[Spontaneous and treatment-induced virological dynamic in the plasma, PBMC and liver tissue in a patient with chronic HBV and HCV coinfection]. / Dinamica virologica di HBV e HCV spontanea e correlata alla terapia nel plasma, nei PBMC e nel tessuto epatico in un paziente con coinfezione cronica da HBV e HCV.

Here it is reported the virological dynamic of HBV and HCV, identified in the plasma, peripheral blood mononuclear cells and tissue liver, in a patient with chronic HBV-HCV coinfection. A treatment with pegylated Interferon plus Ribavirin determined a sustained virological response for HCV in all the three studied compartments, but a reactivation of chronic HBV infection was observed. In fact, while at the first observation HBV-DNA was detectable only in the liver tissue, after antiviral therapy it was detectable in all the three compartments; moreover this HBV reactivation was associated with a hepatic flare. Then, the patient was treated with Entecavir, which has been determining the clearance of HBV from the peripheral compartments (plasma and PBMC) until today.

Virological pattern in plasma, peripheral blood mononuclear cells and liver tissue and clinical outcome in chronic hepatitis B and C virus coinfection.

BACKGROUND: We aim to evaluate in chronic hepatitis B virus-hepatitis C virus (HBV-HCV) coinfection the interplay of these viruses in liver tissue, peripheral blood mononuclear cells (PBMC), and plasma and to analyze the effect on disease course and response to treatment. METHODS: We enrolled 19 patients with chronic HBV-HCV coinfection, 20 with chronic HCV and 20 with chronic HBV infection at their first liver biopsy, all were naive for antiviral therapy. The patients' plasma, PBMC and liver biopsy samples were tested for HBV DNA and/or HCV RNA by real-time PCR, according to the presence/absence of hepatitis B surface antigen and antibodies against HCV in the serum. RESULTS: Contemporary presence of HBV DNA and HCV RNA was rare in plasma (5.3% of cases) and PBMC (10.6%), but frequent in liver tissue (52.6%). Of 10 cases circulating only HCV RNA and treated with pegylated interferon (PEG-IFN) plus ribavirin for 12 months, two showed a sustained response, and eight cleared HCV RNA but became HBV-DNA-positive in plasma; these eight had detectable HBV DNA in liver at baseline. One patient, who was plasma HBV-DNA-positive/HCV-RNA-negative at baseline, showed a sustained response after 18 months of PEG-IFN treatment; another, who was plasma HBV-DNA/HCV-RNA-positive at baseline, cleared only HCV RNA during 12 months of PEG-IFN plus ribavirin treatment. Seven cases remained untreated. CONCLUSION: Despite a reciprocal inhibition in plasma, HBV and HCV frequently coexist in liver tissue, a condition to be taken into consideration when deciding therapy.

Acute hepatitis with severe cholestasis and prolonged clinical course due to hepatitis A virus Ia and Ib coinfection.

BACKGROUND: Acute viral hepatitis due to hepatitis A virus is a self-limited illness that infrequently has a severe clinical course. METHODS: We analyzed the virological characteristics of acute hepatitis A in a patient with a severe clinical presentation (peak total and conjugated bilirubin levels, 65.5 mg/dL and 40.1 mg/dL, respectively) and a course of disease that lasted 7 months. RESULTS: Hepatitis A virus sequencing revealed coinfection with 2 subgenotypes of hepatitis A virus (Ia and Ib) as etiological factors of the illness. CONCLUSIONS: Hepatitis A virus Ia and Ib coinfection may have accounted for the prolonged and severe course of illness.

Anti-HCV IgG avidity index in acute hepatitis C.

BACKGROUND: The diagnosis of acute hepatitis C (AHC) is based on seroconversion to positive anti-HCV, which is usually not clinically possible. OBJECTIVE: To determine if avidity of anti-HCV IgG can be used for the diagnosis of AHC infection. STUDY DESIGN: We enrolled 40 consecutive patients with AHC, 16 drug addicts (IVDA) with exacerbation of chronic hepatitis C (IVDA e-CHC group), 21 non-IVDA with exacerbation of chronic hepatitis C (IVDA-free e-CHC group) and 40 with chronic hepatitis C (CHC group). HCV avidity index (HCV-AI) was determined by ELISA on sera pre-diluted 1:10 with 1M guanidine. RESULTS: On admission, HCV-AI values were significantly lower in the AHC group (mean+/-S.D.: 0.50+/-0.30) than in IVDA-free e-CHC group (0.97+/-0.08, p<0.0001), IVDA e-CHC group (0.90+/-0.29, p<0.0001) or CHC group (1.06+/-0.20, p<0.0001). An HCV-AI lower than 0.7 obtained within the 8th day of illness distinguished patients with AHC infection from the IVDA-free e-CHC cases. An increase in HCV-AI was observed in 24 (72.7%) of 33 in AHC group, in none of 13 in IVDA-free e-CHC group and in 3 (27.3%) of 11 in IVDA e-CHC group. CONCLUSION: HCV-AI is useful in identifying AHC infection in patients observed within the 8th day from the onset of symptoms.

Viral blips during long-term treatment with standard or double dose lamivudine in HBe antigen negative chronic hepatitis B.

AIM: To evaluate safety and effect on hepatitis B virus (HBV) suppression of a long-term treatment with lamivudine (LAM) at standard (100 mg/d) or double (200 mg/d) dose in chronic hepatitis B. METHODS: This was a case study with matched controls (1:3) in patients with chronic hepatitis B with anti-HBe antibodies. RESULTS: Twelve patients received LAM 200 mg/d and 35 LAM 100 mg/d, for a median of 28 mo. A primary response (PR; i.e. negative HBV-DNA with Amplicor assay) was achieved in 100% of LAM-200 patients and 83% of LAM-100 patients. A virological breakthrough occurred in 16.7 and 24.7%, respectively, of the PR-patients, with the appearance of typical LAM resistance mutations in all but one patient. Viremia blips (i.e. transient HBV-DNA below 80 IU/mL in patients who tested negative at Amplicor assay) were detected using a real time polymerase chain reaction (PCR) and occurred in seven out of nine patients with subsequent BT and in four out of 32 patients with end-of-study response (77.7% vs 12.5%; P = 0.001) at chi-square test). At the end of the study, 51.4% of LAM-100 patients and 83.3% of LAM-200 patients had remained stably HBV-DNA negative. Double-dose LAM was well tolerated. CONCLUSION: Long-term treatment of anti-HBe positive chronic hepatitis B with double dose lamivudine causes a more profound and stable viral suppression as compared to conventional treatment.

Clinical and virological improvement of hepatitis B virus-related or hepatitis C virus-related chronic hepatitis with concomitant hepatitis A virus infection.

BACKGROUND: We evaluated the clinical and virological characteristics of hepatitis A virus infection in persons concomitantly infected with hepatitis B virus (HBV) or hepatitis C virus (HCV). METHODS: We enrolled 21 patients with acute hepatitis A and chronic hepatitis with no sign of liver cirrhosis, 13 patients who were positive for hepatitis B surface antigen (case B group), 8 patients who were anti-HCV positive (case C group), and 21 patients with acute hepatitis A without a preexisting liver disease (control A group). Two control groups of patients with chronic hepatitis B (control B group) or C (control C group) were also chosen. All control groups were pair-matched by age and sex with the corresponding case group. RESULTS: Fulminant hepatitis A was never observed, and hepatitis A had a severe course in 1 patient in the case B group and in 1 patient in the control A group. Both patients recovered. On admission, HBV DNA was detected in 1 patient in the case B group (7.7%) and in 13 patients (50%) in the control B group; HCV RNA was found in no patient in the case C group and in 16 patients (81.2%) in the control C group. Of 9 patients in the case B group who were followed up for 6 months, 3 became negative for hepatitis B surface antigen and positive for hepatitis B surface antibody, 2 remained positive for hepatitis B surface antigen and negative for HBV DNA, and 4 became positive for HBV DNA with a low viral load [corrected] Of 6 patients in the case C group who were followed up for 6 months, 3 remained negative for HCV RNA, and 3 had persistently low viral loads. CONCLUSION: Concomitant hepatitis A was always self-limited, associated with a marked inhibition of HBV and HCV genomes, and possibly had a good prognosis for the underlying chronic hepatitis.

[An attempt to improve classification of HCV-correlated chronic hepatitis]. / Un tentativo di migliorare la classificazione delle epatiti croniche HCV-correlate.

To verify the clinical efficacy of the Desmet classification of chronic hepatitis C we reviewed 801 liver biopsies from patients with HCV-chronic hepatitis (CH). The diagnosis of chronic hepatitis was assessed according to the Desmet classification based on the Knodell Histological Activity Index (HAI) (minimal CH=score 1-3; mild CH= 4-8; moderate CH= 9-12; severe CH= 13-18). Liver fibrosis was assessed according to the Scheuer scoring system. One hundred forty-eight patients had cirrhosis and 653 CH. Of these 653, according to the Desmet classification 145 patients showed minimal, 424 mild, 73 moderate and 11 severe chronic hepatitis. Since the classification underestimated the moderate and severe forms of HCV-related chronic hepatitis, we evaluated the possibility of improving the Desmet classification of chronic hepatitis C using our classification: minimal CH= score 1-3; mild CH= 4-6; moderate CH= 7-8; severe CH= 9-18. According to our classification 145 showed minimal CH, 363 mild CH, 61 moderate CH and 84 severe CH. All the 61 patients who crossed over from mild CH under the Desmet to moderate CH under our classification showed a periportal inflammation of grade 3, and all the 73 patients but 8 who crossed over from moderate to severe showed a grade of periportal inflammation higher than 3. The Desmet classification of HCV-related chronic hepatitis underestimated the severe forms of HCV-CH, while our classification seems to be suitable also for chronic hepatitis C.

Uselessness of liver biopsy in patients with hepatitis C virus chronic infection and persistently normal aminotransferase levels.

This case-control study evaluated the real need for liver biopsy in subjects with persistently normal aminotransferase values over a long period by comparing the histological features of these subjects with those of patients with abnormal aminotransferase values. We considered as "Cases" all 32 consecutive anti-HCV/HCV-RNA positive subjects with at least eight normal serum ALT values during the last twelve months; for each "Case", we selected as a "Control" one anti-HCV/HCV-RNA positive patient with at least two abnormal serum ALT values during the last twelve months. The Cases and Controls were matched for age ( 5 years) and sex. In the Case group, 1 subject showed normal liver tissue, 18 minimal chronic hepatitis (CH) and 13 mild CH. In the Control group, 7 subjects showed minimal CH, 19 mild CH, 3 moderate CH, 1 severe CH and 2 cirrhosis. The subjects in the Control group showed a significantly higher HAI score (5.39+2.81) than those in the Case group (2.96+1.62, p < 0.001). The subjects in the Control group more frequently showed a fibrosis score greater than 1 (28.1%) compared to the Case group (9.4%; p<0.05). Finally, steatosis was more frequent and more severe in the Control group than in the Case group (respectively, 78.1% vs 50%, p < 0.05; and 1.47+1.16 vs 0.6+0.71, p < 0.001). The HAI and fibrosis scores did not correlate with the ALT value, HCV genotype or HCV viral load in either the Case or Control group. Our findings showed that the subjects with a persistently normal serum ALT value had minimal or mild chronic hepatitis, thus demonstrating that a liver biopsy is not indicated for these subjects.

Hepatitis viruses and HIV infection in the Naples area.

In 189 anti-HIV positive subjects (130 males and 59 females; median age 32 years, range 17-57) we evaluated the prevalence of patients with hepatitis infections, the role of parenteral and sexual risk factors on the acquisition of these infections and the reciprocal influence between HIV and HCV infections. HCV infection was detected in 53.9% of cases and HBV infection in 8.4%. In only 32% of our patients no marker of hepatitis virus infection was detected. The presence of a hepatitis virus infection was associated to drug addiction; indeed in 91 drug abusers HIV/HCV co-infection was present in 80% of cases and HIV infection alone in 7.7%, p<0.0001. On the other hand, the association between unsafe sexual activity, whether homosexual or heterosexual, and sexual activity with a steady anti-HIV positive partner with HCV infection was less evident, although the high prevalence of anti-HCV in these cases (10.4%, 15.4% and 26.4% respectively) clearly suggests that HIV infection may improve the sexual transmission of HCV. No substantial differences in the level of immunodeficiency, nor in the HIV viral load nor in the frequency of AIDS cases were observed between patients with HIV infection alone and those with HIV/HCV co-infection. In fact, the percentage of patients with AIDS was similar in these two groups. However, we observed a statistically significant association between an advanced HIV clinical stage and the presence of HIV/HCV co-infection (p<0.005), since subjects with co-infection more frequently than with HIV infection alone were in the CDC-B clinical stage. The presence of a more severe liver disease was linked to a multiple hepatitis virus infection, regardless of the degree of immunodeficiency.

Helicobacter spp. and liver diseases.

To test whether Helicobacter species play a role in the enhancement of liver necro-inflammation and fibrosis and in the development of hepatocellular carcinoma (HCC), we sought DNA sequences of Helicobacter species in liver specimens from patients with viral-related chronic hepatitis, HCC or metastatic liver carcinoma. We enrolled 28 consecutive patients with ultrasound evidence of hepatic nodule(s) on their first liver biopsy: 21 had histological evidence of HCC (Group I) and 7 of metastatic liver carcinoma (Group II). In the same period we observed 27 consecutive patients with chronic hepatitis on their first liver biopsy (Group III). Helicobacter sequences were sought by PCR using primers for the 16S rDNA of Helicobacter spp, designed to amplify a 400 base-pair fragment, and detected by 2% agarose gel and hybridization with a specific biotinylated probe. We used, as positive controls for the DNA extraction from liver tissue, hepatic biopsy sections in which HBV infection was confirmed by HBcAg positivity and in which we amplified HBV-DNA by specific primers; positive controls for the amplification of Helicobacter spp were obtained from gastric biopsy sections in which Helicobacter pylori infection was confirmed by biochemical and histochemical tests. HBV-DNA was found in all five HBcAg positive liver biopsies. Helicobacter spp 16S rDNA was detected in all five biopsy specimens of gastric mucosa and in none of liver specimens from patients in any group. Our data suggest that Helicobacter species were not involved in the pathogenesis of virus-related HCC, chronic hepatitis or liver carcinoma metastasis.

Real-world outcomes in patients with chronic hepatitis C: primary results of the PROBE study.

BACKGROUND: This large prospective multicentre cohort study aimed to improve knowledge of therapy for chronic hepatitis C (CHC) in real clinical practice. METHODS: A diverse population of adults with CHC including patients with comorbid conditions, laboratory abnormalities and demographic features [comorbidities or special populations (CSP)] who were under-represented or excluded from peginterferon registration studies was treated with peginterferon α-2a (40 kDa) or α-2b (12 kDa) plus ribavirin at the investigator's discretion. RESULTS: During the study, 5399 treatment-naive patients [2527 (46.8%) with CSP] received peginterferon α-2a (n=3513, 65.1%) or peginterferon α-2b (n=1886, 34.9%). The sustained virological response rate was 56.6% (3057/5399) overall, 59.7% (1716/2872) in patients without CSP and 53.1% (1341/2527) in patients with CSP. Significant predictors of sustained virological response included hepatitis C virus genotype 2 or 3 infection, absence of cirrhosis, hepatitis C virus RNA≤500 000 IU/ml, alanine transaminase quotient >3× the upper limit of normal, age ≤65 years, BMI<25 kg/m, at least 80% of the planned exposure to peginterferon and ribavirin and prescription of peginterferon α-2a. CONCLUSION: The results provide detailed information on the outcome of therapy for CHC in a diverse Italian population that included a large number of patients with CSP and provides an insight into the generalizability of the results obtained in the more restricted setting of randomized registration trials.

Liver biopsy in chronic hepatitis C: the experience of 15 Italian wards of infectious diseases.

To evaluate the impact of liver histology on the management of HCV-related chronic hepatitis, 281 patients with chronic HCV infection who consecutively underwent percutaneous liver biopsy (LB) at one of the 15 participating Italian Units of Infectious Diseases were investigated in 2005. Demographic, aetiological, laboratory and clinical data and information on methods applied to perform ultrasonography (US) and LB were recorded. Males predominated (61.6%), mean age was 47.5 years and the mean BMI 22.3. In each case LB was US-guided or US-assisted. An 18-gauge Menghini-type needle was used in 203 (72.2%) cases. The length of the specimen ranged between 1.5 and 5 cm in 279 (99.3%) cases, it was smaller in two cases, but the diagnosis was still possible. Haemoperitoneum was the only (0.4%) major unpredictable complication; minor complications were also infrequent (4%). Using both clinical and laboratory data and US examination the physician misdiagnosed liver histology in 25% of cases. After LB the physicians changed their opinion on whether to treat with PEG-INF plus ribavirin in 43 (15.5%) cases. Liver histology allows more accurate diagnosis and enables physicians to make the most appropriate choic.

Treatment of chronic hepatitis B: update of the recommendations from the 2007 Italian Workshop.

The Italian recommendations for the therapy of hepatitis B virus (HBV)-related disease were issued in 2008. Subsequently in 2008 the nucleotide analogue (NA) Tenofovir was approved for antiviral treatment. The introduction of this important new drug has called for the current guidelines update, which includes some additional revisions: (a) the indication for therapy is extended to mild liver fibrosis and the indication for treatment is graded as "possible", "optional" or "mandatory" according to the fibrosis stage; (b) two different treatment strategies are described: first line definite duration treatment with interferon, long-term treatment of indefinite duration with NA; (c) the indication to follow either strategy is also based on the stage of liver fibrosis; (d) virological monitoring is modified to include the definitions of failure and of sustained virological response to interferon therapy; (e) the recommendation to use HBV DNA assays with high sensitivity and wide linear ranges is underlined (f) guidelines on post-treatment follow-up after finite treatment with NA, potential side effects of therapy and non-virological monitoring are defined; (g) definitions and treatment of patients without optimal response to NA are reported; (f) treatment and monitoring of compensated or decompensated cirrhosis and hepatocellular carcinoma are updated.

Recommendations for the management of mixed cryoglobulinemia syndrome in hepatitis C virus-infected patients.

OBJECTIVE: The objective of this review was to define a core set of recommendations for the treatment of HCV-associated mixed cryoglobulinemia syndrome (MCS) by combining current evidence from clinical trials and expert opinion. METHODS: Expert physicians involved in studying and treating patients with MCS formulated statements after discussing the published data. Their attitudes to treatment approaches (particularly those insufficiently supported by published data) were collected before the consensus conference by means of a questionnaire, and were considered when formulating the statements. RESULTS: An attempt at viral eradication using pegylated interferon plus ribavirin should be considered the first-line therapeutic option in patients with mild-moderate HCV-related MCS. Prolonged treatment (up to 72 weeks) may be considered in the case of virological non-responders showing clinical and laboratory improvements. Rituximab (RTX) should be considered in patients with severe vasculitis and/or skin ulcers, peripheral neuropathy or glomerulonephritis. High-dose pulsed glucocorticoid (GC) therapy is useful in severe conditions and, when necessary, can be considered in combination with RTX; on the contrary, the majority of conference participants discouraged the chronic use of low-medium GC doses. Apheresis remains the elective treatment for severe, life-threatening hyper-viscosity syndrome; its use should be limited to patients who do not respond to (or who are ineligible for) other treatments, and emergency situations. Cyclophosphamide can be considered in combination with apheresis, but the data supporting its use are scarce. Despite the limited available data, colchicine is used by many of the conference participants, particularly in patients with mild-moderate MCS refractory to other therapies. Careful monitoring of the side effects of each drug, and its effects on HCV replication and liver function tests is essential. A low-antigen-content diet can be considered as supportive treatment in all symptomatic MCS patients. Although there are no data from controlled trials, controlling pain should always be attempted by tailoring the treatment to individual patients on the basis of the guidelines used in other vasculitides. CONCLUSION: Although there are few controlled randomised trials of MCS treatment, increasing knowledge of its pathogenesis is opening up new frontiers. The recommendations provided may be useful as provisional guidelines for the management of MCS.

Antiviral treatment of HCV-related cirrhosis.

The primary aim of antiviral therapy in HCV liver cirrhosis is to stop viral replication and, consequently, to prevent the clinical progression of fibrosis, liver decompensation and the onset of hepatocellular carcinoma. However, the results of therapy are different according to the different clinical stages of cirrhosis. In patients with bridging fibrosis or histological cirrhosis international trials have demonstrated that the sustained virological response to the highly active combination of pegylated interferon plus ribavirin was substantially similar to that observed in subjects with chronic hepatitis C without cirrhosis. Few data are available as to the efficacy and tolerability of antiviral treatment in patients with fully developed clinical cirrhosis, with or without decompensation, and all studies to date underscore the difficulties in the management of the more frequent and severe side effects in these patients. In patients with a more severe disease who do not achieve a sustained virological response, an alternative option is to reduce or suppress inflammation and fibrosis progression with long-term suppressive therapy in the hope to prevent clinical deterioration and the onset of hepatocellular carcinoma. Three international trials are currently evaluating the use of antiviral treatment as a maintenance antiviral therapy.

Sustained virological response to interferon-alpha is associated with improved outcome in HCV-related cirrhosis: a retrospective study.

UNLABELLED: The effect of achieving a sustained virological response (SVR) following interferon-alpha (IFNalpha) treatment on the clinical outcomes of patients with HCV-related cirrhosis is unknown. In an attempt to assess the risk of liver-related complications, HCC and liver-related mortality in patients with cirrhosis according to the response to IFNalpha treatment, a retrospective database was developed including all consecutive patients with HCV-related, histologically proven cirrhosis treated with IFNalpha monotherapy between January 1992 and December 1997. SVR was an undetectable serum HCV-RNA by PCR 24 weeks after IFNalpha discontinuation. HCC was assessed by ultrasound every 6 months. Independent predictors of all outcomes were assessed by Cox regression analysis. Of 920 patients, 124 (13.5%) were classified as achieving a SVR. During a mean follow-up of 96.1 months (range: 6-167) the incidence rates per 100 person-years of liver-related complications, HCC and liver-related death were 0, 0.66, and 0.19 among SVR and 1.88, 2.10, and 1.44 among non-SVR (P<0.001 by log-rank test). Multivariate analyses found that non-SVR was associated with a higher risk of liver-related complications (hazard ratio, HR, not applicable), HCC (HR 2.59; 95% CI 1.13-5.97) and liver-related mortality (HR 6.97; 95% CI 1.71-28.42) as compared to SVR. CONCLUSION: Thus, in patients with HCV-related, histologically proven cirrhosis, achievement of a SVR after IFNalpha therapy was associated with a reduction of liver-related mortality lowering both the risk of complications and HCC development. Irrespective of SVR achievement, all patients should continue surveillance because the risk of occurrence of HCC was not entirely avoided.

Lipodystrophy and serum lipid abnormalities in HIV-positive sub-Saharan population on ART.

To evaluate whether racial factors may be involved in the development of ART-induced lipodystrophy and/or lipid serum abnormalities, we carried-out a case-control study on all 23 consecutive anti-HIV-positive sub-Saharan black African patients observed from September 20fc01 to December 2001 ('Cases') and 23 Caucasian 'Controls' pair-matched for sex, age (+/-5 years), number of CD4 cells (+/-100 cells), clinical stage of HIV infection, overall duration (+/-3 months) of anti-retroviral treatment and type and duration (+/-3 months) of the last anti-retroviral regimen. The cases, as compared with the controls, less frequently showed lipodystrophy (4.4 vs. 65.2%, P<0.001) and hypertriglyceridemia (8.8 vs. 56.5%, P<0.005), whereas the prevalence of subjects with hypercholesterolemia was similar in the two groups (30 and 39.1%, respectively). Overall, the prevalence of patients lacking both lipodystrophy and serum lipid abnormalities was markedly higher for the cases than for the controls (69.5 vs. 13%, P<0.001). This study seems to indicate that anti-retroviral-induced lipodystrophy and hypertriglyceridemia may be associated to some racial factor.

Liver histology in patients with HBsAg negative anti-HBc and anti-HCV positive chronic hepatitis.

The liver histology of 68 consecutive anti-HCV/HCV-RNA positive chronic hepatitis patients who were HBsAg/anti-HBs negative, anti-HBc positive (Case bC group) was compared with that of 68 anti-HCV/HCV-RNA positive chronic hepatitis patients who were HBsAg/anti-HBc negative (control C group). The patients were pair-matched by age (+/-5 years), sex, and risk factors for the acquisition of parenteral infection. Case bC group showed a significantly higher mean fibrosis score (2.3 +/- 1.1) than control C group (1.5 +/- 1.1, P <0.001) and more histological evidence of cirrhosis (22% vs. 7.3%, P <0.05). In addition, the patients in Case bC group showed more severe inflammation of the portal tracts (3.5 +/- 0.8 vs. 3.0 +/- 1.1, P <0.005) and there was a higher prevalence of patients with rhomboid-shaped hepatocytes (26.4% vs. 2.7%, P <0.005), acidophilic bodies (33.8% vs. 1.4%, P <0.0001), sinusoidal inflammation (29.4% vs. 10.3%, P <0.01), lymphoid follicles in the portal tracts (72% vs. 44.1%, P <0.05), Kupffer cell proliferation (29.4% vs. 11.8%, P <0.05), bile duct damage (44.1% vs. 10.3%, P <0.0001), and ductular proliferation (30.9% vs. 2.7%, P <0.001) than in control C group. No difference in these histological features was observed between HBV-DNA negative and positive patients in Case bC group. The data suggest that anti-HBc positive patients with HCV chronic infection have a significantly higher degree of liver fibrosis, and that hepatocellular apoptosis, bile duct damage, and ductular proliferation correlate with the presence of this antibody in the serum.

HAV replication in acute hepatitis with typical and atypical clinical course.

The correlation between the length of viremia as detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and the clinical course of hepatitis A virus (HAV) infection was studied. Sixty-six consecutive patients with acute hepatitis A who were admitted to hospital in two infectious disease units in southern Italy were enrolled: 57 had a self-limited course of the disease (typical course), 4 a prolonged course, and 5 relapsing hepatitis. Plasma HAV RNA was sought by RT-PCR, using primers made at 5'-NTR of HAV, designed to amplify a 273-bp fragment and detected by 2% agarose gel and by hybridization with a specific biotinylated probe. In four patients with prolonged acute hepatitis A, the plasma HAV RNA, which was positive on the day of admission to hospital, was found to be negative from day 62, 46, 84, and 105, respectively, after the onset of the symptoms. In patients with relapsing hepatitis, HAV viremia paralleled the clinical and biochemical course of disease. In all patients with a typical self-limiting course, clearance of plasma HAV RNA was observed within 20 days of the onset of symptoms. In most patients, plasma HAV viremia became undetectable before the normalization of serum aminotransferases, underlining the importance of the immune reaction in the pathogenesis of acute hepatitis A. The data also suggest that the detection of plasma HAV RNA after 20 days of illness may predict a prolonged course of the disease, but relapsing hepatitis remains unpredictable on the basis of plasma HAV determination.