Early histologic changes in fibrosing cholestatic hepatitis C

Abstract

Recurrent hepatitis C (RHCV) after liver transplantation is almost universal, and occasional patients will have an aggressive course characterized histologically by pericellular/sinusoidal fibrosis and cholestasis, known as fibrosing cholestatic hepatitis (FCH). The early stages and evolution of this disease have not been well characterized. A total of 77 liver biopsies performed for indication (nonprotocol) were evaluated for necroinflammation, rejection, cholestasis, and fibrosis. Control groups were composed of protocol biopsies from HCV transplant patients (10 biopsies) as well as non-HCV transplant patients (6 biopsies). Scoring for necroinflammation, rejection, and fibrosis were compiled using standard criteria (hepatic activity index, Banff, Ishak, METAVIR). Pericellular fibrosis was staged with a novel "sinusoidal" system. A cholestasis scoring system was developed to quantitate parenchymal and portal features of cholestasis. Biopsies were categorized as rejection, RHCV, FCH, and stable based on histology and clinical information. FCH was found to have a higher fibrosis stage overall when compared to most diagnostic groups, regardless of the staging system used. Additionally, sinusoidal fibrosis was significantly higher in the FCH diagnosis group. Cholestasis was more prominent in biopsies of FCH in all comparisons. In conclusion, the presence of cholestasis and fibrosis with mild to moderate RHCV should raise the suspicion of FCH. When studying the evolution of these cases, the first abnormality to appear is RHCV and cholestasis, fibrosis develops soon after, and both continue to worsen until the point of allograft failure or patient death. Liver Transpl 13: 219-226, 2007.

Fibrosing Cholestatic Hepatitis in HIV/HCV Co-Infected Transplant Patients—Usefulness of Early Markers After Liver Transplantation

“…Cholestasis and tissue changes due to cholestasis, that is, hepatocellular bile pigment, canalicular bile plugs, kupffer cell bile pigment and/or portal tract features such as bile ductular proliferation or inspissated bile in bile ductules, were also noted. In addition, cholestasis and sinusoidal fibrosis were also semi-quantified according to the scoring systems as previously described by Dixon et al (18).…”

“…The mean age of these predominantly male patients (82%) at LT was 44 years [range: 29-63]; three patients had a previous history of alcohol abuse and one patient suffered from hepatopulmonary syndrome. The principal indication for LT was hepatic insufficiency (Child C = 10 patients) with a mean MELD score of 17.5 [range: [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] except for the patient with hepatopulmonary syndrome who was Child A and had a MELD score of nine at the time of LT. As shown in Table 3, there were no differences in terms of the severity of liver disease (MELD score), virological characteristics (genotype 1 frequency, HCV viral load), CD4 cell count and donor age. Interestingly, in the FCH group, we observed a higher level of HLA-A, B, DR matching (≥2) and acute rejection episodes (54% vs. 35%; p = 0.3) but no more requirement for steroid boluses (36% vs. 33%; p = 1).…”

“…All patients with FCH were treated with anti-HCV therapy, Pegylated Interferon and Ribavirin within a mean period of 7.8 months [range: [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] post-LT. Anti-HCV therapy was .77 log 10 IU/mL ± 1.17 and 6.14 log 10 IU/mL ± 1.95 in the non-FCH and FCH groups, respectively, (p = 0.08). introduced because of the presence of severe acute hepatitis in one patient and at the time of FCH diagnosis in 10 patients (Table 5).…”

Practical Management of Boceprevir and Immunosuppressive Therapy in Liver Transplant Recipients with Hepatitis C Virus Recurrence

“…Progression from decompensation to death is also accelerated after LT, with a 3-year survival rate of Ͻ10% following the onset of HCV-related allograft failure (4). Few patients (Ͻ5%) experience cholestatic hepatitis, but their prognosis is the poorest (7). To prevent or to treat these occurrences, standard anti-HCV therapy, represented by pegylated interferon and ribavirin, can achieve a sustained virological response (SVR) in 30% of patients, who have a less severe outcome and lower mortality than nonresponders (21).…”

Untitled

“…1,3 It is evident that the occurrence of fibrosing cholestatic hepatitis is underscored by the common thread of severe immunosuppression. It has been believed that uninhibited viral replication in hepatocytes is crucial for the initiation and progression of fibrosing cholestatic hepatitis.…”