HBV/HDV co-infection in the Western Brazilian Amazonia: an intriguing mutation among HDV genotype 3 carriers.

HDV infection still remains a serious public health problem in Amazonia. There are few data regarding the biomolecular aspects of HBV/HDV co-infection in this region. We studied 92 patients HBsAg(+) /anti-HDV IgG(+) followed at the Hepatitis Referral Centers of Porto Velho (RO), Rio Branco and Cruzeiro do Sul (AC), Brazil, from March 2006 to March 2007 for whom the HDV and/or the HBV genotype could be determined. The HDV genotype could be determined in 90 patients, while the HBV genotypes could be positively determined in 74. HBV subgenotype F2 is the most prevalent (40.2%), followed by the subgenotypes A1 (15.2%) and D3 (8.7%), while 16.4% were other subgenotypes or genotypes, 4.3% were discordant and 15.2% were unamplifiable. Surprisingly, HDV genotype 3 (HDV-3) was found in all of the HBV/HDV-infected patients that could be genotyped for HDV, confirming that HDV-3 can associate with non-F HBV genotypes. However, a HDV-3 mutant was found in 29.3% of patients and was more frequently associated with non-F HBV genotypes (P < 0.001) than were nonmutant strains, suggesting that the mutation may facilitate association of HDV-3 with non-F HBV genotypes.

The state of hepatitis B and C in the Mediterranean and Balkan countries: report from a summit conference.

The burden of disease due to chronic viral hepatitis constitutes a global threat. In many Balkan and Mediterranean countries, the disease burden due to viral hepatitis remains largely unrecognized, including in high-risk groups and migrants, because of a lack of reliable epidemiological data, suggesting the need for better and targeted surveillance for public health gains. In many countries, the burden of chronic liver disease due to hepatitis B and C is increasing due to ageing of unvaccinated populations and migration, and a probable increase in drug injecting. Targeted vaccination strategies for hepatitis B virus (HBV) among risk groups and harm reduction interventions at adequate scale and coverage for injecting drug users are needed. Transmission of HBV and hepatitis C virus (HCV) in healthcare settings and a higher prevalence of HBV and HCV among recipients of blood and blood products in the Balkan and North African countries highlight the need to implement and monitor universal precautions in these settings and use voluntary, nonremunerated, repeat donors. Progress in drug discovery has improved outcomes of treatment for both HBV and HCV, although access is limited by the high costs of these drugs and resources available for health care. Egypt, with the highest burden of hepatitis C in the world, provides treatment through its National Control Strategy. Addressing the burden of viral hepatitis in the Balkan and Mediterranean regions will require national commitments in the form of strategic plans, financial and human resources, normative guidance and technical support from regional agencies and research.

Proficiency of transient elastography compared to liver biopsy for the assessment of fibrosis in HIV/HBV-coinfected patients.

Transient elastography (TE) is a noninvasive technique to evaluate liver fibrosis. We compared the performance of TE with liver biopsy (LB) in patients with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection. Patients prospectively underwent TE and LB. The diagnosis accuracy of TE was calculated using receiver operating characteristic (ROC) curves for different stages of fibrosis, and optimal cut-off values were defined. A sequential algorithm combining TE with biochemical score (Fibrotest) is proposed. Fifty-seven patients had both TE and LB (median time: 3 days) and two with proven cirrhosis, only TE. Forty-six (78%) were under antiretroviral therapy with anti-HBV drugs in 98%, and 19 (32%) had elevated alanine aminotransferase (ALT). A significant correlation was observed between liver stiffness measurement (LSM) and METAVIR fibrosis stages (P < 0.0001). Patients with elevated ALT tended to have higher LSM than those with normal ALT. The areas under the ROC curves were 0.85 for significant fibrosis (≥ F2), 0.92 for advanced fibrosis (≥ F3) and 0.96 for cirrhosis. Using a cut-off of 5.9 kPa for F ≥ 2 and 7.6 kPa for F ≥ 3, the diagnosis accuracy was 83% and 86%, respectively. With an algorithm combining TE and Fibrotest, 97% of patients were well classified for significant fibrosis. Using this algorithm, the need for LB can be reduced by 67%. In HIV/HBV-coinfected patients, most of them with normal ALT under antiretroviral treatment including HBV active drugs, TE was proficient in discriminating moderate to severe fibrosis from minimal liver disease.

A randomized trial of viral hepatitis prevention among underprivileged people in the Lyon area of France.

BACKGROUND: We compared the efficacy of two viral hepatitis B and C (VHBC) screening strategies, relative to no intervention, among underprivileged people (UP) living in shelters in the Lyon area. METHODS: Eighteen of 37 shelters were randomly sampled after stratification based on the accommodation capacity and the screening centres/shelters distance. Through randomization, the S0 strategy (no intervention), the S1 strategy [group information (GI) and referral for screening] and the S2 strategy (GI and in situ screening) were each applied in six shelters. A standardized questionnaire was offered to each participant. Follow-up of positive cases was organized via the reference centre of VHBC of Lyon. RESULTS: The screening completion rate (SCR) among 1276 included subjects in S0, S1 and S2 was 1.5, 42.8 and 59.7%, respectively (P < 10(-6)). This rate was higher in S2 regardless of the sociodemographic variable considered. Odds ratios (OR) of screening completion (SC) was significantly higher in S1 versus S0, OR = 49.8 [95% confidence interval (CI): 26.1-102.1], in S2 versus S0, OR = 98.5 (95% CI: 51.9-200.8) and in S2 versus S1, OR = 2.0 (95% CI: 1.3-2.9). Age, country of birth and professional inactivity were independently associated with SC. CONCLUSIONS: Health authorities must ensure widespread screening of UP, which is more effective when conducted in shelters than in screening centres.

[Results of a satisfaction survey carried out among patients living with the virus of human immunodeficiency (HIV) following therapeutic education sessions]. / Résultats d'une enquête de satisfaction réalisée auprès des patients vivant avec le virus de l'immunodéficience humaine (VIH) suivis en consultation d'éducation thérapeutique.

INTRODUCTION: Within the framework of a quality initiative aiming to improve HIV patients' care in our therapeutic educational unit, and to meet the recommendations of the Haute Autorité de Santé (HAS) regarding the evaluation of educational programs, we carried out a satisfaction survey among patients. Our goal was to identify their needs thanks to the analysis of questionnaires in order to improve their care. PATIENTS AND METHOD: Anonymous questionnaires were proposed and collected for two months during a medical or educational consultation or during a renewal of prescription. All 21 questions related to the organization of our unit, the patients' expectations, the tools used and the quality of life. An appreciation scale at four levels was proposed. RESULTS: Twenty-eight questionnaires were returned out of 60 given out; 96.4% of the patients were satisfied and found the sessions to be beneficial and to answer their needs; 85.7% changed their opinion on HIV and 78.6% altered their behaviour; 89.3% were satisfied by the number of sessions; 96.4% thought that the place, duration and frequency of consultations were adapted, and 89.3% approved the educational tools; 67.8% thought that follow-up pad would be useful. DISCUSSION-CONCLUSION: Patients were satisfied with the educational sessions, which constituted a real place of exchange and support, allowing them to evoke all the difficulties they meet. Any improvements must concern information media given out to patients and the ease of access to educational teams in case of difficulties.

[Treatment of hepatitis B: new perspectives]. / Traitement de l'hépatite B: progrès attendus.

Despite the development of new anitiviral agents, the treatment of chronic hepatitis B remains a major clinical challenge. Major achievements have been made with the rationale use of antivirals exhibiting a complementary cross resistance profile to prevent antiviral drug resistance. The current concept of modern antiviral therapy of chronic hepatitis B relies on a precise virologic monitoring and early treatment adaptation to prevent drug resistance. The difficulty of achieving viral clearance and the risk of drug resistance development are major arguments to continue research in the field of antivirals and to identify new targets for therapy. The development of true combination therapy is highly desirable to fulfil the objective of long-term viral suppression, clearance of viral cccDNA and infected cells and ultimately cure of the disease.

Common dysregulation of Wnt/Frizzled receptor elements in human hepatocellular carcinoma.

Dysregulation of growth factors and their receptors is central to human hepatocellular carcinoma (HCC). We previously demonstrated that the Frizzled-7 membrane receptor mediating the Wnt signalling can activate the beta-catenin pathway and promotes malignancy in human hepatitis B virus-related HCCs. Expression patterns of all the 10 Frizzled receptors, and their extracellular soluble autoparacrine regulators (19 Wnt activators and 4 sFRP inhibitors) were assessed by real-time RT-PCR in 62 human HCC of different etiologies and their matched peritumorous areas. Immunostaining was performed to localise Frizzled on cell types in liver tissues. Regulation of three known Frizzled-dependent pathways (beta-catenin, protein kinase C, and C-Jun NH(2)-terminal kinase) was measured in tissues by western blot. We found that eight Frizzled-potentially activating events were pleiotropically dysregulated in 95% HCC and 68% peritumours as compared to normal livers (upregulations of Frizzled-3/6/7 and Wnt3/4/5a, or downregulation of sFRP1/5), accumulating gradually with severity of fibrosis in peritumours and loss of differentiation status in tumours. The hepatocytes supported the Wnt/Frizzled signalling since specifically overexpressing Frizzled receptors in liver tissues. Dysregulation of the eight Frizzled-potentially activating events was associated with differential activation of the three known Frizzled-dependent pathways. This study provides an extensive analysis of the Wnt/Frizzled receptor elements and reveals that the dysregulation may be one of the most common and earliest events described thus far during hepatocarcinogenesis.

Effect of early initiation of highly active antiretroviral therapy on CD4 cell count and HIV-RNA viral load trends within 24 months of the onset of acute retroviral syndrome.

OBJECTIVES: The effect of starting highly active antiretroviral therapy (HAART) early after the onset of acute retroviral syndrome (ARS) on CD4 and HIV-RNA trends was studied over a 2-year follow-up period. METHODS: Four groups of HIV-infected patients stratified according to the time interval from ARS onset to HAART initiation and a control group of untreated patients were compared. RESULTS: The results indicated that the earlier the start of HAART, the faster was the rate of CD4 increase and HIV-RNA decrease. However, this difference did not seem to persist at 24 months. CONCLUSIONS: The optimal treatment strategy for HIV-infected patients needs to be explored further.

[Hepatitis C: which strategy in case of treatment failure ?]. / Hépatite C : quelle stratégie en cas d'échec thérapeutique ?

After a treatment by peginterferon alpha and ribavirin, the percentages of non response and relapse are approximatively 33 and 18 % respectively. These treatment failures may be due either to viral resistance or to an insufficient treatment. The prevention of treatment failure is based on a good knowledge of the predictive factors of failure before and during the treatment. Among the patients who did not respond to interferon alpha and ribavirin, a new treatment with peginterferon alpha-2b and ribavirin makes it possible to obtain 45 % of sustained virological response (SVR) among the relapsers and 17 % of SVR among the non responders. Among the patients who did not respond to peginterferon alpha and ribavirin, a new treatment with peginterferon alpha-2b and ribavirin makes it possible to obtain 36 % of SVR among the relapsers and only 4 % of SVR among the non responders. New therapeutic strategies are necessary for the non responders. Until now no new therapeutic strategy allowed a significant benefit in term of SVR. Protease inhibitors are currently tested in non responders but there are some concerns about the risk of selection of multi-resistant strains.

A French prospective observational study of the treatment of chronic hepatitis C in drug abusers.

The objective of this prospective, multicenter, observational study was to evaluate healthcare for hepatitis C virus (HCV)-infected drug abusers in France and to determine predictors of successful therapeutic intervention. A total of 170 drug users were recruited from 40 French centers. Three centers recruited 66 participants (38.8%), and one to eight patients each were enrolled from 37 other centers (n=104). A sustained viral response (SVR) was seen in 65 (38.2%) patients. SVR rates were significantly higher in compliant than in non-compliant patients (43.5% versus 23.9%; P=0.019), in patients from high- rather than low-recruiting centers (54.5% versus 27.9%; P<0.001) and in patients receiving Buprenorphine rather than methadone (48.1% versus 21.8%; P=0.001). In patients, who completed both the treatment and follow-up (n=94), SVR rate was 57.4%. Buprenorphine substitution therapy and genotypes 2 or 3 HCV infection were associated with significantly higher rates of SVR (P<0.01, for both comparisons). In conclusion, successful care of hepatitis requires an active treatment policy of every center toward drug addicts. Additional studies are needed to explore the difference in SVR with methadone versus Buprenorphine therapy.

Discordance between biochemical markers of liver activity and fibrosis (Actitest-Fibrotest) and liver biopsy in patients with chronic hepatitis C.

INTRODUCTION: The purpose of this clinical trial was to determine in routine practice and in comparison with liver biopsy the limitations of two blood tests, Actitest and Fibrotest, for the evaluation of hepatic activity and fibrosis in patients with chronic hepatitis C. METHODS: Routine blood tests, Actitest and Fibrotest, and liver biopsy were performed in 96 patients with chronic hepatitis C attending routine outpatient clinics. Receiver operating characteristics (ROC) curves were used to assess the diagnostic value of the biochemical tests in comparison with the METAVIR classification. RESULTS: The study population was predominantly male (63.5%) with a mean age of 48 years; 83.3% of the patients had genotype 1 hepatitis C virus infection. Treatment status was naive (62.5%), nonresponders (17.7%), relapsers (7.3%), or unknown (12.5%). The comparison of F0-F2 versus F3-F4 estimated the negative predictive value at 92% and the positive predictive value at 52% for a cut-off of 0.455. Discrepancies in activity score were more frequently due to a higher score of the biochemical test compared to biopsy (18 cases out of 19). Discrepancies for fibrosis were observed in 18 patients with a higher score for biochemical test in eight and a higher score for liver biopsy in 10 cases. A significant increase of gamma-glutamyl-transferase (GGT) (p=0.0001) and alanine aminotransferase (ALT) (p<0.0001) was observed in case of biochemical test overestimation of activity, and a significant increase of alpha2-macroglobulin (p=0.006) and GGT (p=0.018) in case of biochemical test overestimation of fibrosis. CONCLUSION: This prospective study confirms the good diagnostic value of biochemical tests for necrotico-inflammatory activity and fibrosis as compared with the histological analysis of liver biopsy. Clinicians must interpret Actitest and Fibrotest results with caution in patients with a significant elevation of ALT, and/or GGT and/or alpha2-macroglobulin which could overestimate hepatic injury.

Long-term results of liver transplantation for Wilson's disease.

UNLABELLED: Wilson's disease is a hereditary defect in hepatic copper metabolism, causing hepatic, neurological and/or psychiatric manifestations. For patients with severe disease, liver transplantation is the treatment of choice. The aim of this study was to report the long-term outcome of patients who underwent liver transplantation for Wilson's disease. PATIENTS AND METHODS: Thirteen patients with Wilson's disease, transplanted in Lyon France between January 1987 and May 2006, were including in this study: eight women and five men, aged eight to 53 years (median 20 years, seven children and six adults). The diagnosis of Wilson's disease was established before liver transplantation. RESULTS: The indication for liver transplantation was chronic (69%) or fulminant liver failure (31%). The median follow-up after liver transplantation was 10 years with 100% patient survival. Copper metabolism returned to normal in all patients. None of the patients with exclusive liver disease required chelation treatment after liver transplantation and none developed neurological symptoms of Wilson's disease. CONCLUSION: Liver transplantation totally reverses the abnormalities of copper metabolism and subsequent hepatic failure, but the course of neurological symptoms remains unpredictable. Long-term patient survival can be excellent without occurrence of neurological complications.

Specific detection of hepatitis C virus minus strand RNA in hematopoietic cells.

The presence of hepatitis C virus (HCV) negative strand RNA in extrahepatic compartments based on PCR detection assays has been suggested in many reports with a very heterologous detection rate (from 0 to 100%). In this study, we have analyzed the presence of HCV negative strand in hepatic (liver biopsies, n = 20) and extrahepatic (sera, n = 32; PBMC, n = 26 and fresh bone marrow cells, n = 8) compartments from infected patients with three different reverse transcriptase (RT)-PCR-based assays using primers located in the 5' noncoding region, with or without a tag selected to display different viral loads (10(5)-3 x 10(7) genomic equivalent/ml or gram) and viral genotypes (n = 5). Using synthetic as well as biological templates, we could document extensive artifactual detection of negative strand RNA, due to self priming and mispriming events, even either 5' noncoding region primer pair was used, whereas both artifacts were dramatically reduced (mispriming) or eliminated (selfpriming) using CAP-based RT-PCR assay. Mispriming artifacts were directly correlated to the titer of positive strand RNA present in the sample. Using the CAP-PCR assay, the presence of HCV negative strand RNA was found in 75% of livers (16:20) and only 8% of PBMC, independent of the genotype involved, but could not be documented in sera (0:32) and fresh bone marrow cells (0:6). These findings suggest that caution regarding the type of RT-PCR assay used and the level of HCV positive strand RNA present in the biological sample analyzed has to be taken to avoid false identification of viral reservoirs. The findings suggest that hematopoietic peripheral cells can support HCV replication, although in a very limited number of carriers.

Symptomatic relapse of neurologic syphilis after benzathine penicillin G therapy for primary or secondary syphilis in HIV-infected patients.

We describe 3 symptomatic cases of neurologic syphilis that occurred after the administration of the usual therapy for primary or secondary syphilis in human immunodeficiency virus (HIV)-infected patients. We discuss the difficulty of diagnosing neurosyphilis, the need for lumbar puncture, and risk factors of relapse. Because HIV infection may alter the natural history and response of neurologic syphilis to treatment, scrupulous follow-up and repeated cycles of therapy are warranted.

Ser-249 p53 mutations in plasma DNA of patients with hepatocellular carcinoma from The Gambia.

BACKGROUND: A selective mutation, an arginine-to-serine substitution in codon 249, of the p53 gene has been identified as a "hotspot" mutation in hepatocellular carcinoma (HCC). This mutation occurs in populations that are exposed to aflatoxins and have a high prevalence of hepatitis B virus carriers. We evaluated whether this mutation could be detected in cell-free DNA isolated from the plasma of subjects from The Gambia to detect this mutation that is strongly associated with HCC. METHODS: Fifty-three patients with HCC, 13 patients with cirrhosis, and 53 control subjects were prospectively recruited from The Gambia. Sixty patients, of non-African origin, with various liver pathologies were also selected from France. DNA was extracted and purified from 200-microL aliquots of plasma. The Ser-249 p53 mutation was detected by restriction endonuclease digestion of polymerase chain reaction products from exon 7 and was confirmed by direct sequencing of the amplified DNA. RESULTS: The Ser-249 p53 mutation was detected in plasma DNA from 19 (36%) of the 53 patients with HCC, two (15%) of the 13 patients with cirrhosis, and three (6%) of the 53 control subjects. This mutation was not detected in any plasma DNA from the European patients. The adjusted odds ratio for having the mutation was 16.4 (95% confidence interval = 3.0-90.5) for patients with HCC compared with the control subjects. CONCLUSION: The Ser-249 p53 mutation in plasma DNA is strongly associated with HCC in Gambian patients. This mutation was also detected at a much lower prevalence in plasma DNA from Gambian patients with cirrhosis and in Gambian control subjects, findings that may lead to the earlier detection of HCC. Use of the Ser-249 p53 mutation should facilitate further molecular epidemiologic studies on the development of HCC.

Mutagenesis of ras proto-oncogenes in rat liver tumors induced by vinyl chloride.

Vinyl chloride is a DNA-damaging carcinogen which induces liver angiosarcomas in humans and animals. Activation of the Ki-ras 2 gene by a GC-->AT transition at the second base of codon 13 in human liver angiosarcomas associated with occupational exposure to vinyl chloride has been reported recently. In order to compare the molecular pathways of carcinogenesis in humans and animals, Sprague-Dawley rats were exposed to vinyl chloride and hepatic tumors, including two hepatocellular carcinomas and five liver angiosarcomas, were investigated for mutations at codons 12, 13 and 61 of the Ha-ras, Ki-ras and N-ras genes. High molecular weight DNA was amplified by the polymerase chain reaction and point mutations were analyzed by allele specific oligonucleotide hybridization, direct sequencing of polymerase chain reaction products and sequencing after cloning. None of the tumors exhibited a mutation in codons 12, 13 and 61 of the Ki-ras gene, nor in codons 12 of the Ha-ras gene or 61 of the N-ras gene. However, an activating AT-->TA transversion at base 2 of codon 61 of the Ha-ras gene was detected in the two hepatocellular carcinomas. Mutations involving codon 13 (GGC-->GAC) and codon 36 (ATA-->CTA) of the N-ras A gene were detected in two liver angiosarcomas, suggesting that the nature of the ras gene affected by a given carcinogen depends on host factors specific to cell types. Several additional base pair substitutions were found in exon 1 of the N-ras B and C sequences. NIH 3T3 transfection assays and Southern blot analysis of DNA from transformed NIH 3T3 cells confirmed the presence of a dominant activated N-ras gene. These results emphasize the differences in the molecular pathways leading to tumors in humans and rats and within a given species between different cell types.

Contribution of aflatoxin B1 and hepatitis B virus infection in the induction of liver tumors in ducks.

The study of two major risk factors in the development of hepatocellular carcinoma, namely persistent hepatitis virus infection and exposure to dietary aflatoxins, has been hampered by lack of an experimental system. To this end we have used a Pekin duck model to examine the effect of congenital duck hepatitis B virus (DHBV) infection and aflatoxin B1 (AFB1) exposure in the induction and development of liver cancer. AFB1 was administered to DHBV infected or noninfected ducks at two doses (0.08 and 0.02 mg/kg) by i.p. injection once a week from the third month posthatch until they were sacrificed (2.3 years later). Two control groups of ducks not treated with AFB1 (one of which was infected with DHBV) were observed for the same period. Each experimental group included 13-16 ducks. Higher mortality was observed in ducks infected with DHBV and treated with AFB1 compared to noninfected ducks treated with AFB1 and other control ducks. In the groups of noninfected ducks treated with high and low doses of AFB1, liver tumors developed in 3 of 10 and 2 of 10 ducks; in infected ducks treated with the high dose 3 of 6 liver tumors were observed and none in the low dose of AFB1. No liver tumors were observed in the two control groups. Ducks infected with DHBV and treated with AFB1 showed more pronounced periportal inflammatory changes, fibrosis, and focal necrosis compared to other groups. All DHBV carrier ducks showed persistent viremia throughout the observation period. An increase of viral DNA titers in livers and sera of AFB1 treated animals compared to infected controls was frequently observed. No DHBV DNA integration into the host genome was observed, although in one hepatocellular carcinoma from an AFB1 treated duck, an accumulation of viral multimer DNA forms was detected. The metabolism of AFB1 in infected and noninfected duck liver was also examined. The study on the role of DHBV infection and AFB1 in the etiopathogenesis of liver tumors may help to clarify some of the basic mechanisms of carcinogenesis.

Clinical impact of occult HBV infections.

HBV infection in the absence of HBsAg has been a matter of debate for years, but its existence and clinical relevance are now supported by many publications, editorials and reviews. HBV DNA without HBs antigenemia was detected in the following clinical situations: (1) Chronic, presumably viral, hepatitis unrelated to HCV, atypical alcoholic hepatitis and hepatocellular carcinoma (HCC); (2) viral reactivation following immunosuppression; (3) Transmission through transplantation, transfusion or experimental transmission to chimpanzees. Occult HBV infections are not restricted to areas of high HBV endemicity. Indeed, such cases have been described in Western countries including France. It is now established that occult HBV infection among non-HCV patients suffering from chronic hepatitis varies from 20% to 30% in Europe, and in the context of HCV infection it varies from 20% in France up to 80% in Japan. The percentage of occult HBV infections among non A-E cases depends on several parameters: (1) The method of detection, including PCR primer selection; (2) patient recruitment; (3) patients from countries highly endemic for HBV are more likely to develop occult HBV infections; (4) prevalence may also vary depending on the nature of biological material tested, with a higher proportion for liver compared to serum specimen. The mechanisms leading to HCC in occult HBV infection seem similar to those overt cases, patients with low-grade but diagnosable HBV replication that retains its pro-oncogenic properties. During the course of HCV infection, occult HBV infection may worsen liver damage induced by HCV and reduce the response to HCV antiviral treatment. Occult HBV infection is a frequent phenomenon and HBV DNA testing with highly sensitive PCR in the clinical setting is therefore becoming of paramount importance.

Analysis of HCV co-infection with occult hepatitis B virus in patients undergoing IFN therapy.

BACKGROUND/AIM: Occult hepatitis B virus (HBV) infection is characterized by the presence of HBV DNA in the absence of hepatitis B surface antigen (HBsAg) in the patient serum. Although such infections have been identified in patients with chronic hepatitis C, the clinical significance of those co-infections is still not understood. Our aim was, therefore, to assess the prevalence and clinical consequences of occult HBV infection in chronic hepatitis C patients undergoing antiviral therapy. METHODS: The study population consisted of 53 HBsAg-negative patients with chronic hepatitis C treated with IFN/ribavirin or IFN/ribavirin/amantadine. Nine patients experienced a viral breakthrough (BT), 30 were non-responders (NR) and 14 were responders (R). HBV-DNA detection by PCR was performed using primers specific for the S region of the HBV genome and HCV-RNA detection by PCR with primers localised in both the 5'NC and core region of HCV genome, before, during and after treatment. Viral genome sequences were also studied. RESULTS: Occult HBV genomes were found in the serum of four of 53 (7.5%) patients, unrelated to anti-HBc status. No significant differences in biochemical, virological, or histological markers, age, duration of infection, were observed in patients with or without HBV DNA. There was an inverse correlation in the evolution of HBV DNA and HCV RNA levels. Direct sequencing showed that S gene of occult HBV presented mutations in the "a" determinant while no specific mutation in the core region of HCV was observed. None of the four patients co-infected with HBV and HCV were responders to anti-HCV therapy. CONCLUSION: In our clinical setting, the prevalence of occult HBV co-infection among patients with chronic hepatitis C was low and independent of the presence of markers of previous HBV infection. Further studies in larger cohort of patients are warranted to determine if occult HBV co-infection may be involved in HCV resistance to combination therapy.

[Tolerance and efficacy of conformal radiotherapy for hepatocellular carcinoma in cirrhotic patients. Results of the French RTF1 phase II trial]. / Tolérance et efficacité de la radiothérapie de conformation en cas de carcinome hépatocellulaire chez le patient cirrhotique. Résultats de l'essai de phase II RTF1.

PURPOSE: While some patients presenting with hepatocellular carcinoma (HCC) benefit from curative therapies (transplantation, surgery, percutaneous ablation), others are only candidates for palliative options such as chemoembolization or symptomatic care. Although conventional external-beam radiotherapy of the liver is regarded as little efficient and potentially toxic in cirrhotic patients, 3-dimensional conformal radiotherapy (CRT), by decreasing the amount of normal liver included in the radiation portal, allows dose escalation to occur without increasing the risk of radiation-induced hepatitis. This trial was designed to assess the efficacy and tolerance of CRT for small-size HCC in cirrhotic patients. PATIENTS AND METHODS: Prospective phase II trial including stage A/B cirrhotic patients with small-size HCC not suitable for curative treatments; CRT consisted in a standard fractionation radiation, with a total dose of 66 Gy. RESULTS: Twenty-seven patients were included, 15 of whom had previously been treated for HCC; mean age was 68. Among the 23 assessable patients, 18 (78%) presented with complete response, 3 (13%) with partial response, and 2 with no response. Acute complications occurred in 24 patients, and were mainly acceptable (grade 1/2: 22 patients, grade 3/4: 11 patients, 4 (15%) of whom had clinical and/or hematological toxicities). Only 2 (9%) grade 3/4 clinical and/or hematological late toxicities are reported. CONCLUSION: CRT is a non-invasive curative technique highly suitable for small-size HCC in cirrhotic patients; further investigations are needed to compare it to the other available treatments, and to integrate it into the curative therapeutic algorithm of HCC.