Ursodeoxycholic Acid Treatment of Refractory Chronic Graft-versus-Host Disease of the Liver

Fried, R; Murakami, Carol S.; Fisher, Lloyd D.; Willson, Richard A.; Sullivan, Keith M.; McDonald, George B.

doi:10.7326/0003-4819-116-8-624

Cited by 93 publications

(38 citation statements)

References 24 publications

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“…In our series, immunosuppressive therapy led to normalisation of LFTs in all patients with C-GVHC as the only cause of CLD and to improvement in liver dysfunction in patients with multifactorial disease, although most of them required more than one treatment. UDCA, with or without immunosuppression, controlled hepatic C-GVHD, as previously reported by Fried et al, 32 but in contrast to their observations, our patients had a sustained response after cessation of therapy.…”

Section: Discussionsupporting

confidence: 70%

Long-term liver dysfunction after allogeneic bone marrow transplantation: clinical features and course in 61 patients

Tomás

Pinilla

García-Buey

et al. 2000

Bone Marrow Transplant

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Summary:This retrospective study has aimed at determining the prevalence, aetiology and clinical evolution of chronic liver disease (CLD) after allogeneic bone marrow transplantation (BMT). A total of 106 patients who had been transplanted in a single institution and who had survived for at least 2 years after BMT were studied. The prevalence of CLD was 57.5% (61/106). In 47.3% of cases more than one aetiopathogenic agent coexisted. The causes of CLD were iron overload (52.4%), chronic hepatitis C (47.5%), chronic graft-versus-host disease (C-GVHD) (37.7%), hepatitis B (6.5%), non-alcoholic steatohepatitis (NASH) (4.9%), autoimmune hepatitis (AIH) (4.9%) and unknown two (3.3%). Twenty-three patients with iron overload underwent venesections which were well tolerated. An improvement in liver function tests (LFTs) was observed in 21 (91%) patients. All six patients with siderosis as the only cause of CLD normalized LFT as well as three patients with HCV infection. Clinical evolution was satisfactory for patients with GVHD, AIH, NASH and hepatitis B. At the last visit 23 patients continued with abnormal LFTs, and 19 of them were infected by the HCV. A sustained biochemical and virologic response was achieved in only one case out of six patients with CHC who received interferon . We have found that CLD is a common complication in long-term BMT survivors. The aetiology is often multifactorial, iron overload, CHC and C-GVHD being the main causes. The CLD followed a rather 'benign' and slow course in our patients as none of them developed symptoms or signs of liver failure and we did not observe an increase in morbidity or mortality in these patients, but a longer follow-up is necessary in HCV infected patients based on the natural history of this infection in other populations. Bone Marrow Transplantation (2000) Liver disease is a well-known cause of early morbidity and mortality following an allogeneic bone marrow transplantation (BMT) which affects 80% of patients and is responsible for up to 5-10% of toxic-related deaths.

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Section: Discussionsupporting

confidence: 70%

Long-term liver dysfunction after allogeneic bone marrow transplantation: clinical features and course in 61 patients

Tomás

Pinilla

García-Buey

et al. 2000

Bone Marrow Transplant

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“…In primary biliary sclerosis, ursodeoxycholic acid has improved liver function tests but not changed the natural history of the disease. 102 No long-term studies of this drug in chronic GVHD have been reported.…”

Section: Minimize Effects On Target Tissuesmentioning

confidence: 99%

New approaches for preventing and treating chronic graft-versus-host disease

Lee

2005

Blood

127

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Despite improvements in the practice of allogeneic hematopoietic stem cell transplantation (HCT) over the last 25 years, chronic graft-versus-host disease (GVHD) remains a substantial problem with little change in the incidence, morbidity, and mortality of this complication. In fact, with increased use of peripheral blood, transplantation of older patients, and less immediate transplantation-related mortality, the prevalence of chronic GVHD may increase. One of the difficulties in combating chronic GVHD is a lack of understanding about the pathophysiology of the syndrome. IntroductionChronic graft-versus-host disease (GVHD) is the most serious and common long-term complication of allogeneic hematopoietic stem cell transplantation (HCT), occurring in 20% to 70% of people surviving more than 100 days. 1,2 Approximately half of affected people have 3 or more involved organs, and treatment typically requires immunosuppressive medications for a median of 1 to 3 years. Because of higher treatment-related (nonrelapse) mortality, chronic GVHD remains the major cause of late death despite its association with a lower relapse rate. 3,4 In addition, secondary malignancies are more common in people with chronic GVHD, particularly of commonly involved tissues such as mouth and skin, suggesting that chronic inflammation, prolonged exposure to immunosuppressive medications, or immune dysregulation facilitates the development of new cancers. 5 Finally, the functional consequences of chronic GVHD organ involvement are major determinants of the health and quality of life of survivors. 6,7 Despite the well-recognized adverse effects of chronic GVHD on the long-term success of allogeneic transplantation, its pathophysiology is poorly understood, and management strategies beyond systemic corticosteroids have not been established.While there are some lessons that can be translated from basic and clinical studies of acute GVHD, several lines of evidence suggest that chronic GVHD is not simply a continuation of acute GVHD, and that separate approaches will be required for its prevention and management. First, except for T-cell depletion and use of umbilical cord blood, the major innovations that have improved acute GVHD rates do not seem to have affected chronic GVHD incidence. Second, while there is significant overlap between the organs involved in acute and chronic GVHD, the distribution of affected organs in chronic GVHD is much broader. Fully evolved chronic GVHD is largely an inflammatory and fibrotic process, while acute GVHD is more likely to reflect apoptosis and necrosis. Although traditionally the boundary between acute and chronic GVHD has been set at 100 days after transplantation, more recent definitions hinge on different clinical manifestations rather than time of onset. Third, while acute GVHD is highly associated with subsequent chronic GVHD, approximately 25% to 35% of chronic GVHD is de novo without any preceding acute manifestations, while 20% to 30% of people who had acute GVHD do not go on to develop chronic GVH...

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“…In PBC and liver allograft rejection treatment with ursodeoxycholic acid (UDCA) has been shown to delay progression of the disease . It is therefore not surprising that UDCA was tested for treatment of refractory hepatic GVHD in adults after allogeneic BMT (Fried et al, 1992). The additional use of UDCA has not yet been described in SCID.…”

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confidence: 99%

Hepatic GVHD after HLA‐haploidentical bone marrow transplantation in children with severe combined immunodeficiency: the effect of ursodeoxycholic acid

et al. 1997

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We describe two children with a severe combined immune deficiency (SCID) with B cells. Following a T‐cell‐depleted haploidentical bone marrow transplantation (BMT), they both developed a chronic graft‐versus‐host disease (GVHD) of the skin and a severe persisting hyperbilirubinaemia and elevated liver enzymes. The diagnosis of a vanishing bile duct syndrome was confirmed by liver biopsies. Because corticosteroids and cyclosporin A induced only a partial response, ursodeoxycholic acid (UDCA) was added to their treatment schedule. Serum bilirubin and liver enzymes returned to normal within months. A control liver biopsy showed normal and proliferating bile ducts without cholestatic damage. We conclude that UDCA was well tolerated and may be of value as an additional treatment for hepatic GVHD in SCID.

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Ursodeoxycholic Acid Treatment of Refractory Chronic Graft-versus-Host Disease of the Liver

Abstract: Therapy with UDCA was safe, well-tolerated, and efficacious in the short-term treatment of refractory chronic GVHD of the liver. Further investigation is needed to evaluate the long-term effects of UDCA therapy.

Cited by 93 publications

References 24 publications

Long-term liver dysfunction after allogeneic bone marrow transplantation: clinical features and course in 61 patients

Long-term liver dysfunction after allogeneic bone marrow transplantation: clinical features and course in 61 patients

New approaches for preventing and treating chronic graft-versus-host disease

Hepatic GVHD after HLA‐haploidentical bone marrow transplantation in children with severe combined immunodeficiency: the effect of ursodeoxycholic acid

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