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Post Info TOPIC: Cirrhosis in HepC. Do we need a better Grading system?


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Cirrhosis in HepC. Do we need a better Grading system?
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Hi all,

I've been meaning to do a post on this for some time, and was even going to send it to a Journal, but couldn't be bothered with all the Bibliography, rewriting, references etc. I've been through that before.

Cirrhosis ( from the Greek- 'yellow condition') has long been regarded as the end stage of a variety of conditions, and was thought to be irreversible. It's not a good name as yellow condition refers to jaundice, a late manifestation. Cirrhosis from HepC is now the leading reason for liver transplants. As we are seeing more and more SVR's from the new DAA's, there is much talk about reversal of cirrhosis.

The true histological diagnosis should mean bridging fibrosis, haphazard fibrous bands (of varying thickness) and the presence of regenerative nodules . Using the METAVIR scoring system, this is called F4.

Most patients with chronic HepC will develop cirrhosis eventually, although this may take anything from 20-50 years. We've discussed conditions likely to promote progression to cirrhosis- drinking alcohol, coinfection with HIV/HBV, Genotype 3, fatty liver, iron disorders etc. Cirrhosis should be suspected in any patient who has had HepC for a long time, particularly those with a high VL and high ALT levels. High ALT levels (>200) are usually associated with increased inflammation and piecemeal necrosis, which translates into increased fibrosis.

DIAGNOSIS: The long-taught feature of cirrhosis is a scarred liver containing regenerative nodules. We obviously can't pull our liver out and look at it, so liver biopsy is the 'gold standard' for diagnosis, but even this has some errors. Cirrhosis can be suspected from clinical symptoms, and physical examination can confirm this when a hard, nodular liver can be palpated, or when there is ascites, oesophageal varices or hepatic encephalopathy. All of these only occur in the later stages of cirrhosis. Blood tests such as bilirubin, liver enzymes, albumin, Prothrombin time (or INR), platelet count may all raise the suspicion of cirrhosis.  Imaging with Ultrasound, CT or MRI may also show features typical of cirrhosis, but again these may not appear in early stages. So we try a variety of Biochemical markers- some of these are APRI, AST/ALT ratio, FIB-4, FibroSure (FibroTest) and ActiTest. All have a varying degree of success in the diagnosis.  Fibroscan (Transient Elasticity) using an Ultrasound beam or MRI gradient is one of the latest tools. The accuracy in diagnosing cirrhosis is about 90%. The severity of cirrhosis was proposed using the Child-Turcotte-Pugh score. In cases that may need a transplant, the MELD score was used.

GRADING of CIRRHOSIS: A diagnosis of cirrhosis will be frightening to many, particularly after researching the internet. To date, the only accepted Grading system is Compensated or Decompensated cirrhosis. Clinicians disagree about whether oesophageal varices should be considered 'Decompensated'. A system was proposed:

Grade A: Compensated

Grade B: Beginning to decompensate

Grade C: Decompensated- End Stage.

As usual, there is disagreement about what Grade B means. I propose a better system:

Stage 1: No symptoms, no significant clinical findings, biochemical parameters well within normal limits ( apart from liver enzymes), normal oesophagus and stomach.

Stage 2: May have symptoms (eg fatigue), may have liver and /or spleen enlargement, may have some changes on imaging, some biochemical parameters may be abnormal, may have changes of portal hypertensive   gastropathy in the stomach.

Stage 3: Usually have symptoms, obvious liver/spleen enlargement, changes noted on imaging, some abnormal blood parameters (platelets, bilirubin, albumin etc), oesophageal and/or gastric varices.

Stage 4: Symptomatic, obvious clinical signs ,obvious changes on imaging, abnormal blood parameters, with any/all of the following: jaundice, varices (bleeding or not), ascites, hepatic encephalopathy.

Obviously this covers a wide range of patients. When I read 'x' number of cirrhotics are included in a Clinical Trial,it means little as I'm sure most are preselected and are Stages 1 or 2.

DISCUSSION: Cirrhosis is progressive, and eventually we'll progress to a lower stage. Patients could remain at Stage 1 for up to 10 years- others progress more quickly and some of these factors are unknown. Most of us will be Stages 1 or 2 at presentation.  Some members are told they have 'mild' or 'early' cirrhosis and this should mean Stage 1. Any system such as this has some blurring of the boundaries. The importance in knowing where you stand is in the expectations post-SVR.  If I was Stage 1, I would expect a high likelihood of cirrhosis reversal to F3 or even F2. Stages 2 and 3 have progressively less likelihood. In most cases, SVR removes the cause for liver inflammation/ fibrosis, so progression of cirrhosis should be halted. SVR also causes a reduction in portal vein pressure, so varices often disappear.

This is also important in followup for HCC. As long as there is a high turnover of liver cells, there is an increased risk of HCC. Cirrhotics form nodules that often outstrip their blood supply, leading to necrosis, resorption and regeneration. In time, as fibrosis is resorbed , many post-SVR HepC cirrhotics will revert to F3 and lower, so HCC will not be as much of a worry.

If you haven't been fully assessed and don't want to know if you're cirrhotic, I understand. It does make a difference regarding treatment decisions and followup. Hopefully, cirrhosis from HepC will eventually disappear, and transplants will not be required. Cheers.

* This is basically about cirrhosis from Hepc. It can be applied to other causes of cirrhosis. Treating HBV or AIDs, stopping drinking and dietary changes etc., can help stop progression in other cases.



-- Edited by mallani on Sunday 1st of March 2015 06:41:52 AM


Geno 1b, IL28B CT,  x3 prior relapser,  ex-cirrhotic, 74 yo, did 48 weeks with Victrelis/Peg./Riba.  VL 1.28m at start, UNDET. at 8 ,12 ,16 ,24 ,30  and 48 weeks.  EOT 15 Feb 2013 , UNDET. at EOT + 28 weeks. SVR!  Still Undet. at EOT +4 years


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