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Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) share the same routes of transmission, which explains the high rate of HCV and HIV coinfection (approximately 9%). HIV/HCV coinfection leads to high rates of indeterminate recombinant immunoblot assay patterns and seroreversion; high levels of viral replication; and a more severe histopathologic course. By contrast, HCV infection does not seem to accelerate the progression of HIV infection. Interferon alpha (IFN-alpha) in coinfected patients leads to a similar rate of primary responses, but sustained responses are less frequent. The potential severity of hepatitis C virus infection evidences the need for early diagnosis. Liver biopsy should be performed for all HCV RNA-positive patients in order to evaluate the activity of the liver disease. Given the poor efficiency of IFN-alpha in terms of sustained response in HIV-infected patients, reinforced therapeutic procedures (long-term administration of IFN-alpha or combined ribavirin/IFN-alpha) should be proposed, at least for those patients with severe liver disease.

Using conventional immunosuppressive regimen, renal transplantation is associated with a more severe evolution of chronic hepatitis C as compared with HCV-infected immunocompetent subjects. Thus, the histopathological evaluation should be performed and anti-viral therapy discussed before renal transplantation.

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Background-More severe liver disease together with a poor response rate to interferon argue for the use of more potent anti-hepatitis C virus (HCV) therapies in human immunodeficiency virus (HIV)-HCV coinfected patients, but the eYcacy and safety of interferonribavirin combination therapy in HIV infected subjects are unknown. Aim-To retrospectively evaluate the eYcacy and safety of anti-HCV combination therapy in 21 HCV-HIV coinfected patients receiving antiretroviral therapy, and to access the clinical relevance of in vitro inhibition of phosphorylation by ribavirin of potent inhibitors of HIV-that is, zidovudine, stavudine, and zalcitabine. Patients-Twenty one patients were treated with combined antiretroviral therapy including zidovudine (n=8) or stavudine (n=13) (in association with protease inhibitors in 12). All received ribavirin (1000 or 1200 mg/day) and interferon (3 MU three times/week) for chronic hepatitis C infection. All patients had not responded (n=20) or relapsed (n=1) after a previous six month course of interferon therapy. Methods-HIV viral load (Monitor test)and CD4 cells count were measured at the beginning and every three months during and after ribavirin plus interferon therapy over a mean period of 11 (1) months. Clinical and biological adverse eVects were recorded. Results-There was no significant variation in HIV viral load or CD4 cell counts after three or six months of ribavirin therapy compared with baseline values. Of the 21 subjects, three (14%) had an increase in HIV viral load of more than 0.5 log leading to discontinuation of ribavirin in one. Eleven of 21 (52.4%) had initial negative HCV viraemia at three (n=10) or six (n=1) months but only six were polymerase chain reaction negative at the end of therapy, leading to rates for primary response and breakthrough of 23.8% and 28.5%, respectively. Six months after completion of therapy, three patients relapsed (14.3%) and three (14.3%) had sustained virological response. Median haemoglobin concentration decreased significantly after three and six months of ribavirin therapy (p= 0.0002 and p=0.0003, respectively) leading to withdrawal of therapy in one patient. Conclusions-These preliminary results show that: (1) despite in vitro interactions between ribavirin, zidovudine, and stavudine, significant variation in HIV replication does not usually occur in HCV-HIV coinfected patients receiving ribavirin and diVerent antiretroviral regimens, including zidovudine and stavudine; (2) interferon and ribavirin combination therapy induced primary and sustained virological responses in 28.5% and 14.3% of treated subjects (who were previous non-responders to interferon therapy), respectively; (3) anaemia is a frequent adverse event. Such results should be confirmed in larger prospective trials. (Gut 2000;47:694-697)

We have investigated whether liver resection and needle liver biopsy cause dissemination of liver cells into peripheral blood circulation, using a reverse-transcription polymerase chain reaction (RT-PCR)-based assay targeted against ␣-fetoprotein (AFP) mRNA. Twelve patients with and 16 without primary liver cancer (PLC) undergoing liver resection were tested before skin incision, after liver mobilization, after hepatic parenchyma transection, after abdominal wall suture, and 4 days after surgery. Two patients with and 20 without PLC were tested before, 20 minutes after, and 24 hours after needle liver biopsy. Six of 14 patients with and 0 of 36 patients without PLC scored positive before intervention (P F .001). Liver cell spreading was induced at different times after surgery and liver biopsy in 14 of 14 patients with but also 23 of 36 without PLC (P F .05). We conclude that liver resection and needle liver biopsy induce release of cells from the liver, which are not necessarily liver tumor cells, into the peripheral blood circulation. This may be, however, an important mechanism of liver cancer cell dissemination deserving further investigations. (HEPATOL-OGY 1999;29:879-882.)Despite several previous reports on the dissemination of tumorous cells during needle liver biopsy, 1-6 the issue of surgical and diagnostic iatrogenic speading of liver cells has never been addressed with appropriated molecular methods and study design.The possibility of detecting circulating tumorous cells in patients with solid tumors, through highly sensitive reversetranscription polymerase chain reaction (RT-PCR)-based assays, has raised major interest and hopes during the last 5 years. 7 We and others 8,9 have used ␣-fetoprotein (AFP)-specific primers to detect spontaneously circulating tumorous cells in patients with primary liver cancer (PLC) and found that a positive test directly correlates with the risk of developing extrahepatic metastases. 10 We have now applied this method, with a carefully defined specificity and sensitivity, to patients with and without PLC. The protocol used consisted in blood sampling before and at different time points during and after liver resection and needle liver biopsy.Our results show that hematogenous dissemination of liver cells is induced very early in surgically treated patients, after liver mobilization, and before hepatic parenchyma transection. It also occurs, albeit less frequently, during needle liver biopsy. These data, therefore, point out a potentially important mechanism of liver cancer spreading that deserves further investigations.