Diagnosis
PSC is a chronic cholestatic liver disease of unknown cause that is characterized by progressive bile duct destruction and biliary cirrhosis. Eighty percent of patients have an IBD (most often ulcerative colitis). Characteristic findings are:
• pruritus or jaundice
• elevated serum alkaline phosphatase level • elevated total bilirubin level
• modestly elevated AST and ALT levels
Abdominal ultrasonography is often the initial diagnostic study; if intrahepatic biliary dilation is seen, select MRCP or ERCP to establish the diagnosis (look for the “string of beads” pattern). Patients with PSC are at risk for developing cholangiocarcinoma as well as gallbladder carcinoma and colon cancer (when associated with IBD). The risk of colon cancer in patients with PSC and IBD is high enough that surveillance is recommended, regardless of duration or extent of the IBD. In these patients select annual screening for colon cancer (colonoscopy). Patients with cirrhosis require screening for HCC with ultrasonography every 6 months. No consensus has been reached regarding screening for cholangiocarcinoma and gallbladder cancer.
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◆Don’T BE TrickED
• Do not confuse PSC with AIDS cholangiopathy (CD4 cell count <100/μL) due to CMV or Cryptosporidium infection.
STUDY TABLE: Differentiating Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis
Primary Biliary Cirrhosis Primary Sclerosing Cholangitis
Demographic Women aged 40–60 years Men aged 20–30 years
Pathology Cholestatic liver disease of small bile ducts Cholestatic liver disease of large bile ducts
Associated conditions Other autoimmune disease IBD
Look for… Positive antimitochondrial antibody titer “String of beads” on MRCP or ERCP
Therapy Ursodeoxycholic acid Endoscopic therapy for extrahepatic dominant strictures Liver transplantation
Therapy
There is no effective medical therapy for PSC. Pruritus can be treated with cholestyramine; otherwise, patients with a dominant biliary stricture, bile duct stones, or cholangitis may benefit from endoscopic bile duct dilatation/stenting or removal of stones. Liver transplantation is associated with improved quality of life and survival.
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❖Test Yourself
A 45yearold man with a 15year history of ulcerative colitis develops fatigue and pruritus. Serum alkaline phosphatase level is 750 U/L, AST is 48 U/L, ALT is 60 U/L, and total bilirubin is 2.0 mg/dL.
ANSWER: The probable diagnosis is PSC. Schedule ultrasonography followed by MRCP or ERCP.
Gastroenterology and Hepatology
Cirrhosis
Diagnosis
Patients with cirrhosis but no complications have compensated cirrhosis; they may be asymptomatic or have nonspecific symptoms such as fatigue, poor sleep, or itching. Patients with complications of cirrhosis (hepatic encephalopathy, variceal hemorrhage, ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, jaundice, or HCC) have decompensated cirrhosis. Portal hypertension is responsible for the majority of these complications. Portal hypertension also causes spleno megaly and hypersplenism (thrombocytopenia) and loss of hepatic synthetic function (coagulopathy and hypoalbuminemia).
Portal hypertension can be divided into prehepatic, intrahepatic, and posthepatic causes. The most common cause of portal hypertension is cirrhosis, an intrahepatic form. Examples of pre and posthepatic portal hypertension are portal vein thrombo sis and BuddChiari syndrome, respectively.
Portal hypertension develops in cirrhosis owing to mechanical factors of fibrosis and regenerative liver nodules as well as increased intrahepatic vascular resistance and increased portal inflow. The high pressure in the portal vein is decompressed through collateral portosystemic shunts that occur in the mucosa of the distal esophagus and proximal stomach.
Select the following options for care of patients with cirrhosis:
• upper endoscopy for all new patients to screen for varices • ultrasonography to diagnose ascites
• paracentesis for newly discovered ascites and calculation of the serumascites albumin gradient (SAAG) to diagnose the
cause of ascites
• paracentesis with ascitic fluid granulocyte count and culture for any change in mental status or clinical condition to diag
nose spontaneous bacterial peritonitis
• vaccination of nonimmune patients against HAV and HBV as well as other routine vaccinations • ultrasound screening for HCC every 6 months
STUDY TABLE: Evaluation of Ascites
Ascitic Fluid Protein SAAG >1.1 SAAG <1.1
<2.5 g/dL Cirrhosis Nephrotic syndrome
>2.5 g/dL Right-sided HF, Budd-Chiari syndrome Malignancy, TB
Ascitic fluid granulocyte count >250/μL confirms spontaneous bacterial peritonitis.
Hepatic encephalopathy is a neuropsychiatric syndrome that develops in patients with hepatic dysfunction. Symptoms range from minimal cognitive changes to coma. The plasma ammonia level can be helpful in cases of diagnostic uncertainty.
Diagnose hepatopulmonary syndrome in patients with:
• dyspnea • hypoxemia • cirrhosis
• increased Aa while breathing ambient air
Patients may exhibit platypnea (increased dyspnea sitting up and decreased dyspnea lying flat). The diagnosis of hepatopulmo nary syndrome is confirmed by contrastenhanced TTE with agitated saline administration.
Portopulmonary hypertension is PH in the presence of portal hypertension. Patients without other obvious causes of dyspnea should undergo echocardiography; RV systolic pressure >50 mm Hg requires investigation for causes of PH. Select patients will benefit from liver transplantation.
Gastroenterology and Hepatology
Hepatorenal syndrome diagnostic criteria consist of:
• an increase in the creatinine to >1.5 mg/dL over days to weeks
• lack of response to an albumin challenge of 1 g/kg/d for 2 days • exclusion of other causes of AKI
Type 1 hepatorenal syndrome is more severe, with a doubling of the creatinine level in excess of 2.5 mg/dL in <2 weeks. Type 2 hepatorenal syndrome is less severe, with a more gradual increase in the creatinine level and association with diuretic refractory ascites.
Hepatic osteodystrophy encompasses osteoporosis, osteopenia, and rarely osteomalacia in the context of liver disease. Standard evaluation includes calcium, phosphate, and vitamin D levels. DEXA scanning is recommended for patients with cirrhosis or primary biliary cirrhosis and before liver transplantation. Osteoporosis should be managed with a bisphosphonate (after vitamin D repletion).
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◆Don’T BE TrickED
• There is no utility in monitoring serial ammonia values in patients with hepatic encephalopathy.
• Head CT is only warranted in patients with unwitnessed falls, or head trauma.
• Use only IV, not oral, bisphosphonate therapy in patients with esophageal varices.
Therapy
Patients with type 1 hepatorenal syndrome treated in the ICU should receive norepinephrine and albumin, whereas nonICU patients are treated with midodrine, octreotide, and albumin. Type 1 patients who do not respond to medical therapy should undergo liver transplantation.
STUDY TABLE: Therapy for Cirrhosis
Indications Treatment
Primary prophylaxis of variceal bleeding First choice: propranolol or nadolol (must be nonselective β-blockers)
Second choice: endoscopic band ligation if β-blocker not tolerated or contraindicated
Active variceal bleeding First choice: octreotide with endoscopic band ligation and prophylactic oral norfloxacin or IV ciprofloxacin
Second choice: TIPS or shunt surgery if endoscopic therapy is unsuccessful
Transfusion for active bleeding Hemoglobin transfusion goal 7 g/dL Ascites not responding to low-sodium diet Spironolactone with or without furosemide
Diuretic-refractory ascites Serial large-volume paracentesis (with albumin if >5 L), TIPS, or liver transplantation
Prevention of spontaneous bacterial peritonitis in hospitalized patients with cirrhosis and ascitic fluid protein <1.0 g/dL, variceal bleeding with or without cirrhosis, or previous history of spontaneous bacterial peritonitis and other high-risk categories
Fluoroquinolones chronically if history of spontaneous bacterial peritonitis or otherwise high risk*
Fluoroquinolones while hospitalized if fluid protein <1 g/dL Fluoroquinolones for 7 days if active bleeding
Spontaneous bacterial peritonitis Cefotaxime and albumin infusion. Administer 1.5 g/kg of albumin on day 1 and 1 g/kg of albumin on day 3 if creatinine is >1 mg/dL, bilirubin >4 mg/dL, or BUN >30 mg/dL
Acute hepatic encephalopathy Correct precipitating factors, lactulose; add rifaximin if unresponsive
Prevention of hepatic encephalopathy Lactulose, titrated to 3 stools per day Hepatic osteodystrophy Calcium, vitamin D, and IV bisphosphate
*High risk = ascitic total protein <1.5 g/dL and any of the following: serum sodium ≤130 mEq/L, creatinine ≥1.2 mg/dL, BUN ≥25 mg/dL, bilirubin ≥3 mg/dL.
Gastroenterology and Hepatology
The primary complication of TIPS is portosystemic encephalopathy. Liver transplantation is the definitive treatment for patients with endstage liver disease and complications such as variceal bleeding, ascites, hepatic encephalopathy, or hepatorenal/ hepatopulmonary syndromes.
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◆Don’T BE TrickED
• Stop ACE inhibitors, ARBs, and NSAIDs in patients with ascites.
• More liberal blood transfusion to hemoglobin >7.0 g/dL leads to increased portal pressures and risk of further bleeding.
• Antimicrobial prophylaxis should be administered during variceal bleeding even if ascites are absent.
• Do not select prophylactic protein restriction to prevent hepatic encephalopathy.
• Do not select neomycin to treat hepatic encephalopathy because of the significant adverse effects of this drug.
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❖Test Yourself
A 55yearold man with alcoholic cirrhosis is hospitalized with fever and abdominal pain. Paracentesis is performed. The ascitic fluid granulocyte count is 650/μL and the albumin is <1.0 g/dL.
ANSWER: The diagnosis is spontaneous bacterial peritonitis. Begin IV cefotaxime and albumin. Do not wait for results of
Gram stain or cultures before beginning therapy.