Liver disease Flashcards
A 49-year-old man presents to the emergency department after an episode of vomiting blood. Two hours ago, the patient vomited up one-half cup of dark red blood with the appearance of coffee grounds. He has not vomited since.
The patient has known cirrhosis due to untreated hepatitis C virus infection. Temperature is 37.2 °C (99.0 °F), pulse is 96/min, and blood pressure is 112/68 mmHg. On physical examination, the patient is fatigued but otherwise has normal mentation and no asterixis. The skin is jaundiced. There is minimal abdominal distention and no appreciable fluid wave. Laboratory results are listed below. Which of the following is the most appropriate treatment?
A) Sofosbuvir-velpatasvir
B) Albumin
C) Ceftriaxone
D) Lactulose
E) Packed red blood cells
Acute management for patients with an HCV infection may include treatment of complications related to cirrhosis or fulminant liver failure. This may include therapies aimed at treating variceal bleeding (e.g., blood products, ceftriaxone), hepatic encephalopathy (e.g. lactulose), and ascites (e.g. paracentesis). This patient with untreated hepatitis C infection and resultant cirrhosis presents with an acute upper Gl bleed (e.g. variceal bleed, peptic ulcer disease). In patients with cirrhosis who present with an upper Gl bleed, empiric antibiotics (e.g. ceftriaxone) should be started since these patients are at significant risk of resultant infection, such as spontaneous bacterial peritonitis. Lactulose should be given if there is evidence of hepatic encephalopathy, and the abdomen should be evaluated for ascites, which may require paracentesis. Hepatitis C virus (HCV) is a bloodborne infection transmitted via exposure to contaminated blood or through sexual contact. It typically causes an asymptomatic acute infection. If the infection is not cleared, it can lead to chronic infection which predisposes the patient to cirrhosis and hepatocellular carcinoma. Hepatitis C should be suspected in patients with known high-risk behaviors or exposures (e.g., tattooing with non-sterile equipment, IV drug use, sexual contact with a known HCV carrier). It should also be part of the differential diagnosis for patients presenting with jaundice, abdominal pain, anorexia, and other symptoms of liver damage.
When HCV is suspected, serum HCV antibody testing should be performed. If positive, serum HCV RNA should then be tested to determine if this is an old, resolved infection or an active infection. Patients with active infection (positive HCV RNA) should be treated with antivirals, such as sofosbuvir-velpatasvir or glecaprevir-pibrentasvir. Patients should be counseled about lifestyle modifications (e.g. alcohol cessation) and vaccinated against hepatitis A and B virus. If HCV RNA is negative and there is a high suspicion of infection, HCV RNA testing should be repeated in six months. If HCV RNA is still negative at that point, then the HCV antibody was likely a false positive.
A 52-year-old man presents to the emergency department due to right upper quadrant abdominal pain and jaundice for the past two days. The patient normally drinks 20 ounces of whiskey per day but has not had a drink in five days due to the fact that he has been feeling ill. Past medical history is significant for CKD stage 3b, dyslipidemia, hypertension, and a mechanical heart valve. Current medications include atorvastatin, hydrochlorothiazide and warfarin. Vital signs are within normal limits. Bloodwork is obtained and results are shown below. Alcohol-induced hepatitis is suspected. Which of the following tests should be performed to confirm the diagnosis?
A) Serum indirect bilirubin
B) Transjugular liver biopsy
C) CT of abdomen and pelvis with contrast
D) Abdominal ultrasound
E) CT of abdomen and pelvis without contrast
Alcohol-induced hepatitis presents with right upper quadrant pain, jaundice, elevated transaminases, and elevated PT/INR. Some patients may have comorbid diagnoses or take medications that make interpretation of the Maddrey discriminant function and MELD score challenging. If alcoholic-induced hepatitis is suspected in such cases, a liver biopsy can be performed to confirm the diagnosis. This patient with alcohol use disorder who presents with RUQ abdominal pain, elevated transaminases, and jaundice, has a clinical picture that is concerning for alcohol-induced hepatitis. When the diagnosis is clear, the patient’s Maddrey discriminant function (DF) or MELD score should be calculated to determine severity and treatment options. In some patients, however, comorbid medical conditions and certain medications can significantly affect the serum studies used to calculate these scores. MDF uses total bilirubin and prothrombin time. MELD score uses sodium, creatinine, total bilirubin, and INR. This patient has several lab abnormalities that can be from alcohol-induced hepatitis or from other conditions. The patient’s hyponatremia can be from hydrochlorothiazide use, and the baseline creatinine elevation may be from CKD which will affect the MELD score. This patient with elevated creatine kinase and significantly elevated AST may have statin myopathy and/or hepatopathy. The INR (and PT) are likely elevated from the warfarin. In cases where alcohol-induced hepatitis is highly suspected, but the diagnosis cannot be made with history, physical and laboratory findings, a transjugular liver biopsy should be performed. In alcohol-induced hepatitis, pathology will show macrovesicular steatosis in a centrilobular pattern. Imaging is frequently unable to differentiate between alcohol-induced hepatitis and cirrhosis.
What is the pathogenesis of ascites and how it develops?
Portal hypertension can cause arterial vasodilation of the splanchnic circulation via increased levels of circulating vasodilators (eg, nitric oxide). This, in turn, can result in hypotension, renal hypoperfusion/dysfunction, and ascites (eg, abdominal distension)
What does SAAG stand for?
Serum-Ascites Albumin Gradient.
What is the clinical significance of SAAG?
SAAG helps differentiate portal hypertension-related ascites (transudate) from non-portal hypertension-related ascites (exudate).
How is SAAG calculated?
SAAG = Serum Albumin - Ascitic Fluid Albumin.
What does a SAAG greater or equal to 1.1 g/dL indicate?
Indicates portal hypertension as the cause of ascites.
What does a SAAG <1.1 g/dL indicate?
Indicates non-portal hypertension causes of ascites, such as malignancy or infection.
What are the common causes of high SAAG (≥1.1 g/dL)?
- Cirrhosis
- Heart Failure
- Budd-Chiari Syndrome
- Alcoholic Hepatitis
- Portal Vein Thrombosis
Why does cirrhosis cause high SAAG ascites?
Portal hypertension increases hydrostatic pressure, leading to ascites formation.
Why does heart failure cause high SAAG ascites?
Increased central venous pressure and hepatic congestion raise hydrostatic pressure.
Why does Budd-Chiari Syndrome cause high SAAG ascites?
Budd-Chiari syndrome (BCS) causes high SAAG ascites (≥1.1 g/dL) due to hepatic venous outflow obstruction, which leads to increased sinusoidal hydrostatic pressure and forces protein-poor fluid into the peritoneal cavity while keeping albumin in the bloodstream.
Why does Portal Vein Thrombosis cause high SAAG ascites?
Portal vein thrombosis (PVT) causes high SAAG ascites (≥1.1 g/dL) due to increased hydrostatic pressure in the portal venous system. This pressure forces protein-poor fluid into the peritoneal cavity, while albumin remains in the serum, resulting in a high SAAG.
A 25-year-old man is seen in the emergency department for evaluation of abdominal pain. For the past five days, the patient has had a dull ache in the right upper quadrant that does not change with position or eating. The patient has been drinking 13 beers per day for the past three months and his last drink was two days ago. Temperature is 37.0 °C (98.6 °F), pulse is 126/min, blood pressure is 155/98 mmHg, and SpOz is 100% on room air. On physical examination, the patient is tremulous and anxious. Bloodwork is obtained and results are shown below. Abdominal ultrasound shows increased echogenicity and surface nodularity of the liver with patent venous flow into the liver. The gallbladder and pancreas are not well-visualized due to overlying bowel gas. Which of the following is the most likely diagnosis?
A) Portal vein thrombosis
B) Alcohol-induced cirrhosis
C) Acute cholecystitis
D) Alcohol-induced pancreatitis
E) Alcohol-induced hepatitis
Alcohol-induced hepatitis can manifest in patients with alcohol use disorder as RUQ abdominal pain, elevated transaminases, elevated bilirubin, and elevated prothrombin time (or INR). Careful history and physical examination can help differentiate alcohol-induced hepatitis from other alcohol-induced or hepatobiliary pathologies. This patient with alcohol use disorder presents with RUQ abdominal pain, elevated transaminases, elevated bilirubin, and elevated prothrombin time, indicating alcohol-induced hepatitis. Alcohol use disorder can cause hepatitis (such as in this patient), cirrhosis (with chronic long-term use), and pancreatitis. The patient’s history can generally differentiate between these three etiologies. Alcohol-induced hepatitis (and sometimes cirrhosis) will typically cause RUQ pain that does not change with eating or position. Pancreatitis can cause RUQ or LUQ pain but classically causes epigastric pain that worsens with eating and with lying down. Older age and a longstanding history of alcohol use increases the likelihood of cirrhosis. Younger patients or those with shorter duration of alcohol use are more likely to have hepatitis or pancreatitis. Nausea, vomiting, and weight loss can be common features due to the underlying alcohol use disorder. Patients with any of these three pathologies may also present with alcohol withdrawal symptoms. Physical examination in alcohol-induced hepatitis and alcohol-induced pancreatitis may be similar; however, tenderness to palpation is more likely to be in the epigastric region with pancreatitis. Patients with hepatitis may have scleral icterus or jaundice which would not be present with pancreatitis. Patients may also show signs of alcohol withdrawal including tremulousness, anxiety/agitation, confusion, and hallucinations. Patients with severe alcohol-induced hepatitis may also have asterixis. Patients with cirrhosis will often have other physical examination stigmata of cirrhosis such as ascites, gynecomastia, palmar erythema, and spider angiomata.
A 36-year-old woman presents to the emergency department due to nausea, vomiting, and right upper quadrant abdominal pain for the past day. The patient drinks one liter of vodka per day and her last drink was about 36 hours ago. Temperature is 37.7 °C (99.9 °F), pulse is 122/min, blood pressure is 162/101 mmHg, respiratory rate is 22/min, and SpO is 99% on room air. On physical examination, the patient is diaphoretic, agitated, and tremulous. During the examination, it appears as though the patient is speaking to someone else in the room, although no one else is present.
Serum alcohol level is negative. CBC, CMP, and PT/INR are drawn and the patient’s Maddrey discriminant function is 30 and MELD score is 16, respectively. Which of the following medications should be administered at this time?
A) Intravenous lorazepam
B) Intravenous methylprednisolone
C) Oral pentoxifylline
D) Intravenous naltrexone
E) Oral prednisolone
This patient likely has alcohol-induced hepatitis. The acute management addresses this underlying condition. Most severe complications occur within 48-72 hours of the patient’s last drink, but this is not always the case. Lorazepam and diazepam are both frequently used, with oral or IV routes depending upon the severity of the symptoms. Severe alcohol withdrawal can have life-threatening consequences such as delirium tremens and seizures. Patients should receive benzodiazepine therapy to help treat symptoms and prevent seizures. All patients should have the underlying alcohol use disorder addressed and treated with alcohol cessation counseling and potential medications such as oral naltrexone. Patients with alcohol-induced hepatitis should have Maddrey discriminant function and MELD scores calculated to determine if treatment is indicated (MDF>32 or MELD >20). Since the Maddrey discriminant function is <32 and the MELD score is <20, no treatment is indicated with oral prednisolone (main agent of choice for alcohol-induced hepatitis), intravenous methylprednisolone (second-line agent), or oral pentoxifylline (used for alcohol-induced hepatitis when patient is actively bleeding or there is another contraindication for steroid use). Patients may have alcohol withdrawal symptoms which should be managed acutely with benzodiazepines and treated long-term with alcohol cessation counseling and possibly medications. This patient with alcohol use disorder presents with RUQ abdominal pain, nausea, vomiting, and an elevated Maddrey discriminant function (MDF) and MELD score, indicating alcohol-induced hepatitis. This patient is agitated, tachycardic, tremulous, and having hallucinations indicating severe alcohol withdrawal. After diagnosing alcohol-induced hepatitis, the next step is to calculate the Maddrey discriminant function (MDF) which uses total bilirubin and prothrombin time (PT). The MELD (model for end-stage liver disease) score can also be calculated using sodium, creatinine, total bilirubin, and INR. Patients with DF >32 or MELD >20 should receive treatment with (methyl) prednisolone or pentoxifylline, if steroids are contraindicated. When the Maddrey discriminant function ≤32 or model for end-stage liver disease score ≤20, patients should receive supportive care without pharmacologic treatment of the hepatitis.
What are the common causes of low SAAG (<1.1 g/dL)?
- Peritoneal Carcinomatosis
- Peritoneal Tuberculosis
- Pancreatitis
- Nephrotic Syndrome
- Serositis
A 56-year-old woman presents to the primary care clinic due to weight gain and constipation. She has no significant past medical history and does not drink alcohol or use tobacco products. The patient has gained 5 kg (11 lbs) in the last month and feels very bloated. She has also experienced mild lower abdominal pain. The patient was previously having daily bowel movements and is now only having two bowel movements per week. There is no associated hematochezia, melena, rectal pain, or tenesmus. Past medical history is unremarkable. On physical examination, the patient’s abdomen is distended and a fluid wave is present. There is mild abdominal tenderness to palpation diffusely. Paracentesis is performed and shows a serum-ascites albumin gradient (SAAG) of 0.8. Which of the following tests will most likely provide this patient’s diagnosis?
A) Transthoracic echocardiogram
B) Ascites fluid cell count
C) Liver biopsy
D) Ascites fluid cytology
E) Serum lipase
The serum-ascites albumin gradient (SAAG) is helpful for differentiating between various causes of ascites. SAAG ≥1.1 indicates portal hypertension-related causes (e.g. cirrhosis, spontaneous bacterial peritonitis) and SAAG <1.1 indicates other causes (e.g. malignancy, secondary infection, nephrotic syndrome). Ascites fluid cytology and cell count are useful as well to narrow down the diagnosis. Ascites can occur from intra-abdominal diseases or systemic diseases. The clinical history and physical examination can often tease out the cause. However, paracentesis with ascites fluid analysis provides additional information and is sometimes required to make a diagnosis. The serum-ascites albumin gradient (SAAG) can be used to distinguish between portal hypertension-related causes and other causes of ascites. It is calculated by subtracting ascites albumin concentration from serum albumin concentration. SAAG ≥1.1 indicates that there is mostly fluid (and not much protein) “leaking out” into the ascites and indicates portal hypertension-related causes. In contrast, a SAAG <1.1 implies there is much more albumin “leaking out” into the ascites fluid and is somewhat analogous to exudative pleural effusions (i.e. infection and malignancy are high on the differential diagnosis). SAAG <1.1 indicates causes not related to portal hypertension, such as peritoneal carcinomatosis which is likely in this case, nephrotic syndrome, and secondary (not spontaneous) bacterial peritonitis (e.g. peritoneal dialysis catheter infection). If an ascites fluid cell count shows ≥250 PMN/mm3, this finding is diagnostic of spontaneous bacterial peritonitis. Elevated ascites fluid amylase may indicate acute pancreatitis. Ascites fluid cytology may diagnose peritoneal carcinomatosis. This patient’s presentation is concerning for malignancy, possibly ovarian cancer, which is challenging to detect early. Patients may actually present with weight gain and increased abdominal girth (rather than weight loss) due to significant accumulation of ascites.
Why does malignancy cause low SAAG ascites?
Increased capillary permeability allows high-protein fluid to leak into the peritoneal cavity.
Why does peritoneal tuberculosis cause low SAAG ascites?
Granulomatous inflammation increases protein concentration in ascitic fluid.
Why does nephrotic syndrome cause low SAAG ascites?
Severe hypoalbuminemia reduces oncotic pressure, causing fluid leakage without portal hypertension.
How does SAAG help differentiate cirrhotic ascites from malignancy-related ascites?
- Cirrhotic ascites has SAAG ≥ 1.1 g/dL (portal hypertension)
- Malignancy-related ascites has SAAG <1.1 g/dL (non-portal hypertension)
What ascitic fluid findings suggest spontaneous bacterial peritonitis (SBP)?
- Neutrophils >250 cells
- Positive culture (most commonly E. coli)
- SAAG ≥ 1.1 g/dL
When are steroids used in liver failure?
- Steroids are only useful if there’s no active infection or gastrointestinal bleeding
- Severe Alcoholic Hepatitis (Maddrey Discriminant Function ≥32 or MELD >20)
- Autoimmune-mediated hepatocyte destruction
A 54-year-old man is seen in the emergency department for evaluation of abdominal pain and black stool for the past six days. The patient normally drinks 11 beers per day, but his last drink was five days ago due to abdominal pain. The patient is prescribed omeprazole for peptic ulcer disease but does not take this medication. Temperature is 37.2 °C (99.0 °F), pulse is 90/min, blood pressure is 122/81 mmHg, and SpOz is 100% on room air. On physical examination, the patient has normal mentation and no asterixis. There is mild epigastric and right upper quadrant tenderness to palpation. Digital rectal examination shows black stool in the rectal vault without hematochezia. Hemoglobin is 11.1 g/dL, AST is 175 U/L and ALT is 90 U/L. The patient’s Maddrey discriminant function is calculated as 39. Which of the following is the best next step in management?
Patients with alcohol-induced hepatitis should have their Maddrey discriminant function and/or MELD score calculated to assess severity. Patients with DF >32 or MELD >20 should receive (methyl)prednisolone, or pentoxifylline if corticosteroids are contraindicated. This patient with alcohol use disorder presents with right upper quadrant abdominal pain, elevated transaminases, and a severely elevated Maddrey discriminant function, indicating alcohol-induced hepatitis. This patient has known peptic ulcer disease which is likely causing a subacute or chronic upper GI bleed, complicating management of the hepatitis. After diagnosing alcohol-induced hepatitis, the next step is to calculate the Maddrey discriminant function (DF or Maddrey score) which uses total bilirubin and prothrombin time (PT) to calculate a number. If that number is >32, it indicates advanced liver injury and inpatient treatment should be started with intravenous steroids or pentoxifylline if steroids are contraindicated (active GI bleed). The MELD (model for end-stage liver disease) score can also be used, and it uses sodium, creatinine, total bilirubin, and INR. A MELD score >20 indicates advanced injury and the need for treatment. Patients with DF ≤32 and/or MELD less than 20 should receive supportive care without steroids or pentoxifylline. Prednisone is converted to prednisolone in the liver, so patients with alcohol-induced hepatitis should be treated with (methyl)prednisolone rather than prednisone as this conversion may be impaired. In patients with contraindications to corticosteroids (e.g., active Gl bleed, active infection), pentoxifylline should be given instead. In patients receiving treatment, the Lille score should be calculated after several days of treatment to determine response to treatment and whether or not patients should stay on the treatment. The underlying alcohol use disorder must always be addressed in patients with alcohol-induced hepatitis.
When is pentoxifylline provided for alcoholic hepatitis?
This medication can be used for alcoholic hepatitis in patients who cannot receive prednisolone (e.g. due to active gastrointestinal bleeding). With normal transaminases, alcoholic hepatitis is highly unlikely, and the most appropriate next step in management is to treat the encephalopathy. Of note: Transaminases can be normal or only mildly elevated in long-term cirrhosis.
A 53-year-old man presents to the emergency department with confusion and abdominal distention. The patient is not able to provide a history. Temperature is 37.3°C (99.1°F), pulse is 90/min, blood pressure is 100/58 mmHg, and respirations are 20/min. On physical examination the patient is jaundiced. The heart and lungs are normal upon auscultation. The abdomen is distended, and there is mild non-pitting edema in both feet. Serum transaminases are normal. Serum albumin is 2.5 g/dL and INR is 1.5. Diagnostic paracentesis is performed at bedside. Ascites albumin is 1.0 g/dL and white blood cell count is 300 cells/mm* (50% neutrophils and 50% lymphocytes). Administration of which of the following medications is the next best step in management?
A) Intravenous furosemide
B) Oral pentoxifylline
C) Intravenous prothrombin complex concentrate
D) Intravenous ceftriaxone
E) Oral lactulose
Most patients with cirrhosis eventually develop ascites, which can be treated long-term with diuretics and serial paracentesis. Acute changes in patients with cirrhosis and ascites should raise concern for spontaneous bacterial peritonitis and a diagnostic paracentesis should be performed. This patient most likely has cirrhosis and hepatic encephalopathy which can be managed with oral lactulose. Hepatic encephalopathy is due to poor liver clearance and subsequent increase in blood ammonia levels. An elevated serum ammonia level may suggest hepatic encephalopathy but is not diagnostic of hepatic encephalopathy and should not be trended. Hepatic encephalopathy is treated with lactulose to promote excretion of ammonia in the stool. Rifaximin can be added to help decrease intra-intestinal bacterial production of ammonia. Paracentesis should be considered in most patients with ascites to allow for ascites fluid studies. The serum-ascites albumin gradient (SAAG), ascites fluid cell count, and cytology are typically ordered. Other studies (e.g. ascites fluid amylase level or total protein) may be useful in certain circumstances. Any patient with confirmed or suspected cirrhosis and a change in clinical status (e.g. confusion, new significant abdominal pain, decompensated cirrhosis requires a diagnostic paracentesis to look for spontaneous bacterial peritonitis.
Spontaneous bacterial peritonitis typically only occurs in patients with cirrhosis and can be deadly if not recognized and treated. Neutrophil (PMN) count ≥250 cells/mm^3 in the ascites fluid is diagnostic. The reason intravenous ceftriaxone is not indicated in this instance is because PMNs (neutrophils) ≥250 cells/mm3 in ascites fluid is diagnostic of spontaneous bacterial peritonitis (SBP) and this patient has >250 white blood cells in the fluid, however, only 50% of them are neutrophils, so the PMN count is only 150 cells/mm^3 and does not represent SBP. Portal vein thrombosis can be seen on abdominal venous imaging and is treated with anticoagulation. Acute liver failure is another life-threatening diagnosis that can present with ascites. Diagnosis of this condition requires encephalopathy, coagulopathy, and elevated transaminases. If a patient has true acute liver failure, they need to be transferred immediately to a liver transplant center for consideration of liver transplant.
What is the pathophysiology of hepatorenal syndrome (HRS)?
HRS is caused by splanchnic vasodilation due to advanced cirrhosis, leading to renal hypoperfusion. In response, the renin-angiotensin-aldosterone system (RAAS) is activated, causing overwhelming renal vasoconstriction, which leads to acute kidney injury (AKI). It is a functional renal failure with no intrinsic kidney damage.
What are the clinical findings in hepatorenal syndrome?
1) Severe liver disease (e.g., cirrhosis, portal hypertension, ascites).
2) AKI with very low urine sodium (<10 mEq/L).
3) Bland urinalysis (no casts, protein, or blood).
4) No improvement with IV fluids (unlike prerenal azotemia).
Why is intravascular volume expansion with albumin the first step in suspected hepatorenal syndrome?
IV Albumin + Terlipressin (or Midodrine/Octreotide/Norepinephrine) is needed because HRS mimics prerenal azotemia, so volume expansion is needed to confirm the diagnosis. Failure to improve renal function with albumin infusion supports HRS. It also helps restore effective circulatory volume and temporarily improves renal perfusion.
What are the diagnostic criteria for hepatorenal syndrome (HRS)?
1) Cirrhosis with ascites.
2) Serum creatinine >1.5 mg/dL (progressive kidney failure).
3) No response to IV fluids (albumin challenge).
4) No other identifiable cause of renal failure (e.g., shock, nephrotoxic drugs, intrinsic kidney disease).
How is HRS differentiated from other causes of AKI in cirrhosis?
- HRS: Very low urine sodium (<10 mEq/L), bland urine, no response to fluids.
- Prerenal AKI: Improves with IV fluids, high BUN/Cr ratio.
- Acute tubular necrosis (ATN): Muddy brown casts, FeNa >2%.
- Glomerulonephritis: RBC casts, proteinuria.
What are the key treatments for hepatorenal syndrome?
1) IV albumin + splanchnic vasoconstrictors (terlipressin, norepinephrine, midodrine, octreotide).
2) Definitive treatment: Liver transplantation.
3) Avoid diuretics, NSAIDs, and nephrotoxic drugs.
What is the role of vasoconstrictors in HRS?
Splanchnic vasoconstrictors (terlipressin, norepinephrine, midodrine, octreotide) help counteract the excessive vasodilation seen in HRS, improving renal perfusion and function.
Why are diuretics avoided in hepatorenal syndrome?
Diuretics worsen intravascular volume depletion and can further exacerbate renal failure in HRS.
What is the only curative treatment for HRS?
Liver transplantation is the definitive treatment, as it reverses the underlying cirrhosis and restores normal renal function.
What laboratory finding is characteristic of HRS?
Very low urine sodium (<10 mEq/L) due to extreme renal sodium retention.
Which conditions commonly precipitate hepatorenal syndrome?
Spontaneous bacterial peritonitis (SBP), gastrointestinal bleeding, severe infections, excessive diuretic use.
