UNASSIGNED: Hepatic sarcoidosis is an uncommon clinical condition in which clear recommendations are lacking in its treatment. We aimed to review systematically the literature on hepatic sarcoidosis treatment to guide clinicians.
UNASSIGNED: Using MEDLINE, PubMed, CINAHL, Cochrane Library, and Google Scholar databases, we searched original articles on clinical studies reporting the outcome of adult hepatic sarcoidosis patients following treatment with various pharmacological agents. The primary end point was focused on assessing symptomatic relief and biochemical improvement posttreatment.
UNASSIGNED: Out of 614 retrieved references, 34 published studies were eligible, providing data for a total of 268 patients with hepatic sarcoidosis. First-line therapy with corticosteroids alone was reported in 187 patients, whilst ursodeoxycholic acid (UDCA) was used in 40 patients. Symptomatic and biochemical responses were reported among 113(60.4%) and 80(42.8%) cases of corticosteroids respectively, whereas UDCA showed a complete response in 23(57.5%) patients. Second-line therapy was used in steroid-refractory cases, with most cases being reported for azathioprine (n = 32) and methotrexate (n = 28). Notably, 15(46.9%) and 11(39.2%) patients showed both clinical and biochemical responses respectively. Biological therapy including anti-tumor necrosis factor (anti-TNF) was used as third line therapy in twelve cases with a 72.7% symptomatic and biochemical response rate each.
UNASSIGNED: The quality of evidence for the treatment of hepatic sarcoidosis was poor. Nevertheless, it appears that corticosteroid or UDCA may be utilized as first-line therapy. For cases that are refractory to corticosteroids, steroid-sparing immunosuppressive agents and anti-TNF have shown some promising results, but further high-quality studies are required.

Non-neoplastic tumor-like conditions of the liver can appear similar to hepatic neoplasms. In many cases, a biopsy is required to confirm the pathology. However, several tumor-like conditions can be correctly diagnosed or suggested prospectively, thus saving patients from unnecessary anxiety and expense. In this image-focused review, we present the ultrasound, computed tomography, magnetic resonance imaging, and positron emission tomography scan features of eight such entities. Clues that indicate the correct pathology are discussed, and the usual clinical setting is described. Many of these lesions are treated differently from true neoplasms, and the current treatment plan is discussed in many of the cases presented. After reviewing this article, the reader will have a better understanding of these lesions and the situations in which they should be included in the differential diagnosis.

In certain cases, it is difficult to distinguish hepatic sarcoidosis from malignant lymphoma or drug-induced liver injury and to select the proper treatment for this condition. The present study describes the case of a female patient in her 30s who was referred to the hospital due to fever, arthralgia, myalgia and abnormal liver function test results for 4 months. A laboratory examination revealed elevated levels of serum angiotensin-converting enzyme (ACE) and soluble interleukin-2 receptor (sIL-2R), as well as an increase in serum hepatic and biliary tract enzymes. Gallium scintigraphy revealed a marked uptake in the liver, as well as an uptake in the mediastinal, inguinal and external iliac lymph nodes. Magnetic resonance imaging revealed extensive hepatosplenomegaly with multiple non-enhancing splenic nodules. Hepatic sarcoidosis was diagnosed by a liver biopsy as non-caseating hepatic granulomas, and multinucleated giant cells were observed. The patient responded to treatment with 20 mg prednisolone daily, and exhibited an improvement in her symptoms. An improvement was also observed in her serum levels of ACE, sIL-2R, and serum hepatic and biliary tract enzymes; decreased gallium uptake in the liver was also observed. On the whole, the present case report reconfirms that liver biopsy is a useful diagnostic tool for hepatic sarcoidosis.

A 50-year-old female who presented to our hospital for recurrent diarrhea was found to have worsening aminotransferase and alkaline phosphatase levels. Workup revealed lymphadenopathy and hepatomegaly prompting a biopsy of the liver and axillary lymph node, confirming a diagnosis of hepatic sarcoidosis. Our patient later developed cutaneous sarcoidosis. She is currently asymptomatic and is followed by gastroenterology, pulmonary, and dermatology. Recognition of extrapulmonary manifestations of sarcoidosis is important for proper management of patients. Treatment often requires a multidisciplinary approach when more than one organ system is involved.

We report the case of a 48-year-old male with a history of pulmonary and ocular sarcoidosis. Non-caseating granulomas, identified histologically, are the most characteristic manifestation of sarcoidosis. Hepatic sarcoidosis is difficult to diagnose using radiological imaging. In the patient reported in this study, ultrasound and contrast-enhanced computed tomography scans identified multiple intra-abdominal lymphadenopathies, with evidence of liver and splenic infiltrations. The first liver biopsy revealed non-caseating granulomatous hepatitis consistent with hepatic sarcoidosis. The patient was treated with ursodeoxycholic acid (UDCA), but his laboratory parameters did not improve. Prednisone was initiated at a dose of 30 mg daily and slowly tapered. At a dose of 12.5 mg daily, marked improvements in the fibrotic and sarcoid-like lesions were noted at the second biopsy. A third biopsy was performed, with the patient on a prednisone taper of 5 mg/day showed mild fibrous expansion in the portal tracts and mild parenchymal necro-inflammatory lesions. However, overall, fibrosis marker levels remained stable over the course of treatment. A fourth biopsy was performed after a 5-year course of 5 mg/day prednisone. This revealed minimal lobular inflammation without fibrosis. Thus, treatment of this patient with corticosteroids and UDCA resulted in marked improvements in his biochemical and histological parameters.

Sarcoidosis is a multisystemic disease of unknown etiology that can involve lungs, abdominal organs, and lymph nodes. The incidence of sarcoidosis is highest between the ages of 20 and 40 years, and it affects both sexes equally. The most frequent localization is in the lungs, and about half of the affected patients are generally asymptomatic but can involve in small percentages of various other parts such as the biliary tract, pancreas, stomach, and urinary tract. Hepatic and splenic localization is infrequent, and lesions are often mistaken for metastases due to their morphologic similarity. The histological lesion of sarcoidosis is a noncaseous granuloma always associated with high levels of angiotensin-converting enzyme, hypercalcemia, hypercalciuria, and, in a significant percentage of cases (35%-40%), liver enzyme alteration. The pathological evolution of granulomas is fibrosis, and the most severe cases of hepatic sarcoidosis can develop into cirrhosis or portal hypertension. Imaging is essential for lesion localization and is represented by ultrasound, computed tomography (CT), magnetic resonance imaging, and positron emission tomography/CT. The differential diagnosis is very difficult and is almost always histological. We describe a case of hepatic sarcoidosis in an asymptomatic patient with elevated liver enzymes.

UNASSIGNED: Sarcoidosis is a systemic granulomatosis of unknown etiology, characterized by the presence of immune granulomas. Liver damage is a relatively common extra-pulmonary manifestation, occurring in 3.6-30% of cases. Some patients can develop symptomatic portal hypertension (PH). Few series have evaluated the prognosis of symptomatic PH as well as the efficacy and safety of specific treatment on this complication.
UNASSIGNED: This is a multicenter retrospective study of cases of histologically proven hepatic sarcoidosis with symptomatic PH (ascites, digestive hemorrhage) and/or hepatic encephalopathy. Demographic characteristics, comorbidities, clinical manifestations of sarcoidosis, biological data, imaging study of the liver, treatment, and clinical outcomes were collected.
UNASSIGNED: Twelve patients were identified, with a mean follow-up of 140 months. The M/F ratio was 1 and Caucasian origin was the most represented (75%). Seven patients presented with hepatic comorbidities: metabolic syndrome, chronic alcoholism or chronic viral hepatitis. Apart from hepatic involvement, mediastino-pulmonary involvement was the most common followed by osteoarticular and skin. Liver damage was inaugural in two thirds of cases. Nine patients developed ascites, six presented esophageal varices complicated by gastrointestinal bleeding. Three patients presented with both ascites and variceal bleeding. One case of hepatic encephalopathy was observed. Five patients presented signs of hepatocellular insufficiency during follow-up, of whom three had hepatic comorbidities. Eight out of 12 patients required second-line treatment after failure of corticosteroids, three patients underwent ligation of esophageal varices but with recurrent digestive bleeding in all cases. Two patients benefited from a transjugular intrahepatic portosystemic shunt (TIPS), also with poor result. At the end of follow-up, five patients were alive and seven patients died. Two patients received a liver transplant, with good result and without recurrence of sarcoidosis on the transplant thereafter. Two patients had quiet sarcoidosis on low dose of corticosteroids and one patient was lost to follow-up.
UNASSIGNED: Symptomatic PH related to hepatic sarcoidosis is a severe complication, with high morbidity and mortality, and frequent failure of specific treatments of PH. Early management of these patients, with detection of hepatic comorbidities seems important. In case of therapeutic failure, liver transplantation is an option to consider.

Hepatic granulomas can have various causes and their detection requires a systematic diagnostic evaluation. First, identification of risk factors for granulomatous diseases and the exclusion of extrahepatic organ manifestation are necessary. Laboratory investigations and serological screening for the most common underlying diseases of liver granulomas in Germany, such as primary biliary cholangitis (PBC), sarcoidosis and infectious causes (primarily tuberculosis and hepatitis C infections), are recommended. A liver biopsy is essential for confirming the diagnosis, whereby a minilaparoscopically guided tissue sampling offers many advantages, such as the macroscopic detection of granulomas on the liver surface, on the peritoneum or on the spleen. Whether the detection of hepatic granulomas results in a therapeutic consequence, depends decisively on the underlying primary disease. If hepatic granulomas are present without concomitant liver parenchymal damage or other manifestations that would make treatment necessary, a watch and wait approach under close clinical and laboratory monitoring is sufficient. If liver values increase or in cases of hepatic parenchymal damage, urgent treatment of the underlying disease is indicated.
UNASSIGNED: Hepatische Granulome können diverse Ursachen haben und bedürfen einer systematischen Diagnostik. Zunächst müssen Risikofaktoren für die verschiedenen granulomatösen Erkrankungen erfragt und extrahepatische Organmanifestationen abgeklärt werden. Es empfiehlt sich ein laborchemisches und serologisches Screening auf die häufigsten zugrunde liegenden Erkrankungen von Lebergranulomen in Deutschland wie die primär biliäre Cholangitis (PBC), die Sarkoidose und infektiöse Ursachen (vorrangig Tuberkulose und Hepatitis-C-Infektionen). Essenziell für die Diagnosesicherung ist die Leberbiopsie, wobei die minilaparoskopisch gesteuerte Materialgewinnung viele Vorteile wie Detektion von Granulomen auf der Leberoberfläche, am Peritoneum oder auf der Milz bietet. Ob sich aus dem Nachweis hepatischer Granulome eine therapeutische Konsequenz ergibt, hängt dabei entscheidend von der zugrunde liegenden Erkrankung ab. Liegen hepatische Granulome ohne begleitenden Leberparenchymschaden oder anderweitige Manifestationen vor, die eine Therapie notwendig machen, ist unter engmaschiger klinischer und laborchemischer Verlaufskontrolle ein abwartendes Verhalten vertretbar. Bei steigenden Leberwerten oder Hinweisen für einen Leberparenchymschaden ist eine Therapie der zugrunde liegenden Erkrankung dringend indiziert.

Hepatic involvement of sarcoidosis is usually hard to detect on radiological imaging. We present a case of a 60-year-old female with symptoms of pulmonary sarcoidosis. Subsequent imaging work-up showed diffuse hepatic granulomas consistent with abdominal involvement of sarcoidosis. A literature review regarding hepatic sarcoidosis is provided and radiological appearances as well as considerations for differential diagnosis are described.

OBJECTIVE: Clinical manifestation of hepatic involvement in sarcoidosis can vary from asymptomatic disease to severe complications such as cirrhosis and portal hypertension. However, data on hepatic sarcoidosis are limited, and evidence-based recommendations are lacking. Our study aimed to assess the features and clinical course of hepatic sarcoidosis in a predominantly Caucasian cohort.
METHODS: We performed a retrospective study including all patients with hepatic sarcoidosis between 2004 and 2020 in 5 German centres. The median follow-up time was 36 months (range 0.0-195). Data on demographic parameters, clinical manifestations, diagnostic test results, treatment, and outcome were collected.
RESULTS: A total of 1,476 patients with sarcoidosis and 62 patients with hepatic involvement (4.2%) were identified. Of the patients, 51.6% were female, and 80.6% were Caucasian. Most patients were asymptomatic and were observed to have a cholestatic pattern of liver enzyme elevations. Cirrhosis was detected in 9 patients (14.5%), of whom 6 developed clinical manifestations of portal hypertension. Fifty-four patients were medically treated, most commonly with glucocorticoids (69.4%) or ursodeoxycholic acid (UDCA) (40.3%). Levels of alkaline phosphatase (ALP) decreased by 60.8% on average from baseline in patients treated with glucocorticoids and by 59.9% in patients treated with UDCA. Seventeen patients received treatment augmentation with a second line agent, of whom 8 patients normalised ALP levels during follow-up. None of the patients underwent liver transplantation or developed hepatocellular carcinoma (HCC). Three of the patients died during follow-up owing to liver-related complications.
CONCLUSIONS: Hepatic involvement in sarcoidosis was found in 4.2% of patients with sarcoidosis and was clinically significant in 14.5% of those. These findings highlight the importance of early identifying, monitoring, and treating hepatic sarcoidosis, given its increased mortality when associated with end-stage liver disease.
BACKGROUND: Clinical diagnostic and surveillance of hepatic involvement in sarcoidosis has not been standardised, and management of hepatic involvement is a clinical challenge, since it remains poorly characterised in many ways. Our results show that one-third of patients with hepatic sarcoidosis presented with clinically significant portal hypertension, 14.5% suffered from cirrhosis, and 3 patients died owing to liver-related complications. Regarding pharmacological treatment options, corticosteroids and UDCA were the medical agents most frequently used, and both of them have been shown to induce biochemical response in the majority of patients. These findings highlight the importance of correctly and early identifying hepatic involvement in sarcoidosis, because of the potentially progressive course of disease.