Some results of recent blood testing from Auckland Hospital. Getting enough blood to run the tests was, as always, difficult, but at least was possible on this occasion. It’s worth mentioning this because anything I report about my status should be seen in context. I’m 54 years old, I’ve been diagnosed HCV+ since 1991 (this was the first year testing became available here, I likely was infected much earlier), I was an IVDU, polydrug user from the 1980s till well into this century, an alcoholic and solvent abuser as well for much of the last. I gave up methadone, my last drug of addiction, about a year ago.
My fibroscan (elastography) result was 6.8. This is very light scarring (healthy livers go up to 5, cirrhosis starts at 12).
My ALT is 67 U/L; all the other LFT scores are normal (WNL).
Albumin is 52; this is the maximum normal, and I think a pretty reliable sign of a functioning liver.
Iron saturation was high at 0.55, and ferritin high at 251. This is definitely something I’ll be looking at. However, I don’t have the signs of inflammation that I used to attribute in part to high iron. I'm fit, sleeping well, and pain-free.
Hemoglobin was 154 g/L. MCV and MCH were maximum normal.
WBC count was low at 3.86 (4.0-11.0 is normal). Individual WBC counts were all low but WNL.
This is interesting because I haven’t had any infections all year (it’s almost spring) beyond one light cold. Are my WBCs low because some other aspect of innate immunity is taking care of business? Because my diet is low in allergens, pathogens and toxins, and the probiotics I take are working?
IgG was 14.3, IgM 0.89, both WNL.
Platelets were WNL at 237, haemostatis PR = 0.9, HbA1c = 36
Negative for coeliac markers, but then I never touch grains, so I would be.
Vitamin B12 = 495 pmol/L (ref. 170-800)
Folate = 28 nmol/L (ref. 9-45)
HIV negative, HBV antibody positive, HBs Ag negative. As I haven’t had an HBV vaccine, this means I’ve been exposed to hepatitis B and cleared it at some stage. I’m pretty sure I know when that was; everyone else in that room got sick.
The most interesting news for me; my HCV genotype is 3. If you’re wondering why it took so long to find this out, you don’t understand the New Zealand health service.
HCV Genotype 3 and Cholesterol.
Genotype 3 is the form of HCV most specifically associated with fatty liver (steatosis) and hypocholesterolaemia. Steatosis can be a negative factor in any case of HCV infection but in G3 it is promoted by viral mechanisms as well as host dietary factors. One of the mechanisms is the suppression of distal sterol synthesis beyond the proto-sterol lanosterol.
HCV G3, but not G2, selectively interferes with the late cholesterol synthesis pathway, evidenced by lower distal sterol metabolites and preserved lanosterol levels. This distal interference resolves with SVR. Normal lanosterol levels provide a signal for the continued proteolysis of 3-hydroxyl-3-methylglutaryl coenzyme A reductase, which may undermine other host responses to increase cholesterol synthesis. These data may provide a hypothesis to explain why hypocholesterolemia persists in chronic HCV infection, particularly in HCV G3, and is not overcome by host cholesterol compensatory mechanisms.http://www.ncbi.nlm.nih.gov/pubmed/22318926
G3 wants HMG-CoA reductase to keep ticking over; as completed cholesterol accumulates it suppresses HMG-CoA reductase. By lowering conversion of lanosterol to cholesterol, the virus keeps the enzyme active – and cholesterol low.
(The reduction in cholesterol - distal sterol - synthesis seems to be achieved by lowering expression of the cytochromes CYP51 and CYP11A - see table II).
Without the cholesterol, fats can’t leave the cells of the liver easily. They stay there till the virus is completed and ride out whenever triglycerides (and the HCV virions) are released as VLDL. This should mean a relatively high TG/LDL ratio.
There's another benefit to the virus, perhaps the main one; with serum cholesterol levels low, LDL-receptors are increased to compensate, and the LDL-receptors mediate the entry of HCV virions into uninfected cells.
Less cholesterol equals more LDL-R; more LDL-R equals greater ease of entry for HCV.
This is why we should limit PUFA (cut out vegetable oils), this plus the damage from the oxidation of highly polyunsaturated membrane lipids. Animal PUFAs - AA, DHA, EPA - have antiviral benefits and we want to be eating these, but probably not supplementing them that much (Krill oil is better than fish oil).
Put another way, the viral strategy is to corner the market in cholesterol and restrict the supply. This increases demand in uninfected cells, increasing their exposure to the virus, which enters using LDLR associated receptors like CD81 and NPC1L-1.
What happens if you just eat a lot of eggs? The cholesterol from the diet suppresses HMG-CoA reductase (http://www.lipidworld.com/content/6/1/34/), as well as eventually decreasing LDL-R expression (http://ajcn.nutrition.org/content/39/3/360). The viral strategy is stymied from both ends.
Not everyone with HCV G3 develops steatosis or hypocholesterolaemia. Could the difference be something as simple as having adequate cholesterol in the diet and limiting carbohydrate?
Higher LDL is a good indication that someone with HCV will respond to antiviral drugs, and is associated with lower rates of fibrosis.
However, clinical experience (thanks, Silvia) is that high LDL doesn’t always mean good response, low LDL doesn’t always mean non-response.
It’s worth remembering that a crappy diet of cake and biscuits can elevate LDL (at least, it usually does this in people without HCV) as surely as a good grain-free diet of eggs, meat and vegetables. We’re not really talking about the same phenomenon at all. Just as, in physics, the phenomenon we call weight can be produced by gravity (on the surface of the earth) or by acceleration (in a centrifuge or rocket), and its meaning and implications may be quite different. Shooting across space in an accelerating rocket ship may well have different long-term consequences compared to standing on the Earth’s surface, even if both sets of scales are reading the same weight at present.
Think about it: saturated fat supposedly elevates serum cholesterol, which is a risk factor for heart disease (I tried to find a scientific reference for this simple statement, without added nuances about particle size, ApoE, and BMI, but it has proved surprisingly difficult. However, most governments, and quite a few doctors, still say it; for example, the Australians here: http://www.aihw.gov.au/high-blood-cholesterol/).
Increasing consumption of saturated fats doesn't correlate with CVD risk, but obesity does.
So either fat doesn't make you fat (which is the case in some scenarios, but surely not all), or something else that also makes you fat gives you heart disease.
My GP is still encouraging me to lower my cholesterol, and the hospital didn’t take a reading. Me, I feel thankful it’s still “a bit high”. If I was in the cholesterol range that the NZ government thinks is optimal, I’d start to get a bit worried.
One size fits all? Wasn’t there a chap called Procrustes once who believed that? Whatever became of him?
Appendix:
Current lipid panel (fasting): mmol/L converted to (mg/dL). Ok, only when the frickin' HTML will allow it. Note how no reading except HDL can be "too low".
Total Cholesterol: 6.7 H
Triglyceride: 0.8
HDL: 1.63 (63.57)
LDL (calc.) 4.7 H
Chol/HDL ratio: 4.1
HCV viral load on this day (21st May 2012): 60,690 IU/mL (4.78 log)
Lipid panel from 07 Feb 2012, during ketogenic diet phase:
Total Cholesterol: 8.9 HH (347.1)
Triglyceride: 1.3 (115.7)
HDL: 1.65 (64.35)
LDL (calc): 6.7 H (261.3)
Chol/HDL ratio: 5.4 H
HCV viral load on this day: 25,704 IU/mL (4.41 log)
"Total blood cholesterol levels above 5.5 mmol/L are an indication
of a greatly increased risk of developing coronary heart disease.
Levels above 6.5 mmol/L are considered to indicate extremely high
risk.".
5.5 mmol/L = 214.5 mg/dL, 6.5 mmol/L = 263.5 mg/dL.
This is interesting: http://renegadewellness.files.wordpress.com/2011/02/cholesterol-mortality-chart.pdf
And this:
"In 1987, in the Journal of the American Medical Association Framingham Study investigators reported these two important findings: 1) Over age 50 there is no increased overall mortality with either high or low serum cholesterol levels, and 2) In people with a falling cholesterol level (over the first 14 years of the study), for each 1% mg/dl drop in cholesterol there was an 11 percent increase in all-cause mortality over the next 18 years. (JAMA 1987;257:2176-2180)"
Hey, I'm over age 50! Better keep my cholesterol up.
More on the adverse consequences of low cholesterol from Chris Masterjohn.
It gets worse:
"There were 27 deaths due to suicide. Adjusting for age and sex, we found that those in the lowest quartile of serum total cholesterol concentration (less than 4.27 mmol/liter) had more than six times the risk of committing suicide (rate ratio = 6.39; 95% confidence interval = 1.27-32.1) as did subjects in the highest quartile (over 5.77 mmol/liter). Increased rate ratios of 2.95 and 1.94 were observed for the second and third quartiles, respectively. The effect persisted after the exclusion from the analysis of the first 5 years of follow-up and after the removal of those who were unemployed or who had been treated for depression. These data indicate that low serum total cholesterol level is associated with an increased risk of suicide."
Zoe Harcombe lists the conflicts of interests of the scientists who set UK cholesterol guidelines; every single one of them receives money from companies that market "cholesterol lowering" statin drugs. Hmmn.
Well I guess they can always start prescribing antidepressants once they get your cholesterol down.
