Evangelista Sagnelli

Complications following percutaneous liver biopsy. A multicentre retrospective study on 68,276 biopsies

This paper reviews the complications that arose after 68 276 percutaneous liver biopsies performed from 1973 to 1983. The complications are analyzed in relation to the underlying liver disease and to the type of needle used. Death was infrequent (9/100 000); it was always due to haemoperitoneum and occurred only in patients with malignant diseases or cirrhosis. Complications were less frequent in AVH (44/100 000) than in other liver diseases (from 125 to 278/100 000). Death, serious haemorrhagic complications, pneumothorax and biliary peritonitis were more frequent after biopsy with the Trucut needle than after biopsy with Menghinis needle (3/1000 against 1/1000). Sixty-one percent of complications were discovered within two hours of biopsy and 96% within one day. The data indicate a post biopsy observation period of at least 24 hours. The day-case procedure should be reserved for patients not presenting liver tumour or cirrhosis.

Infection with the delta agent in chronic HBsAg carriers

To establish the mechanism of progression to chronicity of the HBsAg-associated delta infection, serum hepatitis B virus and delta markers were tested in five babies born to HBsAg-positive mothers with anti-delta, in 42 follow-up patients with acute hepatitis B virus and delta hepatitis, and in collections of sera from 8 HBsAg carriers with anti-delta. Evidence of delta infection was found in the baby born to a mother with serum HBeAg and in none of the four babies born to mothers with anti-HBe. Hepatitis was self-limited in the 42 patients acutely infected by hepatitis B virus and delta agent; none developed persistent HBs-antigenemia and the majority displayed transient anti-delta of IgM class. In seven HBsAg carriers high titers of anti-delta developed during the follow-up; coincident with the rise of the antibody, aminotransferase elevation occurred in five previously asymptomatic carriers and persisted in three of them. No sign of infectious hepatitis B virus replication was detected in five of the carriers throughout the follow-up, and all of them had anti-HBe before the rise of anti-delta and of aminotransferase. HBsAg carriers with diminished hepatitis B virus synthesis appear to be at high risk of developing chronic delta infection and disease when exposed to the delta-infectious serum of other carriers.

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.

SERUM LEVELS OF HEPATITIS B SURFACE AND CORE ANTIGENS DURING IMMUNOSUPPRESSIVE TREATMENT OF HBsAg-POSITIVE CHRONIC ACTIVE HEPATITIS

One of the following treatments was randomly assigned to 101 consecutive patients with biopsy-proven chronic active hepatitis: prednisone 20 mg daily, azathioprine 100 mg daily, prednisone 20 mg and azathioprine 50 mg daily, or B vitamins 2 tablets daily (control group). Patients were observed at the beginning of the study, then at 2, 6, and 12 months after treatment. At each visit levels of HBsAg and Dane-particle-associated core-antigen (HBcAg) and their corresponding antibodies were determined. 42 patients were HBcAg positive at the beginning of the study. Of these 42 patients, the 34 who were under treatment remained HBcAg positive and showed a rise in HBcAg titre, while the 8 who were not treated had a fall in HBcAg titre (6 patients) or became HBcAg negative (2 patients) in 6 months. Among 59 patients who were HBcAg negative at the beginning of the study, this antigen became persistently detectable in 40% of the 42 patients who were treated, and was transiently present in 2 (12%) out of the 17 untreated patients (p < 0.05). Our data indicate that long-term prednisone and/or azathioprine treatments favour the replication of hepatitis-B virus in patients with HBsAg-positive chronic active hepatitis.

Impact of occult hepatitis B virus infection in HIV patients naive for antiretroviral therapy.

Objective:To study the impact of occult hepatitis B virus (HBV) infection in 115 consecutive anti-HIV-positive, hepatitis B surface antigen-negative patients, naive for antiretroviral treatment. Methods:Of these 115, 86 patients were followed for at least 6 months (range 6–36) with serial determinations of HIV RNA and HBV DNA by polymerase chain reaction and other laboratory tests. Results:Of the 86 patients having a follow-up, plasma HBV DNA was detected in 17 (19.8%), 13 on admission and four during follow-up. HBV DNA was more frequently found in patients with isolated anti-hepatitis B core (HBc; 35.5% of 31 cases) than in those lacking anti-HBc and anti-hepatitis B surface (8.8% of 41, P < 0.005), or showing both (21.4% of 14). Twenty-eight patients (32.5%) experienced a hepatic flare during the follow-up; this event was more frequent in the 17 HBV-DNA-positive patients than in the 69 negative (64.7% versus 24.6%, P < 0.005). Of the 13 HBV-DNA-positive patients on admission, 11 receiving HAART containing lamivudine became HBV-DNA negative, but two of these again became positive and experienced a hepatic flare during treatment and two both during and after lamivudine treatment. A hepatic flare also occurred under lamivudine treatment in two of the four patients in whom HBV DNA became detectable during follow-up. The role of immune reconstitution inflammatory syndrome and HAART in inducing a hepatic flare was found to be marginal in 49 patients with no HBV or hepatitis C virus marker. Conclusion:The study suggests that HBV occult infection, relatively frequent in anti-HIV-positive patients, is associated with hepatic flares.

Decrease in HDV endemicity in Italy.

BACKGROUND/AIMS To evaluate a possible variation in hepatitis D virus endemicity in Italy, the data from a multicentre study concerning HBsAg chronic carriers first observed in 31 liver units during 1992 were compared with the corresponding figures from a similar study performed in 1987. METHODS/RESULTS In both studies the methodology for the recruitment of cases was the same. The overall anti-HD prevalence in 1992 was 14.4%, a significantly lower rate than that observed in 1987 (23.4%, p < 0.01). The decrease significantly (p < 0.01) affected both males and females; it occurred in all geographical areas, although to a greater extent in northern regions. It was evident in subjects below 50 years of age, but not in subjects older than 50. A significant reduction in the anti-HD prevalence was seen in all forms of chronic hepatitis. CONCLUSIONS These findings indicate a lower level of hepatitis D virus endemicity in Italy, probably as a consequence of the reported decreased pool of HBsAg chronic carriers, the reduced size of families, the improved socio-economic conditions and changes in intravenous drug abuser behaviour. All these factors may have affected the strength of hepatitis D virus infection which has greatly reduced the spread of the virus.

Does HIV infection favor the sexual transmission of hepatitis C

Background There are widely discrepant findings on the sexual transmission of hepatitis C virus (HCV), commonly transmitted by the parenteral route. Coinfection with HCV is common in subjects infected with HIV. Goal This case–control study evaluated the prevalence of anti–HCV in subjects with hetero- or homosexual contact and no history of intravenous drug abuse or blood transfusion, according to the presence or absence of HIV infection. Study Design In this case–control study, the cases considered were 106 consecutive patients who showed positive anti-HIV test results. For each case, two control subjects were selected who had been screened for HIV infection at the authors’ center and found to have anti–HIV-negative test results, and who matched the case in terms age (± 5 years), gender, and risk factor for parenterally transmitted infections. Results The prevalence of subjects with positive test results for hepatitis B surface antigen (HBsAg) was similar between cases and control subjects (4.7% versus 2.4%). Positivity for anti-hepatitis B core antigen in connection with negative test results for HBsAg was observed more frequently in the 106 cases than in the 212 control subjects (33.9% versus 15.6%;P = 0.0003). Anti–HCV positivity was more frequent in the cases than in the control subjects (15.1% versus 5.2%;P = 0.005). In particular, among subjects who had hetero- or homosexual intercourse with a steady partner who had positive anti-HIV test results, anti-HCV positivity was observed in 18.7% of the 32 cases and 1.6% of the 64 control subjects (P = 0.008). Conclusion This study demonstrated that in subjects who had only a sexual risk factor for parenterally transmitted infections, HIV may enhance the sexual transmission of HCV.

HBV superinfection in HCV chronic carriers: A disease that is frequently severe but associated with the eradication of HCV

The impact of hepatitis B virus (HBV) superinfection in hepatitis C virus (HCV) chronic carriers was evaluated in a long‐term follow‐up study on 29 chronic anti‐HCV carriers with acute hepatitis B (AVH‐B) (Case group BC) and 29 anti‐HCV negative patients with AVH‐B (Control group B), pair‐matched for age (±5 years), sex, and risk factors for the acquisition of HBV infection. Patients in Case group BC and those in Control group B showed similar initial HBV viral load and a similar trend of becoming negative for HBV‐DNA. AVH‐B showed a severe course more frequently in Case group BC than in Control group B (34.5% versus 6.9%, P < 0.05). Of the 28 patients in Case group BC alive at the end of the acute illness (one death from liver failure), 24 were followed up for 2‐6 years, median 5 years: 22 patients became HBsAg‐negative and two progressed to HBsAg‐positive chronic hepatitis. HCV‐RNA was undetectable in all patients during AVH‐B; in the 24 patients with a long‐term follow‐up, HCV‐RNA was detected in seven (29.2%) after 1 year, in 14 (58.3%) after 2 years, and in 18 (75%) after 3‐6 years. The six patients who eradicated chronic HCV infection, compared with 18 showing reactivation of HCV replication, had higher values of aspartate aminotransferase and alanine aminotransferase and a higher prevalence of cases with severe AVH‐B (83.3% versus 22.2%, P < 0.05). Conclusions: Although it can be life‐threatening, HBV superinfection in HCV chronic carriers may lead to clearance of chronic HCV infection, especially in patients with severe AVH‐B. (HEPATOLOGY 2009.)

Influence of chronic coinfection with hepatitis B and C virus on liver histology.

Abstract.Background:Few data are available on histological features of chronic hepatitis B (HBV) and C (HCV) virus coinfection.Patients and Methods:We enrolled 142 consecutive patients with viral chronic hepatitis on their first liver biopsy: 27 HBsAg and anti-HCV positive (case BC group), 57 HBsAg positive and anti-HCV negative (control B group) and 58 anti-HCV positive, HBsAg/anti-HBs/anti-HBc negative (control C group).Results:Patients in the case BC group showed serum HBVDNA (37% vs 71.9%, p < 0.005) and ground-glass hepatocytes (37% vs 66.7%, p < 0.01) less frequently than those in the control B group. The case BC group showed a lower prevalence of patients with detectable HCV-RNA than the control C group (60% vs 92.3%, p < 0.001) and a significantly higher fibrosis score (2.1 ± 1.2 vs 1.5 ± 1.1, p < 0.05). Of the 27 patients in the case BC group, 10 lacked serum HCV-RNA and showed significantly higher histological activity index (HAI) and fibrosis scores than those found in the 17 HCV-RNA positive (8.5 ± 4.4 vs 5.4 ± 2.4 for HAI, p < 0.05; 3.0 ± 1.3 vs 1.69 ± 1.0, p < 0.05 for fibrosis).Conclusion:Liver histology seems to be more severe in chronic coinfection with HBV and HCV than in single infection, particularly when HCV replication is impaired.

Randomised study comparing 48 and 96 weeks peginterferon α-2a therapy in genotype D HBeAg-negative chronic hepatitis B

Objective Treatment with peginterferon α-2a (PegIFN) for 48 weeks is the standard of care for selected HBeAg-negative patients chronically infected with hepatitis B virus (HBV), but with limited treatment efficacy. A study was undertaken to investigate whether treatment extension to 96 weeks improves the outcome in this patient population. Methods 128 HBeAg-negative patients (120 genotype D) were randomised to weekly 180 μg PegIFN for 48 weeks (group A, n=51), 180 μg PegIFN for 48 weeks followed by 135 μg weekly for an additional 48 weeks (group B, n=52) or 180 μg PegIFN plus lamivudine (100 mg/day) for 48 weeks then 135 μg PegIFN for 48 weeks (group C, n=25). Endpoints were alanine aminotransferase normalisation plus HBV DNA <3400 IU/ml (primary), HBV DNA <2000 IU/ml and HBsAg clearance at 48 weeks after treatment. Results Forty-eight weeks after treatment, six patients in group A and 13 in group B achieved alanine aminotransferase normalisation plus HBV DNA <3400 IU/ml (11.8% vs 25.0%, p=0.08), 6 vs 15 patients had HBV DNA <2000 IU/ml (11.8% vs 28.8%, p=0.03), 0 vs 3 achieved HBsAg clearance (0% vs 5.8%, p=0.24) and 0 vs 5 had HBsAg <10 IU/ml (0% vs 9.6%, p=0.06). While extended PegIFN treatment was the strongest independent predictor of response, the combination with lamivudine did not improve responses. Discontinuation rates were similar among the groups (19.6%, 23.1%, 32.0%, p=0.81) and were mostly due to PegIFN-related adverse events. Conclusions In HBeAg-negative genotype D patients with chronic hepatitis B, PegIFN treatment for 96 weeks was well tolerated and the post-treatment virological response improved significantly compared with 48 weeks of treatment. Trial registration number http://ClinicalTrials.gov registration number: NCT01095835.