The liver is frequently involved in patients with systematic amyloid, up to 90 % in some studies [28]. Signs related to liver involvement can be seen in up to one-half of patients, but symptomatic dysfunction due to amyloid is uncommon and typically a late manifestation of the disease (Table 30.3). Alkaline phosphates’ elevation may be detected early, but it is a relatively nonspecific finding with a wide differential diagnosis—amyloidosis being very far down on the list. It is unclear why the hepatic deposition of amyloid results in the elevation of the serum alkaline phosphates. Hepatomegaly is also commonly noted, but the amount of protein deposition may not correlate directly with liver size. Some of the liver enlargement may be due to passive congestion related to amyloid-induced cardiac failure. As the functioning hepatic parenchyma becomes further compromised by the deposits, jaundice, encephalopathy, and hepatic failure may ensue. Jaundice is a poor sign with most patients succumbing within 6 months of its development.

Fibroscan has been suggested as a noninvasive modality that can be employed to diagnose hepatic amyloid; however, its sensitivity and specificity remain to be determined in everyday clinical use [29]. In the meantime, the liver biopsy remains the gold standard for diagnosis [30–32]. When pathologists think about amyloid deposition in the liver, they typically know about the sinusoidal pattern—by far the most common pattern. The term parenchymal has been used for this pattern by the Japanese; others have called it linear. It is the pattern of amyloid deposition that is present when the patient is symptomatic. However, it is important to remember that there are three other basic patterns of amyloid deposition that can be seen in the liver (Table 30.4). Failure to appreciate these uncommon patterns can greatly complicate the patient’s clinical course. Like the GI tract, the type of amyloid in general does not dictate the pattern of deposition with some exceptions that will be noted. In the sinusoidal pattern, hyalinized material is deposited in the space between the sinusoidal lining endothelium and the hepatocyte cytoplasm (Fig. 30.18). As with all amyloid depositions it generally has a pinkish tint on H&E stain, but in some preparations it may exhibit a blue-gray tint. This deposition begins in the sinus around the central veins (zone 3) and then spreads throughout the lobule (Fig. 30.19). As the amount of amyloid deposition increases, there is corresponding atrophy of the hepatic plates. In its most extreme form, the underlying liver is almost unrecognizable (Fig. 30.20). Amyloid deposition can also spread into the portal tract. The involvement of the tract can be variable from case to case and also from tract to tract within the same biopsy specimen. Branches of the hepatic artery may also be involved, but again, this is variable (Fig. 30.21). The differential diagnosis includes entities that produce sinusoidal fibrosis including the hepatitis, vitamin A toxicity, venous outflow obstruction, and congenital syphilis as well as light chain deposition disease (Table 30.5). Trichrome stains are a routine part of liver biopsy interpretation and they stain the amyloid in basically the same fashion as fibrosis (Fig. 30.22). This may lead to further confusion if the subtleties of the appearance of amyloid in H&E-stained sections are not appreciated.