Remember this from last year? Statins Stop Hepatitis C Virus From Replicating

Does anyone know what ever happened about it?  Did they pursue it?

[frijole]

It seems that I just read something this week about that but I will have to think about where it was.  Clinical Care Options, maybe.  I believe the bottom line was that they didn't work for hepatitis C -- that the avenue would not be pursued.  Maybe someone else saw it.

frijole

[JRenquist]

Thanks - guess it was too easy to be true.

[frijole]

Found the reference.  It is kind of buried within a summary of new treatments so I went ahead and copied the whole thing.  If you google, and the references are from July 06. This is current.

http://clinicaloptions.com/Hepatitis/Conference%20Coverage/Washington%202007/Tracks/New%20Data/Conference%20Report/Pages/Page%205.aspx

Rosuvastatin Therapy Does Not Impact HCV RNA Levels
Kris V. Kowdley, MD, FACP:
The replication of HCV is largely dependent on the use of host cellular components, and lipid moieties or lipid-containing molecules, such as sterol proteins, may play an important role in facilitating viral replication, either via assembly, packaging, or release. It has been hypothesized that HMG-CoA reductase inhibitors or “statins,” which can lower certain lipid levels, therefore could potentially have anti-HCV properties. Previous studies of statins have shown them to be effective in preventing HCV replication in vitro.[15,16] For example, lovastatin induced depletion of membrane sterols and was associated with suppression of HCV RNA in a replicon cell line.[15] Strong in vitro inhibition of HCV replication has also been achieved with the combination of interferon with fluvastatin.[16]

Rosuvastatin is believed to target a compound called geranylgeraniol, which plays a role in the last stages of cholesterol synthesis. It has a long half-life as it is not readily metabolized by the cytochrome P450 system. Furthermore, the drug is considered to be safe in patients with underlying aminotransferase elevation. A study by George and colleagues[17] evaluated whether blocking lipid synthesis via the use of rosuvastatin might interfere with some steps in HCV viral assembly or packaging and reduce HCV RNA levels in treatment-experienced hepatitis C patients. Eleven patients were screened for this study, each with measurable serum HCV RNA, nonresponse to standard peginterferon plus ribavirin therapy, and compensated liver disease. Baseline characteristics revealed a population of mostly middle aged, predominantly male patients with moderate levels of viremia (mean HCV RNA level of 7.13 ± 0.61 log10 copies/mL). The mean liver enzymes were moderately elevated at 90.04 ± 53.69 IU/L, and the mean body mass index was fairly high at 29.58 ± 4.54.

The patients received rosuvastatin dose escalation from 20-40 mg/day for a 12‑week period, followed by a 4-week off-treatment evaluation phase. The drug was well tolerated with only 1 patient experiencing a transient increase in creatine phosphokinase and some nausea. There was a positive association between the change in serum triglycerides and the change in HCV RNA (Rho = 0.75; P = .007). However the overall mean HCV RNA levels remained fairly constant from baseline through the 2 dosing periods and the follow-up. Total serum cholesterol and triglycerides decreased from 174 mg/dL and 128 mg/dL, respectively, at baseline to 114 mg/dL and 90 mg/dL, respectively, during the 40-mg dosing period and returned approximately to baseline levels during the follow-up phase. Although high density lipoprotein levels were not significantly affected, low density lipoprotein levels decreased considerably. There was no significant change in serum ALT, which remained at approximately 90 IU/mL during treatment and reduced to 82 IU/mL during the follow-up. In summary, short-term therapy with rosuvastatin improved some aspects of the patients’ lipid profiles but was not associated with significant changes in HCV RNA or liver enzyme levels. Whether the dosing was insufficient or whether, in fact, this particular HMG‑CoA reductase inhibitor does not interfere with viral packaging or assembly remains unknown.

Mark S. Sulkowski, MD:
This result adds further doubt as to whether the use of statins or other lipid-lowering agents is an effective treatment for hepatitis C. The inability of these drugs to inhibit HCV in human beings infected with HCV has been observed in other small studies as well. Recently, O’Leary and colleagues[18] published a paper revealing that atorvastatin also failed to produce an anti-HCV effect. Why is there an antiviral effect of statins in the replicon system but not in humans? While more research is needed, this may represent an issue with the drug concentrations achieved in humans compared with a test-tube or some other effect that has yet to be identified. Although interest concerning this class remains an area of active research, statins should not currently be considered a treatment option for chronic HCV infection.

Kris V. Kowdley, MD, FACP:
A confounding factor is that statins have antioxidant properties by clearing fat from the liver and thereby reducing oxidative stress. Oxidative stress is clearly an important mechanism for hepatocyte injury in the replicon system. Therefore, the reduction in HCV RNA associated with use of statins in this system may not be because of a direct antiviral effect but instead may be secondary to the reduction in oxidative stress, which creates a milieu in which host mechanisms are better able to keep viral replication controlled.

[frijole]

My post should have said if you google ( statins hepatitis C treatment) all the references that pop up are from July 2006.  What I posted is from "Highlights in Viral Hepatitis: CCO Independent Conference Report on the 2007 Digestive Disease Week"

hope that helps. It would have been nice if we could have red rice yeasted our hep c away, wouldn't it?
frijole

[JRenquist]

Yes It would have.  Thanks for checking on this.  Really was too easy to be true, it seems. Still have hope in Telaprvir (sp?)  

[ClippedWings]

Hmmm.  I wouldn't toss out the statins based on this study.  For one thing, they only used one type and it was not one of the statins previous studies have shown promise with.  Secondly the group was small (11) and were all previous nonresponders to SOC.  What about treatment naive patients?  Hopefully some larger studies come along.