Hepatotoxicity (liver damage)

Liver damage can result from certain disease states, including infections, vascular disorders, and metabolic disease, or by the consumption of hepa- totoxins such as alcohol, certain drugs and chemicals, or deadly amanita mushroom poisons.

Chronic damage to the liver results in the condition termed cirrhosis. It is characterized by a diffuse increase in the fibrous connective tissue of the liver, with areas of both necrosis and regeneration of parenchymal cells imparting a nodular texture and hardening of the liver. In the United States, cirrhosis follows only cardiovascular disease and cancer as a cause of death in the forty-five to sixty-five age group, with most cases a result of chronic alcohol abuse. In many parts of Asia and Africa cirrhosis due to chronic viral hepatitis B is a major cause of death.

In general, the treatment of liver damage is supportive, with the exception that the recent availability of liver transplantation for patients with advanced cirrhosis or acute life-threatening liver damage from tox- ins has been life saving. Supportive treatment involves withdrawal of toxic agents, attention to nutrition (including supplemental vitamins), and

48 Tyler's herbs of choice: The therapeutic use of phytomedicinals the treatment of complications as they arise. Specific therapies focusing

on the alteration of fibrous connective tissue and collagen formation are experimental and still being evaluated. Corticosteroids and penicillamine are two drugs in this category that have uncertain value.

Four herbal medicinal preparations commonly used in the treatment of liver disease—namely, Phyllanthus amarus Schum. (family Euphorbiaceae), Silybum marianum (L.) Gaertn. (family Asteraceae), Glycyrrhiza glabra L. (fam-

ily Fabaceae), and Liv-52, a combination Ayurvedic herbal preparation—have been reviewed. 99 Phyllanthus showed a positive effect on clearance of hepatitis

B viral (HBV) markers, and no major adverse effects were evident in consid- eration of twenty-two RCTs (n = 1,947) (thirteen monopreparations and nine combination products). However, due to the low methodological quality of most of these trials and limited follow-up, Phyllanthus was not recommended for clinical use in patients with chronic HBV infection until larger-scale pro- spective multicenter, randomized controlled trials demonstrate consistent benefit. Recently, a potent ex vivo anti-HIV activity was detected in sera of volunteers after administration of a P. amarus preparation. 100

Although milk thistle extract appears safe and well tolerated, it does not reduce mortality among patients with chronic liver disease and improves neither biochemical markers nor histology at biopsy among such patients. As such, a recommendation of such preparations for treatment of liver disease is not warranted.

The licorice preparation here evaluated is actually an aqueous extract of G. glabra root containing 0.2 percent glycyrrhizin, combined with 0.1 percent cysteine and 2 percent glycine, a Japanese product termed “stron- ger neominophagen C” (SNMC). RCTs with SNMC indicate that it does not have antiviral properties, acting primarily as an anti-inflammatory or cytoprotective drug. It improves mortality in patients with subacute liver failure, compared to historical controls, but does not prevent chronic sequelae in uncontrolled experiments. However, it appears to improve liver function in patients with subacute hepatic failure and to prevent development of hepatocellular carcinoma in patients with chronic hepatitis C in similar experiments.

Liv-52 has been judged “not useful in the management of alcohol- induced liver disease.” However, a contemporary RCT concluded that the combination herbal product possesses hepatoprotective effect in cirrhotic patients, attributable to diuretic, anti-inflammatory, antioxidative, and immunomodulating properties of the component herbs. 101

Hepatotoxicity (liver damage)