A Tough Egg to Crack

The patient’s temperature was 37.8°C, pulse 73 beats/minute, blood pressure 133/69 mmHg, respiratory rate 12 breaths/minute, and oxygen saturation 98% on ambient air. Her body mass index (BMI) was 19 kg/m². She was somnolent but was moving all four extremities spontaneously. Her pupils were symmetric and reactive. There was no facial asymmetry. Biceps and patellar reflexes were 2+ bilaterally. Babinski sign was absent bilaterally. The patient could not cooperate with the assessment for asterixis. Her sclerae were anicteric. The jugular venous pressure was estimated at 13 cm of water. Her heart was regular with no murmurs. Her lungs were clear. She had a distended, nontender abdomen with caput medusae. She had symmetric pitting edema in her lower extremities up to the shins.

The elevated jugular venous pressure, lower extremity edema, and distended abdomen suggest volume overload. Jugular venous distention with clear lungs is characteristic of right ventricular failure from pulmonary hypertension, right ventricular myocardial infarction, tricuspid regurgitation, or constrictive pericarditis. However, chronic biventricular heart failure often presents in this manner and is more common than the aforementioned conditions. ESRD and cirrhosis may be contributing to the hypervolemia.

Although Asian patients may exhibit metabolic syndrome and NAFLD at a lower BMI than non-Asians, her BMI is uncharacteristically low for NAFLD, especially given the increased weight expected from volume overload. There are no signs of infection to account for worsening of hepatic encephalopathy.

Laboratory tests demonstrated a white blood cell count of 4400/µL with a normal differential, hemoglobin of 10.3 g/dL, and platelet count of 108,000 per cubic millimeter. Mean corpuscular volume was 103 fL. Basic metabolic panel was normal with the exception of blood urea nitrogen of 46 mg/dL and a creatinine of 6.4 mg/dL. Aspartate aminotransferase was 34 units/L, alanine aminotransferase 34 units/L, alkaline phosphatase 289 units/L (normal, 31-95), gamma-glutamyl transferase 104 units (GGT, normal, 12-43), total bilirubin 0.8 mg/dL, and albumin 2.5 g/dL (normal, 3.5-4.5). Pro-brain natriuretic peptide was 1429 pg/mL (normal, <100). The international normalized ratio (INR) was 1.0. Urinalysis showed trace proteinuria. The chest x-ray was normal. A noncontrast computed tomography (CT) of the head demonstrated no intracranial pathology. An abdominal ultrasound revealed a normal-sized nodular liver, a nonocclusive portal vein thrombus (PVT), splenomegaly (15 cm in length), and trace ascites. There was no biliary dilation, hepatic steatosis, or hepatic mass.

The evolving data set presents a mixed picture about the state of the liver. The distended abdominal wall veins, thrombocytopenia, and splenomegaly are commonly observed in advanced cirrhosis, but these findings reflect the associated portal hypertension and not the liver disease itself. The normal bilirubin and INR suggest preserved liver function and decrease the likelihood of cirrhosis being responsible for the portal hypertension. However, the elevated alkaline phosphatase and GGT levels suggest an infiltrative liver disease, such as lymphoma, sarcoidosis, or amyloidosis.

Furthermore, while a nodular liver on imaging is consistent with cirrhosis, no steatosis was noted to support the presumed diagnosis of NAFLD. One explanation for this discrepancy is that fatty infiltration may be absent when NAFLD-associated cirrhosis develops. In summary, there is evidence of liver disease, and there is evidence of portal hypertension, but there is no evidence of liver parenchymal failure. The key features of the latter – spider angiomata, palmar erythema, hyperbilirubinemia, and coagulopathy – are absent.

Noncirrhotic portal hypertension (NCPH) is an alternative explanation for the patient’s findings. NCPH is an elevation in the portal venous system pressure that arises from intrahepatic (but noncirrhotic) disease or from extrahepatic disease. Hepatic schistosomiasis is an example of intrahepatic but noncirrhotic portal hypertension. PVT that arises on account of a hypercoagulable condition (eg, abdominal malignancy, pancreatitis, or myeloproliferative disorders) is a prototype of extrahepatic NCPH. At this point, it is impossible to know if the PVT is a complication of NCPH or a cause of NCPH. PVT as a complication of cirrhosis is less likely.

An abdominal CT scan would better assess the hepatic parenchyma and exclude abdominal malignancies such as pancreatic adenocarcinoma. An echocardiogram is indicated to evaluate the cause of the elevated jugular venous pressure. A liver biopsy and measurement of portal venous pressure would help distinguish between cirrhotic and noncirrhotic portal hypertension.