JIM or Any Lab Guru

[gauf]

Just got the results for my tx baseline. I know some of this stuff but much is a mystery. Can any lab guru tell me how sick I am?  My LFTs' have come down since July when they were around 160-170, so I guess the supplements are helping. My VL was 3,995,000 in July so that is a little better. Last platelet check 6 weeks ago at 88, so that is worse. Anyway here are results:

Protein, Total 7.9 6.0-8.4 g/dL  
Albumin 4.1 3.5-5.0 g/dL  
Calcium 8.8 8.5-10.5 mg/dL  
WBC 2.67 4.0-11.0 k/uL L
RBC 4.74 4.5-6.0 M/uL  
Hemoglobin 14.3 13.5-17.5 g/dL  
Hematocrit 41.8 40-52 %  
MCV 88.2 80-100 fL  
MCH 30.2 27-34 pG  
MCHC 34.2 32-36 g/dL  
RDW-CV 14.4 11.7-15.0 %  
Platelet Count 71 150-400 K/uL L
MPV 10.3 7.3-11.1 fL  
Neut% 57.3 40-70 %  
Abs Neut 1.53 1.8-7.7 K/uL L
Lymph% 26.2 22-44 %  
Abs Lymph 0.70 1.0-4.0 k/uL L
Mono% 8.2 0-7.0 % H
Abs Mono 0.22 0-0.8 K/uL  
Eosin% 7.9 0-4 % H
Abs Eosin 0.21 0-0.4 K/uL  
Baso% 0.4 0-1 %  
Abs Baso 0.01 0-0.2 K/uL Bilirubin, Total 0.9 0.0-1.5 mg/dL  
Alkaline Phosphatase 64 40-150 U/L  

Glucose 72 65-100 mg/dL  
BUN 10 10-25 mg/dL  
Creatinine 0.7 0.7-1.4 mg/dL  
Sodium 141 135-146 mmol/L  
Potassium 3.7 3.5-5.0 mmol/L  
Chloride 104 98-110 mmol/L  
CO2 25 23-32 mmol/L  
Anion Gap 12 0-15 mmol/L  
ALT 73 5-50 U/L
AST 96 7-40 U/L H



AFP 5.0 1.0-10.0 ng/mL
Cryo Quantitative Bl 9 0-50 ug/mL
TSH 1.110 0.400-5.500 uU/mL


HCV Quant RNA by PCR 3,440,000  -      
  IU/mL
The linear range of this assay is 600 IU/mL to 700,000 IU/mL.

[gauf]

Thanks much!  On the one hand it seems I do have steatosis and G3 fibrosis, although my glucose level is normal. On the other hand my bilirubin, albumin, and prothombin time are normal. So seems to conflict somewhat. I have been diagnosed with portal hypertension by a hemotologist which indicates advanced fibrosis.

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CS, That is a good point by my bud down under about the PCR limit!?!

Exact wording follows:

HCV Quant RNA by PCR 3,440,000  -      
  IU/mL
The linear range of this assay is 600 IU/mL to 700,000 IU/mL.
Value was extrapolated outside the linear range of the assay.
This test was developed and its performance characteristics determined by the
Clinical Laboratories of the Cleveland Clinic. It has not been cleared or
approved by the US Food and Drug Administration. The FDA has determined that
such clearance or approval is not necessary.

[jmjm530]

Re the steatosis -- Gauf has lost a ton of weight, but not sure if the dx of statosis was before, after, or during the weight loss. If before or during, hopefully the steatosis has reversed itself somewhat.

[jmjm530]

MS: Don't you think his steatosis and advanced liver damage are the real obstacles to achieving SVR? That is what occurs to me. Based on his platelet count it would not surprise me if Gauf was Stage 4.
----------------------------------------------------
Yes, if stage 4, and I do agree that the signs you mention point in that direction. Still, given 3 years since his last biopsy -- and I think a tx inbetween -- it would be nice to get a more recent take on liver damage via another biopsy and/or Fibroscan.

As to riba, and past treatments, your points are well taken but the riba mechanism is still so misunderstood that I just felt it couldn't hurt IF he can tolerate it, therefore the advice re Procrit on hand. Not sure if he used it last time around.

Yeah, Gauf was UND at 12, so the Dr. S. null-response argument would not pertain to previous treatments but doesn't mean it wouldn't pertain to the current treatment. It also doesn't mean that down the road, very early viral load data might offer different types of information for future treatments that might be useful, which may be the better argument in which case the Dr. S. argument would just be used as an example.

Just know that if I theoretically would have to treat now, I'd want weekly tests, not sure how you'd feel about that in a hypothetical scenario for yourself.

Be well,

-- Jim

[CockSparrow]

Gauf
From a purely Tx angle your blood results that are of concern to me are
Platelet Count 71 150-400 K/uL L
WBC 2.67 4.0-11.0 k/uL L
The reason being is that interferon will hit these and as they are already low you don’t have much room to move. DoubleDosing would carry a risk of needing to stop IFN for a while.

RBC 4.74 4.5-6.0 M/uL
While your Red cells are in the normal range they are on the low side. Riba could well hit these. Reducing RBV could well be an option.

I would want to know before Tx how your Doc plans to handle any worst case scenario. Much better for my mind at least to know what is going to happen if any of your bloods drop to levels that could necessitate dose reductions.

As for how sick you are.
True indicators of overall liver function are serum bilirubin, serum albumin, and prothrombin time
And yours are in the normal range.

Albumin - is a major protein which is produced by the liver, and chronic liver disease causes a decrease in the amount of albumin produced. Therefore, in liver disease, and particularly more advanced liver disease, the level of the serum albumin is reduced

Bilirubin is generally considered a true test of liver function (LFT), since it reflects the liver's ability to take up, process, and secrete bilirubin into the bile.

The Prothrombin Time, there is a good correlation between abnormalities in coagulation measured by the prothrombin time and the degree of liver dysfunction.

HCV Quant RNA by PCR 3,440,000IU/mL
The linear range of this assay is 600 IU/mL to 700,000 IU/mL.
I don’t understand this. How can your VL be in the Millions if the upper limit is only 700K?

Other than that
All the Best
CS

[mikesimon]

Hepatitis C and steatosis.
Björnsson E, Angulo P.

Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.

Hepatitis C infection and non-alcohol-related hepatic steatosis are the most common liver diseases worldwide, and both conditions often co-exist in the same patient. Hepatitis C virus (HCV) genotype 3 directly induces development of steatosis, whereas in patients with non-genotype 3 chronic hepatitis C infection, insulin resistance plays a key role in the pathophysiology of steatosis. Insulin resistance and its clinical components including obesity, hyperglycemia, hypertriglyceridemia, increased blood pressure, and low HDL-cholesterol levels are often seen in patients with chronic hepatitis C infection. Both increased adipocity and presence of steatosis may increase the risk of fibrosis progression, and both have been associated with a decreased rate of response to antiviral treatment. Hence, liver steatosis in the setting of HCV infection is a distinct condition with specific clinical and prognostic implications. Accumulating evidence suggests that weight management may lead not only to a decrease in steatosis but also improvement in fibrosis severity. However, further studies are necessary to determine whether weight reduction improves response to antiviral therapy.

Fibrosis in genotype 3 chronic hepatitis C and nonalcoholic fatty liver disease: Role of insulin resistance and hepatic steatosis.
Bugianesi E, Marchesini G, Gentilcore E, Cua IH, Vanni E, Rizzetto M, George J.

Gastroenterology Department, University of Turin, Italy. ***@****

Hepatic steatosis has been associated with fibrosis, but it is unknown whether the latter is independent of the etiology of fat infiltration. We analyzed the relationship between clinical characteristics, insulin resistance (HOMA-R) and histological parameters in 132 patients with "viral" steatosis caused by genotype 3 chronic hepatitis C (CHC-3) and 132 patients with "metabolic" steatosis caused by nonalcoholic fatty liver disease (NAFLD), matched by age, BMI, and degree of liver fat accumulation. Tests of liver function were comparable in the two study populations. The prevalence of features of insulin resistance was higher in NAFLD, as was HOMA-R (P = .008). Logistic regression analysis confirmed that steatosis was associated with a high viral load and low serum cholesterol in CHC-3, and with high aminotransferase, glucose, ferritin and hypertriglyceridemia in NAFLD. At univariate analysis, advanced fibrosis was associated with steatosis in NAFLD, but not in CHC-3. Other parameters related to fibrosis severity were HOMA-R and a low platelet count in CHC-3, and high aminotransferases, HOMA-R, ferritin and low HDL-cholesterol in NAFLD. On multivariate analysis, only low platelet count (OR = 0.78; 95% CI, 0.67-0.92) and HOMA-R (OR = 2.98; 1.13-7.89) were independent predictors of advanced fibrosis in CHC-3. In NAFLD, severe fibrosis was predicted by fat grading (OR = 3.03; 1.41-6.53), ferritin (OR = 1.13; 1.03-1.25) and HOMA-R (OR = 1.16; 1.02-1.31). In conclusion, insulin resistance is an independent predictor of advanced fibrosis in both NAFLD and CHC-3, but the extent of steatosis contributes to advanced disease only in NAFLD. Virus-induced hepatic steatosis as seen in CHC-3 does not contribute significantly to liver fibrosis.

PMID: 17133473 [PubMed - indexed for MEDLINE]

[mikesimon]

From his profile it appears that Gauf relapsed so I doubt the issue of null responder vs slow responder would apply here (as an argument for weekly VL testing), unless I am missing something. That's not to suggest that I don't favor frequent testing because I most certainly do.
I also question whether concern about ribavirin absorption will be an issue since Gauf reported anemia with his past treatments.Don't you think his steatosis and advanced liver damage are the real obstacles to achieving SVR? That is what occurs to me. Based on his platelet count it would not surprise me if Gauf was Stage 4. I know that platelet count is not conclusive but his are consistent with significant architectural changes. And I have suspected that AST and ALT are not as elevated when there is advanced fibrosis and/or cirrhosis present and his numbers are not really that high. So that too makes me suspect F4 or at the least not rule it out.
Mike

[jmjm530]

Gauf: I did not know that hbg curve relates to Riba absorption
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A couple of studies correlated riba absorption (hgb response) with RVR and SVR and one did not. Several members here -- "Fishdoc" is one -- reported their doctors upping the riba based on poor hemoglobin response. The Swedish researchers had a very early paper on this not avail on the net as far as I could tell, but avail in medical libraries. I believe the pub was " Ther Drug Monit". that said, therapeutic riba levels/relationship with RVR/sVR hemoglobin repsonse, etc, are not concepts often incorporated into treatment here.

Gauf: but are these blood markers indicative of a stage 4 do you think?  Also wondering if an ultrasound? would help.
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Can't really answer that other than to repeat that it's a whole package a good liver specialist will look at, with liver biopsy receiving weight. Don't understand why they would downgrade you to stage 4, yet not give you a biopsy as it's been 3 years. Stage 4's may have to treat harder/longer, so I think you have a very good clinical argument for a biopsy but their argument is probably just to treat you as a stage 4. An alternative is Fibroscan. Maybe you should contact "HR" if you can't qualifty for one at a trial center.

As to the testing frequency, Cleaveland Clinic has an excellent reputation, but apparently they have their protocols. A few of us have been lucky IMO to have had the opportunity for weekly PCRs early in treatment. And while some question their utility, I see them helpful as both reality checks and also as useful future info should tx not work. You might read Susan400's comments re Dr. Shiffman's thoughts on this which basically said that it's hard to determine true null responders from slow responders unless VL is tested more frequently than usual during the first 12 weeks. It appears that Shiffman believes knowing this would help qualify people better for the treatment experienced Telaprevir trials. Maybe try that one on your doc and see what he says.

-- Jim

[gauf]

I requested another biopsy (been 3 years) but denied. I too wonder why I was downgraded to stage 4. I suppose being a 3a and failing 2 treatments may have something to do with it, but are these blood markers indicative of a stage 4 do you think?  Also wondering if an ultrasound? would help.

[gauf]

Thanks Jim. I finished last tox 1 year ago. My platelets and wbc have not changed in that time. Catscan showed slightly enlarged spleen.  i am "pushing" sensitive testing, but they check VL at 4 and 12 weeks and they won't budge. CBC weekly. I have a bonafide hepotologist at Cleveland Clinc. I did not know that hbg curve relates to Riba absorption. That is good to know as the doc first was going with 1400 riba, and then decided on 1200 due to past amemia problems. I will discuss it with him.

[jmjm530]

To your original question on "how sick am I" -- left out other data to factor in such as the result of an endoscophy (varisces?) or detection of Ascites via imaging.

[jmjm530]

I'm assumng this is pre-treatment baseline.

As to "how sick you are", I would look more at the whole picture, including biopsy reports, imaging studies (size of spleen, etc) as well as physical exam -- with heavy emphasis on biopsy staging.

I was going initally going to say your low platelet count was consistent with compensated cirrhosis per your profile, but after re-reading your profile, I'm a bit confused on where they staged you at and why. Abs Neuts and WBC are also a little low but that could be a holdover from your last treatment depending on how long ago that was, not that yours are that low.  My Abs Neuts took time to return to normal range after treatment.  Not sure of the significance -- if any -- of your slighlty low Abs Lymph, given your lymph% is in the normal range.

Other than saying it's ambitious, can't comment too much on your re-treatment plan without studying your prior response more. But assuming that you were a slow responder, I think pre-dosing the riba is a good idea -- just try and monitor frequently and have Procrit (epo) ready in case. Also, if your hgb curve suggests slow riba absorption, you might want to try more than 1200 mg/day depending on side effects. I'm also assuming that as a stage 4? relapser, you're treating with a liver specialist (hepatologist) or at least a GI that you have lots of confidence in.

But the bottom line is you want to shoot for RVR, or as close as possible, so weekly viral load testing from week one would give you maximum data in terms of seeing how things are working and offereing earlier opportunites of tweaking meds such as the riba.

To give yourself even earlier data, try and research out how long your lab takes to get the results back to you and/or the doctor -- and ideally use a lab with a relatively quick turnaround. "Heptimax" (Quest) for example, is an excellent test but turnaround for members here have varied from 3 days to two weeks, with 7-10 days seeming to be the average. That said, Heptimax is a two-part test and the Part I results (down to 50 IU/ml) are usually avaliable within 5 days -- if the doctor calls in -- but the reporting will probably be delayed until part 2 is ready if you just want for the lab to report.

Using "Heptimax" as an example, and knowing this, you can take a proactive stance and get your doctor or nurse to call the lab for these interim results which offer a lot of information. Unfortunately, the customer service rep that will answer the phone may not be familiar with the two-part format and simply tell you that results are pending. That's when you either have to ask/point out that you're looking for the interim real-time PCR results or ask to speak to a supervisor who you may have more luck with.



-- Jim

[gauf]

missed one: Bilirubin, Total 0.9 0.0-1.5 mg/dL