Domenico Infantolino

Hepatitis C virus infection in spouses: sexual transmission or common exposure to the same risk factors?

OBJECTIVES:The aim of this study was to evaluate whether the transmission of hepatitis C virus (HCV) between spouses occurs through sexual contact or through other types of exposure.METHODS:We consecutively enrolled 311 chronic HCV carriers and their spouses. The spouses underwent HCV blood testing. Exposure to parenteral risk factors was compared between couples of which both partners were HCV positive and couples with one positive partner. In couples with both partners positive, qualitative detection of serum HCV RNA and genotyping were performed.RESULTS:The prevalence among spouses was 10.3% (32/311). The mean age was higher for HCV-positive spouses (57.7 vs 49.6 yr for HCV-negative spouses; p < 0.01). The prevalence among spouses increased with the duration of marriage, whereas no difference was found in relation to the clinical status of the index case. The 32 HCV-positive spouses reported parenteral exposure (blood transfusion, drug use, and use of multiple-use glass syringes inside or outside the family) more often than the 279 HCV-negative spouses (84.4% vs 26.2%; odds ratio [OR], adjusted for age by multiple logistic regression analysis, 12.4; 95% CI = 4.5–34.0). The percentage of couples sharing glass syringes was significantly higher among those with both partners infected (65.6% vs 12.9%; OR = 12.9; 95% CI = 5.4–31.4). Qualitative serum HCV RNA was determined in 22 couples with both partners infected; in 13 of them, both partners were HCV RNA positive, whereas in the remaining nine, only one partner was positive. In eight of the 13 couples with both partners HCV RNA positive, the same genotype was found for both partners.CONCLUSIONS:The findings that the same genotype was detected for both partners in relatively few couples, and that a history of parenteral exposure was an independent predictor of HCV positivity, suggest that the risk of sexual transmission is low. The sharing of glass syringes may have played an important role in transmission between spouses.

High prevalence of HCV-RNA in the saliva cell fraction of patients with chronic hepatitis C but no evidence of HCV transmission among sexual partners.

The aims of this study were to evaluate the prevalence of HCV-RNA in different fractions of saliva taken from patients with chronic hepatitis C, to establish whether virologic parameters or disease severity exert any influence on the detectability of HCV-RNA in saliva, and to evaluate the prevalence of HCV infection in partners of HCV-infected subjects with respect to the presence of HCV-RNA in saliva. Sera samples and different fractions of saliva (whole saliva, surnatant, and cell fraction) from 48 subjects (45 with chronic hepatitis C and three healthy anti-HCV+ carriers) were examined for HCV-RNA by RT nested PCR and DEIA hybridization. HCV-RNA-positive sera were also tested for genotype and viral titer (bDNA2 method). Twenty-seven stable sexual partners (25 females and 2 males) were screened for anti-HCV antibodies at least twice over a minimum of 12 months, HCV-RNA was detected in the sera of 39/45 patients and of 22/39 viremic patients. In all of the latter, the presence of HCV-RNA was restricted to the cell fraction. Viral titer was significantly higher in patients with HCV-RNA in saliva than in those without (12.3×106 versus 4.6×106 eq/ml, P<0.01). HCV-RNA positivity was unrelated to genotype, duration of disease, Hepatitis Activity Index scores or transminase levels. Anti-HCV was positive in one of 13 sexual partners of patients with HCV-RNA in saliva and in 1/14 of those without (P=NS). In conclusion, HCV-RNA is detectable in the cell fraction of saliva in a high proportion of highly viremic patients with chronic hepatitis C, but its presence does not seem to be associated with an increased risk of HCV transmission among sexual partners.SummaryThe aims of this study were to evaluate the prevalence of HCV-RNA in different fractions of saliva taken from patients with chronic hepatitis C, to establish whether virologic parameters or disease severity exert any influence on the detectability of HCV-RNA in saliva, and to evaluate the prevalence of HCV infection in partners of HCV-infected subjects with respect to the presence of HCV-RNA in saliva. Sera samples and different fractions of saliva (whole saliva, surnatant, and cell fraction) from 48 subjects (45 with chronic hepatitis C and three healthy anti-HCV+ carriers) were examined for HCV-RNA by RT nested PCR and DEIA hybridization. HCV-RNA-positive sera were also tested for genotype and viral titer (bDNA2 method). Twenty-seven stable sexual partners (25 females and 2 males) were screened for anti-HCV antibodies at least twice over a minimum of 12 months, HCV-RNA was detected in the sera of 39/45 patients and of 22/39 viremic patients. In all of the latter, the presence of HCV-RNA was restricted to the cell fraction. Viral titer was significantly higher in patients with HCV-RNA in saliva than in those without (12.3×106 versus 4.6×106 eq/ml, P<0.01). HCV-RNA positivity was unrelated to genotype, duration of disease, Hepatitis Activity Index scores or transminase levels. Anti-HCV was positive in one of 13 sexual partners of patients with HCV-RNA in saliva and in 1/14 of those without (P=NS). In conclusion, HCV-RNA is detectable in the cell fraction of saliva in a high proportion of highly viremic patients with chronic hepatitis C, but its presence does not seem to be associated with an increased risk of HCV transmission among sexual partners.

Three times weekly versus daily dose α-interferon treatment in patients with acute hepatitis C

Even if both CAH and LC are diseases with homogeneous diffusion of the liver damage, it may happen that the damage might be not uniformously distributed into the hepatic parenchyma. Based on this observation, different authors support the idea that by liver biopsy the diagnosis of LC might be underestimated in about 50% of the patients (4). Some data indicate that the diagnoses of LC from two consecutive specimens, obtained one after the other during a short period of time, diverted in about 50% of the cases (4). The results presented in Table 1 differ from those of Regev et al. (5), recently published at the American Association for the Study of Liver Diseases meeting. In this paper the authors describe, for grading and staging, respectively, 24.2% and 33.1% of discordances between the two biopsies made in the two lobes via laparoscopy. They concluded that the diagnosis of LC was underestimated in 14.5% of the cases. The difference with our results might be explained by the characteristics of the populations considered in the two studies. In our cohort we excluded patients with LC, but they were included in the study of the French group. Results presented in this letter support the hypothesis that the histological examination of a unique liver specimen may be considered a reliable and reproducible marker either of the inflammatory activity or of the fibrosis of the entire liver. This seems to be valid at least in the case of patients affected with noncirrhotic chronic liver disease.

TTV infection in patients with acute hepatitis of defined aetiology and in acute non-A-E hepatitis

BACKGROUND/AIMS Recently, the presence of a novel nonenveloped single-stranded DNA virus (TTV) has been associated with either acute or chronic hepatitis of unknown aetiology, suggesting a possible aetiological role. The aim of this study was to evaluate the prevalence, the significance and the clinical impact of TTV infection in patients with acute viral hepatitis of defined aetiology and in patients with non-A-E acute hepatitis. METHODS TTV-DNA was tested by hemi-nested PCR in serum samples collected from 121 patients during and after acute hepatitis (103 with acute viral hepatitis of defined aetiology and 18 with acute non-A-E hepatitis) and in 30 healthy controls. RESULTS Overall, the rate of TTV infection was 12.6% (13/103) in patients with acute hepatitis of defined aetiology, 16.6% (3/18) in patients with non-A-E acute hepatitis and 6.6% (2/30) in the healthy control group, (p=n.s). TTV-DNA was detected in the following proportions: hepatitis B, 13.2% (7/53); hepatitis C, 16.6% (4/24); hepatitis A, 4.7% (1/21); hepatitis E 20% (1/5). Moreover, acute hepatitis with and without TTV infection/coinfection were comparable in terms of both liver biochemistry and chronicity rate. The results of TTV re-testing after serial dilutions of six TTV-DNA positive serum samples during and after the peak of liver transaminases failed to demonstrate a correlation between liver damage and viral titre. CONCLUSIONS The prevalence of TTV infection appeared to be comparable in patients with non-A-E hepatitis, in acute hepatitis of defined aetiology and in the control group. Hence, an aetiological role of TTV for acute hepatitis of unknown aetiology seems questionable. Moreover, TTV infection does not modify the natural history of acute hepatitis of defined aetiology.

Usefulness of human papilloma virus testing in the screening of cervical cancer precursor lesions: a retrospective study in 314 cases

OBJECTIVE To assess the usefulness of human papilloma virus (HPV) typing for predicting pre-malignant and malignant cervical lesions. STUDY DESIGN 314 women, who underwent colposcopy, biopsies and high and low-risk HPV typing after a confirmed abnormal routine Pap test were studied. HPV-DNAs were typed by using PCR technique. RESULTS We found a significant increasing rate of high-risk-HPV by the increasing severity of histology, ranging from 40% in negative cases to 86.9% in those with CIN3 lesions. The positive predictive value of high-risk-HPV ranged from 13.3% in patients with atypical squamous cells of undetermined significance (ASCUS) to 29.4% in those with HSIL. By contrast, negative predictive value was 96% in patients with ASCUS, 97.2% in low-grade squamous intraepithelial lesions (LSIL), and 71.4% in high-grade squamous intraepithelial lesions (HSIL). Sensitivity and specificity for detecting CIN2 or CIN3 was 86.0% and 41.3%, respectively. CONCLUSIONS The high negative predictive value of high-risk HPV testing suggests that HPV negativity could be used for predicting the absence of important cervical lesions, and therefore avoiding unnecessary colposcopy in ASCUS and LSIL cases.

HGV/GBV-C infection in patients with acute hepatitis of different etiology and in patients with chronic hepatitis C

Abstract: To investigate the prevalence of hepatitis G virus (HGV/GBV-C) in patients with liver disease and to confirm its hypothesized ability to cause liver damage, we studied 130 subjects; 61 had chronic hepatitis C virus infection and 69 had acute hepatitis of either defined etiology (n = 57) or of unknown origin (n = 12). Positivity for HGV/GBV-C RNA was detected in 10 of the 61 subjects with chronic hepatitis C (16.3%) and in 11 of the 57 subjects with acute hepatitis of defined etiology (19%), whereas we failed to detect HGV/GBV-C viremia in subjects with hepatitis of non-established etiology. Patients exhibiting positivity for HGV/GBV-C RNA were found to be comparable to those exhibiting negativity for HGV/GBV-C RNA in terms of both liver function tests and Knodells score (in liver biopsies); the affect of HGV/GBV-C infection on the biohumoral and histological activity in patients with chronic hepatitis C therefore appears to be minimal or absent. Similar clinical features were observed in patients with acute hepatitis of known etiology whether they were positive or negative for HGV/GBV-C RNA. However, long-term clinical studies are still required to clarify the actual impact of HGV/GBV-C co-infection. In our geographic, i.e., a region or north-east Italy, HGV/GBV-C infection appears to be strictly related to intravenous drug use, and this agent does not seem to be responsible for acute hepatitis of unknown etiology; other etiological agents are probably involved.

HGV/GBV-C in liver tissue and in sera from patients with chronic hepatitis C

SummaryForty-eight persons (M=45, F=3; age range=20–53, mean=32.2) affected with chronic hepatitis C were tested for HGV/GBV-C RNA and HCV-RNA by nested PCR and DEIA in serum and in liver specimens to evaluate the prevalence and the impact of HGV/GBV-C coinfection in patients with chronic HCV-related hepatitis. Sera were also assayed for antibodies to HGV/GBV-C E2 protein. Serum HGV/GBV-RNA could be detected in nine (19%) patients, and anti-E2 antibodies in 22 (46%) patients. The presence of HGV/GBV-C RNA or anti-E2 antibodies was mutually exclusive. The cumulative prevalence of HGV/GBV-C infection was 65% (31/48); the majority of these patients (26/31, 84%) were intravenous drug users (IVDUs). In eight of nine patients viraemic for HGV/GBV-C, RNA positivity could be revealed even in liver specimens; these eight patients were also positive for HCV-RNA both in serum and the liver and did not exibit any specific association with HCV genotype. HGV/GBV-C RNA negative strand RT-PCR testing was negative in all of the eight liver specimens, providing little support to the hypothesis that liver represents the primary site of HGV/GBV-C replication. Moreover, patients with HGV/GBV-C and HCV coinfection were comparable to those with HCV infection alone in terms of biochemistry and liver histology.

HGV Infection in Patients with Acute Hepatitis of Known and Unknown Aetiology

The hepatitis G virus (HGV/GBV-C) is a recently discovered, parenteral-transmitted flavivirus that has been isolated from patients with either fulminant non A-E or chronic viral hepatitis [1-3]. The prevalence of HGV infection has already been extensively investigated in patients with chronic hepatitis, but at present, knowledge on the features of HGV infection/coinfection in patients with acute hepatitis of known and unknown aetiology remains scarce. In order to assess the prevalence and course of HGV infection in patients with acute hepatitis, a total of 76 patients (57 men, 19 women; mean age = 32.3, range 9-63) were tested for HGVRNA. Serum specimens were collected from 64 consecutive patients who had been admitted to our unit from March 1995 to November 1996 because of aetiologically defined acute hepatitis (40 patients with HBV-related hepatitis, six of them positive for anti-HCV; 14 patients with HCV-related hepatitis; 10 patients with HAV-related hepatitis) and from 12 patients with acute hepatitis of unknown aetiology referred to our Center in the course of 5 years preceding the study commencement. These last 12 patients had never presented any evidence of known hepatotropic viral infection (i.e., HBV, HCV, HAV, EBV, CMV, HSV) or other causes of acute liver disease (e.g., alcoholor drug-related toxicity or metabolic disorder). After RNA extraction and reverse transcription with random hexamers, semi-nested PCR was run with degenerated primers derived from the helicase region. Amplicons were hybridized with a specific probe by DEIA (Sorin, Italy). The HGV infection rate was 12:76. With respect to the aetiology of acute hepatitis, HGV-RNA positivity was detected in the following proportion: HBV-related hepatitis, 8:40; HCV-related hepatitis, 4:14; HAV-related hepatitis, 0:10. Remarkably, HGVRNA could never be detected amongst the 12 patients with acute hepatitis of unknown origin. Of the 12 HGV-positive cases, seven reported previous intravenous drug use (IVDU), two had a sexual partnership with carriers of chronic HBV-related hepatitis. In three cases risk for blood-borne infection was excluded. None of the patients with acute hepatitis of unknown aetiology had had parenteral exposure. The clinical course of acute hepatitis appeared to be alike when comparing patients coinfected with HGV to those carrying a single aetiotogy (Table 1 ). The disease displayed a fulminant course in three cases (two HBV-related and one nAnBnC-hepatitis), in none of which HGV-RNA could be detected. Eleven of the 12 HGV-positive cases were re-assayed for HGVRNA after a mean period of 10.7 months (range = 3-17 months) and ten of these cases were still exhibiting HGV-RNA positivity. Amongst this latter group of patients, seven cases had recovered from an HBV-related acute hepatitis as witnessed by seroconversion from HBsAg to anti-HBs and consistently had normal transaminases, whereas abnormal transaminases were observed in three carriers of chronic hepatitis C with positive HCV-RNA. Based upon our data, HGV infection appears to be common in North-east Italy as a co-infection occurring either in acute HCVrelated or in acute HBV-related hepatitis, the main risk factor for transmission being related to intravenous drug use. Although the severity of acute hepatitis appears to be hardly influenced by Table 1: Clinical and biochemical features of patients with acute hepatitis, related to HGV-RNA detection.