fatty liver effected by hepatitis c

Hepatitis C

Hepatitis C

Last Section Update: 05/2019

Contributor(s): Cindy Embleton, MS; Shayna Sandhaus, PhD

Table of Contents

  1. Overview
  2. Introduction
  3. Hepatitis C Virus Transmission
  4. Disease Course and Outcomes
  5. Diagnosis
  6. Conventional Treatment
  7. Nutrients
  8. Update History
  9. References

1 Overview

Summary and Quick Facts for Hepatitis C

  • Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV), which infiltrates the liver and other organs. Approximately 75%-85% of people infected with HCV develop a chronic infection and face the risk of advanced liver fibrosis, cirrhosis, cancer and other complications.
  • In this protocol, you will learn how HCV is transmitted and the consequences of HCV infection. You will also discover the importance of early detection and learn about breakthroughs that have vastly improved medical treatment outcomes, as well as several natural compounds that support liver health.
  • Direct-acting antiviral (DAA) drugs have eliminated HCV in the majority of treated patients. Natural, integrative interventions may support liver and general health but are not replacements for highly effective modern DAA drugs.

What is Hepatitis C?

Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV). HCV infection generally infiltrates the liver and is the primary reason for liver transplants in the United States. Many HCV infections become chronic and can increase the risk of advanced liver fibrosis, cirrhosis, cancer, and other complications.

Many people may not realize they have hepatitis C, as it is usually asymptomatic until advanced stages of liver damage. Proactive regular blood tests in high-risk populations may help detect abnormalities early. HCV is transmitted via infected blood, commonly by sharing needles during intravenous (IV) drug use. It is not usually transmitted sexually.

Due to medical advances, HCV infections are often curable. In addition, natural interventions such as N-acetylcysteine and selenium may help protect the liver from damage.

What are the Risk Factors for Hepatitis C?

  • Illicit IV drug use
  • Tattooing or body piercing
  • Exposure to contaminated items (eg, toothbrushes, razor blades)
  • Blood transfusion before 1992
  • Infant born to HCV-infected mother (Note: risk increases if HCV-infected mother also has HIV)

What are the Signs and Symptoms of Hepatitis C?

Note: Most cases of acute hepatitis C are asymptomatic. Symptoms, if present, may include:

  • Fever
  • Fatigue
  • Tenderness in the liver area
  • Nausea
  • Decreased appetite
  • Jaundice

What are Conventional Medical Treatments for Hepatitis C?

Note: Treatment regimen will vary depending on the genotype of the virus and the patient’s specific needs, and will usually include a combination of medications.

  • Direct-acting antivirals (DAAs), the gold standard treatment, target specific HCV proteins and disrupt replication and infection
  • Ribavirin is sometimes used as an add-on to DAAs to prevent viral replication
  • Pegylated interferons (rarely used now) help the immune system recognize and attack the virus

What Natural Interventions May Be Beneficial for Hepatitis C?

Note: Because modern medicine has been so successful in treating hepatitis C, it is very important to seek professional medical attention for the disease and adhere to prescribed treatment regimens. Do not attempt to use natural interventions instead of seeking conventional medical care. The natural, integrative interventions discussed in this section may support liver and general health but are not replacements for highly effective modern DAA drugs.

  • N-acetylcysteine (NAC). NAC, because it raises glutathione levels, is used to detoxify the liver in the case of acetaminophen poisoning. It is unclear whether NAC can help patients with HCV, but it is well tolerated.
  • S-adenosyl-L-methionine (SAMe). SAMe is a methyl donor involved in glutathione synthesis. Addition of SAMe to pegylated interferon plus ribavirin treatment may result in improved responses.
  • Lipoic acid. Lipoic acid is an antioxidant that can repair damage from oxidative stress. Clinical studies have shown antioxidant blends containing lipoic acid favorably modulate HCV RNA level and liver biopsy score in HCV-infected patients.
  • Whey protein. Whey protein improves glutathione levels and immune function. One study found that supplementation reduced viral load and had other positive effects in HCV-infected patients.
  • Selenium. Selenium is an essential cofactor of glutathione peroxidase. Patients with hepatitis B and C have been found to have lower selenium levels than healthy individuals, and therefore may benefit from supplementation.
  • Lactoferrin. Lactoferrin, an iron-binding glycoprotein with antiviral activity, has been shown to significantly lower the HCV RNA titer and improve efficacy of subsequent treatments.
  • Milk thistle. Milk thistle derivatives have demonstrated antiviral and antifibrotic activity in the liver. In one trial, patients using silymarin (a milk thistle derivative) had fewer liver-related symptoms and somewhat higher quality-of-life scores.
  • Polyenylphosphatidylcholine (PPC). PPC is an important component of essential phospholipids that can protect against liver damage. Numerous clinical trials have shown essential phospholipids improve chronic hepatitis.
  • Vitamin D. Vitamin D levels are diminished in patients with hepatitis C. One trial showed that adding vitamin D to a pegylated interferon plus ribavirin drug regimen improved outcome.
  • Zinc and zinc-carnosine. Zinc has HCV-inhibiting activity. Supplementation with chelated zinc-carnosine has been found to reduce liver damage and improve long-term outcome in patients with chronic HCV infection or liver cirrhosis.
  • Other natural interventions that may help patients with hepatitis C include Schisandra chinensis, licorice root extract, coffee, green tea, curcumin, quercetin, and L-carnitine.

2 Introduction

Hepatitis is a medical term meaning inflammation of the liver. Hepatitis can result from a variety of infectious (eg, hepatitis B and C viruses) and noninfectious causes (eg, alcohol abuse).

Hepatitis C is an infectious disease caused by the hepatitis C virus, which infiltrates the liver and other tissues.1 The virus causes inflammation, oxidative stress, and DNA damage. Manifestations of hepatitis C can range from a mild illness lasting a few weeks to a serious lifelong disease that culminates in liver cirrhosis or cancer. In the United States, chronic hepatitis C has long been a leading cause of chronic liver disease and a top indication for liver transplantation. However, the advent of new, curative drugs offers the promise to significantly alter the public health impact of this disease.

Hepatitis C represents a case study in the marvels of modern medicine. Treatment regimens have evolved rapidly in recent decades, and the once-feared infectious disease can now be cured in most cases. By the late-2010s, the U. S. Food and Drug Administration (FDA) had approved several members of a new class of drugs called direct-acting antivirals (DAAs). These drugs eliminate hepatitis C virus (HCV) from patients’ bodies in about 95% of cases in as little as eight weeks. Although they remain costly, DAAs embody a tremendous success in the battle against chronic hepatitis C.2

Unfortunately, many people live with an HCV infection for many years without realizing their health has been compromised. The insidious nature of chronic hepatitis C can cause delays in diagnosis until advanced liver damage is already present.3 This is why blood tests for the presence of HCV among high-risk populations are important. Preventive testing for hepatitis C can allow early detection so treatment may begin before the disease reaches a critical stage.4 Periodic blood testing can also help monitor liver health in those with hepatitis C as well as healthy individuals.

In this protocol, you will learn about HCV transmission and the consequences of HCV infection. You will also discover the importance of early detection and learn about breakthroughs that vastly improved medical treatment outcomes, as well as several natural compounds that support liver health.

3 Hepatitis C Virus Transmission

HCV is transmitted primarily via exposure to infected blood or blood products. Any HCV carrier can potentially transmit the infection.5 The most common mode of transmission is sharing contaminated needles during intravenous (IV) drug use.6 Having had a blood transfusion before 1992 is a known risk factor as well. Other possible risk factors include body piercing, tattooing, and exposure to contaminated items such as toothbrushes, razor blades, or nail clippers.7,8 While sexual transmission of HCV is possible, rates are low.8-11

Approximately 6% of infants born to HCV-infected mothers acquire the infection during childbirth. Transmission risk increases 2- to 3-fold if the HCV infected mother also has human immunodeficiency virus (HIV). Breastfeeding does not increase risk of transmission.7

4 Disease Course and Outcomes

Acute Phase

The first six months of HCV infection encompass the acute phase.12 Because it passes with few, if any signs or symptoms in most cases, this stage of the illness is usually dismissed by the patient. About 15‒25% of adults with acute HCV infection may develop clinical symptoms. The symptomatic onset ranges from 3 to 12 weeks after exposure.13,14 Symptoms, if they occur, can include fever, fatigue, tenderness in the liver area, nausea or decreased appetite, and jaundice.12,13

Chronic Phase

Approximately 75‒85% of HCV-infected persons will progress to chronic HCV infection.13

The chronic phase is generally established when HCV genetic material (RNA) persists in the patient's serum for 6 months or more.13,14

Numerous factors appear to affect the likelihood of developing chronic HCV infection. Females are more likely to clear the virus, for example, as are people who develop jaundice during the acute phase. In contrast, the virus is prone to persisting in patients co-infected with HIV.13,14

Although the disease is transmittable during the chronic phase through blood, chronic HCV infection is usually either asymptomatic or has only non-specific symptoms such as fatigue or depression.15

While elevations of alanine transaminase (ALT)—a liver enzyme that increases in response to liver cell death13—may be observed, ALT testing is commonly used to monitor disease progression or liver function recovery after treatment, rather than in the diagnosis of HCV infection or disease.

Importantly, although chronic hepatitis C infection is generally thought of as primarily affecting the liver, it can manifest as health problems throughout the body. Chronic hepatitis C can give rise to insulin resistance and diabetes, autoimmune conditions, and some non-liver cancers, such as lymphoma. Recent studies revealed associations between HCV infection and cardiovascular, kidney, and central nervous system diseases.1 About three-quarters of those with chronic hepatitis C develop these non-liver manifestations.16

Outcomes

Within the first 20 years of infection, advanced liver disease may develop. During this timeframe, roughly 10‒15% of patients develop cirrhosis of the liver—the replacement of healthy liver tissue by dysfunctional fibrous tissue and nodules.13,14

Up to 4% of patients with HCV-related liver cirrhosis develop liver cancer each year.17 Liver cancer may be suspected in someone with advanced HCV-related liver cirrhosis who experiences sudden weight loss, elevated liver function tests, or pain or fullness in the right upper abdomen.18

More than a third of liver transplants are a consequence of hepatitis C.19,20 Although five-year survival following transplant is good (up to 85%), hepatitis C patients who receive liver transplants can have a recurrence of the infection.20,21

Iron Overload and HCV

HCV-induced oxidative stress appears to disrupt iron balance by suppressing levels of a hormone called hepcidin, which is a regulator that helps control iron absorption.22-24 Low hepcidin levels lead to increased iron accumulation in the liver24,25; this is common in HCV.26-28 Excess iron in the liver may, in turn, create more oxidative stress, causing liver injury and fibrosis.29,30

In a study of the impact of iron overload on oxidant/antioxidant systems, scientists found evidence that the HCV core protein inhibits iron-induced activation of antioxidants in the liver, exacerbating oxidative stress, which could facilitate the development of liver cancer.31 Hepatic iron depletion has been postulated to decrease the risk of hepatocellular carcinoma in patients with cirrhosis due to chronic hepatitis C.23

Phlebotomy (ie, therapeutic bloodletting) to reduce iron levels significantly improves liver enzyme levels in HCV patients32 and yields histological improvements33 as well as increased response to interferon treatment.34-36 Additional findings suggest iron depletion may lower the risk of developing hepatocellular carcinoma.37

At a minimum, most hepatitis C patients should avoid supplements containing iron and seek to reduce dietary sources of iron such as red meat. Vitamin C facilitates iron absorption while calcium and green tea impede it. Hepatitis C patients should take vitamin C at a different time than when eating iron-rich foods.

5 Diagnosis

HCV infection usually does not cause symptoms, so diagnosis depends on laboratory blood tests. Baby boomers (people born between 1945 and 1965) and certain other populations with a high risk of infection should undergo HCV screening, which measures HCV antibodies and HCV ribonucleic acid (RNA). Testing positive for HCV antibodies means you have been exposed to HCV in the past but do not necessarily have an active infection at the time of testing. Some people fight off HCV infection, but the antibodies persist to help the immune system respond efficiently if it encounters the virus again.15 The HCV RNA test can determine if you have an active HCV infection.

In the event of positive screening tests, testing for HCV genotype helps guide selection of the most appropriate antiviral regimen.

Non-Invasive Tools to Monitor Hepatitis C Progression

In HCV patients, determining the degree of fibrosis progression in the liver is crucial—and new methods may make this possible without the need for an invasive liver biopsy.

One approach synchronously combines blood tests (FibroMeters) and ultrasound-based transient elastography (Fibroscan), which are then algorithmically analyzed to yield a thorough liver fibrosis assessment.38-41

In a large study of 1,785 patients with chronic hepatitis C, the diagnostic accuracy of this method did not differ significantly from that of standard algorithms, but it provided a more precise diagnosis.42 Also, this new combination method is much more accurate at classifying fibrosis stage than FibroMeters or Fibroscan alone.38

Another noninvasive strategy, FibroTest, uses the results of five blood tests to generate a score that correlates with the degree of liver damage.43

In a study involving 1,457 patients with chronic hepatitis C, noninvasive liver fibrosis tests helped predict 5-year survival of people with chronic HCV. Patient outcomes declined with increased liver stiffness and FibroTest values. FibroTest may facilitate an earlier prognosis so certain treatments, such as liver transplant, can be evaluated.44 FibroTest and ActiTest (an assessment of necroinflammatory activity) are marketed in the United States as FibroSure.40,45

6 Conventional Treatment

HCV infection is now curable in most cases. “Cure” is defined as absence of HCV from the bloodstream after treatment. This is called sustained virologic response, or SVR.46 This remarkable advancement is the result of the effectiveness of direct-acting antivirals (DAAs). Viral clearance makes possible a range of benefits, both to the liver and other body systems, and can prevent ongoing destruction of cells, tissues, and organs by active HCV.47 As a result of these medical advances, the goals of HCV treatment are now eradication of the virus and preventing progression to negative outcomes like liver cancer or death.

An encouraging example of how these benefits extend beyond just the liver is the improvement in glucose metabolism seen after viral clearance. Although this phenomenon occurred before the advent of DAAs, the high cure rates and short treatment courses with current treatments mean the risk of a common and serious non-hepatic consequence of HCV infection is now far lower in the majority of patients. Several studies found DAA-induced SVR resulted in lower serum glucose and hemoglobin A1C levels, improved insulin sensitivity, a reversal of prediabetes, and a markedly decreased risk of diabetes.48-50 Improvement in conditions related to disturbed glucose and insulin metabolism, including elevated serum triglycerides, low HDL-cholesterol, high blood pressure, and even atherosclerosis has also been observed.50

It is very important to note that achieving a cure with medications does not make you immune to another HCV infection in the future. Re-infection with HCV after an initial cure (often with a different genotype than the original infection) is a concern for some people who engage in high-risk behavior.16

Direct-acting Antivirals (DAAs)

The development and approval of DAA therapy, which first became available in 2011, has rapidly transformed the hepatitis C treatment landscape. In the recent past, standard HCV treatment typically consisted of 24 to 48 weeks of treatment with injected pegylated interferon alpha plus oral ribavirin, which produced SVR rates of 40‒50%. These treatment regimens often caused adverse side effects such as hemolytic anemia, psychiatric disturbances, and flu-like symptoms.51 Pegylated interferon has a poor safety profile and is now rarely used for treating hepatitis C. Ribavirin, also associated with significant adverse effects, is sometimes used as an add-on to DAA treatment in certain cases of hepatitis C.52,53

In contrast, DAA regimens can result in SVR rates of over 95% after 8‒16 weeks of treatment, are taken as convenient oral pills, and have a far better side effect profile. In cases with more intractable virus types and more extensive disease, SVR rates of 78‒87% have been reported. Although DAAs remain cost-prohibitive in some cases, the approval of less expensive combination drugs, notably glecaprevir-pibrentasvir (Mavyret), has begun to make treatment more affordable for some.54

There are a variety of DAA medications available. The best approach for any patient is determined by his or her physician, who will take into consideration viral genotype and medical history factors such as liver health, previous treatments, and presence of concomitant infections (eg, HIV or HBV). Table 1 provides a general outline of some of the main variables affecting the choice of medication.47

Table 1: Direct-Acting Antivirals for Hepatitis C Treatment

Drug

HCV genotypes treated

Dosage Regimen

Cirrhosis

Details

Sofosbuvir (Sovaldi)

Suitable for all 6 genotypes

Now primarily used in combination medications, including with daclatasvir

With daclatasvir in advanced cirrhosis

Sofosbuvir in combination with ribavirin was the first FDA-approved all oral therapy for hepatitis C

Daclatasvir (Daklinza)

Genotypes 1‒4

Combined with sofosbuvir and sometimes ribavirin

With sofosbuvir in advanced cirrhosis

Ledipasvir-Sofosbuvir (Harvoni)

Genotypes 1, 4, 5, and 6; including 1A*

(*not including those with 1A and with cirrhosis or who have failed prior treatment)

One pill per day

Yes

For many patients, an eight-week course of treatment is as effective as 12 weeks

The first FDA-approved interferon- and ribavirin-free regimen to treat hepatitis C

Glecaprevir-Pibrentasvir (Mavyret)

Suitable for most patients. SVR rates in the range of 98‒100% for 8 or 12 weeks in genotypes 1, 2, 5, or 6

3 tablets, once daily, with food

Early cirrhosis (class A) only, 12-week treatment

Eight-week treatment of genotypes 3 and 4 resulted in SVR of 95% and 93%

A slightly lower cost option, but availability may be somewhat limited

Sofosbuvir-Velpatasvir (Epclusa)

Genotypes 1–4. Regimens and durations differ depending on genotype

One pill per day

Yes

Elbasvir-Grazoprevir (Zepatier)

Genotypes 1 and 4; genotype 1A requires resistance testing

One pill per day

Yes; not for advanced cirrhosis

Ombitasvir-Paritaprevir-Ritonavir (Technivie)

Genotype 4, including those who have received prior treatment

Oral, two tablets once daily with a meal

No

Ombitasvir-Paritaprevir-Ritonavir and Dasabuvir (Viekira Pak)

Genotype 1a (without cirrhosis or with compensated cirrhosis when given with ribavirin); Genotype 1b (without cirrhosis or with compensated cirrhosis)

Oral, two ombitasvir/ paritaprevir/ritonavir 12.5/75/50 mg tablets once daily in the morning, and one dasabuvir 250 mg tablet twice daily, morning and evening, with a meal

In some cases

Ritonavir boosts efficacy of other medications; it does not have anti-HCV activity

Sofosbuvir-Velpatasvir-Voxilaprevir (Vosevi)

Important option for multiple genotypes when previous DAA treatment has failed

One pill per day, with food

Not suitable for moderate-to-severe (class B or C) cirrhosis or post liver transplant with cirrhosis

7 Nutrients

Because modern medicine has been so successful in treating hepatitis C, it is very important to seek professional medical attention for the disease and adhere to prescribed treatment regimens. You should not attempt to use natural interventions instead of seeking conventional medical care. The natural, integrative interventions discussed in this section may support liver and general health but are not replacements for highly effective modern DAA drugs.

Liver Glutathione and Oxidative Stress

Glutathione acts as a cellular detoxifier and helps prevent damage from free radicals.55 However, glutathione depletion is a common finding among HCV-infected patients.56 The following compounds may help increase glutathione levels.

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.57 Intravenous and oral NAC is used to treat acetaminophen poisoning in the hospital setting. In children with acute liver failure from causes other than acetaminophen poisoning, receiving NAC was associated with a shorter hospital stay, greater incidence of liver recovery, and better survival after transplantation.58 In an early trial, addition of NAC to interferon boosted glutathione levels in white blood cells of patients with chronic hepatitis C and normalized ALT levels in 41% of interferon non-responders.59 While more recent trials have been unable to confirm the therapeutic role of NAC in chronic hepatitis C, they have established that it is very well tolerated.60,61

S-adenosyl-L-methionine. S-adenosyl-L-methionine (SAMe), a methyl donor for numerous methylation reactions, has been studied for its antidepressant properties.62 SAMe also regulates glutathione synthesis.63 In HCV-infected patients who were non-responders to previous antiviral therapy, adding SAMe to a pegylated interferon plus ribavirin (PEG-IFN/RBV) regimen improved early viral response.64 In a separate trial, SAMe and trimethylglycine (another methyl donor) were given along with PEG-IFN/RBV to chronic hepatitis C patients. The treatment resulted in an early virologic response (EVR) in 59% of subjects, whereas PEG-IFN/RBV alone previously achieved only a 14% EVR.65

Lipoic acid. This free-radical scavenger helps repair damage caused by oxidative stress, assisting in the regeneration of important antioxidants such as glutathione and vitamin E.66 In animals, lipoic acid has been found to prevent fatty liver disease.67 In human trials, administration of antioxidant blends containing lipoic acid was shown to favorably modulate liver enzymes, HCV RNA levels, and liver biopsy score in HCV patients.68,69

Whey protein. Whey protein boosts glutathione levels and improves immune system function.70 In an animal model of hepatitis, whey protein supplementation attenuated chemical-induced liver enzyme elevations.71 Moreover, a clinical study found oral whey protein reduced viral load, decreased inflammation, lowered ALT levels, and exerted other beneficial effects in compensated chronic HCV-infected patients.70

Selenium. Selenium is an essential component of glutathione peroxidase, an enzyme that protects cells from free radical damage. Patients with hepatitis C or B have been found to have lower serum selenium concentrations than healthy individuals.72 Moreover, selenium deficiency is thought to contribute to insulin resistance in people with HCV-related chronic liver disease; and reduced selenium levels have been observed in patients with hepatocellular carcinoma.73,74

Glutathione. A 1989 study found consumption of oral glutathione increased plasma glutathione levels.75 Preclinical trials found oral glutathione increases glutathione levels in tissues such as the lungs, liver, and kidneys.76-80

Targeting Excess Iron Levels

Lactoferrin. Lactoferrin, an iron-binding glycoprotein, may be beneficial as an adjunctive treatment for serum iron overload in hepatitis patients. Lactoferrin is a potent antioxidant, antiviral agent, and scavenger of free iron. In addition, it is directly involved in the upregulation of natural killer cell activity, making it a natural mediator of immune function.81 As an immune mediator, lactoferrin may work synergistically with interferon to reduce viral load.82 In a study of patients with chronic HCV, lactoferrin alone significantly lowered HCV RNA titer and improved efficacy of subsequent treatment with interferon and ribavirin.83

Green tea. Epigallocatechin-3-gallate (EGCG) from green tea has been found to interrupt the first step of HCV infection by blocking the virus from entering target cells. In addition, EGCG inhibited cell-to-cell transmission of HCV. Both effects were observed regardless of the genotype tested. These findings carry important implications for the prevention of HCV re-infection in liver transplant patients.84 In addition, green tea has been shown to inhibit iron absorption in intestinal cells85 and accumulation in liver tissue,86 which can contribute to excessive oxidative stress.

Elemental calcium. Calcium inhibits iron absorption.87 Taking 600 mg elemental calcium can reduce iron absorption by as much as 60%.88

Additional Natural Liver Support

Milk thistle. Silymarin and its chief active ingredient, silibinin, are derived from milk thistle, a member of the daisy family. Both substances help the liver avoid toxic damage and regenerate after injury.

Silymarin

Findings from several studies suggest silymarin has potential antiviral,89 antioxidant,90 anti-inflammatory,89,91 and antifibrotic92 effects within the liver. It may also improve liver enzyme levels in HCV patients.93

In a recent cell culture study, silymarin inhibited HCV entry into cells, inhibited viral RNA and protein expression, and decreased cell-to-cell transmission of HCV.94

A clinical study involving 1,145 HCV-infected participants showed patients using silymarin had fewer liver-related symptoms and somewhat higher quality-of-life scores.95 Doses greater than 700 mg may improve bioavailability of silymarin; and oral doses up to 2.1 grams per day have been found to be safe and well tolerated.96

Silibinin

The antioxidant, antifibrotic, and metabolic effects of silibinin have been demonstrated in numerous studies.97,98 Silibinin also has antiviral capabilities.99,100

The clinical efficacy of oral silibinin in active chronic hepatitis C has not yet been clearly established.97,101 However, intravenous silibinin effectively treated HCV re-infection following liver transplantation in a small number of patients in one trial,102 and helped 85% of non-responders to standard of care achieve undetectable HCV RNA levels in another.103 Likewise, administering high doses of intravenous silibinin in addition to PEG-IFN/RBV therapy lowered viral loads in HCV-infected patients who were previous non-responders to treatment100; and 1,400 mg intravenous silibinin daily for 14 days successfully induced SVR in a 57-year-old liver transplant patient.104

A medical literature review found no significant side effects with silybin phytosome at doses up to 10 grams per day, and no significant interactions with other medications.97

Polyenylphosphatidylcholine. Polyenylphosphatidylcholine (PPC) is a major component of essential phospholipids.105 In addition to improving liver enzymes in HCV, 106 PPC replenishes levels of SAMe, a precursor to the potent antioxidant glutathione.107 PPC protects against liver damage105 and improves liver function.106,108 In animal studies, it has demonstrated antioxidant, cytoprotective, anti-inflammatory, and antifibrotic effects, inhibiting oxidative stress and the development of alcoholic liver disease.105,106 Numerous double-blind placebo-controlled clinical trials have shown essential phospholipids improve chronic hepatitis among human subjects.109

Schisandra chinensis. Berries from the Schisandra chinensis plant contain active ingredients that protect the liver. Crude schisandra and its extracts have traditionally held a role in Chinese and Japanese medicine,110 and S. chinensis has been used to treat chemical and viral hepatitis.111 A study examining the effects of a Japanese herbal combination containing S. chinensis indicated Schisandra fruit could inhibit HCV infection.112 The seed extract from S. chinensis appears to have liver-detoxifying capabilities, and components of the seed extract are thought to have anticancer, anti-inflammatory, liver-protective, anti-HIV, and immunomodulating effects.113

Licorice root extract. Licorice root extract (glycyrrhizin) is known to exert an antiviral effect against HCV.114 In Japanese HCV patients, long-term use of glycyrrhizin was shown to be helpful in preventing inflammation, liver cirrhosis, and hepatocellular carcinoma.115,116 The broad anti-inflammatory activity117 and antioxidant capabilities 118 of glycyrrhizin have also been observed. Adding a nutritional supplement containing vitamin C, glycyrrhizic acid, and other antioxidants to standard PEG-IFN/RBV treatment has been linked to a notably higher rate of biochemical and histologic improvements in patients with chronic HCV.119,120 In chronic HCV patients, oxidative stress and immunological parameters showed marked improvement following treatment with this blend.119

A preparation known as Stronger Neo-Minophagen C (SNMC) contains glycyrrhizin as an active component and has been used in Japan for more than 30 years to treat chronic hepatitis.116 In animals with HCV, SNMC has been found to prevent fatty liver disease121 and protect liver cells against carbon tetrachloride-induced oxidative stress by restoring depleted glutathione levels.122 A possible side effect associated with ingestion of large amounts of licorice is hypertension123; therefore, blood pressure should be monitored regularly.

Vitamin D. Diminished vitamin D levels have been observed in HCV patients.124,125 Low serum vitamin D levels are associated with severe fibrosis, as well as a low SVR to PEG-IFN/RBV treatment in patients with chronic HCV infection125; and vitamin D supplementation has been found to enhance HCV response to PEG-IFN/RBV therapy.126 In a recent study involving patients with HCV genotype 2-3 receiving PEG-IFN/RBV treatment, supplementing with oral vitamin D significantly improved viral response. Twenty-four weeks after treatment, 95% of the treatment (vitamin D) group was HCV RNA negative versus 77% of the control group.127

Coffee. A recent study showed patients with advanced HCV-related chronic liver disease who drank 3 or more cups of coffee per day were about 3 times more likely to respond to PEG-IFN/RBV treatment than non-drinkers. These patients were previous non-responders to interferon treatment.128 Published study reports have documented an association between coffee consumption and lower risk of liver cirrhosis,129,130 hepatocellular carcinoma,131,132 liver disease progression in HCV infection,133 and lower serum ALT activity.134 Population studies have shown coffee drinking reduces the risk of clinically significant chronic liver disease.135 These effects may be due in part to the antiviral activity of chlorogenic acid, a coffee polyphenol found in especially high concentrations in green coffee extracts.136

Zinc and zinc-carnosine. Zinc has HCV-inhibiting capabilities.137 Zinc supplementation has resulted in a higher reported rate of HCV eradication among patients receiving interferon treatment,138 decreased gastrointestinal disturbances and hair loss, and improved fingernail health in patients with chronic HCV. It may also improve patient tolerance to IFN-alpha-2a and ribavirin.139

A chelate compound consisting of zinc and L-carnosine may induce antioxidative functions in the liver, thereby decreasing liver cell injury.140 Supplementation with chelated zinc-carnosine has been found to lessen the degree of liver damage and improve long-term outcome of patients with chronic HCV infection or liver cirrhosis.141 In patients with HCV-related chronic liver disease, it appears to have an anti-inflammatory effect on the liver by decreasing iron overload.142 In addition, fewer gastrointestinal side effects were observed when zinc-carnosine was added to combination PEG-IFN/RBV therapy.143

Curcumin. Curcumin is a yellow pigment present in the curry spice turmeric. It possesses antioxidant, anti-inflammatory, anti-fungal, antibacterial, and anti-proliferative capabilities.144-146 In addition, curcumin has been found to exert antiviral activity against a variety of viruses including HIV,147 influenza virus,148 and coxsackievirus.149 One team of researchers found that curcumin reduces HCV gene expression, and combining curcumin with IFN-alfa treatment had "profound inhibitory effects" on HCV replication. The authors concluded curcumin may be valuable as a novel anti-HCV agent.150 Curcumin has also been shown to protect against liver cancer.151

Quercetin. Quercetin, a flavonoid present in fruit, vegetables, wine, and tea, has antioxidant and anti-inflammatory properties. Studies indicate it also possesses anti-hypertensive, antibacterial, anti-fibrotic, anti-atherogenic, and anti-proliferative properties.152 Quercetin has also been found to attenuate HCV virus production.153,154

L-carnitine. Chronic HCV patients received PEG-IFN/RBV plus the amino acid L-carnitine or PEG-IFN/RBV alone for 12 months. A significant improvement in sustained virologic response was observed in 50% of the L-carnitine group versus 25% of the non-L-carnitine group.155 Supplementing PEG-IFN/RBV treatment with L-carnitine has also been associated with decreased mental and physical fatigue, as well as improved health-related quality of life in patients with chronic HCV. These latter outcomes could potentially improve patient compliance with PEG-IFN/RBV treatment.156

2019

  • May: Comprehensive update & review

Disclaimer and Safety Information

This information (and any accompanying material) is not intended to replace the attention or advice of a physician or other qualified health care professional. Anyone who wishes to embark on any dietary, drug, exercise, or other lifestyle change intended to prevent or treat a specific disease or condition should first consult with and seek clearance from a physician or other qualified health care professional. Pregnant women in particular should seek the advice of a physician before using any protocol listed on this website. The protocols described on this website are for adults only, unless otherwise specified. Product labels may contain important safety information and the most recent product information provided by the product manufacturers should be carefully reviewed prior to use to verify the dose, administration, and contraindications. National, state, and local laws may vary regarding the use and application of many of the therapies discussed. The reader assumes the risk of any injuries. The authors and publishers, their affiliates and assigns are not liable for any injury and/or damage to persons arising from this protocol and expressly disclaim responsibility for any adverse effects resulting from the use of the information contained herein.

The protocols raise many issues that are subject to change as new data emerge. None of our suggested protocol regimens can guarantee health benefits. Life Extension has not performed independent verification of the data contained in the referenced materials, and expressly disclaims responsibility for any error in the literature.

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