Sickle cell disease (SCD) is a common hemoglobinopathy which can affect multiple organ systems in the body. Within the digestive tract, the hepatobiliary system is most commonly affected in SCD. The manifestations range from benign hyperbilirubinemia to overt liver failure, with the spectrum of acute clinical presentations often referred to as “sickle cell hepatopathy”. This is an umbrella term referring to liver dysfunction and hyperbilirubinemia due to intrahepatic sickling process during SCD crisis leading to ischemia, sequestration and cholestasis. In this review, we detail the pathophysiology, clinical presentation and biochemical features of various acute and chronic hepatobiliary manifestations of SCD and present and evaluate existing evidence with regards to management of this disease process. We also discuss recent advances and controversies such as the role of liver transplantation in sickle cell hepatopathy and highlight important questions in this field which would require further research. Our aim with this review is to help increase the understanding, aid in early diagnosis and improve management of this important disease process.

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BACKGROUND Sickle cell disease (SCD) is a disorder that results in increased hospitalizations and higher mortality. Advances in management have resulted in increases in life expectancy and led to increasing awareness of sickle cell hepatopathy (SCH). However, its impact in patients on the natural history and outcomes of SCD is not known. Our study aims to describe the prevalence of extreme hyperbilirubinemia (EH), one form of SCH, its effect on morbidity and mortality, and correlations between sickle cell genotype and SCH type. We hypothesize that EH is associated with higher morbidity and mortality. AIM To investigate the effects of EH on morbidity and mortality among patients with SCD. METHODS This retrospective cohort study was performed using a database of patients with SCD treated at Grady Memorial Hospital between May 2004 and January 2017. Patients with EH (defined as total bilirubin above 13.0 mg/dL) were identified. A control group was identified from the same database with patients with total serum bilirubin ≤ 5.0 mg/dL. Electronic medical records were used to extract demographic information, laboratory values, radiology results, current medications, need for transfusions and mortality data. Two samples T -test, chi-squared test and Fisher’s exact test were then used to compare the parameters between the two groups. RESULTS Out of the database, fifty-seven charts were found of patients with bilirubin > 13 mg/dL. Prevalence of severe SCH as defined by EH was 4.8% (57/1172). There were no demographic differences between patients with and without EH. Significant genotypic differences existed between the two groups, with hemoglobin SS SCD being much higher in the EH group ( P < 0.001). Patients with severe EH had a significant elevations in alanine aminotransferase (157.0 ± 266.2 IU/L vs 19.8 ± 21.3 IU/L, P < 0.001), aspartate aminotransferase (256.5 ± 485.9 U/L vs 28.2 ± 14.7 U/L, P < 0.001) and alkaline phosphatase (218.0 ± 176.2 IU/L vs 85.9 ± 68.4 IU/L, P < 0.001). Patients with EH had significantly higher degree of end organ failure measured with quick Sequential Organ Failure Assessment scores (0.42 ± 0.68 vs 0.01 ± 0.12, P < 0.001), increased need for blood products (63% vs 5%, P < 0.001), and exchange transfusions (10.5% vs 1.3%, P = 0.022). CONCLUSION Among patients with SCD, elevated levels of total bilirubin are rare, but indicative of elevated morbidity, mortality, and need for blood transfusions. Large differences in sickle cell genotype also exist, but the significance of this is unknown. ...

INTRODUCTION: Plasma cell infiltration of the liver can be detected in up to 45% of patients with multiple myeloma (MM) at autopsy. However, only a few cases have been reported of plasma cell infiltration of the liver leading to plasmacytoma formation and non-obstructive cholestasis with progression to liver failure. CASE DESCRIPTION/METHODS: A 53-year-old African American male with history of IgG multiple myeloma status post AlloimmuneStem Cell transplant (ASCT) in 2010 was admitted for intermittent epistaxis, hemoptysis and fatigue found to have relapse. Patient was started on salvage therapy with bortezomib, dexamethasone, cyclophosphamide, etoposide and cisplatin (VDCEP). Physical exam revealed an alert and lethargic male in no acute distress but with asterixis. Sclera were icteric. Abdominal exam revealed marked hepatomegaly without tenderness. Laboratory data showed an ALT of 60 IU/L, total bilirubin of 11mg/dL and normal AST and ALP . INR was 3.0, platelets 38 × 103 mcL, Hgb 7.6gm/dL and WBC 1.6 × 103 mcL. Factor VIII activity was 311.1%. Ammonia levels were 67mcmol/L. Imaging with MRI showed an enlarged liver measuring 22.4cm without mass lesions. A transjugular liver biopsy was then performed revealing atypical mononuclear cell infiltration with positive stain for CD138 and MUM1 consistent with patient’s known history of labda-restricted plasma cell neoplasm (Figures 1 and 2). His clinical course deteriorated with worsening total bilirubin, hepatic encephalopathy and coagulopathy consistent with liver dysfunction and acute liver failure. Eventually there was development of multiorgan failure and death. Autopsy confirmed presence of myeloma cells in the liver forming a subcapsular plasmacytoma with associated extensive cholestasis and hepatocyte necrosis. DISCUSSION: Hepatic involvement of multiple myeloma most commonly presents with hepatomegaly and portends poor prognosis. It is important to recognize that patients may present with a cholestatic pattern of liver injury which can lead to severe hepatic dysfunction and liver failure such as the case of our patient. The histological pattern of liver involvement in MM can be in the form of light chain deposition disease, extramedullary plasmacytoma, amyloidosis, or a diffuse infiltrative pattern. Liver biopsy is thus an imperative way of diagnosis particularly to differentiate it from other entities causing similar pattern of injury such as sinusoidal occlusive syndrome or drug induced liver injury.

INTRODUCTION: Pancreatic fistulas to adjacent organs may develop as a result of severe pancreatitis and pancreatic cystic lesions, which can lead to infectious complications. The aim of this case is to recognize pancreaticocolonic fistula (PCF) as an unusual cause of persistent infection such as infective endocarditis (IE). CASE DESCRIPTION/METHODS: 59-year-old male with a history of chronic alcoholic pancreatitis, recurrent mitral valve IE (Proteus, Morganella and Enterococcus species), end stage renal disease, and heart failure (HF) was admitted after a fall. Initial labs showed almost 2 g drop in baseline hemoglobin (9.8 to 8.1 g/dL). Non-contrasted computed tomography (CT) of abdomen to assess for retroperitoneal bleed revealed a 1.3 × 1.6 cm air-filled cavity at the pancreatic tail communicating with the colonic splenic flexure in addition to moderate ascites. Contrasted CT showed similar findings (Figure 1), suggestive of a PCF. Ascites fluid analysis was consistent with a transudative process (attributed to HF) with amylase <10. An endoscopic ultrasound with fine needle aspiration for a pancreatic tail cyst two years prior revealed a hemorrhagic cyst. A colonoscopy two years ago showed 13 polyps up to 1 cm in size with histology consistent with tubular adenomas and tubulovillous adenomas. Given concern for colonic pathology as a nidus of the PCF, a colonoscopy was pursued. This revealed a small fistulous opening (Figure 2) 45 cm from the anal verge, which was closed with a clip. There was no evidence of malignancy. The PCF was thought to be the sequela of recurrent pancreatitis with cyst formation eroding into the colonic wall, resulting in recurrent polymicrobial bacteremia and IE. Endoscopic retrograde cholangiopancreatography (ERCP) with pancreatic sphincterotomy and pancreatic stent placement is planned. Repeat culture data on broad-spectrum antibiotics has remained negative. DISCUSSION: PCF is a rare complication of severe acute necrotizing pancreatitis with a high mortality rate. Surgery is the main treatment modality, but conservative and endoscopic management are alternative options in non-surgical candidates. Our patient was deemed high surgical risk. Conservative management includes nutritional support (preferably enteral), electrolyte repletion, broad-spectrum antibiotics, somatostatin analogues, and percutaneous drainage. Endoscopic treatment with ERCP and subsequent pancreatic sphincterotomy and pancreatic duct stenting lead to fistula closure in many cases.