Approximately half of patients undergoing liver transplantation (LT) for hepatitis C virus (HCV) develop histologic evidence of recurrence within the first postoperative year. Early identification of recipients at risk for more severe recurrence of HCV may be useful in selecting patients for antiviral therapy. We determined whether recipients at greatest risk for more severe recurrence of HCV can be identified by pre-and/or early post-LT HCV-RNA levels in serum or tissue. Serum and tissue samples were prospectively collected pre-LT and at 7 days, 4 months, 1 year, and at 3 years posttransplantation from patients undergoing LT for HCV. Hepatitis activity index (HAI) and fibrosis stage (FS) were assessed in all liver biopsies. Forty-seven patients (32 men) were studied. Higher HCV-RNA levels at 4 months post-LT (>10 9 copies/mL, n ‫؍‬ 29) were associated with higher HAI at 1 year and at 3 years post-LT. The HAI seen on protocol biopsies at 4 months correlated significantly with fibrosis stage (FS) at 1 year (r ‫؍‬ .56, P < .001) and 3 years (r ‫؍‬ .53, P ‫؍‬ .002). Higher HCV-RNA levels at 7 days and 4 months post-LT were sensitive (66% and 84%, respectively) and specific (92% and 63%, respectively) in identifying recipients with an HAI greater than 3 at 3 years. End-stage liver disease secondary to chronic hepatitis C infection is the leading indication for liver transplantation in the United States. 1 Approximately 3 million people in the United States are infected with the hepatitis C virus (HCV). 2,3 Although recurrent infection with HCV is almost universal after orthotopic liver transplantation (LT), 4,5 histologic recurrence varies widely from patient to patient. [6][7][8][9][10][11][12] Although the majority of patients who undergo transplantation for hepatitis C do well, it has become increasingly apparent that recurrent disease can be progressive and may adversely affect patient and graft survival. 13 Allograft failure secondary to recurrence of HCV infection is the most common cause of death and retransplantation in the first 5 years after LT. 13 To date, the use of antivirals has had little impact on the course of posttransplant hepatitis C infection because of a combination of poor efficacy and tolerability. [14][15][16][17] In the setting of a chronic and worsening donor-organ shortage, the identification of recipients at greatest risk for more severe recurrence of posttransplant HCV recurrence has become a high priority. To date, viral genotype 1b 7,12,18-20 and higher viral load 13,[21][22][23] have been inconsistently associated with more severe recurrence of HCV after LT. The inconsistency of the reported association of viral load and histologic progression of HCV infection after LT is likely to be caused, at least in part, by differences in study design (e.g., sample handling, quantification methods, histopathologic sampling protocol, and interpretation). In most reports of the impact of viral load and histologic progression, the level of HCV viremia has been assessed in serum rather than in live...

Some patients with inflammatory bowel disease (IBD) have chronic cholestasis and hepatic histology compatible with primary sclerosing cholangitis (PSC) but normal findings on cholangiography. These patients with small-duct PSC have remained largely unstudied. Our aim was to determine the prevalence and long-term outcomes of patients with small-duct PSC. Eighteen patients with small-duct PSC (7 female and 11 male patients; mean age, 39.9 ؎ 15.3 years [range, 13-68 years]) seen over a 4-year period were matched blindly by age and sex to 36 patients with classic PSC and followed up for 32.5 years. Small-duct PSC represented 5.8% of patients (18 of 309) with sclerosing cholangitis. Subsequent endoscopic retrograde cholangiography (ERC) performed in 5 patients with small-duct PSC showed progression to typical PSC in 3 patients at 4, 5.5, and 21 years of follow-up. None of the patients with small-duct PSC but 4 of the patients with classic PSC developed hepatobiliary malignancy. There were 3 deaths (17%) or liver transplantations in patients with small-duct PSC (2 after progressing to classic PSC) and 15 (42%) in the classic PSC group. Survival free of liver transplantation was significantly greater in the small-duct than in the classic PSC group (P ‫؍‬ .04). Compared with the general U.S. population, survival in patients with small-duct PSC was similar (P ‫؍‬ .4) but significantly lower in patients with classic PSC (P < .001). In conclusion, small-duct PSC may represent an earlier stage of PSC associated with a significantly better long-term prognosis. Some patients, however, progress to classic PSC and/or end-stage liver disease with the consequent necessity of liver transplantation.

The frequency of elevated HAI and fibrosis stage in recipients who undergo transplantation for cryptogenic cirrhosis is similar to that of recipients who undergo transplantation for cholestatic etiologies and significantly less than that of HCV-infected recipients. Fibrosis stage and HAI are generally stable after transplantation for cryptogenic cirrhosis. These data do not suggest a viral etiology of liver disease in the majority of patients with cryptogenic cirrhosis.

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