Research - Hepatitis
Coffee and Caffeine Intake Are Associated with Lower Risk for Advanced Hepatic Fibrosis in Patients with Hepatitis C
Khalaf N, White D, Kanwal F, et al. Coffee and caffeine are associated with decreased risk of advanced hepatic fibrosis among patients with hepatitis C. Clin Gastroenterol Hepatol. August 2015;13(8):1521-1531.e3.
One of the most popular beverages worldwide, the consumption of coffee (Coffea arabica, Rubiaceae) is associated with a number of health benefits, including protection against the development of liver injury (hepatoprotection). Also, there is an inverse association between coffee consumption and hepatocellular carcinoma with or without chronic hepatitis C virus (HCV) infection. These authors used data from a cross-sectional study among U.S. veterans with chronic HCV infection to investigate the association between caffeinated and decaffeinated coffee, tea (Camellia sinensis, Theaceae), and soda intake and the development of HCV-related advanced liver fibrosis. Their secondary objective was to determine the extent to which insulin resistance mediates the association between caffeine intake and the severity of liver fibrosis.
The study was conducted at the Michael E. DeBakey Veterans Affairs Medical Center in Houston, Texas. Participants were veterans aged 18 to 70 years with confirmed HCV viremia who were prospectively recruited from a dedicated HCV clinic at the medical center between January 5, 2009 and November 30, 2013. The participants were not receiving antiviral therapy at the time of recruitment.
At baseline and after 12 weeks, participants underwent fasting blood draws for clinical laboratory tests, had anthropometric measurements taken, and body mass index (BMI) scores calculated. They completed a detailed questionnaire about their lifetime use of alcohol, tobacco (Nicotiana tabacum, Solanaceae), injection drugs, marijuana (Cannabis sativa, Cannabaceae), and other recreational drugs, as well as the presence of comorbid conditions, such as diabetes mellitus. All participants were scored using the Model for End-Stage Liver Disease (MELD) instrument, which assesses the severity of chronic liver disease.
The participants also provided information on their intake of caffeinated and decaffeinated coffee, tea, and carbonated soda, and their use of creamers and sweeteners. Cumulative lifetime exposure to coffee was determined by their reported daily intake in each decade of life starting with the 20s. For assessing average caffeine content, the authors estimated 137 mg for each 8 oz cup of coffee, 30 mg for each 8 oz cup of tea, 46 mg for each 12 oz can of caffeinated soda, and 0 mg for decaffeinated beverages.
The exposure variables were caffeinated and decaffeinated coffee intake, tea intake, and soda intake, and caffeine intake overall and from each beverage. The main outcome variable was advanced hepatic fibrosis as scored by using the FibroSURE test, which estimates the level of liver fibrosis and inflammation.
The study included 910 veterans with chronic HCV infection. Based on FibroSURE scores, 342 (37.6%) had advanced fibrosis (AF); the remaining 568 (62.4%) with mild fibrosis served as controls for the analysis. Most of the participants were male (98%), African-American, and chronic alcohol users. Those with AF were older (average, +1.8 years), had a higher BMI, and were more likely to have type 2 diabetes mellitus, metabolic syndrome, and higher MELD scores than the controls. Among nondiabetic participants, AF cases were more likely than controls to be insulin resistant based on a baseline fasting homeostasis model assessment-insulin resistance (HOMA-IR) score of ≥ 3. They were also more likely to have received prior HCV antiviral therapy. Though none were receiving treatment at the time of the study, all participants had detectable HCV RNA levels, confirming the presence of HCV in the blood.
In terms of liver inflammation, 252 participants (27.7%) were classified as advanced inflammatory activity cases and 658 (72.3%) were classified as mild inflammatory activity controls based on FibroSURE scores. There was no association between caffeine intake and severity of inflammation.
Most participants (54.6%) reported drinking some caffeinated coffee within the year before the study, with 47.2% drinking 1 or more cups daily. The controls had a higher average daily intake of caffeinated coffee compared with the AF cases (P=0.038) and more controls than AF cases reported drinking an average of 1 or more cups daily (P=0.045).
About 70% of participants reported drinking caffeinated tea within the preceding year; 22.7% consumed 1 or more cups daily. Tea intake, both caffeinated and decaffeinated, was not significantly different between the AF cases and controls. However, among the 413 non-coffee drinkers, caffeinated tea use was more common among controls than among AF cases (P=0.03).
There was no association between any consumption of caffeinated or decaffeinated soda and AF. Although consuming ≥ 1 can of caffeinated soda daily was significantly associated with a decreased risk for hepatic fibrosis (P=0.015), this association was reduced after adjusting for age, BMI, and alcohol use, and for MELD score and the presence of metabolic syndrome (P=0.047). And it was further attenuated when adjusted for diabetes and HOMA-IR scores (P=0.063). In addition, among the subset of non-coffee drinkers, intake of ≥ 1 can of caffeinated soda was not significant.
Overall, average daily caffeine consumption from all beverages was higher in the controls (273.8 mg) than in the AF cases (218.2 mg) (P=0.013), as was the average daily intake of caffeine from coffee (P=0.028). Caffeine was consumed mostly from coffee, followed by soda and then tea. Stratified by dose, participants consuming ≥ 100 mg caffeine daily from any source had a significantly reduced risk of AF (P=0.014), as did those consuming ≥ 100 mg caffeine daily from coffee (P=0.035); however, the association was not significant among non-coffee drinkers consuming ≥ 100 mg caffeine daily. The average daily intake of coffee in prior life decades was not significant.
There were no significant associations between AF and the use of creamers/whiteners (37% of the participants) or sweeteners (23.8% of the participants).
Among the 650 nondiabetic participants, those with a HOMA-IR value ˂ 3 (in the normal range) were significantly more likely to consume more than 100 mg of caffeine daily than were the participants with HOMA-IR values of ≥ 3 (P=0.012). This association between caffeine intake and decreased risk of insulin resistance was significant after adjusting for age, BMI, and alcohol use (P=0.022); MELD score (P=0.024); and the presence of metabolic syndrome (P=0.017).
An average daily intake of 100 mg or more of caffeine from all sources was associated with a significantly decreased risk for AF (P=0.02) after adjusting for age, alcohol use, and BMI, and after adjusting for MELD scores in a second multivariate model. In a third model, adjusting for insulin resistance minimally reduced the association; however, the association between caffeine intake and decreased risk for AF remained significant after adjusting for the presence of metabolic syndrome (P=0.014).
In this study, an average daily intake of ≥ 100 mg of caffeine was associated with a lower risk for advanced hepatic fibrosis in patients with chronic HCV infection. In non-coffee drinkers, daily caffeinated tea intake (but not caffeinated soda) was also associated with decreased risk of progressive liver disease. Overall, consuming caffeinated coffee or caffeinated tea is more beneficial for patients with HCV than consuming other caffeinated beverages or decaffeinated coffee.
"If validated in other HCV-infected populations in the United States, our results suggest that a relatively low (and therefore potentially more tolerable dose) of caffeine, particularly from caffeinated coffee and possibly from tea, may convey a substantial reduction in fibrosis progression." The authors conclude that "prospective studies are warranted to determine the optimal dose and preparation of caffeinated beverage intake that could be safely and tolerably recommended for prevention of progressive liver disease in HCV patients in routine clinical practice."
--Shari Henson
Source : American Botanical Council
Link to Source
Inhibitory effect of Phyllanthus urinaria L. extract on the replication of lamivudine-resistant hepatitis B virus in vitro
Jaesung Jung12, Nam Keun Kim3, Sun Park12, Ho-Joon Shin12, Seong Gyu Hwang34* andKyongmin Kim12*
Abstract
BackgroundLong-term treatment of chronic hepatitis B (CHB) with nucleos(t)ide analogs results in the emergence of drug-resistant hepatitis B virus (HBV) harboring mutations in the polymerase (P) gene. The Phyllanthus extract has anti-HBV activity; however, its antiviral activity against lamivudine (LMV)-resistant mutants has not been examined.
MethodsHBV harboring LMV-resistant mutations (rtM204I, rtM204V, and rtM204S) in the P gene at the YMDD ( 203 tyrosine-methionine-aspartate-aspartate 206 ) reverse transcriptase (RT) active site were generated and their sensitivity to Phyllanthus urinaria koreanis extract examined. Southern blotting and real-time PCR were used to determine the concentration of plant extract required to inhibit HBV DNA synthesis by 50 and 90 % (EC 50 and EC 90 , respectively). An enzyme-linked immunosorbent assay was used to measure the EC 50 of HBV surface antigen (HBsAg) and HBV core antigen (HBcAg) secretion, and the 50 % cytotoxic concentration of the extract was measured in a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Real-time RT-PCR was used to measure mRNA expression levels.
ResultsThe expression of intracellular HBV DNAs in HBV WT- or mutant-transfected HepG2 cells decreased upon treatment with Phyllanthus extract. The secretion of HBsAg and HBcAg also fell in a dose-dependent manner. Phyllanthus extract induced interferon-beta (IFN-β), cyclooxygenase-2 (COX-2), and interleukin-6 (IL-6) mRNA expression in HBV WT-transfected HepG2 cells, possibly via activation of extracellular signal-regulated kinases and c-jun N-terminal kinases and the induction of retinoic acid inducible gene-I, toll-like receptor 3, myeloid differentiation primary response gene 88, and/or tumor necrosis factor receptor-associated factor 6 gene expression. HBV transfection in the absence of extract or exposure of cells to extract alone did not trigger these signaling cascades.
ConclusionsPhyllanthus extract inhibited HBV DNA synthesis and HBsAg and HBcAg secretion by replicating cells harboring HBV wild-type and LMV-resistant mutants, likely by inducing the expression of IFN-β, COX-2, and IL-6. These data indicate that Phyllanthus extract may be useful as an alternative therapeutic agent for the treatment of drug-resistant CHB patients.
Source : BMC Complementary and Alternative Medicine
Link to Full Article
Glycyrrhizin as antiviral agent against Hepatitis C Virus
Usman A Ashfaq1*, Muhammad S Masoud1, Zafar Nawaz2 and Sheikh Riazuddin3
1 Division of Molecular Medicine, National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan
2 Braman Family Breast Cancer Institute, University of Miami, USA
3 Allama Iqbal Medical College, University of Health sciences, Lahore
Abstract
Background
Hepatitis C virus is a major cause of chronic liver diseases which can lead to permanent liver damage, hepatocellular carcinoma and death. The presently available treatment with interferon plus ribavirin, has limited benefits due to adverse side effects such as anemia, depression, fatigue, and "flu-like" symptoms. Herbal plants have been used for centuries against different diseases including viral diseases and have become a major source of new compounds to treat bacterial and viral diseases.
Material
The present study was design to study the antiviral effect of Glycyrrhizin (GL) against HCV. For this purpose, HCV infected liver cells were treated with GL at non toxic doses and HCV titer was measured by Quantitative real time RT-PCR.
Results and Discussion
Our results demonstrated that GL inhibit HCV titer in a dose dependent manner and resulted in 50% reduction of HCV at a concentration of 14 ± 2 μg. Comparative studies were made with interferon alpha to investigate synergistic effects, if any, between antiviral compound and interferon alpha 2a. Our data showed that GL exhibited synergistic effect when combined with interferon. Moreover, these results were verified by transiently transfecting the liver cells with HCV 3a core plasmid. The results proved that GL dose dependently inhibit the expression of HCV 3a core gene both at mRNA and protein levels while the GAPDH remained constant.
Conclusion
Our results suggest that GL inhibit HCV full length viral particles and HCV core gene expression or function in a dose dependent manner and had synergistic effect with interferon. In future, GL along with interferon will be better option to treat HCV infection.
Source : Journal of Translational Medicine
Link to full Article
Study Shows Possible Benefit of Milk Thistle Extract for Hepatitis C Virus
Silymarin is a polyphenolic flavonoid derived from milk thistle
Recent research, funded in part by NCCAM and published in the journal Gastroenterology, has shown that an extract of the milk thistle plant may help treat hepatitis C virus infection. Hepatitis C, a liver disease caused by a virus, is usually chronic (long-lasting), with symptoms ranging from mild (or even none) to severe.
Researchers from the University of Washington School of Medicine, the Fred Hutchinson Cancer Research Center, Harvard Medical School, and the University of North Carolina used cells from healthy volunteers and those with chronic hepatitis C infection to test the effects of silymarin, an extract of milk thistle. Specifically, they tested peripheral blood nuclear cells and T cells—immune cells that multiply and increase inflammation. Results of the study showed that silymarin was able to inhibit the production and secretion of proteins called cytokines—tumor necrosis factor‑alpha, interferon‑gamma, and interleukin‑2—that trigger inflammation and respond to infections. Other extracts of milk thistle—silybin A, silybin B, and a combination of the two called silibinin—similarly inhibited cytokine production and cell production.
These findings suggest that silymarin could potentially control the inflammation that is characteristic of chronic liver disease in humans. Researchers indicated that these findings, combined with knowledge from previous studies, could lead to clinical benefits for patients with hepatitis C virus infection, but more studies are needed.
Reference
Link to Source
Multiple Effects of Silymarin on the Hepatitis C Virus Lifecycle
Silymarin, an extract from milk thistle (Silybum marianum), and its purified flavonolignans have been recently shown to inhibit HCV infection, both in vitro and in vivo. In the current study, we further characterized silymarin's antiviral actions. Silymarin had antiviral effects against HCVcc infection that included inhibition of virus entry, RNA and protein expression, and infectious virus production. Silymarin did not block HCVcc binding to cells, but inhibited the entry of several viral pseudoparticles (pp), and fusion of HCVpp with liposomes. Silymarin but not silibinin inhibited JFH-1 genotype 2a NS5B-dependent RNA polymerase activity at concentrations 5–10 times higher than required for anti-HCVcc effects. Furthermore, silymarin had inefficient activity on the genotype 1b BK and four 1b RDRPs derived from HCV-infected patients. Moreover, silymarin did not inhibit HCV replication in 5 independent genotype 1a, 1b, and 2a replicon cell lines that did not produce infectious virus. Silymarin inhibited microsomal triglyceride transfer protein activity, apolipoprotein B secretion, and infectious virion production into culture supernatants. Silymarin also blocked cell-to-cell spread of virus. While inhibition of in-vitro NS5B polymerase activity is demonstrable, the mechanisms of silymarin's antiviral action appear to include blocking of virus entry and transmission, possibly by targeting the host cell.
Source : Hepatology. 2010 June; 51(6): 1912–1921. doi: 10.1002/hep.23587
Link to Full Article
Hepatoprotective Activity of Ficus carica Leaf Extract on Rifampicin-Induced Hepatic Damage in Rats
Shade dried leaves of Ficus carica were extracted using petroleum ether (60-80°) and tested for antihepatotoxic activity on rats treated with 50 mg/kg of rifampicin orally. The parameters assessed were serum levels of glutamic oxaloacetate transaminase, glutamic pyruvic transaminase, bilirubin and histological changes in liver. Liver weights and pentobarbitione sleeping time as a functional parameter were also monitored. There was significant reversal of biochemical, histological and functional changes induced by rifampicin treatment in rats by petroleum ether extract treatment, indicating promising hepatoprotective activity. “Liver diseases remain one of the serious health problems. In the absence of reliable liver protective drugs in allopathic medical practices. Herbs play important role in the management of various liver disorders1. However, in ayurveda many indigenous plants have been used as hepatoprotective agents. A number of reviews are published stating the importance of plant drugs in the diseases of liver. Indigenous plant Ficus carica was selected for investigating hepatoprotective activity” Source : Indian J Pharm Sci. 2008 May-Jun; 70(3): 364–366.
doi: 10.4103/0250-474X.43003
Link to Source
Antioxidant therapy for chronic hepatitis C after failure of interferon: results of phase II randomized, double-blind placebo controlled clinical trial.
Abstract
AIM: To assess the safety and efficacy of antioxidant therapy for patients with chronic hepatitis C virus (HCV) infection.
METHODS: One hundred chronic HCV infection patients failed in interferon treatment were enrolled and randomly assigned to receive combined intravenous and oral antioxidants or placebo, or oral treatment alone. Primary end points were liver enzymes, HCV-RNA levels and histology.
RESULTS: Combined oral and intravenous antioxidant therapy was associated with a significant decline in ALT levels in 52% of patients who received antioxidant therapy vs 20% of patients who received placebo (P = 0.05). Histology activity index (HAI) score at the end of treatment was reduced in 48% of patients who received antioxidant therapy vs 26% of patients who received placebo (P = 0.21). HCV-RNA levels decreased by 1-log or more in 28% of patients who received antioxidant therapy vs 12% who received placebo (P = NS). In part II of the trial, oral administration of antioxidants was not associated with significant alterations in any of the end points.
CONCLUSION: Antioxidant therapy has a mild beneficial effect on the inflammatory response of chronic HCV infection patients who are non-responders to interferon. Combined antiviral and antioxidant therapy may be beneficial for these patients.
Source: World J Gastroenterol 2007 October 28; 13(40): 5317-5323
Link to Full Article
Treatment of chronic hepatitis C virus infection via antioxidants: results of a phase I clinical trial.
BACKGROUND:
The pathogenesis of chronic hepatitis C virus (HCV) infection is associated with a defective host antiviral immune response and intrahepatic oxidative stress. Oxidative stress and lipid peroxidation play major roles in the fatty liver accumulation (steatosis) that leads to necro-inflammation and necrosis of hepatic cells. Previous trials suggested that antioxidative therapy may have a beneficial effect on patients with chronic HCV infection.
AIMS:
To determine the safety and efficacy of treatment of chronic HCV patients via a combination of antioxidants.
METHODS:
Fifty chronic HCV patients were treated orally on a daily basis for 20 weeks with seven antioxidative oral preparations (glycyrrhizin, schisandra, silymarin, ascorbic acid, lipoic acid, L-glutathione, and alpha-tocopherol), along with four different intravenous preparations (glycyrrhizin, ascorbic acid, L-glutathione, B-complex) twice weekly for the first 10 weeks, and followed up for an additional 20 weeks. Patients were monitored for HCV-RNA levels, liver enzymes, and liver histology. Assessment of quality of life was performed using the SF-36 questionnaire.
RESULTS:
In one of the tested parameters (eg, liver enzymes, HCV RNA levels, or liver biopsy score), a combination of antioxidants induced a favorable response in 48% of the patients (24). Normalization of liver enzymes occurred in 44% of patients who had elevated pretreatment ALT levels (15 of 34). ALT levels remained normal throughout follow-up period in 72.7% (8 of 11). A decrease in viral load (one log or more) was observed in 25% of the patients (12). Histologic improvement (2-point reduction in the HAI score) was noted in 36.1% of the patients. The SF-36 score improved in 26 of 45 patients throughout the course of the trial (58% of the patients). Treatment was well tolerated by all patients. No major adverse reactions were noted.
CONCLUSIONS:
These data suggest that multi antioxidative treatment in chronic HCV patients is well tolerated and may have a beneficial effect on necro-inflammatory variables. A combination of antiviral and antioxidative therapies may enhance the overall response rate of these patients.
Source J Clin Gastroenterol. 2005 Sep;39(8):737-42
Link to Abstract
Khalaf N, White D, Kanwal F, et al. Coffee and caffeine are associated with decreased risk of advanced hepatic fibrosis among patients with hepatitis C. Clin Gastroenterol Hepatol. August 2015;13(8):1521-1531.e3.
One of the most popular beverages worldwide, the consumption of coffee (Coffea arabica, Rubiaceae) is associated with a number of health benefits, including protection against the development of liver injury (hepatoprotection). Also, there is an inverse association between coffee consumption and hepatocellular carcinoma with or without chronic hepatitis C virus (HCV) infection. These authors used data from a cross-sectional study among U.S. veterans with chronic HCV infection to investigate the association between caffeinated and decaffeinated coffee, tea (Camellia sinensis, Theaceae), and soda intake and the development of HCV-related advanced liver fibrosis. Their secondary objective was to determine the extent to which insulin resistance mediates the association between caffeine intake and the severity of liver fibrosis.
The study was conducted at the Michael E. DeBakey Veterans Affairs Medical Center in Houston, Texas. Participants were veterans aged 18 to 70 years with confirmed HCV viremia who were prospectively recruited from a dedicated HCV clinic at the medical center between January 5, 2009 and November 30, 2013. The participants were not receiving antiviral therapy at the time of recruitment.
At baseline and after 12 weeks, participants underwent fasting blood draws for clinical laboratory tests, had anthropometric measurements taken, and body mass index (BMI) scores calculated. They completed a detailed questionnaire about their lifetime use of alcohol, tobacco (Nicotiana tabacum, Solanaceae), injection drugs, marijuana (Cannabis sativa, Cannabaceae), and other recreational drugs, as well as the presence of comorbid conditions, such as diabetes mellitus. All participants were scored using the Model for End-Stage Liver Disease (MELD) instrument, which assesses the severity of chronic liver disease.
The participants also provided information on their intake of caffeinated and decaffeinated coffee, tea, and carbonated soda, and their use of creamers and sweeteners. Cumulative lifetime exposure to coffee was determined by their reported daily intake in each decade of life starting with the 20s. For assessing average caffeine content, the authors estimated 137 mg for each 8 oz cup of coffee, 30 mg for each 8 oz cup of tea, 46 mg for each 12 oz can of caffeinated soda, and 0 mg for decaffeinated beverages.
The exposure variables were caffeinated and decaffeinated coffee intake, tea intake, and soda intake, and caffeine intake overall and from each beverage. The main outcome variable was advanced hepatic fibrosis as scored by using the FibroSURE test, which estimates the level of liver fibrosis and inflammation.
The study included 910 veterans with chronic HCV infection. Based on FibroSURE scores, 342 (37.6%) had advanced fibrosis (AF); the remaining 568 (62.4%) with mild fibrosis served as controls for the analysis. Most of the participants were male (98%), African-American, and chronic alcohol users. Those with AF were older (average, +1.8 years), had a higher BMI, and were more likely to have type 2 diabetes mellitus, metabolic syndrome, and higher MELD scores than the controls. Among nondiabetic participants, AF cases were more likely than controls to be insulin resistant based on a baseline fasting homeostasis model assessment-insulin resistance (HOMA-IR) score of ≥ 3. They were also more likely to have received prior HCV antiviral therapy. Though none were receiving treatment at the time of the study, all participants had detectable HCV RNA levels, confirming the presence of HCV in the blood.
In terms of liver inflammation, 252 participants (27.7%) were classified as advanced inflammatory activity cases and 658 (72.3%) were classified as mild inflammatory activity controls based on FibroSURE scores. There was no association between caffeine intake and severity of inflammation.
Most participants (54.6%) reported drinking some caffeinated coffee within the year before the study, with 47.2% drinking 1 or more cups daily. The controls had a higher average daily intake of caffeinated coffee compared with the AF cases (P=0.038) and more controls than AF cases reported drinking an average of 1 or more cups daily (P=0.045).
About 70% of participants reported drinking caffeinated tea within the preceding year; 22.7% consumed 1 or more cups daily. Tea intake, both caffeinated and decaffeinated, was not significantly different between the AF cases and controls. However, among the 413 non-coffee drinkers, caffeinated tea use was more common among controls than among AF cases (P=0.03).
There was no association between any consumption of caffeinated or decaffeinated soda and AF. Although consuming ≥ 1 can of caffeinated soda daily was significantly associated with a decreased risk for hepatic fibrosis (P=0.015), this association was reduced after adjusting for age, BMI, and alcohol use, and for MELD score and the presence of metabolic syndrome (P=0.047). And it was further attenuated when adjusted for diabetes and HOMA-IR scores (P=0.063). In addition, among the subset of non-coffee drinkers, intake of ≥ 1 can of caffeinated soda was not significant.
Overall, average daily caffeine consumption from all beverages was higher in the controls (273.8 mg) than in the AF cases (218.2 mg) (P=0.013), as was the average daily intake of caffeine from coffee (P=0.028). Caffeine was consumed mostly from coffee, followed by soda and then tea. Stratified by dose, participants consuming ≥ 100 mg caffeine daily from any source had a significantly reduced risk of AF (P=0.014), as did those consuming ≥ 100 mg caffeine daily from coffee (P=0.035); however, the association was not significant among non-coffee drinkers consuming ≥ 100 mg caffeine daily. The average daily intake of coffee in prior life decades was not significant.
There were no significant associations between AF and the use of creamers/whiteners (37% of the participants) or sweeteners (23.8% of the participants).
Among the 650 nondiabetic participants, those with a HOMA-IR value ˂ 3 (in the normal range) were significantly more likely to consume more than 100 mg of caffeine daily than were the participants with HOMA-IR values of ≥ 3 (P=0.012). This association between caffeine intake and decreased risk of insulin resistance was significant after adjusting for age, BMI, and alcohol use (P=0.022); MELD score (P=0.024); and the presence of metabolic syndrome (P=0.017).
An average daily intake of 100 mg or more of caffeine from all sources was associated with a significantly decreased risk for AF (P=0.02) after adjusting for age, alcohol use, and BMI, and after adjusting for MELD scores in a second multivariate model. In a third model, adjusting for insulin resistance minimally reduced the association; however, the association between caffeine intake and decreased risk for AF remained significant after adjusting for the presence of metabolic syndrome (P=0.014).
In this study, an average daily intake of ≥ 100 mg of caffeine was associated with a lower risk for advanced hepatic fibrosis in patients with chronic HCV infection. In non-coffee drinkers, daily caffeinated tea intake (but not caffeinated soda) was also associated with decreased risk of progressive liver disease. Overall, consuming caffeinated coffee or caffeinated tea is more beneficial for patients with HCV than consuming other caffeinated beverages or decaffeinated coffee.
"If validated in other HCV-infected populations in the United States, our results suggest that a relatively low (and therefore potentially more tolerable dose) of caffeine, particularly from caffeinated coffee and possibly from tea, may convey a substantial reduction in fibrosis progression." The authors conclude that "prospective studies are warranted to determine the optimal dose and preparation of caffeinated beverage intake that could be safely and tolerably recommended for prevention of progressive liver disease in HCV patients in routine clinical practice."
--Shari Henson
Source : American Botanical Council
Link to Source
Inhibitory effect of Phyllanthus urinaria L. extract on the replication of lamivudine-resistant hepatitis B virus in vitro
Jaesung Jung12, Nam Keun Kim3, Sun Park12, Ho-Joon Shin12, Seong Gyu Hwang34* andKyongmin Kim12*
Abstract
BackgroundLong-term treatment of chronic hepatitis B (CHB) with nucleos(t)ide analogs results in the emergence of drug-resistant hepatitis B virus (HBV) harboring mutations in the polymerase (P) gene. The Phyllanthus extract has anti-HBV activity; however, its antiviral activity against lamivudine (LMV)-resistant mutants has not been examined.
MethodsHBV harboring LMV-resistant mutations (rtM204I, rtM204V, and rtM204S) in the P gene at the YMDD ( 203 tyrosine-methionine-aspartate-aspartate 206 ) reverse transcriptase (RT) active site were generated and their sensitivity to Phyllanthus urinaria koreanis extract examined. Southern blotting and real-time PCR were used to determine the concentration of plant extract required to inhibit HBV DNA synthesis by 50 and 90 % (EC 50 and EC 90 , respectively). An enzyme-linked immunosorbent assay was used to measure the EC 50 of HBV surface antigen (HBsAg) and HBV core antigen (HBcAg) secretion, and the 50 % cytotoxic concentration of the extract was measured in a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Real-time RT-PCR was used to measure mRNA expression levels.
ResultsThe expression of intracellular HBV DNAs in HBV WT- or mutant-transfected HepG2 cells decreased upon treatment with Phyllanthus extract. The secretion of HBsAg and HBcAg also fell in a dose-dependent manner. Phyllanthus extract induced interferon-beta (IFN-β), cyclooxygenase-2 (COX-2), and interleukin-6 (IL-6) mRNA expression in HBV WT-transfected HepG2 cells, possibly via activation of extracellular signal-regulated kinases and c-jun N-terminal kinases and the induction of retinoic acid inducible gene-I, toll-like receptor 3, myeloid differentiation primary response gene 88, and/or tumor necrosis factor receptor-associated factor 6 gene expression. HBV transfection in the absence of extract or exposure of cells to extract alone did not trigger these signaling cascades.
ConclusionsPhyllanthus extract inhibited HBV DNA synthesis and HBsAg and HBcAg secretion by replicating cells harboring HBV wild-type and LMV-resistant mutants, likely by inducing the expression of IFN-β, COX-2, and IL-6. These data indicate that Phyllanthus extract may be useful as an alternative therapeutic agent for the treatment of drug-resistant CHB patients.
Source : BMC Complementary and Alternative Medicine
Link to Full Article
Glycyrrhizin as antiviral agent against Hepatitis C Virus
Usman A Ashfaq1*, Muhammad S Masoud1, Zafar Nawaz2 and Sheikh Riazuddin3
1 Division of Molecular Medicine, National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan
2 Braman Family Breast Cancer Institute, University of Miami, USA
3 Allama Iqbal Medical College, University of Health sciences, Lahore
Abstract
Background
Hepatitis C virus is a major cause of chronic liver diseases which can lead to permanent liver damage, hepatocellular carcinoma and death. The presently available treatment with interferon plus ribavirin, has limited benefits due to adverse side effects such as anemia, depression, fatigue, and "flu-like" symptoms. Herbal plants have been used for centuries against different diseases including viral diseases and have become a major source of new compounds to treat bacterial and viral diseases.
Material
The present study was design to study the antiviral effect of Glycyrrhizin (GL) against HCV. For this purpose, HCV infected liver cells were treated with GL at non toxic doses and HCV titer was measured by Quantitative real time RT-PCR.
Results and Discussion
Our results demonstrated that GL inhibit HCV titer in a dose dependent manner and resulted in 50% reduction of HCV at a concentration of 14 ± 2 μg. Comparative studies were made with interferon alpha to investigate synergistic effects, if any, between antiviral compound and interferon alpha 2a. Our data showed that GL exhibited synergistic effect when combined with interferon. Moreover, these results were verified by transiently transfecting the liver cells with HCV 3a core plasmid. The results proved that GL dose dependently inhibit the expression of HCV 3a core gene both at mRNA and protein levels while the GAPDH remained constant.
Conclusion
Our results suggest that GL inhibit HCV full length viral particles and HCV core gene expression or function in a dose dependent manner and had synergistic effect with interferon. In future, GL along with interferon will be better option to treat HCV infection.
Source : Journal of Translational Medicine
Link to full Article
Study Shows Possible Benefit of Milk Thistle Extract for Hepatitis C Virus
Silymarin is a polyphenolic flavonoid derived from milk thistle
Recent research, funded in part by NCCAM and published in the journal Gastroenterology, has shown that an extract of the milk thistle plant may help treat hepatitis C virus infection. Hepatitis C, a liver disease caused by a virus, is usually chronic (long-lasting), with symptoms ranging from mild (or even none) to severe.
Researchers from the University of Washington School of Medicine, the Fred Hutchinson Cancer Research Center, Harvard Medical School, and the University of North Carolina used cells from healthy volunteers and those with chronic hepatitis C infection to test the effects of silymarin, an extract of milk thistle. Specifically, they tested peripheral blood nuclear cells and T cells—immune cells that multiply and increase inflammation. Results of the study showed that silymarin was able to inhibit the production and secretion of proteins called cytokines—tumor necrosis factor‑alpha, interferon‑gamma, and interleukin‑2—that trigger inflammation and respond to infections. Other extracts of milk thistle—silybin A, silybin B, and a combination of the two called silibinin—similarly inhibited cytokine production and cell production.
These findings suggest that silymarin could potentially control the inflammation that is characteristic of chronic liver disease in humans. Researchers indicated that these findings, combined with knowledge from previous studies, could lead to clinical benefits for patients with hepatitis C virus infection, but more studies are needed.
Reference
- Morishima C, Shuhart MC, Wang CC, et al. Silymarin inhibits in vitro T-cell proliferation and cytokine production in hepatitis C virus infection. Gastroenterology. 2010;138(2):671–681.
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Multiple Effects of Silymarin on the Hepatitis C Virus Lifecycle
Silymarin, an extract from milk thistle (Silybum marianum), and its purified flavonolignans have been recently shown to inhibit HCV infection, both in vitro and in vivo. In the current study, we further characterized silymarin's antiviral actions. Silymarin had antiviral effects against HCVcc infection that included inhibition of virus entry, RNA and protein expression, and infectious virus production. Silymarin did not block HCVcc binding to cells, but inhibited the entry of several viral pseudoparticles (pp), and fusion of HCVpp with liposomes. Silymarin but not silibinin inhibited JFH-1 genotype 2a NS5B-dependent RNA polymerase activity at concentrations 5–10 times higher than required for anti-HCVcc effects. Furthermore, silymarin had inefficient activity on the genotype 1b BK and four 1b RDRPs derived from HCV-infected patients. Moreover, silymarin did not inhibit HCV replication in 5 independent genotype 1a, 1b, and 2a replicon cell lines that did not produce infectious virus. Silymarin inhibited microsomal triglyceride transfer protein activity, apolipoprotein B secretion, and infectious virion production into culture supernatants. Silymarin also blocked cell-to-cell spread of virus. While inhibition of in-vitro NS5B polymerase activity is demonstrable, the mechanisms of silymarin's antiviral action appear to include blocking of virus entry and transmission, possibly by targeting the host cell.
Source : Hepatology. 2010 June; 51(6): 1912–1921. doi: 10.1002/hep.23587
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Hepatoprotective Activity of Ficus carica Leaf Extract on Rifampicin-Induced Hepatic Damage in Rats
Shade dried leaves of Ficus carica were extracted using petroleum ether (60-80°) and tested for antihepatotoxic activity on rats treated with 50 mg/kg of rifampicin orally. The parameters assessed were serum levels of glutamic oxaloacetate transaminase, glutamic pyruvic transaminase, bilirubin and histological changes in liver. Liver weights and pentobarbitione sleeping time as a functional parameter were also monitored. There was significant reversal of biochemical, histological and functional changes induced by rifampicin treatment in rats by petroleum ether extract treatment, indicating promising hepatoprotective activity. “Liver diseases remain one of the serious health problems. In the absence of reliable liver protective drugs in allopathic medical practices. Herbs play important role in the management of various liver disorders1. However, in ayurveda many indigenous plants have been used as hepatoprotective agents. A number of reviews are published stating the importance of plant drugs in the diseases of liver. Indigenous plant Ficus carica was selected for investigating hepatoprotective activity” Source : Indian J Pharm Sci. 2008 May-Jun; 70(3): 364–366.
doi: 10.4103/0250-474X.43003
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Antioxidant therapy for chronic hepatitis C after failure of interferon: results of phase II randomized, double-blind placebo controlled clinical trial.
Abstract
AIM: To assess the safety and efficacy of antioxidant therapy for patients with chronic hepatitis C virus (HCV) infection.
METHODS: One hundred chronic HCV infection patients failed in interferon treatment were enrolled and randomly assigned to receive combined intravenous and oral antioxidants or placebo, or oral treatment alone. Primary end points were liver enzymes, HCV-RNA levels and histology.
RESULTS: Combined oral and intravenous antioxidant therapy was associated with a significant decline in ALT levels in 52% of patients who received antioxidant therapy vs 20% of patients who received placebo (P = 0.05). Histology activity index (HAI) score at the end of treatment was reduced in 48% of patients who received antioxidant therapy vs 26% of patients who received placebo (P = 0.21). HCV-RNA levels decreased by 1-log or more in 28% of patients who received antioxidant therapy vs 12% who received placebo (P = NS). In part II of the trial, oral administration of antioxidants was not associated with significant alterations in any of the end points.
CONCLUSION: Antioxidant therapy has a mild beneficial effect on the inflammatory response of chronic HCV infection patients who are non-responders to interferon. Combined antiviral and antioxidant therapy may be beneficial for these patients.
Source: World J Gastroenterol 2007 October 28; 13(40): 5317-5323
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Treatment of chronic hepatitis C virus infection via antioxidants: results of a phase I clinical trial.
BACKGROUND:
The pathogenesis of chronic hepatitis C virus (HCV) infection is associated with a defective host antiviral immune response and intrahepatic oxidative stress. Oxidative stress and lipid peroxidation play major roles in the fatty liver accumulation (steatosis) that leads to necro-inflammation and necrosis of hepatic cells. Previous trials suggested that antioxidative therapy may have a beneficial effect on patients with chronic HCV infection.
AIMS:
To determine the safety and efficacy of treatment of chronic HCV patients via a combination of antioxidants.
METHODS:
Fifty chronic HCV patients were treated orally on a daily basis for 20 weeks with seven antioxidative oral preparations (glycyrrhizin, schisandra, silymarin, ascorbic acid, lipoic acid, L-glutathione, and alpha-tocopherol), along with four different intravenous preparations (glycyrrhizin, ascorbic acid, L-glutathione, B-complex) twice weekly for the first 10 weeks, and followed up for an additional 20 weeks. Patients were monitored for HCV-RNA levels, liver enzymes, and liver histology. Assessment of quality of life was performed using the SF-36 questionnaire.
RESULTS:
In one of the tested parameters (eg, liver enzymes, HCV RNA levels, or liver biopsy score), a combination of antioxidants induced a favorable response in 48% of the patients (24). Normalization of liver enzymes occurred in 44% of patients who had elevated pretreatment ALT levels (15 of 34). ALT levels remained normal throughout follow-up period in 72.7% (8 of 11). A decrease in viral load (one log or more) was observed in 25% of the patients (12). Histologic improvement (2-point reduction in the HAI score) was noted in 36.1% of the patients. The SF-36 score improved in 26 of 45 patients throughout the course of the trial (58% of the patients). Treatment was well tolerated by all patients. No major adverse reactions were noted.
CONCLUSIONS:
These data suggest that multi antioxidative treatment in chronic HCV patients is well tolerated and may have a beneficial effect on necro-inflammatory variables. A combination of antiviral and antioxidative therapies may enhance the overall response rate of these patients.
Source J Clin Gastroenterol. 2005 Sep;39(8):737-42
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