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Hepatitis B

Nutritional Strategies for Hepatitis B

Although research on specific nutritional strategies for HBV infection is not as broad as for HCV infection, evidence suggests that natural compounds can be of benefit for both conditions (See the Hepatitis C protocol for more information).

Selenium. Selenium is an essential trace element with protective roles in the defense against free radicals, liver detoxification reactions, and immunity (Rauf 2012). Chronic hepatitis patients (as well as those infected with hepatitis C virus) tend to be selenium deficient compared to their uninfected counterparts. The degree of deficiency relates to the severity of HBV infection (in one study, selenium levels dropped by 50% in HBV-infected men) (Khan 2012). Adequate selenium may also be associated with less liver damage in HBV-infected patients (Abediankenari 2011). It is suggested that HBV and HCV patients be tested for selenium adequacy and supplemented if deficient (Khan 2012). Long-term selenium treatment reduced HBV infection by 77% and liver lesions by over 75% in an animal model. In an 8-year trial, treatment reduced the incidence of liver cancer in HBV patients by 35% (Yu 1997).

Coffee and related compounds. Evidence from several European and Japanese studies suggests coffee consumption is associated with reduced risk of liver cancer in. Heavy coffee consumption (defined in the studies as over 3 cups daily by Europeans, or over 1 cup daily by Japanese) reduced hepatocellular carcinoma (HCC) risk by an average of 55% over 10 observational studies (Bravi 2007; Larsson 2007). Moderate coffee consumption (4 or more cups weekly) in HBV carriers reduced hepatocellular cancer incidence by almost 60% in a separate study (Leung 2011). Chlorogenic acid, a compound isolated from coffee, was shown to inhibit HBV viral replication in isolated liver cells, and reduce blood levels of HBV in an animal model. Its efficacy was comparable to the nucleoside analog lamivudine (Wang 2009a). Special coffee roasting procedures can retain chlorogenic acid, which is normally depleted by Dian roasting procedures. Chlorogenic acid is also supplied by green coffee extract supplements.

Green tea. Green tea and its major antioxidant component epigallocatechin gallate (EGCG) reduce the levels of HBV DNA and hepatitis B antigens in isolated liver cells by inhibiting the replication of HBV DNA (Xu 2008; He 2011). A study of 204 HCC cases in Chinese individuals with HBV infection revealed that green tea consumption reduced the risk of cancer progression by nearly half (Li 2011). But a Japanese study of 110 cases of HCC could not determine any effect of green tea consumption on cancer risk (Inoue 2009).

Zinc. Zinc, which is found in various enzymes, has a role in immunoregulation (Balamtekin 2010). Clearance of viral infection requires the activity of T-cells, which are highly dependent on zinc (Kuloğlu 2011). Levels of zinc (as well as molybdenum, manganese, and selenium) are reduced in HBV-infected children compared to healthy subjects (Balamtekin 2010). Low serum zinc is associated with elevated blood levels of liver enzymes (aspartate aminotransferase and alanine aminotransferase; markers of liver damage) in adults (Abediankenari 2011). In one study, children with higher serum zinc levels had a better response to interferon (IFN) therapy (Ozbal 2002). In another study, the response to combination therapy of zinc and IFN-α in HBV infection was not significantly different than IFN-α alone. However, researchers speculate that the lack of response may have been due to the low dose of zinc administered (7.5 – 10 mg) (Kuloğlu 2011).

Lactoferrin. Lactoferrin is an antimicrobial protein with inhibitory activity against several viruses, possibly through interactions with host cells or direct binding to the invading virus. The antiviral activity of lactoferrin (a major protein in milk) may partially explain the low incidence of mother-to-child transfer of HBV through breastfeeding in humans (Petrova 2010). Isolated human liver cells pre-treated with bovine or human lactoferrin were resistant to HBV infection (Hara 2002). Bovine lactoferrin, as well as zinc- and iron-saturated lactoferrin, inhibited HBV replication in infected human liver cells in culture (Li 2009).

Iron-sequestering compounds. High serum and hepatic iron have been associated with a reduced response to IFN treatment and increased risk of disease progression in chronic hepatitis B patients (Fiorino 2011). While their efficacy in HBV treatment has not been examined, several compounds have been shown to reduce iron absorption from the gut or chelate iron from cells or body fluids; these include several flavonoids (Mladěnka 2011), pectin (Monnier 1980), silybin from milk thistle (Borsari 2001) and curcumin (Thephinlap 2011). Lactoferrin (Brock 1980) and green tea (Mandel 2006) may also have iron-sequestering activity in addition to their anti-viral activity. More information is available in the Iron Overload Disorders protocol.

B Vitamins. Patients with chronic hepatitis B exhibit marked increases in oxidative stress and lipid peroxidation along with decreased antioxidant status (Duygu 2012). Vitamin B1 (thiamine) is required for the formation of dihydrolipoate, an important antioxidant and cofactor in iron metabolism, two functions with relevance to HBV disease mitigation. A small study on Chinese children with chronic HBV demonstrated similar reductions in HBV DNA and hepatitis B e-antigen (HBeAg) between thiamine and standard IFN therapies. But a second study in the same population showed no effect of thiamine on HBV (Fiorino 2011). Chronic HBV infection reduces levels of vitamins B2 (riboflavin) and B6 (pyridoxine) in red blood cells (Lin 2011). Supplementation with these vitamins may be helpful in HBV patients, although their effects on mitigating HBV disease are unknown (Lin 2011).

Vitamins C and E. Vitamin C and E stores are also reduced in chronic HBV patients (Tasdelen Fisgin 2012). Three small studies of vitamin E therapy in HBV-infected children and adults suggest a possible role for the antioxidant in the clearance of HBV DNA, adaptation of immune response to the viral antigen, and normalization of liver enzymes levels (Fiorino 2011).

Resveratrol. In an animal model of HBV-associated liver disease resveratrol reduced fatty changes in the liver and structural alterations of liver cells (such as degradation of mitochondria), raised cellular glutathione levels, and decreased reactive oxygen species. Additionally, resveratrol reduced incidence of HCC by 5-fold, and enhanced liver cell proliferation and liver regeneration (Lin 2012).

Curcumin. Curcumin reduces viral replication and expression of HBV genes in isolated human hepatocytes by inhibiting the activity of the metabolic regulator PGC-1α (Kim 2009; Rechtman 2010). PGC-1α, which is activated during starvation and turns on genes involved in glucose production, also increases the replication of HBV (Rechtman 2010).

N-acetyl-cysteine. N-acetyl-cysteine (NAC) is derived from L-cysteine, a conditionally essential amino acid. This powerful antioxidant diminishes free radicals and raises glutathione levels (Nguyen-Khac 2011). It reduces viral load in experimental models by disrupting the assembly of HBV virus particles (Weiss 1996). The few studies of NAC in HBV patients have had mixed results. Dosages of 1200 to 8000 mg/day were able to raise glutathione levels in chronic HBV patients or lower levels of bilirubin (high bilirubin can indicate liver dysfunction), but did not significantly affect most other markers of liver function (Shohrati 2010; Wang 2008; Shi 2005). Neither oral nor intravenous NAC significantly affected HBV viral load or time to patient recovery, although differences in dosages and small study populations may preclude any conclusions about NAC therapy for HBV (Gunduz 2003; Weidenbach 2003).

Phyllanthus. Phyllanthus, a genus of plant used to treat chronic liver disease in traditional Chinese and Indian medical systems, has demonstrated inhibition of HBV viral replication and antigen synthesis in isolated cells as well as in animal models (Cui 2010). A review of several small clinical trials suggests some positive effects of Phyllanthus on parameters of HBV infection and significant reductions in serum HBV antigen. Several species of Phyllanthus were used in these trials; one of the most commonly used is Phyllanthus amarus at a dose of 600 to 1200 mg daily (Liu 2001). Fifteen trials have investigated combinations of Phyllanthus and antiviral drugs (INF-α, lamivudine, adefovir dipivoxil, thymosin, vidarabine), and demonstrated significant improvements associated with combination therapy over antiviral drugs alone, such as reducing blood levels of HBV DNA & HBV antigen, and increasing immune response to HBV (Xia 2011).

Whey protein. In addition to its anabolic benefits, long-term supplementation with whey protein may increase antioxidant status and reduce markers of liver damage (Marshall 2004). An open label study of 8 chronic hepatitis B patients revealed that 12 grams twice daily of undenatured whey protein reduced alanine aminotransferase (ALT) activity in 6 of the patients and raised glutathione in 5 after 12 weeks of supplementation. Additionally, markers of lipid oxidation significantly decreased, while interleukin-2 levels and natural killer (NK) activity (both involved in immune response) significantly increased (Watanabe 2000).

Astragalus. Astragalus root has a history of traditional usage in Chinese medicine for immune and liver health. It inhibited secretion of HBV antigens from isolated human liver cells infected with the virus, and reduced levels of HBV DNA in a hepatitis B animal model (Wang 2009b). A mixture of astragalus polysaccharide and another plant extract called emodin demonstrated significant reductions in HBV DNA and HBV antigens (HBsAg, HBeAg and HBcAg) in a hepatitis B mouse model (Dang 2009). A Chinese study examined the effectiveness of astragalus and adjuvant compounds (Bupleurum chinense, Salviae miltiorrhizae, curcumin, peony and paeoniae) (116 grams daily as a tea) in 116 chronic HBV patients. Two months of treatment with the tea was clinically effective (defined as improvement in clinical symptoms -- fatigue, anorexia, abdominal distension, jaundice -- and partial or full recovery of liver function) in 91% of patients, compared to 70% of controls (who took a low-dose mixture of silibinin, oleanic acid, and the herb Yi-Gan-Ling) (Tang 2009).

Schizandra. Members of the genus Schizandra inhibited the secretion of virus antigens from isolated human liver cells by up to 76.5% in one experiment (Ma 2009a,b; Wu 2003). A Schizandra-containing herbal formulation reduced the production and secretion of HBsAg and HBeAg surface antigens (a measurement of virus particle secretion) from isolated liver cells, and reduced the growth of isolated hepatocellular carcinoma cells (Loo 2007). In a Phase I trial, 23 volunteers with HBV infection took the herbal formulation daily for 10 weeks. The average number of monocytes (a type of circulating immune cell) in the blood decreased over the course of the study, which the authors suggested may lower self-inflicted host immune response and liver cell destruction (Yip 2007).

Milk Thistle. Milk thistle is a traditional liver tonic; the active compound in milk thistle (silymarin) has antioxidant and antifibrotic activity (Abenavoli 2010). Although it does not affect HBV viral replication, and has yet to demonstrate a significant effect on virus-related mortality in clinical trials (Rambaldi 2005), milk thistle may be beneficial in reducing the inflammation inherent to hepatitis that may precipitate complications such as cirrhosis or cancer (Abenavoli 2010). Silibinin, a component of silymarin, slows the growth of isolated human hepatocellular carcinoma cells, and exhibits the strongest inhibition towards cancer cells positive for the hepatitis B virus (Varghese 2005). In an animal model of hepatitis B infection, silymarin prevented the progression of pre-cancerous lesions into hepatocellular carcinoma, but had no effect on existing cancer. Cancer developed in 80% of control animals (Wu 2008). A small trial in mixed hepatitis patients demonstrated that 480 mg silibinin daily for 7 days could significantly reduce aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltranspeptidase (GGT), and bilirubin, all markers of liver dysfunction (Buzzelli 1993).