**6. Management of liver sarcoidosis**

Guidelines for the management of sarcoidosis are relatively old and have little approach to the possibility of liver sarcoidosis [53]. Staging of sarcoidosis takes into account the pulmonary and mediastinal lymph node involvement, without considering systemic disease. Recommendations for monitoring are as follows:


Mild disease (including skin lesions, uveitis and respiratory symptoms) may be managed with topical steroids. Systemic or progressive disease can be managed with systemic corticotherapy, and if necessary cytotoxic therapy or antimalaric agents. Cardiac or neurologic involvement, hypercalcemia and ocular disease not responsive to topic therapy are clear indications for systemic therapy. Regarding pulmonary disease, the consensus is that progressive pulmonary infiltrates or progressive decrease in pulmonary function may require medical therapy. Recent reviews [5, 54] support the idea of initiating therapy in the case of systemic disease with potential of progression to permanent organ damage or life-threatening conditions (such as arrhythmias).

**133**

**Table 2.**

Mycophenolate mofetil

*Treatment options for liver sarcoidosis.*

*Particularities of Hepatic Sarcoidosis*

sis and portal hypertension [19].

**Drug Dosage Time to** 

Cyclosporine 20–200 mg/day Mean treatment

250 mg/m2

1 g/m2

up to

UDCA is 13–15 mg/kg.

sarcoidosis.

sarcoidosis.

*DOI: http://dx.doi.org/10.5772/intechopen.90694*

megaly falls under this category [55].

complications, medical treatment is required.

Data for the management of liver sarcoidosis is gathered from small trials and

• In patients with asymptomatic liver disease or mildly elevated liver enzymes without cholestasis, observation is required. Incidentally discovered hepato-

• In patients with symptomatic liver disease, cholestasis or risk for hepatic

The first line of treatment includes steroids and ursodeoxycholic acid (UDCA). Alternatively, azathioprine, methotrexate, glutathione, cyclosporine, cyclophosphamide, thalidomide and infliximab have been studied in the management of liver

The beneficial effect of corticosteroids is based on their ability to suppress the inflammatory response, thus decreasing the number of liver granulomas and the liver size, as well as ameliorating constitutional symptoms. Low-dose prednisone (10–20 mg/day) is recommended for patients with mild disease, while higher doses can be required in patients with severe symptoms. Treatment duration varies according to clinical and laboratory response, with up to 1 year of treatment before tapering the doses [56]. However, steroids have not proven beneficial for asymptomatic patients or patients with advanced stages of liver disease, including cirrho-

UDCA has proven effective especially in patients with liver sarcoidosis manifested by pruritus. Recent trials has also proven its effect on delaying disease progression. One study has even proved that UDCA is superior to prednisone in improving cytolysis syndrome, pruritus and fatigue [57]. The usual daily dose of

**Table 2** summarizes case reports with unusual treatment and evolution of liver

**improvement**

Azathioprine 50–150 mg/kg 8 weeks 4 patients [23]

Leflunomide 20 mg/day 6 months 1 patient [60]

duration 4 years

Infliximab 3 mg/kg at 8 weeks 6 weeks A patient with cirrhosis,

Methotrexate 10–15 mg/week 6 months 2 patients, with

Thalidomide 100–200 mg/kg 7–12 months 3 patients with

**Remarks Reference**

[58]

[59]

[61]

[62]

[30]

portal hypertension and refractory ascites

improvement in liver function tests

9 patients after liver transplantation for sarcoidosis

concomitant skin lesions

onset adult sarcoidosis

1 month 1 patient with pediatric-

case reports. The following recommendations may be followed:

*Sarcoidosis and Granulomatosis - Diagnosis and Management*

**6. Management of liver sarcoidosis**

*in the same patient demonstrating hepatosplenomegaly (B).*

**Figure 6.**

signal intensity [50]. However, cases have been described where masses with T2 hyperintensity have proven to be liver sarcoidosis in histology examination [51]. Nodules located in the hilar area need to be differentiated from cholangiocarcinomas. In cases thus located or in the case of hilum adenopathies and subsequent stenosis of biliary ducts, magnetic resonance cholangiopancreatography may reveal the stenosis with dilatation of intrahepatic bile ducts, similar to that in a Klatskin tumor [52]. In this case, the positive diagnosis is set by biopsy, usually obtained by ERCP.

*MRI in a patient with liver and splenic sarcoidosis demonstrating hypoattenuation of splenic lesions (A). MRI* 

Guidelines for the management of sarcoidosis are relatively old and have little approach to the possibility of liver sarcoidosis [53]. Staging of sarcoidosis takes into account the pulmonary and mediastinal lymph node involvement, without consid-

• Surveillance for 2 years to determine the need for systemic therapy (taking into

• Therapy should be initiated in patients with severe, active or progressive disease.

• Patients with remission after corticoid therapy should be more closely monitored as the relapse rate is higher than in patients with spontaneous remission.

Mild disease (including skin lesions, uveitis and respiratory symptoms) may be managed with topical steroids. Systemic or progressive disease can be managed with systemic corticotherapy, and if necessary cytotoxic therapy or antimalaric agents. Cardiac or neurologic involvement, hypercalcemia and ocular disease not responsive to topic therapy are clear indications for systemic therapy. Regarding pulmonary disease, the consensus is that progressive pulmonary infiltrates or progressive decrease in pulmonary function may require medical therapy. Recent reviews [5, 54] support the idea of initiating therapy in the case of systemic disease with potential of progression to permanent organ damage or life-threatening condi-

ering systemic disease. Recommendations for monitoring are as follows:

account the fact that many patients present spontaneous remission).

**132**

tions (such as arrhythmias).

Data for the management of liver sarcoidosis is gathered from small trials and case reports. The following recommendations may be followed:


The first line of treatment includes steroids and ursodeoxycholic acid (UDCA). Alternatively, azathioprine, methotrexate, glutathione, cyclosporine, cyclophosphamide, thalidomide and infliximab have been studied in the management of liver sarcoidosis.

The beneficial effect of corticosteroids is based on their ability to suppress the inflammatory response, thus decreasing the number of liver granulomas and the liver size, as well as ameliorating constitutional symptoms. Low-dose prednisone (10–20 mg/day) is recommended for patients with mild disease, while higher doses can be required in patients with severe symptoms. Treatment duration varies according to clinical and laboratory response, with up to 1 year of treatment before tapering the doses [56]. However, steroids have not proven beneficial for asymptomatic patients or patients with advanced stages of liver disease, including cirrhosis and portal hypertension [19].

UDCA has proven effective especially in patients with liver sarcoidosis manifested by pruritus. Recent trials has also proven its effect on delaying disease progression. One study has even proved that UDCA is superior to prednisone in improving cytolysis syndrome, pruritus and fatigue [57]. The usual daily dose of UDCA is 13–15 mg/kg.

**Table 2** summarizes case reports with unusual treatment and evolution of liver sarcoidosis.


#### **Table 2.**

*Treatment options for liver sarcoidosis.*

Nevertheless, it is essential to remember standard treatment measures in patients with advanced liver disease [19]. These patients may benefit from liver transplantation, with 60% survival at 5 years [63]. Careful monitoring is required as reports of sarcoidosis recurrence after transplantation have emerged.
