Management of Hepatocellular Carcinoma in Cirrhotic Patients with Portal Hypertension: Relevance of Hagen-Poiseuille's Law.

BACKGROUND

Hepatic decompensation in cirrhosis heralds an accelerated course with poor survival. An increase in hepatic venous pressure gradient (HVPG), rather than surrogate tests of liver function, appears to be the sole predictor of decompensation after surgical resection. We propose that hepatic sinusoidal walls become less elastic as cirrhosis progresses. Decompensation signals the development of increased vessel wall rigidity. The pressure-flow characteristics then become subject to Hagen-Poiseuille's law, which applies only to rigid, cylindrical vessels. Thereafter, HVPG rises exponentially (by a factor inversely proportional to the fourth power of the net radius of functional sinusoidal vessels, 1/r(4), at any given hepatic blood flow rate. This review attempts to correlate liver stiffness, risk of decompensation and outcomes from hepatocellular carcinoma (HCC) in patients with cirrhosis.

SUMMARY

We compare the complexity of autoregulation in the normal elastic liver, which has a unique dual blood supply, with that in the rigid cirrhotic liver. We also review, in the context of background liver cirrhosis, the management of HCC which is in essence, a solid mass of unorganized cells that exacerbates liver stiffness. We discuss the differential effects of various therapeutic modalities such as liver transplantation, loco-regional therapy and drugs on HCC outcomes, based on their effects on HVPG.

KEY MESSAGES

Increased hepatic artery supply, or the hepatic artery buffer response, may be the only available method for autoregulation or maintenance of hepatic blood flow in the cirrhotic liver. In HCC, loco-regional therapies, including partial resection of the cirrhotic liver, can exacerbate portal hypertension by increasing blood flow within the remnant organ. We conclude that studies of HVPG reduction as part of HCC management may be beneficial and are warranted.