalent Genotype. Regionally, genotype 1 occurred more frequently in the North-East, North, and Center-East regions of Mexico; genotype 2 was more prevalent in the South, East, and Peninsula regions; and genotype 3 was more prevalent in the North and North-West regions. Only 22.4% of patients with genotype 1 were classified in the low HCV RNA viral load category, and the distribution of this genotype did not differ significantly between regions.Conclusion. The prevalence of HCV genotypes and viral load in Mexico was 70.3% for genotype 1, but only 22.4% of these patients had a low HCV viral load. Distribution was not uniform in Mexico, with greater frequency of genotype 2 in South, East and Peninsula Regions and Genotype 3 in North and North-West Regions.     

Distribution and Predominance of Genotype 3 in Hepatitis C Virus Carriers in the Province of Kahramanmaras,Turkey

Background:

The hepatitis C virus (HCV) has six major genotypes and more than 100 subtypes, and the determination of the responsible genotype, collection of epidemiological data, tailoring antiviral therapy, and prediction of prognosis have an important place in disease management.

Objectives:

The aim of the present study was to determine the distribution of HCV genotypes across geographic regions and compare these data with those obtained from other geographic locations.

Patients and Methods:

The HCV genotypes were identified in HCV RNA positive blood samples, obtained from different centers. The HCV genotype was determined using molecular methods [Real-Time Polymerase Chain Reaction (RT-PCR)] in 313 patients, who were found to be positive for HCV RNA. The presence of HCV RNA was investigated using the RT-PCR method in serum samples delivered to the Microbiology Laboratory at Kahramanmaras Necip Fazıl City Hospital, Kahramanmaras, Turkey, from the centers located in Kahramanmaras City center and peripheral districts of the province, between March 2010 and August 2014. The HCV genotype analysis was performed in HCV RNA positive samples, using RT-PCR reagents kit. Urine samples from the patients were tested for amphetamine with an Amphetamines II (AMPS2) kit, cocaine was tested with a Cocaine II (COC2) kit, opiates were tested with an Opiates II (OPI2) kit, and cannabinoids were tested with a Cannabinoids II (THC2) kit in Roche/Hitachi Cobas c501 device.

Results:

The blood samples collected from 313 patients were included in the study. Of these patients, 212 (67.7%) were male and 101 (32.3%) were female. The mean age of the patients was 41.29 ± 20.32 years. In terms of HCV genotype distribution, 162 patients (51.7%) had genotype 1, 144 patients (46%) had genotype 3, four patients (1.3%) had genotype 2, and three patients (1%) had genotype 4. The results of urine drug tests were available in only 65 patients (20.2%). Of these, 61 (93.8%) patients had HCV genotype 3.

Conclusions:

In conclusion, the prevalence of HCV genotype 1 was 51.7%, which was lower than the rates reported in other studies in Turkey, while the prevalence of HCV genotype 3 was 46%, which was remarkably higher than the reported Turkish data. In addition, the prevalence rate for genotype 3 reported in the present study is the highest that has ever been reported in the literature.     

Genotype distribution of hepatitis C in the Cordoba City, Argentina

"Background: Knowledge of Hepatitis C virus genotype (HCV) present in a patient has an epidemiological interest. In addition, it has an important prognostic value that guides the duration and success of treatment. Aims: To analyze the distribution of genotypes in HCV-positive patients and linking them with the viral load before and after treatment, evaluating sustained viral response. Patients and methods: We retrospectively analyzed the results of genotyping and HCV viral load of 71 patients during the period January 2001 to May 2009. The genotypes were determined by RFLP (restriction fragment length polymorphism) and the viral load by NASBA HVC quantitative. Statistical analysis was performed using the Infostat program. Results: 59% of patients were women. The frequency of genotypes was: 39% type 1, 58% type 2 and 3% type 3. We do not find a cutoff value of viral load to identify the different genotypes, although patients with genotype 1 had a higher number of viral copies than those of genotype 2 (p <0.0001). After treatment, 95% of patients with genotype 2 had a sustained viral response versus 67% of patients with genotype 1.Conclusions: The genotype 2 was the most prevalent in our population. It also confirmed the impact of knowledge of HCV genotype on sustained viral response, which was related related surgical interventions to infection with HCV type 2."     

Association between chronic hepatitis C infection and hepatocellular carcinoma in a Scottish population.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. The geographical prevalence varies considerably in different countries and Scotland is regarded as an area of low risk for the disease. AIMS: To assess the association between chronic hepatitis C infection (HCV) and HCC in a population of patients presenting to a single hospital. PATIENTS: One hundred and fourteen cases of histologically confirmed liver cancer presenting to the Royal Infirmary of Edinburgh between 1985 and 1994 were examined. METHODS: Of 114 cases of HCC, 80 samples of stored sera were available. Samples positive for HCV Ab were genotyped by restriction fragment length polymorphism analysis of HCV c-DNA. A population of 29 cirrhotic patients (diagnosed between 1985 and 1994) with chronic HCV infection was also genotyped. RESULTS: Chronic HCV infection was a major risk factor (30% of tested HCC patients) identified. HCV genotype 1b was predominant (16 of 20 patients). The time from HCV transmission to development of cancer ranged from 10 to 50 years (median 30). In the cirrhotic patient population, a broader distribution of genotypes was present (genotype 1a: 7; genotype 1b: 8; genotype 2b: 3; genotype 3a: 8 and genotype 4: 2). However, this population was significantly younger. (Mean (SD) 52 (14.5) years) (p = 0.0002) and demonstrated a significantly shorter duration of infection: range 10-40 years (median: 19). CONCLUSION: There is a strong association between chronic HCV infection, cirrhosis, and hepatocarcinogenesis in this Scottish population. The study was unable to distinguish whether the high prevalence of genotype 1b in the HCC population reflected increased oncogenicity in itself, or whether 1b was simply the most prevalent genotype in Scotland when these patients were infected.     

Hepatitis C virus genotype 3 was associated with the development of hepatocellular carcinoma in Korea

Although hepatitis C virus (HCV) genotype 3 infection is thought to be an important risk factor for hepatocellular carcinoma (HCC), current evidence is limited because only a few Western studies have evaluated the occurrence of HCC in patients with HCV genotype 3 infection. We evaluated the impact of genotype 3 and non‐3 on HCC incidence and on disease progression in chronic HCV patients; this is the first study reporting such findings in an Asian population. We performed a retrospective cohort study using the data of 1448 consecutive chronic HCV patients evaluated at three centres in Korea between January 2005 and December 2016. Of these, 604, 675 and 169 had genotype 1, genotype 2 and genotype 3 HCV infections, respectively. Over a mean follow‐up period of 53.2 months, 75 and 143 patients of all the patients developed HCC and experienced disease progression, respectively. The incidences of HCC were 1.10, 0.92 and 2.50 per 100 person‐years, and those of disease progression were 1.95, 1.62 and 6.72 per 100 person‐years for HCV genotypes 1, 2 and 3, respectively. In multivariate Cox regression analysis, genotype 3 was associated with an increased risk of HCC (hazard ratio [HR] = 4.26, 95% confidence interval [CI] = 2.02‐8.97) and an increased risk of disease progression (HR = 4.88, 95%; CI = 2.94‐8.08). Our study proposes that HCV genotype 3 is an independent risk factor for HCC and disease progression in chronic HCV patients.     

HCV genotypes--role in pathogenesis of disease and response to therapy.

Hepatitis C virus (HCV) shows considerable variation in its genomic structure, allowing classification into six main genotypes. Epidemiological studies have shown marked differences in genotype distribution by geographical region, and between patient groups. Improved understanding of the rate of nucleotide sequence mutation in HCV has allowed the approximate time of divergence of major genotypes to be estimated, and the origin and spread of the present epidemic of hepatitis C to be better defined. Improved methods of genotype definition over the last few years have enabled the importance of genotype in the progression of HCV-related disease and response to anti-viral therapy to be studied. Present data strongly indicates that HCV genotype is an important determinant of response to treatment, but the effect of genotype on disease progression has been harder to clarify. This is largely due to the absence of model systems of HCV infection, the epidemiological differences in patient groups infected with the different genotypes, and the lack of good prospective longitudinal clinical data. As a result of advances in methodology, and recent results of large clinical trials of combination therapy, a knowledge of HCV genotype is now central to the clinician in the management of patients with chronic hepatitis C.     

Relationship between genotypes of hepatitis C virus and histopathological manifestations in chronic hepatitis C patients

OBJECTIVE: The aim of this study was to assess the relationship between HCV genotype and histological liver injury. DESIGN: Prospective study on a cohort of patients with biopsy proven chronic hepatitis C. SETTING: University medical centre. PARTICIPANTS: Enrolled were 324 consecutive patients (male 197, median age 52 years, range 19-68; chronic hepatitis, 224; cirrhosis, 100). METHODS: HCV genotype was determined by the INNO LiPA assay and HCV RNA levels by the bDNA assay. The histological features were scored according to the histology activity index. RESULTS: The distribution of HCV genotypes was 1a, 4.6%; 1b, 52.4%; 2a/c, 27%; 3a, 8%; 4, 2%; mixed, 6%. Serum HCV RNA levels were similar for all genotypes. There was no difference in the distribution of HCV genotypes between patients with chronic hepatitis and those with cirrhosis. Patients with genotype 1b and those with type 2a/c showed a similar prevalence of cases of cirrhosis (33% versus 31%, respectively). In addition, in a subgroup of 102 patients with an established date of infection, the progression to cirrhosis occurred with a similar length of time for HCV type 1b and 2a/c (median 16 versus 15 years, respectively). Patients with HCV genotype 2a/c or mixed genotype showed a higher histology activity index than those with type 1b (P< 0.01), whereas there was no difference in the fibrosis score for the different genotypes. Patients with genotype 3a showed a significantly higher prevalence of steatosis compared to those infected with other genotypes. Alanine aminotransferase (ALT) values were higher in patients with HCV type 2a/c, 3a and mixed genotype than those with type 1 (P < 0.002). CONCLUSIONS: The data indicate that there is no association between a particular HCV genotype and the progression to cirrhosis, and that specific genotypes are associated with distinct histopathological and biochemical manifestations although none of them is correlated with an increase of the fibrosis stage.     

Hepatitis C virus in non-Hodgkin's lymphoma. A reappraisal after a prospective case-control study of 300 patients. Lombart Study Group of HCV-Lymphoma

It is widely thought, but not yet explained, that there might be a pathogenetic link between the infection of hepatitis C virus (HCV) and the onset of B non-Hodgkin's lymphoma (NHL). We studied the prevalence of serum anti-HCV antibodies among 300 NHL comparing it with the prevalence among 600 age- and sex-matched non-neoplastic subjects as controls, 247 patients with non-lymphomatous neoplasm, and 122 patients treated with immunosuppressive agents. We found a prevalence of 0.16 among NHL and 0.085 among controls and non-lymphomatous patients. Although the difference was statistically significant (P < 0.001), the odds ratio was 2.049 and its confidence intervals included the equality. The HCV prevalence was independent of NHL subset, and the genotypes distribution was the same among NHL and controls. We disclosed a HBsAg prevalence of 0.077 in NHL versus 0.008 in controls (P < 0.001) with an odds ratio of 9.9. We do not believe that these findings support the hypothesis of an HCV pathogenetic role in lymphomagenesis because (i) the risk of previous infection is marginally higher in NHL than in controls, (ii) a typical genotype distribution is lacking, as is a NHL clinico-histological feature associated with HCV, and (iii) the higher prevalence of viral infection is not specific as witnessed by the high HBsAg prevalence.     

cDNA Sequencing of the 5′ Noncoding Region (5′ NCR) to Determine Hepatitis C Genotypes in Patients with Chronic Hepatitis C

Reports suggest that response tointerferon-alpha therapy is influenced by both hepatitisC viral genotype and titer. Our aim was to determine ifdirect, automated, cycle sequencing of the PCR productfrom an HCV RNA detection assay could be used toreliably determine HCV genotype. In addition, theapproach was used to determine the HCV genotypedistribution in our patient population and to learn ifthere was a correlation between HCV genotype and RNAtiter that could be used to predict response totreatment. In all 143 consecutive patients were testedfor both HCV RNA titer and genotype. Automated, cycle sequencing of PCR product was highly effectiveand failed to yield a genotype in only 3 (2%) patients.The distribution of HCV genotypes was: 1a (40%), 1b(39%), 2a (2%), 2b (6%), 3a (4%). There were significant differences in the median HCV RNA titersbetween genotypes 1, 2, and 3. 6 High HCV RNA titers>4.4 × 10⁶ copies/ml were only seenin genotype 1. However, the HCV RNA level should not beused as a surrogate marker of genotype because of a significantoverlap of titers within the genotypes.     

Virological characteristics of HCV infection in Japanese haemophiliacs

It has been found that almost all haemophiliacs treated with pooled concentrates of clotting factor VIII or IX before 1985/6 have been infected with hepatitis C virus (HCV). In order to clarify the characteristics of HCV infection in Japanese haemophiliacs, we investigated the HCV genotype and HCV-RNA level in 80 patients with haemophilia who had been confirmed to be positive by a second-generation HCV antibody test. HCV-RNA was detected in 60 (75.0%) individuals and various HCV genotypes were found. Although 80% (48/60) of the patients had genotype 1b, the frequency of each genotype was quite different from that in HCV-infected non haemophiliac Japanese. Particularly, multiple HCV genotypes were observed in 27 (46.7%) patients. The mean (± SD) level of HCV-RNA was 5.3 × 10⁵ ±  1.1 × 10⁶ copies mL⁻¹. The viral load in patients with genotype 2a was significantly less common than those with genotype 1a ( P = 0.0007), genotype 1b ( P = 0.0009) and combined genotype 1a/1b ( P = 0.0019). In patients co-infected with human immunodeficiency virus (HIV), the HCV-RNA level was significantly higher ( P = 0.05) than in those without co-infection. However, there was no significant difference ( P = 0.25) in the HCV-RNA level with HCV/HIV co-infection among the 40 patients with group 1 genotypes. We conclude that this biased distribution of HCV genotypes in Japanese haemophiliacs reflects their specific mode of HCV infection. Moreover, these results suggest that super-infection with HIV does not greatly influence the HCV load in patients with no marked immunological deterioration.