Hi Tanya,

There are many causes for feeling unwell and having elevated liver functions, but in somebody who has just finished treatment for hep c with Zepatier (or Harvoni or Maviret or Epclusa) treatment failure would be top of the list.

While the treatment failure rates are low 95% cure rate means 5% failure rate – so if I treat 20 patients with Hep C this week one will fail.

As Mar has said – you need an HCV PCR RNA test to see if the virus is still present.

If it is, don’t panic. Retreatment is easily done and very effective.

If it isn’t we need to look for other causes of problems.

Either way you probably need a doctor with more of a clue…

Hello Oregondaisy,

Yes, supplements don’t appear on most interaction charts because it’s impossible to know what’s in most of them and what doses people are taking. There is no doubt that some will interact, and some won’t but we don’t know which ones.

On the general topic it’s probably worth reading this:

More evidence that routine multivitamin use should be avoided

While it’s not true that 100% of supplements are 100% useless, it is basically true they represent 90% marketing on top of 10% fact – more hope than evidence if you like.

Most patients, taking most supplements, are either no better off, or actually worse off because of them.

There are exceptions, but most people need no more than clean air to breathe, clean water to drink, personal hygiene, and a good varied diet to eat to live a long and healthy life.

If you’d like to list your supplements and what benefits you expect from them, we can have a discussion about the pros and cons of each.

Hi John,

Here is the original article (abstract): https://onlinelibrary.wiley.com/doi/abs/10.1111/apt.14391

And here is an editorial talking about it: https://onlinelibrary.wiley.com/doi/full/10.1111/apt.14431

So if you read this:

Background: Proton pump inhibitors are among the most commonly prescribed medications in the United States. Their safety in cirrhosis has recently been questioned, but their overall effect on disease progression in noncirrhotic patients with chronic liver disease remains unclear. Aim: To determine the impact of proton pump inhibitors on the progression of liver disease in noncirrhotic patients with hepatitis C virus (HCV) infection. Methods: Using the electronically retrieved cohort of HCV-infected veterans (ERCHIVES) database, we identified all subjects who received HCV treatment and all incident cases of cirrhosis, hepatic decompensation and hepatocellular carcinoma. Proton pump inhibitor use was measured using cumulative defined daily dose. Multivariate Cox regression analysis was performed after adjusting univariate predictors of cirrhosis and various indications for proton pump inhibitor use. Results: Among 11 526 eligible individuals, we found that exposure to proton pump inhibitors was independently associated with an increased risk of developing cirrhosis (hazard ratio: 1.32; 95% confidence interval: 1.17-1.49). This association remained robust to sensitivity analysis in which only patients who achieved sustained virologic response were analysed as well as analysis excluding those with alcohol abuse/dependence. Proton pump inhibitor exposure was also independently associated with an increased risk of hepatic decompensation (HR: 3.79; 95% confidence interval: 2.58-5.57) and hepatocellular carcinoma (HR: 2.01; 95% confidence interval: 1.50-2.70). Conclusions: In patients with chronic HCV infection, increasing proton pump inhibitor use is associated with a dose-dependent risk of progression of chronic liver disease to cirrhosis, as well as an increased risk of hepatic decompensation and hepatocellular carcinoma.

Then you’d be correct that there appears to be a risk but it needs to be taken in context. With the cirrhosis risk of 1.32 we have a 95% confidence interval of 1.17 to 1.49 which means we think there is a 17% to 49% increase in cirrhosis risk (and are 95% sure it’s in that range). So that’s an increase in cirrhosis risk, but the biggest risk for cirrhosis in HCV is HCV so if you get SVR then your general risk profile changes like this:

So SVR delivers 1/3 the rate of mortality, 1/5 the rate of HCC and 1/10 the rate of HCC.

It looks like PPIs may compromise that improvement slightly. From memory, your 2 major issues were the HCV (now cured) and being overweight (substantially increasing the probability of fatty liver) and which you’re working on. These are the big ticket health issues, and your reflux would almost certainly be improved by weight loss allowing you to use less PPIs.

So, in terms of long term health look after the big ticket items first.

1. Get rid of diseases like HCV and try to be in the healthy weight range
2. Get your blood pressure, cholesterol and blood sugar checked and fix if needs be
3. Don’t smoke or drink too much alcohol
4. Do exercise, eat good food, drink water and get enough sleep

Once you have the basics to hand look at the smaller issues like PPIs. There is no such thing as a drug that does not have side effects and you don’t get any issues with drugs you’re not taking. This advice also applies to supplements, most of which have been shown to have no long term benefits and some long term issues.

Hi Boba,

If you have a look at the first graph you see an early spike of HCV RNA – this is the viral load. It peaks and then the partially (for some people fully) effective antibodies start to rise and knock it down.

Either the antibodies wipe it out or the vius mutates a bit and starts to go up again. It’s all normal and your treatment success probability is very high.

Trust in the force young Jedi!

Hello Penn,

There is quiet a strong association between autoimmunity and Hepatitis C. The immune-related extrahepatic manifestations include:

• Mixed cryoglobulinemia
• Cryoglobulinemic vasculitis
• B-cell non-Hodgkin’s lymphoma.
• Sicca syndrome
• Arthralgia/myalgia
• Polyarthritis/fibromyalgia
• Autoantibody production (i.e. cryoglobulins, rheumatoid factor, and antinuclear, anticardiolipin, antithyroid and anti-smooth muscle antibodies)
• Polyarteritis nodosa
• Monoclonal gammopathies
• Immune thrombocytopenia
• Glomerulonephritis and renal insufficiency

This article speaks to your questions https://rmdopen.bmj.com/content/1/1/e000008 with the answer “we just don’t know”.

This article says “use DMARDs with caution in HCV” http://www.eurjrheumatol.org/sayilar/211/buyuk/194-9.pdf

This article suggests slightly lower SVR rates in patients with autoimmunity https://bmjopengastro.bmj.com/content/5/1/e000203

There is a tiny 3 case series here https://bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-018-0826-7 showing a transient fall in autoantibodies during treatment

But in terms of a study that said something like “patients with HCV and autoimmunity have reduced autoimmunity on and after HCV treatment” – as far as I know nobody has done a large trial to answer that one way or another.

It sounds like you are weighing up treatment options?

Hello Aaron,

The cure rate for GT2 with either Sofosbuvir/Daclatasvir or Sofosbuvir/Velpatasvir (Epclusa) is very high. Not quite 100% but close.

The 12 weeks of waiting is hard. You can check your liver enzymes every 4 weeks and if these remain normal you can be confident that all is well. A CMP from link2labs https://fixhepc.com/link2labs will cost $10 so it’s a cheap way of keeping tabs on things.

Best of luck, but, if you were a horse, I’d be betting on you for the win.

Hello RockHard,

11.6kPa is less than the 12.5kPa for cirrhosis but, given this is a spectrum you are much closer to cirrhosis than not. As you say, for F4 GT3 patients the recommendations are 12 weeks Epclusa with Ribavirin or 24 weeks without.

If you were my patient I would have discussed this in a conversation like GT3 is harder to treat, it’s harder with cirrhosis (which you are close to) so what do you think about Ribavirin?

What country are you in? There are all sorts of rules that restrict what can be used and the options for retreatment also vary. For example, in Australia all I could give you would be 12 weeks Epclusa so the decision here is 12 weeks with Riba or 12 weeks without – there is no 24 week without option. For a patient in Australia, the only way to do 24 weeks without would be 12 weeks PBS funded, and 12 weeks self-funded generic.

All other things being equal I would be happier if undetected at 4 weeks than if you’re still detected.

Yes we could add Ribavirin in later. It’s probably not as good as earlier, but probably better than not at all. The “probablys” relate to the fact it’s not done very often so it’s a best guess, rather than something backed by solid research. I know eminent doctors like Professor Ed Gane would add it in if things did not seem to be going according to plan (at least that’s what he suggested last time I asked!).