Fibrosis progression after liver transplantation in patients with recurrent hepatitis C

Neumann, Ulf; Berg, Thomas; Bahra, Marcus; Seehofer, Daniel; Langrehr, Jan M.; Neuhaus, R.; Radke, Cornelia; Neuhaus, P.

doi:10.1016/j.jhep.2004.06.029

Cited by 329 publications

(284 citation statements)

References 36 publications

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“…There were 25 pressure evaluations (18 patients) that fulfilled our definition of potentially discrepant results with respect to the expected fibrosis stage or HVPG. The median biopsy length of the entire "discrepant" group was 22 mm (range, [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] and the number of fragments was 3.5 (range, 2-8) similar to the population as a whole. In the discrepant group, 56% of biopsies did not show severe nodularity/cirrhosis with 4 (range, 1-9) complete portal tracts and 8 (range, 2-13) partial portal tracts.…”

Section: Total Cohortmentioning

confidence: 85%

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Hepatic venous pressure gradient to assess fibrosis and its progression after liver transplantation for HCV cirrhosis

et al. 2007

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Progression of fibrosis following recurrent hepatitis C virus (HCV) infection is frequent after liver transplantation (LT).Histology remains the gold standard to assess fibrosis, but the value of hepatic venous pressure gradient (HVPG) is being explored. We evaluated patients with recurrent HCV infection after LT to assess whether HVPG correlates with liver histology, particularly fibrosis. A total of 90 consecutive patients underwent 170 HVPG measurements concomitant with transjugular liver biopsy (TJB), with 31.5 (range, 6-156) months of follow up. Median biopsy length was 22 mm and total portal tract count was 12 (complete 6, partial 6). Median HVPG was 4 mmHg: 38% of patients Ն6 mmHg (portal hypertension, PHT), 13% Ն10 mmHg. HVPG correlated with Ishak stage (r ϭ 0.73, P Ͻ 0.001) for mild (0-3) and severe fibrosis (4-6), and grade score (r ϭ 0.47, P Ͻ 0.001), but neither correlated with interval from LT nor biopsy length. HVPG was Ն10 mmHg in 15 patients: 12 had stage 5 or 6, and 3 severe portal expansion. HVPG was repeated in 49, between 7 and 60 months with weak correlation to fibrosis score (r ϭ 0.30, P ϭ 0.045). A total of 12 patients with HVPG Ն6 mmHg had fibrosis score Յ3, while 8 patients had normal HVPG but fibrosis stage Ն4. These discrepancies were mostly associated with specific histological features such as perisinusoidal fibrosis rather than errors in measuring HVPG. In 29 with HVPG Ͻ6 mmHg at 1 yr, none decompensated compared to 4 of 13 (31%) with PHT. In conclusion, HVPG correlates with fibrosis and its progression, due to recurrent HCV infection, assessed in TJB. Liver Transpl 13:1305Transpl 13: -1311Transpl 13: , 2007 The severity of portal hypertension (PHT) correlates with the severity of liver disease and cirrhosis, both functionally and histologically 1 and also with the Model for End-Stage Liver Disease, 2 such that it has independent prognostic value separate from clinical and laboratory assessment. 2,3 Hepatic vein catheterisation 4 was modified by Groszmann et al. 5 using a balloon catheter. The measurement of hepatic venous pressure gradient (HVPG) (the difference between wedge hepatic venous pressure [WHVP] Ϫ free hepatic venous pressure) is reproducible 6 and is the preferred technique for evaluating PHT, correlating 1:1 with the direct measurement of portal vein pressure in patients with sinusoidal and postsinusoidal causes of cirrhosis, 7,8 particularly alcoholic and viral-related cirrhosis. Normally HVPG ranges from 1 to 5 mmHg; pressures Ն6 mmHg indicate PHT. 6 WHVP increases with progression of chronic hepatitis and PHT, before histologically detectable cirrhosis. 9 A gradient Ͼ5 mmHg was always associated with significant changes in liver biopsy in 1 study, although a normal gradient did not completely rule out cirrhosis, 10 suggesting that WHVP could provide supplementary information to liver biopsy, with a higher predictive value for assessing stage and activity of chronic liver disease, than routine biochemical tests. 10 Other studies have correlated HVPG both with severit...

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Section: Total Cohortmentioning

confidence: 85%

“…17 Fibrosis associated with recurrent HCV infection after liver transplantation (LT). [18][19][20] progresses faster to cirrhosis and decompensation compared to the pretransplantation HCV setting. 21 Transjugular liver biopsy (TJB) 22 enables multiple cores of tissue to be obtained 23 and is easily combined with hemodynamic evaluations.…”

mentioning

confidence: 99%

Hepatic venous pressure gradient to assess fibrosis and its progression after liver transplantation for HCV cirrhosis

et al. 2007

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“…Several studies have demonstrated that progression of fibrosis is significantly faster in immunosuppressed than immunocompetent individuals. 4 -6;22-24 For this reason, frequent liver biopsies are part of the routine follow-up of HCV-infected patients after LT. 3,4,8,25,26 Most centers perform liver biopsy by the percutaneous route under ultrasonographic control. Besides the advantages of US (particularly during the first weeks after LT), liver biopsy allows a semiquantitative evaluation of necroinflammatory changes and fibrosis, as well as identification of additional pathological conditions (such as rejection).…”

Section: Discussionmentioning

confidence: 99%

“…Early histological damage after transplantation correlates with long-term outcome; in fact, the presence of significant liver fibrosis in 1-year liver biopsies identifies patients at high risk of graft loss. 3,8 In addition, assessment of liver damage is relevant to adopt therapeutic decisions, particularly because of the low efficacy and high incidence of adverse events of current antiviral therapy in this group of patients. 3,9,10 Sampling variability is a limitation of liver biopsy for the assessment of fibrosis.…”

Section: Hronic Hepatitis C Virus (Hcv) Infection Leadingmentioning

confidence: 99%

Hepatic venous pressure gradient identifies patients at risk of severe hepatitis C recurrence after liver transplantation

et al. 2006

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Liver biopsy is essential in the follow-up of HCV-infected liver transplant recipients. The aim of this study was to prospectively compare percutaneous (PLB) versus transjugular liver biopsy (TLB) in the assessment of liver damage. We also explored the diagnostic value of hepatic venous pressure gradient (HVPG) to identify patients at risk of severe HCV disease recurrence after liver transplantation (LT). One hundred sixteen paired PLB and TLB (with HVPG measurement) were performed 3 or 12 months after LT in 80 patients. Concordance for necroinflammation and fibrosis was fair or good, particularly 1 year after LT (kappa > 0.6). At this point, a significant positive association was seen between the median HVPG and the fibrosis stage C hronic hepatitis C virus (HCV) infection leading to liver cirrhosis and hepatocellular carcinoma is the main indication for liver transplantation (LT) in Western countries and Japan. 1 Regretfully, recurrence of HCV infection is universal after LT, 2 and disease progression is significantly faster in immunosuppressed than in immunocompetent individuals. In liver transplant recipients, chronic HCV infection may lead to cirrhosis in as much as 30% of individuals only 5 years after LT. [3][4][5] Once liver cirrhosis is established, the cumulative probability of developing clinical decompensation is close to 50% 1 year after diagnosis and, more importantly, survival after decompensation is extremely short. 6 As a result of this accelerated course of HCV infection, longterm graft and patient survival are significantly reduced in patients undergoing LT for HCV-related cirrhosis compared with other groups. 7 Frequent liver biopsies are essential to monitor HCV-induced liver damage and are part of the routine follow-up of HCV-infected liver transplant recipients. Early histological damage after transplantation correlates with long-term outcome; in fact, the presence of significant liver fibrosis in 1-year liver biopsies identifies patients at high risk of graft loss. 3,8 In addition, assessment of liver damage is relevant to adopt therapeutic decisions, particularly because of the low efficacy and high incidence of adverse events of current antiviral therapy in this group of patients. 3,9,10

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“…Based on observations up to now, severity and course of recurrent hepatitis C are negatively influenced by a higher viral titre prior to transplantation; repeated intravenous steroid therapy; donors' age exceeding 50 years; steatosis of graft; and higher dosage of postoperative immunosuppressive therapy [10][11][12][13].…”

Section: Factors Influencing Recurrent Hcv Infectionmentioning

confidence: 99%

Treatment of recurrent hepatitis C virus infection in patients after liver transplantation

Lengyel¹,

Tulassay²

2009

Clinical and Experimental Medical Journal

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The main indication for liver transplantation is the final stage of hepatic cirrhosis developed due to hepatitis C virus (HCV) infection. The recurrence of HCV infection after transplantation is a common situation. Recurrent hepatitis C is a progressive disease; in 20% of patients it produces liver cirrhosis without treatment beside immunosuppression within 5 years. Treatment of recurrent HCV infection is the most important factor of survival in patients with transplantation. Based on literary data and their observations, the authors review the factors influencing the progression of recurrent HCV infection. They discuss in details the effect of immunosuppressive therapy, the importance of selecting appropriate immunosuppressive drugs. They review the key points in the diagnosis of recurrent hepatitis C; underline the decisive role of liver biopsy carried out according to protocol in the diagnosis, as well as the hard consultation between specialists of pathology, hepatology and surgery. They demonstrate their observations with the treatment of patients on the waiting list, the results of early pre-emptive treatment of recurrent chronic hepatitis, furthermore treatment modalities and results in patients with histologically proven chronic hepatitis C. The drug of choice for chronic hepatitis C after transplantation is combined therapy with pegylated interferon and ribavirin. This therapy is able to assure sustained virological negativity in 20-50% of patients. In virus-free patients the inflammatory activity in the liver significantly decreases, and the histologic activity index improves. There are data showing a fibrosis-inhibiting effect of the treatment, however, multicentric studies are required for their confirmation. No advantage of early antiviral treatment without histologic alteration has been confirmed by most of the trials. In this group of patients common side effects of the treatment include anaemia and neutropenia, and therefore administration of erythropoietin and granulocyte stimulating factor is recommended. Further research and clinical studies are required in order to establish optimal treatment of patients with recurrent hepatitis C, to determine the dosage of pegylated interferon and ribavirin, to decrease duration of therapy, to reduce side effects and finally to achieve the healing phase in a greater percentage of patients.

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Fibrosis progression after liver transplantation in patients with recurrent hepatitis C

Cited by 329 publications

References 36 publications

Hepatic venous pressure gradient to assess fibrosis and its progression after liver transplantation for HCV cirrhosis

Hepatic venous pressure gradient to assess fibrosis and its progression after liver transplantation for HCV cirrhosis

Hepatic venous pressure gradient identifies patients at risk of severe hepatitis C recurrence after liver transplantation

Treatment of recurrent hepatitis C virus infection in patients after liver transplantation

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