Hepatic amyloidosis as cause of severe intrahepatic cholestasis

The liver is frequently involved by amyloidosis, but hyperbilirubinemia and liver failure are uncommon features. A mild elevation of the serum alkaline phosphatase value and, less frequently, hepatomegaly are the most common findings. Usually the patients have no symptoms related with the liver involvement; the clinical manifestation and the long term prognosis depends on the renal and cardiac disease. We report an unusual clinical presentation of primary amyloidosis in a previously asymptomatic 65 years old woman who was admitted to the hospital because of ictericia and ascitis mimicking a drug induced acute hepatic failure.     

Renal amyloidosis as initial clinical manifestation of Crohn's disease

We present a 20-year-old man with oligosymptomatic Crohn's disease of the terminal ileum complicated by chronic renal insufficiency due to secondary amyloidosis. Definitive diagnosis of Crohn's disease was established 7 years after the onset of the renal disease as a result of symptoms of intestinal obstruction requiring surgery. The affected colonic segment was removed and histopathological examination of the surgical specimen confirmed the diagnosis of Crohn's disease without identifying intestinal amyloidosis. Despite the surgical intervention and the absence of recurrence of inflammatory bowel disease, renal insufficiency steadily progressed, and the patient required kidney transplantation. The patient's subsequent course was excellent and no recurrence of intestinal or renal disease was observed after 8 years of follow-up.     

Severe intrahepatic cholestasis,erythrocytosis and hypoglycemia: Unusual presenting features of systemic AL amyloidosis

We report the case of a 68-year-old African woman who presented with jaundice, hepatomegaly and anasarca. Clinical investigation disclosed severe intrahepatic cholestasis, nephrotic syndrome, erythrocytosis and hypoglycemia. Diagnosis of systemic AL amyloidosis was established by percutaneous liver biopsy. Bone marrow biopsy showed 32% of myeloma cells. The patient started treatment with melphalan and prednisolone, but liver function deteriorated and she died in hepatic failure complicated by septic shock three weeks after the diagnosis. We present possible explanations for the unusual clinical and laboratory findings, which required a multidisciplinary approach and posed challenging problems in differential diagnosis and management.     

Severe intrahepatic cholestasis, erythrocytosis and hypoglycemia: unusual presenting features of systemic AL amyloidosis

We report the case of a 68-year-old African woman who presented with jaundice, hepatomegaly and anasarca. Clinical investigation disclosed severe intrahepatic cholestasis, nephrotic syndrome, erythrocytosis and hypoglycemia. Diagnosis of systemic AL amyloidosis was established by percutaneous liver biopsy. Bone marrow biopsy showed 32% of myeloma cells. The patient started treatment with melphalan and prednisolone, but liver function deteriorated and she died in hepatic failure complicated by septic shock three weeks after the diagnosis. We present possible explanations for the unusual clinical and laboratory findings, which required a multidisciplinary approach and posed challenging problems in differential diagnosis and management.     

Primary amyloidosis presenting as “sicca complex” and severe intrahepatic cholestasis

An elderly man presented with the sicca complex of dry eyes with xerostomia and severe intrahepatic cholestasis simulating bile duct obstruction. No evidence of an underlying connective tissue disorder, chronic illness, scurvy or myeloma was found. Postmortem examination disclosed generalized amyloidosis with extensive involvement of the salivary glands and liver. This unusual combination of rare manifestations of primary amyloidosis once again emphasizes the multiple clinical guises of the disease.     

Portal hypertension and intrahepatic cholestasis in hepatic amyloidosis

Despite the fact that hepatic involvement is frequently seen in systemic amyloidosis, major clinical symptoms or impaired hepatic functional capacity are rare. We describe a patient with primary hepatic amyloidosis, severe intrahepatic cholestasis and portal hypertension, a combination previously reported only three times in the literature. In case of an unexplained intrahepatic cholestasis or portal hypertension the possibility of amyloidosis should be considered and a Congo red staining should be performed.     

Severe heart failure from light chain cardiomyopathy (cardiac amyloidosis)

Primary (AL)amyloidosis is characterized by clonal production of immunoglobulin with subsequent deposition in several organs. We describe the clinical features of a 66-year old female who was referred to our department for congestive heart failure. One year before, she was examined and found to have diastolic dysfunction of the left ventricle. We could evaluate the diagnosis of primary amyloid cardiomyopathy by echocardiography, Doppler echocardiography and laboratory findings and confirmed the diagnosis by biopsy of the rectum mucosa. Clinical outcome was poor, because therapy is poor.     

Severe intrahepatic cholestasis in primary amyloidosis: a report of four cases and a review of the literature.

Liver involvement occurs frequently in patients with systemic amyloidosis, but jaundice is rare. The clinical and histopathologic features are described in four of 78 patients (5.3 per cent) with primary amyloidosis in whom severe intrahepatic cholestasis developed. The data on an additional eight patients recorded in the literature were reviewed. Criteria for inclusion were a tissue diagnosis of amyloidosis, a serum bilirubin level greater than 5 mg/100 ml, histopathologic evidence for cholestasis and no extrahepatic biliary obstruction. Hepatomegaly was present in 12 patients (100 per cent), ascites in nine (75 per cent) and pruritus in eight (67 per cent). The serum bilirubin ranged from 9 to 44 mg/100 ml, the serum alkaline phosphatase was markedly increased in 10 patients (83 per cent) and hypercholesterolemia occurred in seven (58 per cent). Microscopic examination of the liver revealed diffuse amyloid deposition and compression atrophy in 12 patients (100 per cent). The amyloid was prominent in the periportal regions, and some sparing of the centrilobular areas was observed. Bile thrombi and bilirubin staining of hepatocytes were predominantly in the centrilobular zones. Liver cell necrosis, fibrosis or nodularity was uncommon.The pathogenesis of intrahepatic cholestasis in these patients is probably related to the deposition of amyloid in a manner that interferes with the passage of bile from the canaliculi and/or the small intrahepatic bile ducts to the septal bile ducts. Obstructive jaundice carries a poor prognosis. Nine of 12 patients (75 per cent) died of renal failure three weeks to two months after the onset of jaundice. Amyloidosis should be considered in the patient with unexplained intrahepatic cholestasis, and liver tissue should be stained with Congo red and viewed under polarized microscopy.     

Severe hypercalcemia as an initial presenting manifestation of hepatocellular carcinoma.

An 80-year-old white woman who presented with fatigue, weakness, weight loss, constipation and polydipsia is reported. The patient was given a diagnosis of severe hypercalcemia and was subsequently found to have clinical, roentgenographic and pathological evidence of hepatocellular carcinoma. Further studies revealed a low parathyroid hormone level, excluding the possibility of primary hyperparathyroidism, and a negative bone survey, precluding metastatic bone disease. The patient's hypercalcemia was believed to emanate from the humoral secretion of a parathyroid hormone-related peptide, which was found to be elevated, and was abated with conservative management while her cancer was being treated with chemotherapy. The details of this rarely documented presentation, which can easily be mistaken for hepatic encephalopathy, are provided.     

遗传性球形红细胞增多症合并重度肝内胆汁淤积和继发性血色病

一、病例资料 病例1:男性患者,23岁.主因眼黄16年,加重伴皮肤黄染1月余于2008年6月27日10:00入院.患者缘于16年前无明显诱因出现眼黄,无恶心、呕吐、腹胀、腹泻、于当地医院查肝功能异常,应用保肝药物1个月后停药.     

A complete atrioventricular block and polymorphic ventricular tachycardia as the initial manifestation of secondary amyloidosis

Cardiac injury is a frequent characteristic in primary, senile and myeloma related amyloidosis, but it is unusual in secondary amyloidosis. We report a patient with complete atrioventricular block and polymorphic ventricular tachycardia as the initial manifestation of secondary amyloidosis. Necropsy demonstrated amyloidosis deposits in the specific conduction system.     

Familial cholestasis: progressive familial intrahepatic cholestasis, benign recurrent intrahepatic cholestasis and intrahepatic cholestasis of pregnancy

Progressive familial intrahepatic cholestasis (PFIC) type 1, 2 and 3 are due to mutations in ATP8B1, ABCB11 and ABCB4, respectively. Each of these genes encodes a hepatocanalicular transporter, which is essential for the proper formation of bile. Mutations in ABCB4 can result in progressive cholestatic disease, while mutations in ATP8B1 and ABCB11 can result both in episodic cholestasis, referred to as benign recurrent intrahepatic cholestasis (BRIC) type 1 and 2, as well as in progressive cholestatic disease. This suggests a clinical continuum and these diseases are therefore preferably referred to as ATP8B1 deficiency and ABCB11 deficiency. Similarly PFIC type 3 is designated as ABCB4 deficiency. Heterozygous mutations in each of these transporters can also be associated with intrahepatic cholestasis of pregnancy. This review summarizes the pathophysiology, clinical features and current as well as future therapeutic options for progressive familial- and benign recurrent intrahepatic cholestasis as well as intrahepatic cholestasis of pregnancy.     

Benign recurrent intrahepatic cholestasis: late initial diagnosis in adulthood

Benign recurrent intrahepatic cholestasis (BRIC) is a rare autosomal recessive or sporadic disorder, characterized by recurrent episodes of intense pruritus and jaundice that resolve spontaneously without leaving considerable liver damage. The attacks can start at any age, but the first attack is usually seen before the second decade of life. We report the case of a young adult male patient with BRIC who presented with recurrent cholestatic jaundice and pruritus with negative work up for all possible etiologies and a liver biopsy consistent with intrahepatic cholestasis. He improved on treatment with rifampicin and has not suffered another attack on follow up. Although in adulthood, BRIC diagnosis should be kept in mind in patients with recurrent cholestatic attacks with symptom free intervals after main bile duct obstruction and other congenital or acquired causes of intrahepatic cholestasis excluded.     

Update on treatment of light chain amyloidosis

Light chain amyloidosis is the most common type of amyloidosis as a consequence of protein misfolding of aggregates composed of amyloid fibrils. The clinical features are dependent on the organs involved, typically cardiac, renal, hepatic, peripheral and autonomic neuropathy and soft tissue. A tissue biopsy or fat aspirate is needed to confirm the presence/type of amyloid and prognostic tools are important in a risk stratified approach to treatment. Autologous stem cell transplant eligibility should be assessed at baseline, weighing the reversible or non-reversible contraindications, toxicity of treatment and chemotherapy alternatives available. Chemotherapy options include melphalan, thalidomide, bortezomib, lenalidomide, bendamustine in combination with dexamethasone. Many studies have explored these treatment modalities, with ongoing debate about the optimal first line and sequential treatment thereafter. Attaining a very good partial response or better is the treatment goal coupled with early assessment central to optimizing treatment. One major challenge remains increasing the awareness of this disease, frequently diagnosed late as the presenting symptoms mimic many other medical conditions. This review focuses on the treatments for light chain amyloidosis, how these treatments have evolved over the years, improved patient risk stratification, toxicities encountered and future directions.