Treatment of chronic hepatitis C with recombinant interferon alpha in kidney transplant recipients.

Chronic hepatitis C is a common cause of viral liver disease in kidney transplant (KT) recipients. To assess the efficacy and safety of therapy with interferon alpha we conducted a prospective study where 14 cadaveric KT recipients with chronic hepatitis C received recombinant interferon alpha-2b (IFNa) 3 million units three times weekly (scheduled) for 6 months (group A). 14 KT recipients with chronic hepatitis C were not treated and served as controls for the study period (group B). All the patients in both groups had had stable renal function for at least one year. All patients in both groups had a positive HCV viremia at the beginning of the study. Patients of group A were treated for 142 +/- 34.8 days (range 65-168); elevated serum aminotransferase (ALT) levels decreased rapidly and significantly from 100.3 +/- 48.9 to 37.7 +/- 13.9 IU/L (P = 0.001); 10 patients (77%) were "responders," whereas the others experienced a decrease in ALT values but without reaching the normal ranges. With a mean follow-up of twelve months after discontinuation of IFNa therapy, 8 responders--i.e., 80%--relapsed within 1-20 weeks. Only 4 patients had no detectable HCV viremia at the end of the IFNa; two of them already have abnormal values of ALT. Moreover HCV viremia was present in all patients one month after the cessation of IFNa treatment. Side effects of IFNa (fatigue, anorexia, weight loss) were frequent, and 3 patients decided to drop out of the treatment. The hematological tolerance was good although there was a significant decrease in hemoglobin (11.9 +/- 1.7 vs. 13.4 +/- 1.7 g/dl; P = 0.0044). In group B, serum ALT levels did not significantly decrease (84.2 +/- 47.6 vs. 105.2 +/- 68.8 IU/L). At the end of the study period serum ALT levels were significantly lower in group A than in group B (37.7 +/- 13.9 vs. 84.2 +/- 47.6 IU/L, P = 0.013). The major concern in group A was the occurrence of 5 renal failures. Kidney transplant biopsies showed edema, no significant tubulitis, scarcely scattered interstitial inflammatory cellular infiltration, and mesangial thickening. Four patients received methylprednisolone pulses but renal function improved in only two cases. We were not able to discover predictive factors of renal failure. We conclude that IFNa therapy is effective in controlling disease activity--i.e., reducing amino-transferase levels in KT patients with chronic hepatitis C, although relapse and detection of HCV RNA after the cessation of treatment were observed, respectively, in 80% and 100% of patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Efficacy and safety of lamivudine on replication of recurrent hepatitis B after cadaveric renal transplantation.

BACKGROUND: The aim of this pilot study was to evaluate the efficacy and the safety of lamivudine therapy in hepatitis B virus (HBV)-positive/DNA-positive renal transplant recipients. METHODS: Six HBV DNA-positive cadaveric renal transplant recipients ranging in age from 49+/-6 years were administered lamivudine, at 100 mg/day for a period of at least 6 months, on a compassionate-use basis. Lamivudine is the (-) enantiomer of 3'-thiacytidine, which is known to be a potent inhibitor of HBV replication. All of the patients but one were on cyclosporine-based immunosuppression. RESULTS: The mean serum creatinine was 134+/-44 micromol/L. The mean duration of HBV infection was 230+/-54 months (156-288). All of the patients but one had high serum alanine aminotransferase levels (122+/-52 IU/L; range, 45-243). Histological evaluation showed the presence of either chronic active hepatitis (n=4) or cirrhosis (n=2). All of the patients but one were hepatitis B e antigen negative/hepatitis B e antibody positive, but none were coinfected with either hepatitis C virus or hepatitis D virus. CONCLUSIONS: Lamivudine therapy was associated with (i) a normalization of alanine aminotransferase levels in four of five patients when these levels were increased at the beginning (n=5); (ii) a rapid disappearance of HBV DNA from the serum (detected by hybridization) in all of the patients; (iii) the negativity of HBV DNA by polymerase chain reaction in four patients; and (iv) no change in renal function and in proteinuria when present (one patient). Finally, no adverse effects were noted. When lamivudine therapy was stopped for four patients after 6 months, it was associated with a biochemical and virological relapse within the weeks that followed. Lamivudine therapy was therefore resumed for these patients.

Long-term impact of superinfection by hepatitis G virus in hepatitis C virus-positive renal transplant patients.

BACKGROUND: The hepatitis G virus (HGV) has been recently cloned. Studies in immunocompetent patients have shown that HGV superinfection in hepatitis C virus (HCV)-positive patients does not affect (i) clinical presentation, HCV RNA level, or response to interferon-alpha therapy; or (ii) the histopathologic severity and characteristics of chronic hepatitis. No data are currently available on the impact of HGV infection on liver histology of renal transplant (RT) patients although the reported prevalence of serum HGV RNA in this population is high, ranging from 14% to 55%. PATIENTS AND METHODS: We determined the prevalence of HGV infection in 103 HCV-positive RT patients for whom HGV RNA was retrospectively determined by reverse transcription-polymerase chain reaction before, at the time of, and after transplantation (last follow-up). We evaluated the impact of HGV on liver function tests, liver histology (by means of the Knodell score), and renal parameters such as the prevalence of acute rejection and renal function. RESULTS: A total of 29 (28%) of the HCV-positive RT patients had a positive HGV RNA (group 1). The mean duration of HGV infection was at least 119+/-64 months (range: 18-240 months). Group 1 patients were compared to the 74 HGV RNA-negative/HCV-positive RT patients (group 2). Liver histology showed a significantly lower degree of fibrosis in group 1 (0.4+/-0.5) than in group 2 (1+/-1.2; P=0.02); two patients from group 2 but none from group 1 had overt cirrhosis. Conversely, the extent of hepatic inflammation and hepatocellular destruction was not statistically different between the two groups. The number of patients who experienced at least one acute rejection episode was significantly higher in group 1 (69%) than in group 2 (42%; P=0.01). However, the multivariate analysis did not identify the presence of HGV RNA at the time of renal transplantation as an independent factor of acute rejection; conversely, (i) the occurrence of cytomegalovirus infection or disease and (ii) the duration of HCV infection significantly increased the likelihood of having acute rejection. CONCLUSIONS: This study shows that: (i) HGV infection was often present when the patients seroconverted for HCV, (ii) HGV RNA-positive/HCV-positive RT patients experienced acute rejection more frequently than HGV RNA-negative/HCV-positive RT patients, and (iii) HGV infection seems to have no detrimental effect upon liver enzymes or liver histology in HCV-positive RT patients.

Impact of hepatitis C virus duration and hepatitis C virus genotypes on renal transplant patients: correlation with clinicopathological features.

BACKGROUND: The aim of this study was to evaluate the long-term impact of chronic hepatitis C virus (HCV) infection on the liver in renal transplant patients. METHODS: We studied 78 patients for whom at least one posttransplant liver biopsy (LB) was available and for whom the duration of HCV infection was precisely defined. The LB were graded according to a histological activity index, i.e., the Knodell score, divided into the activity score and the fibrosis score. They were also classified as either normal or showing evidence of chronic persistent hepatitis, chronic active hepatitis (CAH), or cirrhosis. RESULTS: The study comprised 7 HCV-positive/hepatitis B surface antigen-positive patients (group 1); 4 HCV-positive/RNA-negative patients (group 2); and 67 HCV-positive/RNA-positive patients (group 3). The three groups were comparable according to demographic data and baseline immunosuppression. The median time from transplantation to LB was 38 months (range, 10-306 months). At that time, alanine aminotransferase (ALT) levels had increased in 71.4%, 0%, and 42% of patients from groups 1, 2, and 3, respectively (P=0.07). The total Knodell score showed significantly more severe lesions in group 1 patients (6.2+/-3.2) than in group 2 (1+/-1.2) or in group 3 (4.6+/-2.4) patients (P=0.007). The Knodell score also showed that the fibrosis score was significantly higher in group 1 (2.3+/-1.6) than in group 2 (0) or in group 3 (0.9+/-1.1) patients (P=0.007). Overall, there were 28 cases of CAH (36%) and 4 cases of cirrhosis (5%). We did not observe any correlation between liver histology and characteristics of HCV infection or the type of chronic immunosuppression (double-drug versus triple-drug therapy). However, liver histology (total Knodell score) and the activity score were significantly correlated with ALT levels. Multivariate analysis did identify (i) four independent variables that could explain the degree of liver fibrosis-the sex of the patient, the number of blood units received before transplantation, increased ALT levels at the time of LB, and the occurrence of at least one acute rejection episode (thus the receipt of methylprednisolone pulses); and (ii) two independent variables associated with the occurrence of CAH-the number of blood units before transplantation and increased ALT levels at the time of LB. CONCLUSION: This study showed that renal transplant patients infected by HCV for more than 10 years, with a mean posttransplant follow-up of more than 5 years, showed more severe liver lesions when coinfected by hepatitis B virus. Overall, we observed only four cases of cirrhosis (5%) and evidence of histological CAH lesions in 36% of the patients.

Study of the association between major histocompatibility complex class II genes and the response to interferon alpha in patients with chronic hepatitis C infection.

OBJECTIVE: The aim of the study was to determine the influence of HLA class II genes on the response to interferon-alpha (IFN-alpha) in patients with chronic hepatitis C. METHODS: The distribution of HLA DRB1 and DQB1 alleles was assessed in 170 caucasoïd patients treated with IFN-alpha for chronic hepatitis C. 50 patients had a long term sustained response to treatment whereas 120 patients were nonresponders. RESULTS: Female sex, non-1 HCV genotype particularly genotype 2 and pretreatment low serum HCV RNA level were associated with long-term sustained response to IFN-alpha. A trend towards a higher prevalence of DRB1*07 allele in non responders than in patients with sustained response (45% vs. 28%, odds ratio 2.1; P < 0.05) on the one hand and of DQB1*06 allele in HCV genotype 1 patients with sustained response than in HCV genotype 1 nonresponders (75% vs 27.3%, odds ration 7.9; P < 0.02) on the other hand, were observed. However, none of these two differences remained significant after Bonferroni's correction. CONCLUSION: Accordingly, we conclude that the response to IFN-alpha therapy is more tightly related to virus factors than to host's HLA class II genes.

[Association between polymyositis and hepatitis C infection. Treatment-related difficulties]. / Association entre polymyosite et infection par le virus de l'hépatite C. Les difficultés du traitement.

INTRODUCTION: Chronic hepatitis C virus infection is often associated with various auto-immune disorders. We report four cases of an association between polymyositis and hepatitis C virus infection. The course and the difficulties of therapy are discussed. EXEGESIS: Among 510 consecutive patients infected by viral hepatitis C, we report four cases of polymyositis. Corticosteroids increased serum alanine aminotransferase levels in two cases, leading to severe liver injury in one patient. Worsening of polymyositis under interferon-alpha therapy was observed in one case. Clinical and biological stability were reported in another case. Aggravation of polymyositis with severe muscle weakness and dyspnea occurred in two patients after disruption of interferon-alpha treatment. Intravenous gamma globulins subsequently improved their condition, without biological worsening of viral hepatitis. CONCLUSION: These observations suggest an association between hepatitis C virus infection and polymyositis. Because corticosteroids can induce adverse effects in the liver, intravenous gamma globulins could be used for the treatment of this particular form of polymyositis.

[Hepatitis C and pregnancy]. / Hépatite C et grossesse.

PURPOSE: Today, the natural course of hepatitis C virus (HCV) infection during pregnancy and the prevalence of mother-to-child transmission are better known. CURRENT KNOWLEDGE AND KEY POINTS: Antenatal screening for HCV infection needs to be proposed to women with risk factors. Viral replication needs to be confirmed by PCR in pregnant women with antibodies against HCV. To date, the clinical course of pregnancy and the mode of delivery have not been changed by HCV infection. Rates of vertical transmission of HCV are about 6% in women with HCV alone and 15% in women co-infected with HIV. A screening for HCV markers is required 18 months after delivery for infants born to HCV mothers. Because of the relatively low rate of HCV vertical transmission, pregnancy can be allowed in infected women. However, taking into account the efficacy of new antiviral strategies, treatment of HCV infection could be proposed before pregnancy. FUTURE PROSPECTS AND PROJECTS: In case of HCV infection, a careful follow-up of both mother and newborns is required. Long-term follow-up of infected infants is needed to assess the consequences of perinatal HCV infection.

[Endoscopic treatment of subcutaneous fat necrosis secondary to pancreatic-vascular fistula: apropos of a case]. / Traitement endoscopique d'une cytostéatonécrose secondaire à une fistule pancréaticovasculaire: à propos d'un cas.

PATIENT AND METHOD: We report the case of a 68-year-old man who presented a pancreatic tumor with a pancreato-vascular fistula and a Weber-Christian syndrome. Pancreatic enzymes levels at the admission were high: amylasemia 2,470 IU/L (N < 110) and lipasemia 11,700 IU/L (N < 220). The treatment consisted in total parenteral nutrition and somatostatin (100 micrograms x 3/day). Because we noted neither clinical nor biological improvement after 10 days of treatment, we performed an endoscopic retrograde pancreatography. During this examination, we put a 7 French diameter prosthesis through the Wirsung stenosis. RESULTS: No problem arose after endoscopy: since the day after the endoscopy, pancreatic enzymes decreased by half and become normal in 4 days; arthralgias and cutaneous injuries, both caused by cytosteatonecrosis, disappeared respectively in 5 and 10 days. There is no evidence of subsequent recurrence after 3 months of follow-up. CONCLUSION: Pancreatic endoscopic prosthesis can replace the surgical treatment of pancreato-vascular fistula with a good efficacy.

[Association of disseminated lupus erythematosus and Crohn's disease]. / Association entre un lupus érythémateux disséminé et une maladie de Crohn.

INTRODUCTION: Association of Crohn's disease and systemic lupus erythematosus is infrequent. We report an observation of Crohn's disease that appeared in an 18-year-old woman followed-up for systemic lupus erythematosus for four years. EXEGESIS: The patient had all the clinical, biological and histological criteria of Crohn's disease and systemic lupus erythematosus was diagnosed according to the American Rheumatism Association criteria. On the base of this observation, we discuss the digestive manifestation of systemic lupus erythematosus and extradigestive manifestations of Crohn's disease. CONCLUSION: The immunological background of both diseases was proposed to explain the mechanism of this rare association.

[Kikuchi syndrome, Hashimoto thyroiditis and lupus serology. Apropos of a case]. / Syndrome de Kikuchi, thyroïdite de Hashimoto et sérologie lupique. A propos d'un cas.

Histiocytic necrotizing lymphadenitis (Kikuchi's disease) is an uncommon disease of the cervical lymph nodes occurring in young women, commonly associated with various auto-immune or infectious diseases. We describe the case of a 17 year-old girl who presented a Kikuchi's lymphadenitis occurring concomitantly with Hashimoto's thyroiditis and lupus serology as anti-nuclear, anti-DNA, anticardiolipid antibodies and hypocomplementemia. The patient was treated with prednisone and hydroxychloroquine. Thirty months after, she is doing well and hydroxychloroquine is continued.

[Systemic manifestations of hemorrhagic rectocolitis: apropos of a case of hemorrhagic rectocolitis associated with multiple sclerosis]. / Manifestations systémiques de la rectocolite hémorragique: à propos d'un cas d'une rectocolite hémorragique associée à une sclérose en plaques.

Extra-intestinal manifestations of inflammatory bowel diseases are frequent and numerous. We report a case of ulcerative colitis associated with multiple sclerosis, ankylosing spondylitis and pyoderma gangrenosum. This observation shows the rare association of ulcerative colitis-multiple sclerosis, and extra-intestinal manifestations of inflammatory colitis are discussed.

[Rheumatic manifestations of chronic hepatitis C and response to the treatment with interferon alpha-2b]. / Manifestations rhumatologiques des hépatites C chroniques et réponse au traitement par interféron alpha-2b.

Chronic hepatitis C can be responsible for a broad range of autoimmune manifestations, including cryoglobulinemia and Sjögren's syndrome. We report our experience with six patients (five women and one man; mean age 55.6 years) in whom hepatitis C was diagnosed during evaluation of joint symptoms. Polyarthralgia was the main symptom and was often accompanied with myalgia; a polyalgic syndrome was seen in some patients. Isolated cytolysis was consistently found, although, in some instances, liver enzyme elevations were moderate and postdated the onset of the clinical symptoms. The diagnosis of hepatitis C was confirmed by recombinant immunoblot assay (RIBA) in every case. The polymerase chain reaction (PCR) detected hepatitis C virus RNA in five of the six patients. Histological findings were characteristic of chronic hepatitis. All six patients had immunological test abnormalities, which included presence of rheumatoid factors (2 of 6), positive antinuclear antibodies without anti-DNA antibodies (3 of 6) and low serum complement levels (3 of 6). A cryoprecipitate was found in four of the six patients. Four patients reported symptoms of sicca syndrome and two had Chisholm grade III lesions upon examination of salivary gland biopsy specimens. Four patients were given a six-month course of interferon alpha. In three of these four patients, evaluation at the end of the treatment showed abatement or resolution of symptoms, normal liver function tests, unchanged or diminished antinuclear antibody titers, and normal serum complement levels. In the remaining patient, no changes in symptoms or transaminase levels occurred during interferon alpha treatment. In conclusion, rheumatic symptoms can be the most prominent manifestation of chronic hepatitis C.(ABSTRACT TRUNCATED AT 250 WORDS)

[Increase of CA 19.9 in dysimmune inflammatory rheumatism. Apropos of 6 cases]. / Elévation du CA 19.9 au cours des rhumatismes inflammatories dysimmunitaires. A propos de 6 observations.

CA 19.9 is a marker for several cancers, including ductal adenocarcinomas of the pancreas. CA 19.9 elevation is rarely found in patients without benign or malignant digestive system disease. We studied serum CA 19.9 levels in patients with a variety of inflammatory joint diseases, including rheumatoid arthritis (n = 20), lupus, Sjögren's syndrome or U1RNP-associated connective tissue syndrome (Sharp's syndrome) (n = 11), dermatopolymyositis (n = 8), and giant cell arteritis or polymyalgia rheumatica (n = 8). The mean CA 19.9 level in each of these groups was not significantly different from the value seen in a group of patients with osteoporosis. Six patients had persistent marked elevation in serum CA 19.9 levels. Two had Sjögren's syndrome, two had Sharp's syndrome and two had dermatopolymyositis. None of these six patients had evidence of tumoral disease despite a follow-up of several years. Likely explanations for the CA 19.9 elevation were chronic pancreatitis in one case and lung disease in the other five. In patients with lung involvement due to inflammatory joint disease, CA 19.9 elevation may indicate severe disease and may be of use for monitoring the lung condition.