Neuropathy in Liver Failure
Abstract & Commentary
By Michael Rubin, MD, Professor of Clinical Neurology, Weill Cornell Medical College. Dr. Rubin reports no financial relationships relevant to this field of study.
Synopsis: Neuropathy occurs with a high frequency in patients with end-stage liver disease, but rarely causes disability.
Source: Cocito D, Maule S, Paolasso I, et al. High prevalence of neuropathies in patients with end-stage liver disease. Acta Neurol Scand DOI: 10.1111/j.1600-0404.2009. 01256.x
If you look up "liver disease" in the index of the two-volume classic tome, Peripheral Neuropathy (Dyck PJ, Thomas PK, 3rd. edition, Philadelphia: Saunders), you will find only five listings: one each for acute and chronic inflammatory demyelinating neuropathy, amyloid, Fabry's disease, and vitamin E deficiency in childhood cholestatic liver disease. The association with acute inflammatory demyelinating neuropathy is tenuous, chronic inflammatory demyelinating neuropathy in liver disease is usually mild and subclinical, Fabry's disease affects Kupffer cells to some degree but not hepatocytes, amyloid affects liver and nerve independently, and neuropathy does not occur with normal vitamin E levels. Neuropathy is clearly unusual in liver disease; but just how unusual, and what type of neuropathy does it cause?
Retrospective analysis of 83 patients with advanced liver failure awaiting transplantation, including 61 men and 22 women with a median age of 53.8 years, was undertaken to determine the presence, distribution, type, cause, and pathogenesis of neuropathy. Correlation between neuropathy, liver disease severity, and disability was also examined. Routine nerve conduction studies (NCS) and autonomic function tests were used to determine the presence of neuropathy. NCS included study of the sural and ulnar sensory nerves, and the ulnar and peroneal motor nerves. Autonomic function tests included heart-rate response to deep breathing, Valsalva maneuver, baro-reflex sensitivity, and postural blood pressure change. Disability was assessed using the Rankin scale, the Medical Research Council scale, the Sensory Sum Score scale, and the Overall Neuropathy Limitations scale. Statistical analysis included Student's t-tests and Pearson correlations.
All patients had cirrhosis, usually from viral hepatitis type C (n = 34), hepatitis type B (n = 7), alcohol abuse (n = 7), primary biliary cirrhosis (n = 5), or miscellaneous (n = 11). None had primary systemic amyloidosis, five were cryptogenic, and 14 had more than one cause. Neuropathy was diagnosed in 65% (54/83) by either nerve conduction studies or autonomic function tests. Nerve conduction studies were abnormal in 48, demonstrating sensorimotor or sensory axonal neuropathy in all but one, a patient with CIDP. Cardiovascular autonomic function tests were abnormal in 21 of 57 patients tested, including six who had normal nerve conduction studies. Neuropathy was more frequent with increased severity of liver disease, and more so in hepatitis C patients compared to other liver diseases, independent of severity of liver failure. Only Rankin and Overall Neuropathy Limitations scales were worse in neuropathy patients, compared to those without neuropathy, indicating a correlation between disability and neuropathy. Other causes for neuropathy were found in 74.5%, including diabetes, alcohol abuse, and hepatitis C infection with or without cryoglobulinemia. Peripheral neuropathy and autonomic neuropathy are common in liver failure and correlate with disease severity.
Neuropathy may occur following liver transplantation as well, but is rare and focal in nature.1 Among 649 liver transplantations performed in The Department of General, Liver and Transplant Surgery at The Medical University of Warsaw, Poland, between 2000-2008, 10 patients (1.5%; five men and five women), mean age 39.3 years, developed symptoms consistent with neuropathy, including peroneal neuropathy (n = 5), arm weakness or paraesthesiae (n = 2 each), and facial nerve paralysis (n = 1). None had a prior history of neurological complaints. Iatrogenic causes predominated, including cannulation of the axillary vein or adverse effects of immunosuppression (n = 2 each), and nerve compression due to forced recumbency (n = 5). Viral infection and trauma were the cause in one patient each and all patients recovered with conservative management and physical therapy.
1. Smoter P, Patkowski W, Zieniewicz K, et al. Peripheral neuropathy after liver transplantation. Ann Transplant 2009;14(Sup 1):44.