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Background: The effect of regression of cirrhosis in chronic hepatitis C is unknown., Objective: To evaluate the relation between regression of cirrhosis and clinical outcome in patients with chronic hepatitis C after antiviral therapy., Design: A cohort of patients with cirrhosis treated between 1988 and 2001., Setting: Hepatology unit of a tertiary care center in France., Patients: 96 patients with chronic hepatitis C and biopsy-proven cirrhosis (METAVIR score F4) who were treated with an interferon-based regimen and had at least 1 posttreatment liver biopsy. Patients were followed until November 2006., Measurements: Occurrence of a combined end point of liver-related events (ascites, hepatic encephalopathy, variceal bleeding, spontaneous bacterial peritonitis, hepatocellular carcinoma, or liver transplantation) and death in patients with regression of cirrhosis (defined as a decrease from 4 to

The aim of this study was to assess the reversibility of cirrhosis after therapy in a large series of patients with cirrhosis from various etiologies. We performed a retrospective study of 113 patients with biopsy-proven cirrhosis who underwent specific therapy and follow-up biopsies. Two pathologists performed blinded analyses of indirect biochemical and morphological signs of cirrhosis. Fourteen (12.4%) of the 113 cirrhotic patients had biopsy-proven disappearance of cirrhosis, defined as a decrease of 2 or greater in their METAVIR fibrosis score: 8 were related to hepatitis C virus, 3 to hepatitis B virus, and 3 to autoimmune cirrhosis. Necro-inflammatory activity decreased from 2.4 +/- 0.65 to 0.85 +/- 0.9 (P = .004), and fibrosis from 4 to 1.7 +/- 0.61 (P = .001). Prothrombin time (n = 1), platelet count (n = 2), serum albumin level (n = 2), and ultrasound abnormalities (n = 6) normalized in patients who had initial abnormalities. Hyaluronic acid and procollagen type III serum level decreased in all. In the 11 patients with regression of viral cirrhosis, 2 were nonresponders and 9 were responders, including 2 relapsers. The 3 patients with regressive autoimmune cirrhosis were complete responders to immunosupressive therapy. Using repeated liver biopsies, clinicobiochemical, radiologic, and endoscopic tests, we provide evidence for potential reversibility of cirrhosis after long-lasting suppression of the necro-inflammatory activity of liver disease.

Hepatitis delta virus is the only representative of the Deltavirus genus, which consists of 7 differentiated major clades. In this study, an eighth clade was identified from 3 distinct strains. Deltavirus genetic variability should be considered for diagnostic purposes. Clinical consequences of the diversity have yet to be evaluated.

Background: Recent studies have suggested an increased risk of acute hepatitis C (HCV) infection in homosexual HIV-infected men and that early treatment with standard or pegylated interferon-alfa, alone or associated with ribavirin, significantly reduces the risk of chronic evolution in HIV-infected patients., Methods: A retrospective analysis of 12 HIV-infected patients who were consecutively diagnosed as developing acute HCV infection, defined by both seroconversion of anti-HCV antibodies and detection of serum HCV RNA in those with previous negative results. Ten of these patients received early antiviral treatment with standard or pegylated interferon-alfa, alone or associated with ribavirin., Results: The only risk factor in these patients was unprotected sexual intercourse with men. Acute HCV infection was asymptomatic in 10 patients, and the HCV genotype was 4d in 10 patients. The 10 genotype 4d viruses formed a monophylogenetic group and clustered separately from other local sequences of HCV genotype 4d, suggesting a common source of infection. None of the 10 patients who were treated early with antiviral therapy had a sustained virological response, as defined by undetectable HCV RNA 6 months after therapy., Conclusions: There is a risk of sexual transmission of HCV in HIV-infected men who have sex with men; the cluster of HCV genotype 4d suggested a common source of infection and a failure in prevention counselling. Early treatment with standard interferon-alfa failed to prevent chronic evolution of HCV infection in this particular group of HIV-infected patients who had acquired this peculiar cluster of genotype 4 strains.

Background: An accurate diagnosis of hepatitis C virus (HCV)-related liver lesions is mandatory in dialysis patients and kidney recipients to better define the treatment of and contraindications to kidney transplantation. The aim of this study was to assess the diagnostic accuracy of the fibrotest (a noninvasive method to assess liver fibrosis in HCV on a scale from 0 to 1) in hemodialysis and renal transplant patients infected by chronic HCV., Methods: In all, 110 patients with biopsy-proven HCV (60 renal transplant recipients and 50 hemodialysis patients), determined using the METAVIR scoring system, were studied., Results: Forty-six percent of patients had fibrosis > or =F2. A positive predictive value of a score >0.6 for the presence of significant fibrosis by comparison with liver biopsy was 71%, and an negative predictive value of < 0.2 for excluding significant fibrosis was 77%, respectively. The areas under the ROC curves for the diagnosis of significant fibrosis were 0.66, 0.47, and 0.71 in the global population, hemodialysis patients, and renal transplant patients, respectively. In all, 75% of patients were correctly classified using the fibrotest. If biopsy was restricted to scores in the intermediate range (< 0.6 and >0.2), the index could reduce the indication for biopsy by 47%. The results did not differ significantly in hemodialysis and renal transplant patients., Conclusion: The fibrotest has a diagnostic value in hemodialysis and renal transplant patients which is similar to that reported in the general population (75%) and its use could avoid 32% of liver biopsies if it were interpreted in detail in nephrology patients.

Background: This study analyzes the biochemical, serological, and virological efficacy and the safety of adefovir dipivoxil in patients with renal disturbances., Methods: Twelve patients with lamivudine-resistant hepatitis B virus (HBV) chronic infection were treated for a median time of 15 (3-19) months. The daily dosage was 10 mg initially and then adjusted according to renal function., Results: Median (range) ALT values remained stable: 55 (13-117) and 37 (17-266) UI/L. After the 12th month, the median decline in serum HBV DNA was from 8.76 (6.3-9.7) to 2.97 (1.15-5.65) log10 Eq/ml (median decline of -5.5 log10). No virologic breakthrough was observed. One of the six HBeAg-positive patients lost HBe Ag but without HBe seroconversion; none had HBs Ag loss. There were no significant clinical and biochemical adverse effects. In the 11 nonhemodialysed patients, the creatinine clearance significantly improved from 70 (30-100) to 88 (38-125) ml/mn (P=0.01) and the mean serum creatinine levels increased only slightly from 114 (91-839) to 130 (81-561) micromol/ml (NS). Serum phosphorus remained stable. The urinary level of protein decreased from 0.16 (0.08-8.63) to 0.12 (0.01-0.74) g/day (NS)., Conclusions: Adefovir dipivoxil is safe for the treatment of chronic hepatitis B in patients with varying degrees of renal dysfunction and lamivudine-resistant HBV and results in biochemical and virological efficacy similar to that reported in the general population.

Primary biliary cirrhosis is a chronic cholestatic liver disease of unknown cause that predominantly affects middle-aged women. Distal tubular acidosis is the main renal complication of primary biliary cirrhosis. Tubulointerstitial nephritis and Fanconi syndrome have been reported more rarely. We report on 2 patients with primary biliary cirrhosis who presented with tubulointerstitial nephritis and Fanconi syndrome and review similar cases published previously. Serum from 1 patient exerted an inhibitory effect on pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase, 2 mitochondrial enzymes that are the main targets of antimitochondrial antibodies in primary biliary cirrhosis. Antimitochondrial antibodies may have a role in the genesis of tubulointerstitial nephritis and Fanconi syndrome, 2 typical renal features of mitochondrial cytopathies. Tubulointerstitial nephritis and Fanconi syndrome have to be added to the spectrum of renal diseases associated with primary biliary cirrhosis.

In mid-2004, three Parisian hospital wards informed the Institut de veille sanitaire of recent acute hepatitis C in HIV-infected (HIV+) men who had sex with men (MSM). These cases for whom none of the usual bloodborne routes for hepatitis C (HCV) transmission was found, reported having had unprotected sex. In October 2004, we conducted a retrospective investigation in Parisian hospital wards to explore HCV modes of transmission in recent acute hepatitis C in HIV+ MSM. Patient demographics, clinical and biological status of HIV infection, reasons for HCV testing, sexual behaviour and risk factors for HCV transmission within the 6 months before hepatitis onset were collected from medical records. An anonymous self-administered questionnaire on sexual behaviour within the six months before hepatitis onset was also offered to all cases. We identified 29 cases of acute hepatitis C in HIV+ MSM with onset from April 2001 to October 2004. HIV infection was asymptomatic for 76%. Median age at hepatitis C onset was 40 (28-54) years. In all records, were noted unprotected anal sex, fisting in 21% and a concomitant sexually transmitted infection (STI) in 41%. Median time between HIV diagnosis and HCV infection was 6.5 years (0-22). From the 11 self-administered questionnaires completed, 10 reported an STI, 8 'hard' sexual practices, 6 bleeding during sex and 5 fisting. HCV transmission probably occurred through bleeding during unprotected traumatic anal sex among HIV+ MSM and may be facilitated by STI mucosal lesions. This report stresses the continuous need to strongly advocate safer sex to MSM.

Aim: To evaluate the benefits of haematopoietic growth factors (HGFs) during the treatment of chronic hepatitis C virus (HCV) infection with severe haematotoxicity., Methods: This was a 1-year retrospective study of HCV-positive patients receiving pegylated interferon and ribavirin. Patients received different HGFs, depending on certain criteria: they received erythropoietin (EPO) when their haemoglobin (Hb) levels were less than 10 g/dl and granulocyte colony-stimulating factor (G-CSF) when their neutrophil count was less than 750 cells/mm3. Haematological data, adherence and virological response were analysed and compared according to HGF use., Results: In total, 132 patients were studied and 31 (23.5%) required HGF. Under multivariate analysis, baseline Hb levels of less than 13g/dl or a drop in Hb levels of over 2% per week predicted severe anaemia, and a baseline neutrophil count under 2900/mm3 predicted severe neutropaenia. HGF administration restored Hb values and the neutrophil count to above 10 g/dl and 1500 cells/mm3, respectively, in all 31 patients. Adherence to antiviral treatment was achieved in 25% of patients versus 58% of controls without severe haematotoxicity. The primary and sustained virological response did not differ statistically between HGF support and the control group (61% versus 57% and 32% versus 39%, respectively)., Conclusion: HGF administration counteracts the severe haematological adverse effects which occur during antiviral therapy and maintains the rate of sustained response.

Background: The deterioration of chronic hepatitis C is frequent in kidney recipients and results in a decrease in survival of patients and allografts. Interferon is contraindicated because of the risk of rejection and its low efficacy. The aim of this study was to analyze the biologic, virologic, and histopathologic efficacy of ribavirin alone in kidney allograft recipients with hepatitis C., Methods: Thirteen kidney recipients (eight men and five women, 46+/-11 years of age) with severe Metavir score of fibrosis (eight F3 and five F4) were treated with ribavirin alone during 22.4+/-13.9 months. Liver biopsy was performed before and during therapy, with a mean interval time of 5.7+/-9.3 years., Results: The transaminase level decreased significantly (128+/-77 vs. 53+/-28, P=0.001) without significant change of serum quantitative hepatitis C virus load. The comparison of pretreatment and on-treatment biopsy specimens showed a significant decrease in the activity Metavir score (1.23+/-1.01 vs. 2.46+/-0.78, P=0.05) and a nonsignificant trend for a decrease in the fibrosis score. Ribavirin tolerance was fair, and only one patient required erythropoietin therapy., Conclusions: Ribavirin alone in kidney allograft recipients results in biologic and histologic improvement without a virologic response and is reasonably well tolerated.

The aim of this retrospective study was to determine the potential reversibility of hepatitis C virus (HCV) cirrhosis with the combined antifibrotic effects of interferon-alpha and the increasing frequency of sustained virologic response. Sixty-four HCV-cirrhotic immunocompetent patients who underwent antiviral therapies (interferon-alpha with or without ribavirin) and pretreatment and posttreatment liver biopsies were included (group 1). Resolution of cirrhosis was defined as a decrease in the fibrosis score from 4 to 2 or less by the Metavir score after blinded analysis by 2 independent pathologists. An additional group of 4 HCV-infected dialysis patients (group 2) who had received antiviral treatment, among whom 3 underwent a combined renal and liver transplantation allowing the analysis of the whole liver, was also studied. In 5 (all stage Child A) of the 64 cirrhotic patients (7.8%), the final biopsy showed only F2 to portal and periportal fibrosis with rare fibrous septa without nodule formation. Four of these 5 were complete sustained responders (negative PCR and normal ALT), and 1 was a relapser. In group 2, reversibility of cirrhosis was observed in 3 of the 4 patients and was clearly shown in 2 patients by the analysis of the whole-liver examination at the time of the hepatectomy preceding the transplantation. In conclusion, long-lasting suppression of the necroinflammatory activity of liver disease and/or antifibrogenetic effects of interferon-alpha may allow regression of cirrhosis.