Cyrille Feray

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Liver Transplantation and Bariatric Surgery

by Cyrille Feray and Nicola de'Angelis

Obesity Surgery

Hepatitis C virus RNA and hepatitis B virus DNA in fulminant hepatitis

Gastroenterology

The role of hepatitis C virus (HCV) in the development of fulminant hepatitis is poorly understoo... more The role of hepatitis C virus (HCV) in the development of fulminant hepatitis is poorly understood. The polymerase chain reaction was used to detect HCV RNA and hepatitis B virus (HBV) DNA in serum and liver of 40 patients with fulminant or subfulminant hepatitis. HCV RNA was detected in none of the 23 subjects with hepatitis B surface antigen (HBsAg)-negative hepatitis of unknown etiology. HBV DNA was found in 1 of these 23 subjects. In contrast, 8 of the 17 patients with HBsAg-positive hepatitis were HCV RNA positive. Among the latter, 5 had immunoglobulin (Ig) M antibody to hepatitis B core antigen (anti-HBc) and thus were acutely coinfected by HBV and HCV, whereas 3 others without IgM anti-HBc had superinfection by HCV. The active replication of HCV in the liver was shown by detection of high titers of HCV RNA and of negative-stranded HCV RNA. This investigation therefore shows no evidence of a role for HCV infection in sporadic cases of fulminant hepatitis without defined etiology. However, it suggests that HCV might be implicated in a significant number of patients with HBV-related fulminant hepatitis.

[Clinical and virological aspects of hepatitis C virus infection in liver transplantation]

Gastroentérologie Clinique et Biologique

The course of hepatitis C after liver transplantation

Hepatology

ABSTRACT

Incidence of hepatitis C in patients receiving different preparations of Hepatitis B immunoglobulins after liver transplantation

Annals of internal medicine

Recurrence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection after liver transplant... more Recurrence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection after liver transplantation is a clinical problem. Polyclonal immunoglobulins against hepatitis B surface antigen (HBIGs) prevent the recurrence of HBV infection, but no effective prophylaxis is available for HCV infection. Before screening of blood donors was introduced in France, HBIGs may have contained antibody to HCV (anti-HCV). To determine the influence of HBIG on the occurrence of hepatitis C after liver transplantation before and after 1990. Retrospective cohort study. Liver transplantation unit of a university hospital. 428 consecutive patients who had liver transplantation because of cirrhosis between 1984 and 1994. Detection of serum HCV RNA before and 1 year after transplantation and findings on liver graft biopsy. Among the 218 patients who had HCV infection before transplantation, the incidence of HCV viremia after transplantation was lower in those receiving HBIG than in those not receiving HBIG (25 of 46 patients [54%] compared with 162 of 172 patients [94%]; P &amp;amp;amp;amp;lt; 0.001). In patients receiving HBIG, the incidence of HCV viremia after transplantation was lower among those who had transplantation before March 1990 than among those who had transplantation after this date (15 of 33 patients [45%] compared with 10 of 13 patients [77%]; P = 0.05). Among the 210 patients without HCV infection before transplantation, acquired infection was significantly less frequent in those receiving HBIG than in those not receiving HBIG (18 of 68 patients [26%] compared with 40 of 86 patients [47%]; P &amp;amp;amp;amp;lt; 0.001). Passively transmitted anti-HCV was transiently detected in patients receiving HBIG before March 1990. Multivariate analysis in patients with HCV infection before transplantation showed that the absence of HBIG and transplantation after March 1990 were independent significant risk factors for chronic hepatitis C after transplantation. Polyclonal immunoglobulins that are treated for viral decontamination and contain anti-HCV could prevent HCV infection.

Pneumocystis carinii and cytomegalovirus pneumonia after corticosteroid therapy in acute severe alcoholic hepatitis: 2 Case reports

Gastroentérologie Clinique et Biologique

Most cases of infections described after steroid treatment for severe acute alcoholic hepatitis a... more Most cases of infections described after steroid treatment for severe acute alcoholic hepatitis are of bacterial origin. However, the rate of bacterial infections in these patients is not higher than in those who are not treated by steroids. The opportunistic infections are even more rare. We report two cases of patients with cirrhosis and human immunodeficiency virus, treated for alcoholic hepatitis with steroids and who subsequently developed severe pneumopathy due to Pneumocystis carinii. One patient had a concommitant cytomegalovirus infection and both of them died. Pneumocystis carinii infections usually occur in patients a decreased immune cellular response. Steroid treatments and also alcohol may be responsible for these opportunistic infections. Alcohol may have an immunosuppressive effect by decreasing recruitment of CD4 and CD8 lymphocytes to the lungs. In conclusion, Pneumocystis carinii pneumonia is a potential complication of steroid treatments for acute alcoholic hepatitis and should be suspected in case of unexplained pulmonary infection.

Clinical outcomes of right-lobe split-liver versus orthotopic liver transplants from donors more than 70 years old

by Cyrille Feray and Nicola de'Angelis

Progress in transplantation (Aliso Viejo, Calif.), 2015

Context-The imbalance between the organ supply and the number of potential transplant recipients ... more Context-The imbalance between the organ supply and the number of potential transplant recipients led to consideration of expanded-criteria liver donors. Objective-To compare right-lobe split-liver transplants (RL-SLTs) with orthotopic liver transplants (OLTs) from donors more than 70 years old (OLT-O) and OLTs from donors less than 55 years old (OLT-Y). Methods-Seventy-one patients who received an RL-SLT were matched for age, sex, and Model for End-stage Liver Disease score with 71 patients who underwent OLT-O and 142 patients who underwent OLT-Y. Clinical outcomes were compared between groups. Results-Longer operation time was associated with RL-SLT (P< .001) as well as more blood loss (P= .03) and transfusions (P= .05). Postoperative morbidity was less in the OLT-Y group, with a lower rate of grades III to IV Clavien-Dindo complication (30%), compared with values in OLT-O (52%) and RL-SLT (38%). Kaplan-Meier analysis demonstrated better 1-year and 3-year survival rates in the O...

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Should we screen blood products for hepatitis E virus RNA ?

The Lancet

Liver transplantation in patients with ESLD requiring Intensive Care Unit admission and intubation The success ration depends upon the denominator

Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, Jan 25, 2015

Hepatectomy for hepatocellular carcinoma larger than 10 cm: preoperative risk stratification to prevent futile surgery

by Cyrille Feray and Chetana Lim

HPB, 2015

Appropriate patient selection is important to achieving good outcomes and obviating futile surger... more Appropriate patient selection is important to achieving good outcomes and obviating futile surgery in patients with huge (≥10 cm) hepatocellular carcinoma (HCC). The aim of this study was to identify independent predictors of futile outcomes, defined as death within 3 months of surgery or within 1 year from early recurrence following hepatectomy for huge HCC. The outcomes of 149 patients with huge HCCs who underwent resection during 1995-2012 were analysed. Multivariate logistic regression analysis was performed to identify preoperative independent predictors of futility. Independent predictors of 3-month mortality (18.1%) were: total bilirubin level &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;34 μmol/l [P = 0.0443; odds ratio (OR) 16.470]; platelet count of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;150 000 cells/ml (P = 0.0098; OR 5.039), and the presence of portal vein tumour thrombosis (P = 0.0041; OR 5.138). The last of these was the sole independent predictor of 1-year recurrence-related mortality (17.2%). Rates of recurrence-related mortality at 3 months and 1 year were, respectively, 6.3% and 7.1% in patients with Barcelona Clinic Liver Cancer (BCLC) stage A disease, 12.5% and 14% in patients with BCLC stage B disease, and 37.8% (P = 0.0002) and 75% (P = 0.0002) in patients with BCLC stage C disease. According to the present data, among patients submitted to hepatectomy for huge HCC, those with a high bilirubin level, low platelet count and portal vein thrombosis are at higher risk for futile surgery. The presence of portal vein tumour thrombosis should be regarded as a relative contraindication to surgery.

The Paul Brousse liver transplant series 1989 to 1992: new trends in the last four years

by Cyrille Feray and M. Johann

Clinical transplants

In the last four years, 551 liver transplantations have been performed at the Paul Brousse center... more In the last four years, 551 liver transplantations have been performed at the Paul Brousse center, for a total of 840 liver transplantations performed from 1984 to 1992. Several changes have been observed in the field of liver transplantation in the past years. The field of immunosuppression was marked mainly by the advent of FK506 as a preventive treatment of rejection and as a treatment of cortico-resistant rejection. Results are still under analysis. From the surgical viewpoint, the main modification was the advent of UW solution, which extends cold ischemic time. However, our policy was to maintain the cold ischemic time at less than 12 hours. Primary indications for liver transplantations have changed with an increase in the rate of patients transplanted for cirrhosis related to hepatitis virus infection: from 24% in the period 1984-1988 to 42% in the period 1989-1992. The difference was due mainly to HCV-related cirrhosis, which increased from 8% to 20%. Alcoholic cirrhosis wa...

Successful tacrolimus therapy for a severe recurrence of type 1 autoimmune hepatitis in a liver graft recipient

Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 2001

A 34-year-old woman underwent orthotopic liver transplantation (OLT) for decompensated type 1 aut... more A 34-year-old woman underwent orthotopic liver transplantation (OLT) for decompensated type 1 autoimmune hepatitis (AIH). She was administered standard triple-drug immunosuppressive therapy (cyclosporine, steroids, and azathioprine). Ten years after OLT, she developed a recurrence of AIH, with emergence of serological markers of autoimmunity (high anti--smooth muscle antibody [ASMA] titer, high serum gamma globulin level), abnormal liver function test results, and characteristic histological features on liver biopsy. Despite intensified steroid therapy, her clinical and liver function deteriorated. The onset of cutaneous alternariosis led to a steroid dose reduction and cyclosporine replacement by tacrolimus. Clear-cut amelioration was observed, with an improvement in liver function test results and reduction in ASMA titer. One year after the recurrence of AIH, the patient has normal liver function and physical findings. Tacrolimus therefore may be effective in patients with severe ...

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Nonrandom distribution of hepatitis C virus quasispecies in plasma and peripheral blood mononuclear cell subsets

by Cyrille Feray and Marie-anne Petit

Journal of virology, 1999

The existence of an extrahepatic reservoir of hepatitis C virus (HCV) is suggested by differences... more The existence of an extrahepatic reservoir of hepatitis C virus (HCV) is suggested by differences in quasispecies composition between the liver, peripheral blood mononuclear cells, and serum. We studied HCV RNA compartmentalization in the plasma of nine patients, in CD19(+), CD8(+), and CD4(+) positively selected cells, and also in the negatively selected cell fraction (NF). HCV RNA was detected in all plasma samples, in seven of nine CD19(+), three of eight CD8(+), and one of nine CD4(+) cell samples, and in seven of eight NF cells. Cloning and sequencing of HVR1 in two patients showed a sequence grouping: quasispecies from a given compartment (all studied compartments for one patient and CD8(+) and NF for the other) were statistically more genetically like each other than like quasispecies from any other compartment. The characteristics of amino acid and nucleotide substitutions suggested the same structural constraints on HVR1, even in very divergent strains from the cellular com...

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[Evaluation of results of liver transplantation: experience based on a series of 1052 transplantations]

Presse médicale (Paris, France : 1983)

The aim of this work was to evaluate outcome in a continuous homogeneous series of more than 1000... more The aim of this work was to evaluate outcome in a continuous homogeneous series of more than 1000 liver transplantations in order to determine risk groups. Between November 1984 and February 1995, 1052 isolated orthotopic liver transplantations were performed in 922 patients (530 males, 392 females; mean age 41.7 years; age range 10 months - 78 years) at the Paul-Brousse Hospital liver transplantation unit. Immunosuppression was based on cyclosporin in all patients with FK506 in the most recent cases. Actuarial survival at 1,5 and 8 years for the 922 patients was 80.9, 71.7, and 69.1%. Certain factors affecting the intrinsic risk of transplantation were identified and could be used to calculate supplementary risk due to one or more other risk factors. In adults under 55 years in UNOS stage 1 or 2 (not hospitalized at call in) transplanted after 1990 for non-recurrent (absence of cancer, non-viral disease) chronic liver disease, the risk of death at 1 year was 6.5% and 4.4% between t...

Paul Brousse Liver Transplantation: the first 1,500 cases

Clinical transplants, 2000

During the past 16 years, more than 1,500 liver transplants were performed at Paul Brousse Hospit... more During the past 16 years, more than 1,500 liver transplants were performed at Paul Brousse Hospital. The overall patient survival rates were 83% at one year and 65% at 10 years. Our group has pioneered a variety of new approaches to liver transplantation, including: 1. Anti-HBs (HBIG) prophylaxis for the prevention of HBV recurrence. To date more than 270 patients have received long-term treatment and the overall 10-year recurrence rate was 27%. 2. Transplantation for hepatocellular carcinoma of the cirrhotic liver in patients with uni- or binodular HCC (< 3 cm). Survival for transplanted patients was 83% compared with 18% if the liver was resected. 3. Transplantation for familial amyloidotic polyneuropathy (FAP). More than 60 patients had 5- and 10-year survival rates of 85% and 83%, respectively. Ten livers obtained after hepatectomy from these FAP patients were transplanted as "domino" living donor livers to patients with unresectable liver cancers with satisfactory ...

[Adult to adult living-related liver transplantation. The Paul-Brousse Hospital preliminary experience]

Gastroentérologie clinique et biologique

Liver-graft shortages justify the development of adult living-related liver transplantation. The ... more Liver-graft shortages justify the development of adult living-related liver transplantation. The preliminary experience with this technique at Paul-Brousse Hospital is reported. PATIENTS ET METHODES: From January to July 2000, 7 adult to adult living-related liver transplantations were performed. Donors were 5 females and 2 males aged 20 to 53 years old (median: 41). A right liver graft was harvested in all cases. Recipients were 5 males and 2 females aged from 17 to 58 years old (median: 50) transplanted for viral cirrhosis (4 cases including 2 with hepatocellular carcinoma), subfulminant hepatitis (1 case), hepatocellular carcinoma on a healthy liver (1 case), and epithelioid hemangioendothelioma (1 case). Follow-up ranged from 41 to 157 days (median: 117 days). One donor had a biliary fistula that healed spontaneously. One donor had asterixis for 24 hours. The 7 donors are alive at home without any late complications. One recipient was retransplanted for hepatic artery thrombosis...

Risk factors for hepatocellular carcinoma in Caucasian patients with non-viral cirrhosis: the importance of prior obesity

Liver International, 2015

In patients with cirrhosis, the risk of hepatocellular carcinoma (HCC) depends upon age, gender a... more In patients with cirrhosis, the risk of hepatocellular carcinoma (HCC) depends upon age, gender and the etiology of liver disease. Few studies are available in Caucasian patients with alcoholic or metabolic cirrhosis without viral hepatitis. Cross-sectional clinical data from 905 HCV- and HBV-negative Caucasian patients with alcoholic or metabolic cirrhosis were prospectively collected in four French centres. The risk factors for HCC were identified by logistic regression analysis in the whole population and in a nested case-control study. The etiology of cirrhosis was alcoholic (48%), metabolic (7%) or mixed (45%). Patients were predominantly male (80%), mean age 62 years old and 31% had HCC. Mean body mass index (BMI) was 27 ± 5 and 30% were obese at inclusion. The maximum BMI reached throughout life was 31 ± 6 and 63% had been obese. Ninety percent of the population had daily alcohol consumption, 73% were smokers. Hepatocellular carcinoma was independently related to male gender (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001), older age (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001), past obesity (P = 0.007), diabetes (P = 0.037), abnormal levels of transaminases (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001) and tobacco consumption (P = 0.007). The case-control study (200 HCC cases matched with 400 non-HCC cases for gender, age and Child-Pugh score) confirmed past obesity, tobacco and abnormal levels of transaminases. Beside diabetes, male gender and age, a past history of obesity, but not an existing overweight, as well as exposure to tobacco and elevated transaminases were three risk factors which could improve the strategy for HCC screening in Caucasian cirrhotic patients without hepatitis B or C.

Moleclar and cinical characteristics of the hepatitis C virus genotype '2c' found in Italians in Italy and France

International Hepatology Communications, 1995

ABSTRACT We found a rare hepatitis C virus (HCV) genotype in 11 Italian and three French patients... more ABSTRACT We found a rare hepatitis C virus (HCV) genotype in 11 Italian and three French patients. The HCV core gene sequence for these patients showed nucleotide similarities of 93–98% to each other, 88–92% to genotypes III (2a) and IV (2b) isolates, and only 82–85% to genotypes I (1a), II (1b), 1c, and V (3a) isolates. The NS5b sequence also indicated the distinctness of this group of HCV, its relatively close relationship to genotype III (2a) and IV (2b), and a high degree of similarity to several isolates provisionally classified as ‘2c’. The El region sequence determined in one French patient also had a high similarity to another ‘2c’ isolate reported previously. Although the prevalence of this ‘2c’ HCV in Italian patients was low (11173: 6%), it was of clinical interest. This genotype was associated with poor responsiveness to interferon therapy and also with poor antibody response to C100-3 antigen, and two of the 11 Italian patients had mixed cryoglobulinemia. Interestingly, all the three French patients with the ‘2c’ HCV were from Italy, and virtually Italians.

The presence of epithelioid granulomas in hepatitis C virus-related cirrhosis

Human Pathology, 1995

We examined surgical liver specimens from 52 patients with hepatitis C virus-related cirrhosis. A... more We examined surgical liver specimens from 52 patients with hepatitis C virus-related cirrhosis. All patients underwent orthotopic liver transplantation at Paul Brousse Hospital. They were found to be seropositive for antibodies to hepatitis C virus by second-generation testing (RIBA 2, Ortho Diagnostic Systems Inc, Westwood, MA). We detected multiple granulomas in five (10%) of the cirrhotic livers. These granulomas were composed of epithelioid cells, sometimes associated with multinucleated giant cells, and were surrounded by small lymphocytes and fibrosis. The epithelioid granulomas were located within the cirrhotic nodules. They were not present within the portal tracts or within the fibrosis. These granulomas were diffusely distributed in the liver. None of the patients with diffuse hepatic epithelioid granulomas had evidence of tuberculosis or brucellosis before transplantation or during the follow-up period (range, 3 to 20 months). They had no detectable cause of granulomatous hepatitis. The role of hepatitis C virus as a cause of epithelioid granulomas is discussed.

Hereditary hemorrhagic telangiectasias with liver involvement and high cardiac output

Liver Transplantation, 2001

A 48-year-old woman with history of recurrent epistaxis and gastric telangiectasias was referred ... more A 48-year-old woman with history of recurrent epistaxis and gastric telangiectasias was referred to our center for chronic abdominal pain in the upper right side of the abdomen. She had a family history of hereditary hemorrhagic telangiectasias (HHT). Laboratory studies disclosed cholestasis (alkaline phosphatases, ϫ9N), mild elevated bilirubin levels (ϫ3N), and cytol-ysis (aspartate aminotransferase, ϫ4N; alanine aminotransferase, ϫ8N). Concomitant liver disease was ruled out (alcohol, autoimmunity, viral diseases), and liver involvement of HHT with secondary ischemia was suspected. Contrast-enhanced computed tomography (CT) scan and visceral aorto-angiogram showed several vascular malformations and arteriovenous shunt communications in the liver and abdominal vessels. Hemodynamic studies using cardiac ultrasonography and right-side catheterization revealed high cardiac output (18 L/min) and pulmonary hypertension (systolic pulmonary artery pressure at 56 mm Hg) with no right-side cardiac cavities dilation. No clinical signs of cardiac failure and/or infection were present at the first time she consulted; but after 4 weeks, lower edemas and infectious cholangitis appeared. HHT with hepatic angiomatosis was diagnosed and liver transplantation (LT) was then considered.

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