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Background: In liver transplant recipients with hepatitis C virus recurrence, there is concern about renal safety of sofosbuvir-based regimens. Changes in serum creatinine or in the estimated glomerular filtration rate (eGFR) under treatment are used to look for possible renal toxicity. However, serum creatinine and eGFR are highly variable., Aim: To analyse renal function trajectory with numerous assays of serum creatinine over a long period of time., Methods: In a multicentre cohort of 139 patients, the eGFR was obtained from serum creatinine using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation. Slopes of eGFR were defined as a change in eGFR during a period divided by time. Pre-treatment, on-treatment and post-treatment periods were 9 months, 3-9 months and 4.5 months. Interactions between eGFR slopes and the pre-treatment eGFR, use of ribavirin or mycophenolate mofetil, and stage of fibrosis were addressed. On-treatment eGFR slopes were separated in tertiles. Pre- and post-treatment eGFR slopes were compared globally and according to tertiles., Results: The post-treatment eGFR slope was significantly better than pre-treatment eGFR slope (+0.18 (IQR -0.76 to +1.32) vs -0.11 (IQR -1.01 to +0.73) mL/min/1.73 m 2 /month, P = 0.03) independently of the pre-treatment eGFR (P = 0.99), ribavirin administration (P = 0.26), mycophenolate mofetil administration (P = 0.51) and stage of fibrosis (F3 and F4 vs lower stages, P = 0.18; F4 vs lower stages, P = 0.08; F4 Child-Pugh B and C vs lower stages, P = 0.38). Tertiles of on-treatment eGFR slopes were -1.71 (IQR -2.54 to -1.48), -0.78 (IQR -1.03 to -0.36) and +0.75 (IQR +0.28 to +1.47) mL/min/1.73 m 2 /month. Pre- and post-treatment eGFR slopes were not significantly different according to tertiles (respectively, P = 0.34, 0.08, 0.73)., Conclusion: The eGFR varies during treatment and gives a confusing picture of the renal safety of sofosbuvir-based regimens. In contrast, longitudinal assessment of the eGFR shows a rising trajectory over longer time, meaning that these therapies are safe for the kidneys in our cohort of liver transplant recipients., (© 2018 John Wiley & Sons Ltd.)

Background: Hepatitis B virus (HBV)/hepatitis C virus (HCV) confection has been rarely studied in nonasian series., Aim: To compare the characteristics of HBV/HCV coinfected patients to those of HBV- or HCV-monoinfected patients in the ANRS CO22 HEPATHER cohort study., Patients and Methods: Of the 20 936 included patients, 95 had HBV/HCV coinfection (hepatitis B surface antigen, anti-HCV antibody and HCV RNA positive) and were matched with 375 HBV- and 380 HCV-monoinfected patients on age, gender and time since HBV or HCV diagnosis., Results: F3-F4 fibrosis was more frequent in coinfected patients (58%) than in HBV- (32%, P < .0001), but similar in HCV-monoinfected patients (52%, P = .3142). Decompensated cirrhosis was more frequent in coinfected patients (11%) than in HBV- (2%, P = .0002) or HCV- (4%, P = .0275) monoinfected patients. Past excessive alcohol use was more frequent in coinfected patients (26%) than in HBV (12%, P = .0011), but similar in HCV monoinfected patients (32%, P = .2868). Coinfected patients had a higher proportion with arterial hypertension (42%) than HBV- (26%) or HCV-monoinfected patients (25%) (P < .003). Multivariable analysis confirmed the association between F3-F4 fibrosis and HCV infection in HBV-infected patients (OR = 3.84, 95% CI 1.99-7.43) and the association between decompensated cirrhosis and coinfection in HBV infected (OR = 5.58, 95% CI 1.42-22.0) or HCV infected patients (OR = 3.02, 95% CI 1.22-7.44)., Conclusions: HCV coinfection harmfully affects liver fibrosis in HBV patients, while decompensated cirrhosis is increased in coinfected patients compared with HBV- or HCV-monoinfected patients. HCV treatment is as safe and effective in coinfected as monoinfected patients and should be considered following the same rules as HCV monoinfected patients., (© 2017 John Wiley & Sons Ltd.)

The reasons for wide variations in the severity of recurrent hepatitis C after liver transplantation are unclear. We studied liver transplant recipients to assess the effect of hepatitis C virus (HCV) genotype and HCV RNA quantification on histologic progression of recurrent hepatitis C after transplantation. Twenty-five patients underwent transplantation for HCV cirrhosis and were followed up with virologic and histologic assessments for a mean of 51 months. HCV genotype was determined by line probe assay. HCV RNA was quantitated in serum samples by nested polymerase chain reaction. The HCV genotype 1 was detected in 17 patients and other genotypes in 8. Acute lobular hepatitis developed in 17 patients 162 days posttransplantation on average. Long-term biopsy specimens (mean, 51 months after the date of liver transplantation; range, 24-86 months) showed chronic hepatitis in 19 patients (mild, 5; moderate, 9; and severe, 5, 2 with extensive scarring). The serum alanine aminotransferase level was correlated with hepatocyte necrosis (piecemeal and lobular) but not with portal inflammation or fibrosis. Patients infected with genotype 1 had a higher Knodell score, and the 5 patients with severe hepatitis C all were infected with genotype 1. HCV RNA levels were significantly higher in patients with genotype 1 than in patients with other genotypes, as were the severity of histologic recurrence and levels of viral replication.

The reasons for the wide variation of incidence and severity of recurrent hepatitis C after liver transplantation are not clear. We have studied liver transplant recipients to assess the impact of hepatitis C virus (HCV) genotype and HCV RNA quantification on HCV recurrence after transplantation. Twenty-two patients received transplants for HCV cirrhosis and were followed up with virological and histological assessments. Mean follow-up was 39 months. HCV genotype was determined with line probe assay (Inno-Lipa). HCV RNA quantity was determined in serum samples by use of polymerase chain reaction nested assay. HCV genotype 1 was detected in 13 patients and other genotypes in 9. Histological recurrence rates were 69% in patients with genotype 1 and 66% in patients with other genotypes. All cases of severe histological injury (chronic active hepatitis or cirrhosis) were observed in patients with genotype 1. HCV RNA quantity was significantly higher in patients with genotype 1 (mean, 2.023 x 10(3) copies/mL) than in patients with other genotypes (mean, 27,403 copies/mL). In conclusion, the severity of histological recurrence after liver transplantation for HCV disease was higher in patients infected by HCV genotype 1 than in those infected with other genotypes. The levels of viral replication were higher in patients with HCV genotype 1 than in those with other genotypes.

Objectives: The intrafamilial transmission of hepatitis C virus infection was assessed in the family members of patients with chronic hepatitis C., Methods: The presence of serum anti-hepatitis C virus (HCV) antibodies and epidemiological features were studied in 193 relatives (104 heterosexual partners, 89 children) of 113 patients with chronic hepatitis C. The presence of serum anti-HCV antibodies was detected by an ELISA 2 test and confirmed by a RIBA 2 test. In all patients, liver injury was ascertained by biopsy (31 cirrhosis, 82 chronic active hepatitis)., Results: Eleven of 104 (10.6%) regular heterosexual partners were positive for anti-HCV antibodies. In 8 of these, risk factors were detected (drug addiction: n = 6, blood transfusion: n = 1, occupational exposure: n = 1). Only 3 of 96 (3.2%) regular heterosexual partners without percutaneous risk factors were positive for HCV. Among couples with heterosexual partners negative for anti-HCV antibodies, the mean duration of the sexual relationship was 12 years. Serum anti-HCV antibodies were present in 1 of 89 (1.1%) children without history of blood transfusion or drug addiction. None of the 35 children born after supposed maternal contamination were positive for serum anti-HCV antibodies., Conclusions: We conclude that the prevalence of serum anti-HCV antibodies, assessed with second generation tests, in sexual partners of patients with chronic hepatitis C, is lower than previously reported with first generation anti-HCV tests but higher than in the general population (3.2% vs approximately equal to 1%). Serum anti-HCV antibodies were very rarely detected in children from patients with chronic hepatitis C.

Background Hepatitis B virus (HBV)/hepatitis C virus (HCV) confection has been rarely studied in nonasian series. Aim To compare the characteristics of HBV/HCV coinfected patients to those of HBV- or HCV-monoinfected patients in the ANRS CO22 HEPATHER cohort study. Patients and Methods Of the 20 936 included patients, 95 had HBV/ HCV coinfection (hepatitis B surface antigen, anti- HCV antibody and HCV RNA positive) and were matched with 375 HBV- and 380 HCV-monoinfected patients on age, gender and time since HBV or HCV diagnosis. Results F3-F4 fibrosis was more frequent in coinfected patients (58%) than in HBV- (32%, P < .0001), but similar in HCV-monoinfected patients (52%, P = .3142). Decompensated cirrhosis was more frequent in coinfected patients (11%) than in HBV- (2%, P = .0002) or HCV- (4%, P = .0275) monoinfected patients. Past excessive alcohol use was more frequent in coinfected patients (26%) than in HBV (12%, P = .0011), but similar in HCV monoinfected patients (32%, P = .2868). Coinfected patients had a higher proportion with arterial hypertension (42%) than HBV- (26%) or HCV-monoinfected patients (25%) ( P < .003). Multivariable analysis confirmed the association between F3-F4 fibrosis and HCV infection in HBV-infected patients ( OR = 3.84, 95% CI 1.99-7.43) and the association between decompensated cirrhosis and coinfection in HBV infected ( OR = 5.58, 95% CI 1.42-22.0) or HCV infected patients ( OR = 3.02, 95% CI 1.22-7.44). Conclusions HCV coinfection harmfully affects liver fibrosis in HBV patients, while decompensated cirrhosis is increased in coinfected patients compared with HBV- or HCV-monoinfected patients. HCV treatment is as safe and effective in coinfected as monoinfected patients and should be considered following the same rules as HCV monoinfected patients. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To define the causes of mortality of patients who died within the first three months after a liver transplantation. Type of study: Retrospective, observational, and single centre study. Patients and methods: Between March 1989 and July 2010, all patients who died within three months after a liver transplantation were included. Demographic characteristics, preoperative and peroperative data, donor characteristics, postoperative complications and causes of mortality were collected. Results: Among the 788 performed liver transplantations, 76 patients died in intensive care unit (11%). The main indications of liver transplantation were alcoholic cirrhosis (30%), hepatitis C (28%), hepatocarcinoma (15%), primitive or secondary biliary cirrhosis (10%). Fifty percent of the patients were categorized as Child C. The main causes of death were non-function or dysfunction with retransplantation contra-indication graft (18%), sepsis (18%), neurological complications (12%), hemorrhagic shock (13%), (9%), multiorgan failures (5%), cardiac complications (6%). Conclusion: In this study, the main causes of mortality were infectious, neurological and hemorrhagic. These results emphasize the necessity for better control of sepsis, haemorrhage and immunosupressors. [Copyright &y& Elsevier]