Indocyanine Green Excretory Defect Research Articles

Genetic alteration of SLCO1B3 defines constitutional indocyanine green excretory defect in patients who underwent hepatectomy.

Constitutional indocyanine green (ICG) excretory defects must be distinguished when assessing liver function. The absence of OATP1B3 expression due to homogenous alterations in the SLCO1B3 gene has been recently reported to induce ICG excretory defects; however, its association with the clinical examinations and the clinical implications of heterogeneous SLCO1B3 gene alteration remain unclear. OATP1B3 expression was evaluated in 49 patients who underwent hepatectomy after evaluation of the ICG retention rate at 15min (ICGR15) and technetium-99 m-galactosyl serum albumin (99mTc-GSA) hepatic scintigraphy. Additionally, alterations in SLCO1B3 were analyzed in patients without OATP1B3 expression. Subsequently, 59 patients who underwent hepatectomy for colorectal liver metastasis (CRLM) were analyzed. Of 49 patients, 6 (12%) had absent OATP1B3 expression. They had significantly higher ICGR15 value (74.7% vs. 23.5%; p<0.0001), better modified albumin-bilirubin (ALBI) grade (≤grade 2A, 100% vs. 42%; p=0.010), more normal 99mTc-GSA hepatic scintigraphy (100% vs. 28%; p=0.0003), and better pathological liver fibrosis (F0-1, 100% vs. 49%; p=0.027) compared to those with OATP1B3 expression. Three available frozen blocks of cases without OATP1B3 expression showed homozygous alterations in SLCO1B3. Of 59 patients with CRLM in normal liver background, five (8.5%) had heterozygous insertion in SLCO1B3, however they had no difference in ICGR15 values or other clinical findings compared to the other patients. Constitutional ICG excretory defects may be defined by the complete absence of OATP1B3 expression. The modified ALBI grade and 99mTc-GSA hepatic scintigraphy were useful for detecting constitutional ICG excretory defects.

Rotor Syndrome: Glucuronidated Bile Acidemia From Defective Reuptake by Hepatocytes.

Organic anion transporting polypeptide (OATP) 1B1 (gene, solute carrier organic anion transporter family member 1B1 [SLCO1B1]) and OATP1B3 (SLCO1B3) serve as transporters for hepatic uptake of important endogenous substances and several commonly prescribed drugs. Inactivation of both proteins together causes Rotor syndrome. How this OATP1B1/1B3 defect disturbs bile acid (BA) metabolism is largely unknown. In this study, we performed detailed BA analysis in 3 patients with genetically diagnosed Rotor syndrome. We found that BAs glucuronidated at the C‐3 position (BA‐3G) accounted for 50% or more of total BAs in these patients. In contrast but similarly to healthy controls, only trace amounts of BA‐3G were detected in patients with constitutional indocyanine green excretory defect (OATP1B3 deficiency) or sodium‐taurocholate cotransporting polypeptide (NTCP; gene, solute carrier family 10 member 1 [SLC10A1]) deficiency. Therefore, substantial amounts of BA‐3G are synthesized in hepatocytes. The cycling pathway of BA‐3G, consisting of excretion from upstream hepatocytes and uptake by downstream hepatocytes by OATP1B1/1B3 may exist to reduce the burden on upstream hepatocytes. Conclusion: Detailed BA analysis revealed glucuronidated bile acidemia in patients with Rotor syndrome. Further exploration of the physiologic role of glucuronidated BAs is necessary.

Expression of OATP1B3 in cases with indocyanine green excretory defect

Expression of OATP1B3 in cases with indocyanine green excretory defect

99mTc-GSA SPECT/CT fusion imaging for hepatectomy candidates with extremely deteriorated ICG value.

The value of indocyanine green (ICG) test is negatively affected in patients with intrahepatic shunt, ICG excretory defect, or jaundice. This study evaluated 99mTc-GSA SPECT/CT fusion imaging for assessing liver function in patients with severely deteriorated ICG values. Thirteen hepatectomy candidates with ICG retention rates over 40% were retrospectively analyzed. The ICG clearance rate (KICG) and estimated KICG obtained by 99mTc-GSA scintigraphy (KGSA) were used to evaluate preoperative whole liver function. Remnant liver function was assessed using the remnant (rem) KICG (= KICG × volumetric rate) and remKGSA (= KGSA × functional rate) indices; hepatectomy was considered unsafe for values < 0.05. The correlations of remKICG and remKGSA with postoperative mortality and morbidity were also investigated. KGSA values were significantly greater than KICG values (median: 0.12 vs. 0.059; p < 0.01); remKGSA values were greater than remKICG values in all patients (median: 0.107 vs. 0.0413; p < 0.01). Hepatectomy was considered unsafe in 70% patients using remKICG, and in none of those using remKGSA; liver failure or postoperative mortality did not occur. 99mTc-GSA SPECT/CT fusion imaging enables more accurate liver function assessment than the ICG test in patients with severely deteriorated ICG values.

Central bisectionectomy for hepatocellular carcinoma in a patient with indocyanine green excretory defect associated with reduced expression of the liver transporter.

BackgroundIndocyanine green (ICG) excretory defect is a dye excretory disorder, and it is characterized by the selective impairment of plasma ICG clearance with normal liver histology. The pathophysiology involves selective loss of active transporters for ICG in the hepatic cell membrane. Several cases of hepatectomy in patients with ICG excretory defect have been reported, but the expression of hepatic transporters involved in ICG excretory defect has not been examined in these cases.Case presentationAn 81-year-old man who was hepatitis B and C virus negative was admitted to our hospital with a diagnosis of HCC. Abdominal computed tomography revealed an 8-cm-diameter tumor in hepatic segments 4 and 8. The retention rate of ICG at 15 min (ICGR15), which has been used to evaluate hepatic functional reserve, was markedly elevated (79.1 %), whereas other liver function test results, were normal. Therefore, we diagnosed the patient with HCC with an ICG excretory defect, and considered major hepatectomy. Central bisectionectomy was performed, and the postoperative course was uneventful. Microscopic examination of the resected specimen showed moderately differentiated HCC. Immunohistochemical staining and polymerase chain reaction analysis of a non-neoplastic site of the resected specimen showed very few expression of the organic anion-transporting polypeptide 1B3 (OATP1B3), which is usually expressed on the basolateral membrane of human hepatocytes and mediates the uptake of ICG.ConclusionsIn this case, we present a case of hepatectomy for HCC in a patient with ICG excretory defect, which may be attributable to a congenital disorder of OATP1B3 expression; however, an ICG excretory defect did not seem to have any effect on the short-term prognosis after hepatectomy.

A case of living donor with Gilbert's syndrome and constitutional indocyanine green excretory defect

A case of living donor with Gilbert's syndrome and constitutional indocyanine green excretory defect

体質性ICG排泄異常症が疑われた肝細胞癌手術症例の4例

他の肝機能検査が正常でありながらインドシアニングリーン15分血中停滞率（indocyanine green retention rate at 15 minutes；以下，ICGR15と略記）のみ異常高値を示す体質性ICG排泄異常症（constitutional ICG excretory defect；以下，CIEDと略記）の疑われる患者に肝細胞癌（hepatocelluar carcinoma；以下，HCCと略記）が発生した場合，術前肝機能評価に難渋する可能性がある．今回，我々はICGR15が高度異常（60%以上）を示すもChild-Pugh grade Aで，術前からCIEDが疑われたHCC手術症例4例を経験した．それぞれICGR15は60.6，72.0，78.8，96.6%であった．全例術後肝不全を起こすことなく経過した．若干の文献的考察を加え報告する．

Hepatectomy in a hepatocellular carcinoma case with Dubin-Johnson syndrome and indocyanine green excretory defect.

A 77-year-old male patient with history of jaundice was referred to our hospital for treatment of hepatocellular carcinoma (HCC). He was found to have Dubin-Johnson syndrome (DJS), a clinical feature of constitutional jaundice with conjugated hyperbilirubinemia, and indocyanine green (ICG) excretory defect, both of which are rare conditions. Total bilirubin was 5.1mg/dl and ICG retention at 15min (ICGR15) (77.1%). Converted ICGR15 from GSA scintigraphy was 15.9%. Resection of the medial segment and ventral region of the anterior segment of the liver as well as cholecystectomy were performed. The background of the liver tissue was blackish yellow and consistent with DJS and chronic hepatitis. Although total bilirubin level increased to 8.2mg/dl on the 2nd postoperative day, the patient ultimately recovered and he was discharged on the 14th day. His 1- and 2-year medical checkups indicated recurrence of HCC. He underwent transarterial chemoembolization and is presently doing well 39months after surgery. We report here on evaluation and treatment of patients with such disorders.

99mTc-DTPA-Galactosyl-Human-Serum-Albumin Liver Scintigraphy for Evaluating Hepatic Functional Reserve Before Hepatectomy in a Patient with Indocyanine Green Excretory Defect: Report of a Case

A 78-year-old woman with indocyanine green (ICG) excretory defect underwent left hepatectomy for cystadenocarcinoma. The retention rate of ICG at 15 min (ICGR(15)) was high, at 79.3%, despite all other liver function tests showing normal values. Conversely, 99mTc-DTPA-galactosyl-human-serum-albumin (GSA) liver scintigraphy showed a reduced accumulation of GSA in the left lateral lobe, the hepatic uptake ratio of the GSA scintigraphy was 0.96, and the arterial ketone body ratio was 1.67. Based on these results, we judged that the hepatic functional reserve of this patient was adequate for left hepatectomy, which was subsequently performed uneventfully. Histopathological examination of the resected liver showed neither fibrosis nor inflammatory cell infiltration. Thus, we consider that GSA liver scintigraphy is the best diagnostic modality for evaluating hepatic functional reserve in a patient with ICG excretory defect.

Hepatic transport of serum bilirubin, bromsulfophthalein, and indocyanine green in patients with congenital non-hemolytic hyperbilirubinemia and patients with constitutional indocyanine green excretory defect.

We carried out a retrospective study of 71 patients with congenital non-hemolytic hyperbilirubinemia who had been treated at our institution over the 25 years from 1965 to 1990. Twenty patients had Gilbert's syndrome, 1 had Crigler-Najjar syndrome, 1 had new type unconjugated hyperbilirubinemia, 21 had Dubin-Johnson syndrome, and 28 had Rotor's syndrome. We also reviewed 20 patients with constitutional indocyanine green (ICG) excretory defect. The study focused on the hepatic transport of serum bilirubin, bromsulfophthalein (BSP), and ICG. In Dubin-Johnson syndrome, a defect appeared in late-stage transport, while uptake and storage capacity were normal. In Rotor's syndrome, defects were found in the early stage, and storage capacity was reduced, while excretion into bile was slightly suppressed. A secondary rise in serum ICG was seen in 5 of the 10 patients with Dubin-Johnson syndrome. The transport defect in Gilbert's syndrome was unclear. It could not be considered to be homogeneous, but it may exist at multiple sites, from the conjugation with serum proteins to excretion into bile. Following phenobarbital administration, the ICG secondary rise in the 5 patients with Dubin-Johnson syndrome disappeared, and ICG was rapidly cleared from blood. However, in patients with Dubin-Johnson syndrome, BSP clearance in serum did not show any change before and after phenobarbital administration. ICG excretion in patients with constitutional ICG excretory defect was due only to the impairment o ICG transport, and the defect was suggested to be hepatic uptake. These results indicate that studies of the hepatic transport of bilirubin, BSP, and ICG are useful for determining the etiological factors involved in congenital hyperbilirubinemia and constitutional ICG excretory defect.

Hepatic transport and metabolism of various organic anions in patients with congenital non-hemolytic hyperbilirubinemia, including constitutional indocyanine green excretory defect.

Hepatic transport and metabolism of various organic anions in patients with congenital non-hemolytic hyperbilirubinemia, including constitutional indocyanine green excretory defect.

Studies on the pathogenesis of the constitutional excretory defect of indocyanine green.

Constitutional excretory defect of indocyanine green (ICG) is characterized by the selective impairment of plasma ICG clearance. We studied binding patterns of ICG to plasma proteins and plasma ICG kinetics in three patients and one relative. Binding patterns of ICG to plasma proteins were modified in subjects with the ICG excretory defect. However, plasma disappearance rates of ICG bound to various protein fractions were not significantly different from each other, except for one case. In the kinetic study of ICG hepatic uptake rates (a values) were decreased, and hepatic reflux rates (b values) were increased in ICG excretory defect and liver cirrhosis. However, a values were unchanged and b values were clearly increased in ICG excretory defect, while a values decreased and changes in b values were slight in liver cirrhosis after loading with a large dose of ICG. These results suggest that active transport of ICG in the hepatic cell membrane is selectively lost in the ICG excretory defect.