Christophe Duvoux

Hepatitis C virus-related chronic hepatitis may be associated with various immunological disorders. The aim of this study was to determine prospectively the prevalence of the clinical, biochemical and pathological immunological abnormalities in a series of 61 consecutive patients with chronic hepatitis C, compared with those in 61 age- and sex-matched control subjects without markers of hepatitis C virus and hepatitis B virus infections and with those in 61 patients with chronic hepatitis B. The following investigations were systematically performed before any treatment: detection of serum cryoglobulinemia and rheumatoid factor, detection of a large variety of serum antitissue antibodies, biopsy of labial salivary glands, ophthalmological examination, dosage of thyroid-stimulating hormone and in vivo capillary microscopy. Cryoglobulinemia was found in 36% of the hepatitis C virus patients, four of whom had dermatological and/or neurological manifestations of vasculitis, and rheumatoid factor was present in 70%. Serum antitissue antibodies were detected in 41% of cases, mostly antinuclear and anti-smooth muscle antibodies. Liver-kidney microsomal and antithyroid antibodies were rare. Salivary gland lesions were found in 49% of the patients: all had lymphocytic capillaritis, sometimes associated with lymphocytic sialadenitis resembling that of Sjögren’s syndrome, but without features of sicca syndrome and Ro/SSA antibodies. Five percent of the patients had lichen planus. The prevalences of cryoglobulinemia, rheumatoid factor and antitissue antibodies were significantly higher than those in the control group and patients with chronic hepatitis B. In conclusion, hepatitis C virus-related chronic hepatitis may be associated with immunological abnormalities that can be classified into several categories: (a) immune complex-mediated disease, mainly represented by mixed cryoglobulinemia that, in rare cases, may be associated with symptoms of vasculitis; (b) autoimmune abnormalities, frequent and mainly represented by serum autoantibodies, especially antinuclear and anti-smooth muscle antibodies; (c) salivary gland lesions, mainly lymphocytic capillaritis, which is found in approximately half the patients and might secondarily lead to lymphocytic sialadenitis resembling Sjögren’s syndrome; and (d) lichen planus, in which hepatitis C virus could be the main agent of frequently associated liver disease. (Hepatology 1994;19:841-848.)

The purpose of this registry study was to provide an overview of trends and results of liver transplantation (LT) in Europe from 1968 to 2016. These data on LT were collected prospectively from 169 centers from 32 countries, in the European Liver Transplant Registry (ELTR) beginning in 1968. This overview provides epidemiological data, as well as information on evolution of techniques, and outcomes in LT in Europe over more than five decades; something that cannot be obtained from only a single center experience.

BACKGROUND: We investigated whether sirolimus-based immunosuppression improves outcomes in liver transplantation (LTx) candidates with hepatocellular carcinoma (HCC). METHODS: In a prospective-randomized open-label international trial, 525 LTx recipients with HCC initially receiving mammalian target of rapamycin inhibitor-free immunosuppression were randomized 4 to 6 weeks after transplantation into a group on mammalian target of rapamycin inhibitor-free immunosuppression (group A: 264 patients) or a group incorporating sirolimus (group B: 261). The primary endpoint was recurrence-free survival (RFS); intention-to-treat (ITT) analysis was conducted after 8 years. Overall survival (OS) was a secondary endpoint. RESULTS: Recurrence-free survival was 64.5% in group A and 70.2% in group B at study end, this difference was not significant (P = 0.28; hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62; 1.15). In a planned analysis of RFS rates at yearly intervals, group B showed better outcomes 3 years after transplantation (HR, 0.7; 95% CI, 0.48-1.00). Similarly, OS (P = 0.21; HR, 0.81; 95% CI, 0.58-1.13) was not statistically better in group B at study end, but yearly analyses showed improvement out to 5 years (HR, 0.7; 95% CI, 0.49-1.00). Interestingly, subgroup (Milan Criteria-based) analyses revealed that low-risk, rather than high-risk, patients benefited most from sirolimus; furthermore, younger recipients (age ≤60) also benefited, as well sirolimus monotherapy patients. Serious adverse event numbers were alike in groups A (860) and B (874). CONCLUSIONS: Sirolimus in LTx recipients with HCC does not improve long-term RFS beyond 5 years. However, a RFS and OS benefit is evident in the first 3 to 5 years, especially in low-risk patients. This trial provides the first high-level evidence base for selecting immunosuppression in LTx recipients with HCC.

Treatment of hepatorenal syndromes (HRSs) is currently based on vasopressin analogs. The aim of this pilot study was to evaluate the efficacy and safety of noradrenalin (NA) in the treatment of type 1 HRS. Between 1998 and 2000, 12 consecutive patients with type 1 HRS (7 men, 5 women; mean age, 54 +/- 11 years; mean Child-Pugh score, 11.3 +/- 1.7) were treated with intravenous NA (0.5-3 mg/h), in combination with intravenous albumin and furosemide. NA was given for 10 +/- 3 days, at a mean dose of 0.8 +/- 0.3 mg/h. Reversal of HRS was observed in 10 of 12 patients (83%; 95% confidence interval, 52%-98%) after a median of 7 days (range, 5-10 days). Serum creatinine levels fell from 358 +/- 161 to 145 +/- 78 micromol/L (P <.001), creatinine clearance rose from 13 +/- 9 to 40 +/- 15 mL/min (P =.003), and urinary sodium output increased from 8 +/- 14 to 52 +/- 72 mEq/d (P =.002). Changes in renal function under NA treatment were associated with an increase in mean arterial pressure (MAP; 65 +/- 7 to 73 +/- 9 mm Hg, P =.01) and a marked reduction in active renin (565 +/- 989 to 164 +/- 196 ng/L, P =.001) and aldosterone plasma concentrations (1,945 +/- 1,931 to 924 +/- 730 ng/mL, P =.02). There was one episode of reversible myocardial hypokinesia (in a patient on 1.5 mg/h NA) that did not recur after a dose reduction. In conclusion, NA combined with albumin and furosemide appears effective and safe for the treatment of type 1 HRS.