Sinusoidal obstruction syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Husnain Shaukat, M.D [2]

Sinusoidal obstruction syndrome is characterized by tender hepatomegaly, ascites, and weight gain. It is most commonly a complication of hematopoietic cell transplantation (HCT). The incidence and severity of sinusoidal obstruction syndrome depends on the conditioning regimen used and presence of pre-existing liver disease. There is no established system for the classification of sinusoidal obstruction syndrome. However, it can be classified on the basis of severity as mild, moderate and severe. It is thought that pre-existing liver disease increases the risk of developing sinusoidal obstruction syndrome (SOS) due to impairment of drug metabolism which predisposes to the endothelial injury. The deposition of fibrinogen and factor VIII within the sinusoids leads to their dilation and congestion by erythrocytes. The progressive occlusion of venules leads to widespread zonal liver disruption and centrilobular hemorrhagic necrosis. The two established criteria for the clinical diagnosis of sinusoidal obstruction syndrome are Baltimore criteria and modified Seattle criteria. Patients with a mild or moderate form of sinusoidal obstruction syndrome require no specific therapy and can be managed with supportive care alone. If left untreated, the severe form of sinusoidal obstruction syndrome is characterized by high mortality and progression to multiorgan failure. The most accurate method to confirm the diagnosis and evaluate the severity of sinusoidal obstruction syndrome is the measurement of the hepatic venous gradient pressure (HVGP). The patient with suspected sinusoidal obstruction syndrome (SOS) requires the following lab studies: complete blood count, liver function tests, complete metabolic profile and viral hepatitis serologies. A transjugular liver biopsy can be helpful in the diagnosis of sinusoidal obstruction syndrome. Common findings on liver biopsy include sinusoidal dilation and congestion by erythrocytes and thrombi within the terminal hepatic venules. The management of sinusoidal obstruction syndrome depends on the severity of the disease. Supportive care is the mainstay of therapy for mild and moderate sinusoidal obstruction syndrome. The severe form of sinusoidal obstruction syndrome needs defibrotide (thrombolytic agent) along with supportive care. Surgical treatment of sinusoidal obstruction syndrome is reserved for patients who do not respond to supportive treatment or defibrotide. The surgical options include transjugular intrahepatic portosystemic shunt (TIPS) and liver transplantation. Primary preventive measures of sinusoidal obstruction syndrome include minimizing risks related to the transplant process such as the source of the graft (allogeneic greater than autologous), choice of chemotherapy and use of antimicrobials. The exposure to the hepatotoxic agents should be minimized and preexisting liver diseases should be managed. The prophylaxis for graft vs host disease should be considered.

Hepatic veno-occlusive disease or sinusoidal obstruction syndrome was first described in 1905 as endophelibitis of the terminal hepatic veins. Ionizing radiations as a cause of sinusoidal obstruction syndrome was identified in the 1960’s and bone marrow transplant in the 1970’s. However, sinusoidal obstruction syndrome or hepatic veno-occlusive disease was a well-established concept by the mid-1960’s.

There is no established system for the classification of sinusoidal obstruction syndrome. However, it can be classified on the basis of severity as mild, moderate and severe.

The development of sinusoidal obstruction syndrome begins with the injury to hepatic venous endothelium. It is thought that preexisting liver disease increases the risk of developing sinusoidal obstruction syndrome (SOS) due to impairment of drug metabolism which predisposes to the endothelial injury. The endothelial cells in patients with hepatitis may have abnormal expression of adhesion molecules and pro-coagulant factors. The deposition of fibrinogen and factor VIII within the sinusoids leads to their dilation and congestion by erythrocytes. The progressive occlusion of venules leads to widespread zonal liver disruption and centrilobular hemorrhagic necrosis. Hepatic sinusoidal obstruction syndrome (SOS) is mainly seen in patients of hematopoietic cell transplantation.

The most common cause of sinusoidal obstruction syndrome is hematopoietic cell transplantation. Other less common causes include chemotherapeutic agents and pyrrolizidine alkaloids.

The differential diagnosis of sinusoidal obstruction syndrome includes other causes of hepatic failure that may have abnormal liver function tests such as increased conjugated bilirubin and alkaline phosphatase or a clinical presentation as right upper quadrant abdominal pain, jaundice or ascites.

The incidence of sinusoidal obstruction syndrome depends on the presence of risk factors, chemotherapy regimen and the clinical criteria used for the diagnosis. The incidence after allogeneic hematopoietic cell transplant ranges from a low of 10,000 persons per 100,000 persons to a high of 15,000 persons per 100,000 persons. The incidence of sinusoidal obstruction syndrome after autologous hematopoietic cell transplant is below 5,000 persons per 100,000 persons.

Common risk factors in the development of sinusoidal obstruction syndrome are stem cell transplantation, preexisting liver dysfunction and high-dose conditioning regimens.

There is insufficient evidence to recommend routine screening for sinusoidal obstruction syndrome.

Patients with a mild or moderate form of sinusoidal obstruction syndrome require no specific therapy and can be managed with supportive care alone.The mild and moderate form of sinusoidal obstruction syndrome has a good prognosis. If left untreated, the severe form of sinusoidal obstruction syndrome is characterized by high mortality and progression to multiorgan failure.

The two established criteria for the clinical diagnosis of sinusoidal obstruction syndrome are Baltimore criteria and modified Seattle criteria. The most accurate method to confirm the diagnosis and evaluate the severity of sinusoidal obstruction syndrome is the measurement of the hepatic venous gradient pressure (HVGP).

Patients with sinusoidal obstruction syndrome may have a positive history of hematopoietic cell transplantation (HCT) or pre-existing liver disease. Common symptoms of sinusoidal obstruction syndrome include tender hepatomegaly, weight gain and ascites.

Common physical examination findings of sinusoidal obstruction syndrome include abdominal pain or distention, tender hepatomegaly, signs of ascites and jaundice.

The patient with suspected sinusoidal obstruction syndrome (SOS) requires the following lab studies: complete blood count, liver function tests, complete metabolic profile and viral hepatitis serologies.

There are no ECG findings associated with sinusoidal obstruction syndrome.

There are no x-ray findings associated with sinusoidal obstruction syndrome.

CT scan findings suggestive of sinusoidal obstruction syndrome include hepatomegaly, nutmeg liver, portal vein dilatation, ascites.

The MRI contrast studies for sinusoidal obstruction syndrome will show a diffuse hypointense reticular pattern.

Ultrasound can be helpful in the diagnosis of sinusoidal obstruction syndrome. Common findings on ultrasound may include: hepatomegaly, heterogeneous echotexture and abnormal portal vein waveform.

There are no other imaging findings associated with sinusoidal obstruction syndrome.

A transjugular liver biopsy can be helpful in the diagnosis of sinusoidal obstruction syndrome. Common findings on liver biopsy include sinusoidal dilation and congestion by erythrocytes and thrombi within the terminal hepatic venules.

The management of sinusoidal obstruction syndrome depends on the severity of the disease. However, supportive care is the mainstay of therapy for mild and moderate sinusoidal obstruction syndrome. The severe form of sinusoidal obstruction syndrome needs defibrotide (thrombolytic agent) along with supportive care. Patients are advised to avoid supplements and medications that are linked to hepatic injury.

Surgical treatment of sinusoidal obstruction syndrome is reserved for patients who do not respond to supportive treatment or defibrotide. The surgical options include transjugular intrahepatic portosystemic shunt (TIPS) and liver transplantation.

Primary preventive measures of sinusoidal obstruction syndrome include minimizing risks related to the transplant process such as the source of the graft (allogeneic greater than autologous), choice of chemotherapy and use of antimicrobials. The exposure to the hepatotoxic agents should be minimized and preexisting liver diseases should be managed. The prophylaxis for graft vs host disease should be considered.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Husnain Shaukat, M.D [2]

Hepatic veno-occlusive disease or sinusoidal obstruction syndrome was first described in 1905 as endophelibitis of the terminal hepatic veins. Ionizing radiations as a cause of sinusoidal obstruction syndrome was identified in the 1960’s and bone marrow transplant in the 1970’s. However, sinusoidal obstruction syndrome or hepatic veno-occlusive disease was a well-established concept by the mid-1960’s.

• Endophlebitis in the terminal hepatic venule was first described by a pathologist from Prague in 1905.^[1]
• In the 1960s, studies on the effects of hepatic vasculature by ionizing radiations were reported. ^[2][3]
• The concept of sinusoidal obstruction syndrome induced by either chemical or radiation toxicity was well established by mid-1960s as a separate entity from Budd-Chiari syndrome.^[4]
• The bone marrow transplant became the therapeutic option during the 1960’s and reports of sinusoidal obstruction syndrome or hepatic veno-occlusive disease emerged in the 1970’s.^[5]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Husnain Shaukat, M.D [2]

There is no established system for the classification of sinusoidal obstruction syndrome. However, it can be classified on the basis of severity as mild, moderate and severe.

There is no established system for the classification of sinusoidal obstruction syndrome. However, it can be classified on the basis of severity as mild, moderate and severe.^[1]

Parameters	Mild	Moderate	Severe
Serum total bilirubin	<5 mg/dL	< (5.1 to 8 mg/dL	>8 mg/dL
Serum aspartate aminotransferase (AST)	<3 x normal	3 to 8 x normal	>8 x normal
Weight above baseline	<2 percent	2 to 5 percent	>5 percent
Serum creatinine	Normal	<2 x normal	>2 x normal
Rate of change	Slow (over 6–7 d)	(over 4–5 d)	Rapid (over2–3 d)

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Husnain Shaukat, M.D [2]

The development of sinusoidal obstruction syndrome begins with the injury to hepatic venous endothelium. It is thought that preexisting liver disease increases the risk of developing sinusoidal obstruction syndrome (SOS) due to impairment of drug metabolism which predisposes to the endothelial injury. The endothelial cells in patients with hepatitis may have abnormal expression of adhesion molecules and pro-coagulant factors. The deposition of fibrinogen and factor VIII within the sinusoids leads to their dilation and congestion by erythrocytes. The progressive occlusion of venules leads to widespread zonal liver disruption and centrilobular hemorrhagic necrosis. Hepatic sinusoidal obstruction syndrome (SOS) is mainly seen in patients of hematopoietic cell transplantation.

• Sinusoidal obstruction syndrome (SOS) occurs due to obstruction of the hepatic venules and sinusoids rather than hepatic vein or inferior vena cava as seen in Budd Chiari syndrome.
• Hepatic sinusoidal obstruction syndrome (SOS) is mainly seen in patients who have undergone hematopoietic stem cell transplantation.
• The development of sinusoidal obstruction syndrome (SOS) begins with the injury to the hepatic venous endothelium. It is thought that preexisting liver disease increases the risk of developing sinusoidal obstruction syndrome (SOS) due to impairment of drug metabolism which predisposes to the endothelial injury.
• The endothelial cells in patients with hepatitis may have abnormal expression of adhesion molecules and pro-coagulant factors.
• The deposition of fibrinogen and factor VIII within the sinusoids leads to their dilation and congestion by erythrocytes. The progressive occlusion of venules leads to widespread zonal liver disruption and centrilobular hemorrhagic necrosis.
• The later changes in sinusoids include deposition of collagen, sclerosis of venular walls, fibrosis of the lumen and ultimately occlusion of hepatic venules.
• The severity of symptoms depends on the number of sinusoids involve and severity of the histologic changes.

• On gross pathology, the liver has diffusely mottled appearance with areas of congestion and normal appearing hepatic parenchyma.^[1]

The most important histopathological characteristics of sinusoidal obstruction syndrome are:^[2][3][4]

• Sinusoidal dilation
• Portal tract changes of fibrosis and bile ductular reaction
• Sclerosis of venular walls
• Sinusoidal endothelial cell detachment from the space of Disse can be seen on electron microscopy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Husnain Shaukat, M.D [2]

The most common cause of sinusoidal obstruction syndrome is hematopoietic cell transplantation. Other less common causes include chemotherapeutic agents and pyrrolizidine alkaloids.

• Sinusoidal obstruction syndrome is most commonly caused by hematopoietic cell transplantation.^[1][2]

Other less common causes include:^[3]

• Chemotherapeutic agents such as 6-mercaptopurine, 6-thioguanine, actinomycin D, azathioprine or busulfan etc
• Pyrrolizidine alkaloids

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Husnain Shaukat, M.D [2]

The differential diagnosis of sinusoidal obstruction syndrome includes other causes of hepatic failure that may have abnormal liver function tests such as increased conjugated bilirubin and alkaline phosphatase or a clinical presentation as right upper quadrant abdominal pain, jaundice or ascites.

Sinusoidal obstruction syndrome should be differentiated from other causes of hepatic failure like Budd-Chiari syndrome, viral hepatitis, liver cirrhosis, splenic vein thrombosis, portal vein thrombosis and inferior vena cava obstruction that may have a similar presentation with right upper quadrant abdominal pain and ascites. The differential diagnosis is as follows:

Condition	Differentiating signs and symptoms	Differentiating Tests
Budd-Chiari Syndrome	Abdominal pain Diarrhea Ascites	Doppler ultrasound and CT of the abdomen shows absence of the hepatic vein filling Abdominal CT scan will show a rapid clearing of the caudate lobe of the liver
Cirrhosis	Abdominal pain and bloating Menstrual irregularities Symptoms of hypogonadism: Impotence Infertility Testicular atrophy Loss of libido Easy bruisability Decompensated cirrhosis may present with Jaundice Increase in abdominal girth due to ascites Pruritus Signs of upper gastrointestinal bleeding: Hematemesis Hematochezia Melena Symptoms due to hepatic encephalopathy: Altered mental status Confusion Sleep disturbances	Ultrasound findings in cirrhosis are as follows:[1][2][3][4][5][6][7][8] Changes in liver contour: shrunken, irregular appearance Non homogeneous appearance of the hepatic tissue Increased surface nodularity Increase in echogenecity from focal fatty infiltration Atrophy of the right lobe and hypertrophy of the caudate or left lobe Splenomegaly Ascites Varices Hepatic or portal vein thrombosis Abdominal MRI may also be helpful in the diagnosis of portal hypertension. Findings on MRI suggestive of cirrhosis with portal hypertension include:[9][10][11][12] Cirrhotic liver, as shrinkage and atrophy in liver Re-canalized umbilical vein—pathognomonic Dilated portal vein and/or splanchnic veins Esophageal varices Collaterals in any abdominal organ Splenomegaly Ascites Transient elastography and the Acoustic Radiation Force Impulse (ARFI) technique are well-established methods for the staging of fibrosis in various liver diseases: [13][14][15][16][17][18][19][20][21][22][23]  The FibroScan (transient elastography) uses elastic waves to determine liver stiffness which theoretically may be converted into a liver score. The FibroScan produces an ultrasound image of the liver (from 20-80mm) along with a pressure reading (in kPa). Transient elastography is much faster than a biopsy (usually lasts 2.5-5 minutes) and is completely painless. Findings on transient elastography may show reasonable correlation with the severity of cirrhosis:[24][25] Increasing scarring of the liver is associated with increasing “stiffness” of the tissue.
Splenic vein thrombosis	Signs and symptoms of: Upper abdominal pain radiating to the back Vomiting Hypoactive bowel sounds Fever Shock Cullen’s sign Grey-Turner’s sign	Ultrasound of the abdomen and CT scan will show evidence of a splenic vein thrombosis Normal hepatic venous pressure gradient is present
Portal vein thrombosis	Symptoms depend on the underlying cause: If pancreatitis is present, the patient may develop: Upper abdominal pain radiating to the back Vomiting Hypoactive bowel sounds fever shock Cullen’s sign Grey-Turner’s sign If the cause is ascending cholangitis, symptoms include: Fever Rigors Right upper quadrant pain Dark urine Pale stools If abdominal sepsis is the cause, symptoms include: Fever Abdominal pain Signs of peritonitis	Doppler ultrasound and abdominal CT scan show a portal vein filling defect and absence of flow in the portal vein. MR or direct angiography show a normal hepatic venous pressure gradient.
Schistosomiasis	Patients may have a history of travel to endemic areas Constitutional symptoms such as Malaise Rigors Anorexia Weight loss Vomiting Diarrhea Headache Muscular aches Weakness Abdominal pain Urticaria Fever Lymphadenopathy	MR or direct angiography shows a normal hepatic venous pressure gradient
Inferior vena cava obstruction	Signs and symptoms of renal cell carcinoma: Hematuria Flank pain Flank or abdominal mass Weight loss Hypertension	Ultrasound of the abdomen shows evidence of inferior vena cava obstruction
Nodular regenerative hyperplasia	None	Liver biopsy shows small regenerative nodules with little or no fibrosis on reticulin staining
Idiopathic portal hypertension (hepatoportal sclerosis)	None	Liver biopsy shows no evidence of cirrhosis

Abbreviations: RUQ= Right upper quadrant of the abdomen, LUQ= Left upper quadrant, LLQ= Left lower quadrant, RLQ= Right lower quadrant, LFT= Liver function test, SIRS= Systemic inflammatory response syndrome, ERCP= Endoscopic retrograde cholangiopancreatography, IV= Intravenous, N= Normal, AMA= Anti mitochondrial antibodies, LDH= Lactate dehydrogenase, GI= Gastrointestinal, CXR= Chest X ray, IgA= Immunoglobulin A, IgG= Immunoglobulin G, IgM= Immunoglobulin M, CT= Computed tomography, PMN= Polymorphonuclear cells, ESR= Erythrocyte sedimentation rate, CRP= C-reactive protein, TS= Transferrin saturation, SF= Serum Ferritin, SMA= Superior mesenteric artery, SMV= Superior mesenteric vein, ECG= Electrocardiogram

Disease Clinical manifestations Diagnosis Comments Symptoms Signs Abdominal Pain Fever Rigors and chills Nausea or vomiting Jaundice Constipation Diarrhea Weight loss GI bleeding Hypo- tension Guarding Rebound Tenderness Bowel sounds Lab Findings Imaging Acute suppurative cholangitis RUQ + + + + − − − − + + + N Abnormal LFT WBC >10,000 Ultrasound shows biliary dilatation/stents/tumor Septic shock occurs with features of SIRS Acute cholangitis RUQ + − − + − − − − − − − N Abnormal LFT Ultrasound shows biliary dilatation/stents/tumor Biliary drainage (ERCP) + IV antibiotics Acute cholecystitis RUQ + − + + − − − − − − − Hypoactive Hyperbilirubinemia Leukocytosis Ultrasound shows: Gallstone Inflammation Murphy’s sign Acute pancreatitis Epigastric + − + ± − − − − ± − − N Increased amylase / lipase Ultrasound shows evidence of inflammation CT scan shows severity of pancreatitis Pain radiation to back Chronic pancreatitis Epigastric − − ± ± − + + − − − − N Increased amylase / lipase Increased stool fat content Pancreatic function test CT scan Calcification Pseudocyst Dilation of main pancreatic duct Predisposes to pancreatic cancer Pancreatic carcinoma Epigastric − − + + − + + − − − − N ↑ Alkaline phosphatase ↑ serum bilirubin ↑ gamma-glutamyl transpeptidase ↑ CA 19-9  MDCT with  PET/CT MRI Skin manifestations may include: Bullous pemphigoid Cicatricial pemphigoid Migratory superficial thrombophlebitis (classic Trousseau’s syndrome) Pancreatic panniculitis Disease Abdominal Pain Fever Rigors and chills Nausea or vomiting Jaundice Constipation Diarrhea Weight loss GI bleeding Hypo- tension Guarding Rebound Tenderness Bowel sounds Lab Findings Imaging Comments Primary biliary cirrhosis RUQ/Epigastric − − − + − − − − − − − N Increased AMA level, abnormal LFTs ERCP Pruritis Primary sclerosing cholangitis RUQ + − − + − − − − − − − N Increased liver enzymes Increased IgM, IgG4 Anti-neutrophil cytoplasmic antibody (p-ANCA) Anti-nuclear antibody (ANA) Anti-smooth muscle antibody (Anti-Sm) Anti-endothelial antibody Anti-cardiolipin antibody ERCP and MRCP shows Multiple segmental strictures Mural irregularities Biliary dilatation and diverticula Distortion of biliary tree The risk of cholangiocarcinoma in patients with primary sclerosing cholangitis is 400 times higher than the risk in the general population. Cholelithiasis RUQ/Epigastric ± − ± ± − − − − − − − Normal to hyperactive for dislodged stone Leukocytosis Ultrasound shows gallstone Fatty food intolerance Gastrointestinal perforation Diffuse + ± – ± − − − + + + ± Hyperactive/hypoactive WBC> 10,000 Air under diaphragm in upright CXR Hamman’s sign Inflammatory bowel disease Diffuse ± − − ± − + + + − − − Normal or hyperactive Anti-neutrophil cytoplasmic antibody (P-ANCA) in Ulcerative colitis Anti saccharomyces cerevisiae antibodies (ASCA) in Crohn’s disease String sign on abdominal x-ray in Crohn’s disease Extra intestinal findings: Uveitis Arthritis Whipple’s disease Diffuse ± − − ± − + + − ± − − N Thrombocytopenia Hypoalbuminemia Small intestinal biopsy for Tropheryma whipplei Endoscopy is used to confirm diagnosis. Images used to find complications Chest and joint x-ray CT MRI Echocardiography Extra intestinal findings: Uveitis Endocarditis Encephalitis Dementia Hepatosplenomegaly Arthritis Ascites Disease Abdominal Pain Fever Rigors and chills Nausea or vomiting Jaundice Constipation Diarrhea Weight loss GI bleeding Hypo- tension Guarding Rebound Tenderness Bowel sounds Lab Findings Imaging Comments Viral hepatitis RUQ + − + + − Positive in Hep A and E + − Positive in fulminant hepatitis Positive in acute + N Abnormal LFTs Viral serology US Hep A and E have fecal-oral route of transmission Hep B and C transmits via blood transfusion and sexual contact. Liver abscess RUQ + + + + − ± + − + + ± Normal or hypoactive CBC Blood cultures Abnormal liver function tests US CT Hepatocellular carcinoma/Metastasis RUQ + − − + − − + − − − − Normal Hyperactive if obstruction present High levels of AFP in serum Abnormal liver function tests US CT Liver biopsy Other symptoms: Splenomegaly Variceal bleeding Ascites Spider nevi Asterixis Disease Abdominal Pain Fever Rigors and chills Nausea or vomiting Jaundice Constipation Diarrhea Weight loss GI bleeding Hypo- tension Guarding Rebound Tenderness Bowel sounds Lab Findings Imaging Comments Budd-Chiari syndrome RUQ ± − − ± − − − Positive in liver failure leading to varices − − − N Elevated serum aspartate aminotransferase and alanine aminotransferase levels may be more than five times the upper limit of the normal range. Elevated serum alkaline phosphatase and bilirubin levels, decreased serum albumin level. Findings on CT scan suggestive of Budd-Chiari syndrome include: Early enhancement of the caudate lobe and central liver around the inferior vena cava Delayed enhancement of the peripheral liver with accompanying central low density (flip-flop appearance) Peripheral zones of the liver show reversed portal venous blood flow In the chronic phase, there is caudate lobe enlargement and atrophy of the peripheral liver in affected areas Ascitic fluid examination shows: Total protein more than 2.5 g per deciliter White blood cells are usually less than 500/μL. Cirrhosis RUQ − − − + − − + + + − − N Hypoalbuminemia Prolonged PT Abnormal LFTs Hyponatremia Thrombocytopenia US Nodular, shrunken liver Ascites Stigmata of liver disease Cruveilhier- Baumgarten murmur Spontaneous bacterial peritonitis Diffuse + − − Positive in cirrhotic patients − + − − ± + + Hypoactive Ascitic fluid PMN>250 cells/mm³ Culture: Positive for single organism Ultrasound for evaluation of liver cirrhosis Biliary colic RUQ − − + + − − − − − − − N ↑ bilirubin and alkaline phosphatase Ultrasound

Disease Clinical manifestations Diagnosis Comments Symptoms Signs Abdominal Pain Fever Rigors and chills Nausea or vomiting Jaundice Constipation Diarrhea Weight loss GI bleeding Hypo- tension Guarding Rebound Tenderness Bowel sounds Lab Findings Imaging Portal vein thrombosis Diffuse ± − + ± − + + ± − − − N Usually normal CT MRI US MRA CEUS Chronic pancreatitis Epigastric − − ± ± − + + − − − − N Increased amylase / lipase Increased stool fat content Pancreatic function test CT scan Calcification Pseudocyst Dilation of main pancreatic duct Predisposes to pancreatic cancer Pancreatic carcinoma Epigastric − − + + − + + − − − − N ↑ Alkaline phosphatase ↑ serum bilirubin ↑ gamma-glutamyl transpeptidase ↑ CA 19-9 MDCT with PET/CT MRI Skin manifestations may include: Bullous pemphigoid Cicatricial pemphigoid Migratory superficial thrombophlebitis (classic Trousseau’s syndrome) Pancreatic panniculitis Dumping syndrome Lower and then diffuse − − + − − + + − + − − Hyperactive Glucose challenge test Hydrogen breath test Upper GI series Gastric emptying study Postgastrectomy Disease Abdominal Pain Fever Rigors and chills Nausea or vomiting Jaundice Constipation Diarrhea Weight loss GI bleeding Hypo- tension Guarding Rebound Tenderness Bowel sounds Lab Findings Imaging Comments Acute appendicitis Starts in epigastrium, migrates to RLQ + Positive in pyogenic appendicitis + − − ± − − Positive in perforated appendicitis + + Hypoactive Leukocytosis Ct scan Ultrasound Positive Rovsing sign Positive Obturator sign Positive Iliopsoas sign Acute diverticulitis LLQ + ± + − + ± − + Positive in perforated diverticulitis + + Hypoactive Leukocytosis CT scan Ultrasound History of constipation Infective colitis Diffuse + − ± − − + − + Positive in fulminant colitis ± ± Hyperactive Stool culture and studies Shiga toxin in bloody diarrhea PCR CT scan Bowel wall thickening Edema Viral hepatitis RUQ + − + + − Positive in Hep A and E + − Positive in fulminant hepatitis Positive in acute + N Abnormal LFTs Viral serology US Hep A and E have fecal-oral route of transmission Hep B and C transmits via blood transfusion and sexual contact. Liver abscess RUQ + + + + − ± + − + + ± Normal or hypoactive CBC Blood cultures Abnormal liver function tests US CT Mesenteric ischemia Periumbilical Positive if bowel becomes gangrenous − + − − + + + Positive if bowel becomes gangrenous Positive if bowel becomes gangrenous − Hyperactive to absent Leukocytosis and lactic acidosis Amylase levels D-dimer CT angiography SMA or SMV thrombosis Also known as abdominal angina that worsens with eating Acute ischemic colitis Diffuse + ± + − − + + + + + + Hyperactive then absent Leukocytosis Abdominal x-ray Distension and pneumatosis CT scan Double halo appearance, thumbprinting Thickening of bowel May lead to shock Pneumonia RUQ/LUQ + + + − − ± − − + − − Normal or hypoactive ABGs Leukocytosis Pancytopenia CXR CT chest Bronchoscopy Shortness of breath Cough

Abbreviations: RUQ= Right upper quadrant of the abdomen, LUQ= Left upper quadrant, LLQ= Left lower quadrant, RLQ= Right lower quadrant, LFT= Liver function test, SIRS= Systemic inflammatory response syndrome, ERCP= Endoscopic retrograde cholangiopancreatography, IV= Intravenous, N= Normal, AMA= Anti mitochondrial antibodies, LDH= Lactate dehydrogenase, GI= Gastrointestinal, CXR= Chest X ray, IgA= Immunoglobulin A, IgG= Immunoglobulin G, IgM= Immunoglobulin M, CT= Computed tomography, PMN= Polymorphonuclear cells, ESR= Erythrocyte sedimentation rate, CRP= C-reactive protein, TS= Transferrin saturation, SF= Serum Ferritin, SMA= Superior mesenteric artery, SMV= Superior mesenteric vein, ECG= Electrocardiogram, MRA= MR angiography, CEUS=Contrast enhanced ultrasound

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Husnain Shaukat, M.D [2]

The incidence of sinusoidal obstruction syndrome depends on the presence of risk factors, chemotherapy regimen and the clinical criteria used for the diagnosis. The incidence after allogeneic hematopoietic cell transplant ranges from a low of 10,000 persons per 100,000 persons to a high of 15,000 persons per 100,000 persons. The incidence of sinusoidal obstruction syndrome after autologous hematopoietic cell transplant is below 5,000 persons per 100,000 persons.

• Incidence of sinusoidal obstruction syndrome depends on the presence of risk factors, chemotherapy regimen used and the clinical criteria used for the diagnosis.^[1]
• The incidence of sinusoidal obstruction syndrome after allogeneic hematopoietic cell transplant ranges from a low of 10,000 persons per 100,000 persons to a high of 15,000 persons per 100,000 persons.^[2]
• The incidence of sinusoidal obstruction syndrome after autologous hematopoietic cell transplant is below 5,000 persons per 100,000 persons.^[3]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Husnain Shaukat, M.D [2]

Common risk factors in the development of sinusoidal obstruction syndrome are stem cell transplantation, preexisting liver dysfunction and high-dose conditioning regimens.

Common risk factors for sinusoidal obstruction syndrome are:^[1][2][3]

• Stem cell transplantation
• Preexisting liver dysfunction (elevated transaminases, fibrosis or cirrhosis, low albumin level pretransplantation)
• Presence of hepatic metastases
• Advanced age
• Prior radiation treatment of the liver
• High-dose conditioning regimens
• Allogeneic transplantation (compared with autologous transplantation)
• High dose radiation therapy
• Liver transplantation

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Husnain Shaukat, M.D [2]

There is insufficient evidence to recommend routine screening for sinusoidal obstruction syndrome.

There is insufficient evidence to recommend routine screening for sinusoidal obstruction syndrome.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Husnain Shaukat, M.D [2]

Patients with a mild or moderate form of sinusoidal obstruction syndrome require no specific therapy and can be managed with supportive care alone.The mild and moderate form of sinusoidal obstruction syndrome has a good prognosis. If left untreated, the severe form of sinusoidal obstruction syndrome is characterized by high mortality and progression to multiorgan failure.

• Sinusoidal obstruction syndrome is a common complication in patients with hematopoietic stem cell transplant.
• If left untreated, the severe form of sinusoidal obstruction syndrome is characterized by high mortality and progression to multiorgan failure.^[1]

Complications that can develop as a result of sinusoidal obstruction syndrome are:^[2][3][4][5]

• Portal hypertension
• Hepatic encephalopathy
• Variceal hemorrhage
• Hepatorenal syndrome
• Hepatic decompensation
• Bacterial peritonitis especially the following paracentesis

• Sinusoidal obstruction syndrome is considered mild, moderate or severe based on the clinical course during the first three months of hematopoietic cell transplantation.^[6]
• Patients with a mild or moderate form of sinusoidal obstruction syndrome require no specific therapy and can be managed with supportive care alone and progressively resolves over a 2- to 3-week period.^[7]
• Patients with the severe sinusoidal obstruction syndrome have a high rate of mortality and can progress to multiorgan failure.^[8]

Morbidity and mortality is associated with following factors:^{[9][10][11][12]}

• Younger age in children
• Older age in adults
• Poor performance status
• Pre-existing hepatic dysfunction
• History of pancreatitis
• Advanced malignancy
• Acute leukemia
• Presence of acute graft-versus-host disease
• Allogeneic HCT
• Unrelated donor HCT
• Mismatched donor
• Prior abdominal irradiation
• High dose cytoreductive therapy
• Total body irradiation

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