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Influence Of Cannabis Use On Severity Of Hepatitis C Disease


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Conclusion

We conclude that daily cannabis use is strongly associated with moderate to severe fibrosis and that HCV-infected individuals should be counseled to reduce or abstain from cannabis use.

 

 

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3184401/

 

 

CB1 inactivation has been shown to inhibit the progression of fibrosis in three models of liver injury [19]; conversely, CB2 blockade enhances experimental liver fibrosis [20] and CB2 activation causes partial fibrotic reversal in cirrhotic rats [21]. CB1 receptors have been shown to mediate both alcohol [22] and diet [18] induced hepatic steatosis by up regulating the lipogenic transcription factor SREBP-1c and increasing de novo fatty acid synthesis [18]. In the obese Zucker rat model, treatment with a CB1 antagonist abolished hepatomegaly and steatosis, and caused normalisation of liver enzymes [23]. Furthermore, in well characterised cohorts with CHC, daily cannabis use, which was reported in 32% of patients, was significantly associated with the progression of fibrosis and the development of severe steatosis and fibrosis [4], [24].

 

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0012841#pone-0012841-g005

 

 

I'd say this might be a good example that serves to underscore the importance of learning about the ECS.

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this study looked at people who have HIV and HEP-C at the same time. it says they got infected mostly from needle drugs.
 
how does the study tell which people had fibrosis of the liver from the needle drugs and which people had fibrosis of the liver from alcohol and which people had fibrosis from cannabis?
 
it DOESNT.
 

An association between daily (compared to non-daily) cannabis use and mild fibrosis was not apparent (OR = 0.65, p = 0.380).

 
so daily use does not cause mild fibrosis, but it causes severe fibrosis? what? no, seriously, what?
 

We have shown that daily cannabis use is an independent risk factor for moderate to severe fibrosis and one of substantial magnitude, with daily cannabis users having a nearly sevenfold higher odds of moderate to severe fibrosis compared to non-daily users.

 

It is of interest that we found a strong association between daily cannabis use and having moderate to severe fibrosis compared to mild fibrosis, but little association was apparent between cannabis use and the presence of mild fibrosis compared to no fibrosis. This suggests that there may be a different or minimal effect of cannabis in early versus later stage disease. Cannabis may have little or no influence on the initiation of fibrosis, but once fibrosis is present, it may be an important cofactor in fibrosis progression. Further studies are needed to confirm this apparent difference in association by stage of fibrosis.

 
what? its possible pigs might fly out of my donkey. further studies are required!
 

First, the cross-sectional design limits our ability to establish a temporal relationship between cannabis use and fibrosis stage. It is possible that having moderate to severe fibrosis may lead to increased usage of cannabis.

 
derp.
 
association and correlation do not equal causation.
 
if i am wrong in any of my analysis please let me know.
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Fibrosis results from an imbalance in the profibrogenic and antifibrogenic factors expressed in the setting of chronic liver injury (25). Studies in human livers and mouse models of fibrosis demonstrate upregulated expression of the cannabinoid receptors, CB1 and CB2, in chronic liver injury compared to normal controls (8, 9). Immunohistochemical staining of human specimen with cirrhosis shows localization of the CB receptors to hepatic myofibroblasts (8, 9). In experimental models of fibrosis, CB1 receptor activation is associated with profibrogenic effects whereas CB2 receptor activation is associated with antifibrogenic effects (8, 9). In, studies of liver injury in mice, blockade of the CB1 receptor by a CB1 antagonist or use of CB1 knockout is associated with lesser fibrosis than control animals (9). Antagonism of the CB1 receptor has been associated with reduced expression of the TGFβ1, a cytokine central to fibrosis production, and decreased stellate cell proliferation and increased apoptosis, all of which would be predicted to reduce fibrosis (9).

 

Additionally, CB1 receptor antagonism has been associated with increased levels of adiponectin (26), an adipokine with antifibrotic properties in animal models (27). Thus, there are several potential mechanisms by which enhanced CB1 receptor expression or activity may lead to increased fibrosis. In terms of the CB2 receptor, activation is associated with antiproliferative and apoptotic effects in myofibroblasts and activated stellate cells, and in a mouse model of chronic liver injury, CB2 receptor blockade is associated with enhanced liver fibrosis compared to control mice (8).

 

The recommendation to avoid cannabis use may be especially important for HCV/HIV coinfected persons given that fibrosis progression is already enhanced in this group (24).

 

 

Here's the French study:

http://www.ncbi.nlm.nih.gov/pubmed/15892090

 

What is important to keep in mind is the role that the cannabinoid expression levels play in health, disease, and treatment. It's anything but unlikely to expect that exogenous cannabinoids can exert varying effects and degrees of effects dependent upon this factor. 

 

Overall, CBD and CB2 agonists might be safer options than THC.

 

Other cannabinoids (magnolol and honokiol) have been found to reverse alcohol fatty liver, and be hepatoprotective:

 

http://www.researchgate.net/publication/24195095_Antioxidative_and_hepatoprotective_effects_of_magnolol_on_acetaminophen-induced_liver_damage_in_rats/file/5bcb9c315e72848ee64c2a98de3a86b8.pdf

 

http://www.researchgate.net/publication/24283488_Magnolia_officinalis_reverses_alcoholic_fatty_liver_by_inhibiting_the_maturation_of_sterol_regulatory_element-binding_protein-1c/file/9fcfd50c78d3b46024.pdf

 

http://www.snupharm.ac.kr/molpath/erp/erpmenus/professor_thesis/uploadfiles/2009_honokiol.pdf

Edited by in vivo
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i'm wary as to people estimating the entire study's numbers. only testing once, picking marijuana out of any number of substances they used, and then claiming it to be the cause of the damage.

 

"fibrosis progression rate was calculated from a single liver biopsy and esti-mated disease duration."

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I get that. There are a number of unknown variables. But there is also a good explanation for the mechanisms involved (from second link in first post):

 

 

Background
 

Activation of hepatic CB1 receptors (CB1) is associated with steatosis and fibrosis in experimental forms of liver disease. However, CB1 expression has not been assessed in patients with chronic hepatitis C (CHC), a disease associated with insulin resistance, steatosis and metabolic disturbance. We aimed to determine the importance and explore the associations of CB1 expression in CHC.

Methods

CB1 receptor mRNA was measured by real time quantitative PCR on extracted liver tissue from 88 patients with CHC (genotypes 1 and 3), 12 controls and 10 patients with chronic hepatitis B (CHB). The Huh7/JFH1 Hepatitis C virus (HCV) cell culture model was used to validate results.

Principal Findings

CB1 was expressed in all patients with CHC and levels were 6-fold higher than in controls (P<0.001). CB1 expression increased with fibrosis stage, with cirrhotics having up to a 2 fold up-regulation compared to those with low fibrosis stage (p<0.05). Even in mild CHC with no steatosis (F0-1), CB1 levels remained substantially greater than in controls (p<0.001) and in those with mild CHB (F0-1; p<0.001). Huh7 cells infected with JFH-1 HCV showed an 8-fold upregulation of CB1, and CB1 expression directly correlated with the percentage of cells infected over time, suggesting that CB1 is an HCV inducible gene. While HCV structural proteins appear essential for CB1 induction, there was no core genotype specific difference in CB1 expression. CB1 significantly increased with steatosis grade, primarily driven by patients with genotype 3 CHC. In genotype 3 patients, CB1 correlated with SREBP-1c and its downstream target FASN (SREBP-1c; R = 0.37, FASN; R = 0.39, p<0.05 for both).

Conclusions/Significance

CB1 is up-regulated in CHC and is associated with increased steatosis in genotype 3. It is induced by the hepatitis C virus.

 

My first quote for that link could have been more clear:

 

CB1 and CB2 receptors are weakly expressed in normal liver, but are strongly up-regulated in experimental liver injury and cirrhosis due to alcohol, hepatitis B, and primary biliary cirrhosis [19]. CB1 inactivation has been shown to inhibit the progression of fibrosis in three models of liver injury [19]; conversely, CB2 blockade enhances experimental liver fibrosis [20]

 

So the expression of CB1 receptors in the liver tissue of those with CHC increases as the stages progress, and are very minimal in a healthy liver. That would seem to indicate a potential mechanism for CB1 agonists to impact the liver in a way that they otherwise wouldn't. Sometimes activating a receptor is good, sometimes blocking it is better suited for a treatment. This might be a case where CBD and/or any number of CB2 agonists are better candidates for treatment. 

Edited by in vivo
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http://www.ncbi.nlm.nih.gov/pubmed/23811492

Marijuana smoking does not accelerate progression of liver disease in HIV-hepatitis C coinfection: a longitudinal cohort analysis.

 

this is also why i am wary of studies that start out with a factual premise (CB1 and CB2 receptors affect the liver) and then make assumptions (since marijuana has CB1/CB2 antagonists, it can affect the liver in a bad way). especially when they make no attempts to test or verify their theory and cite their own estimated statistics as proof that their theory is correct.

Edited by t-pain
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I thought they mentioned the need for further testing and stated unknown variables. This is from your link:

 

Smoking marijuana seemed to accelerate progression to a clinical diagnosis of cirrhosis (HR, 1.33 per 10 joints/week; 95% CI, 1.09–1.62). However, lagging the exposure attenuated this association (HR, 1.12; 95% CI, .94–1.34). Marijuana smoking was also associated with a slightly increased risk of progression to clinically diagnosed cirrhosis and ESLD combined: hazard ratio 1.13 (95% CI, 1.01–1.28). This association was no longer significant when marijuana exposure was lagged (HR, 1.10; 95% CI, .95–1.26). Baseline APRI score was a strong predictor of reaching an APRI score of 1.5 or 2, and of a clinical diagnosis of cirrhosis.

 

Relationship between the number of joints smoked per week and the aspartate aminotransferase-to-platelet ratio (APRI) score, linear spline regression model with knots at 7 and 21 joints/wk. There was no difference in the slope of ln(APRI) observed with increasing marijuana use. The ln(APRI) score would increase by 0.003 units (95% confidence interval [CI], −.001, .006) for each additional joint smoked per week for someone smoking between 0 and 7 joints/wk. For someone smoking between 7 and 21 joints/wk, it would increase by 0.004 units (95% CI, −.020, .028) and would decrease by .009 units (95% CI, −.024, .006) for someone smoking more than 21 joints/wk. Abbreviation: APRI, aspartate aminotransferase-

 

In this first longitudinal study to our knowledge of marijuana smoking and risk of liver disease among HIV-HCV coinfected persons without significant fibrosis at baseline,

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