Anabolic Steroids & Liver [GI]

[Michael Scally MD]

El Rahi C, Thompson‐Moore N, Mejia P, De Hoyos P. Successful Use of N‐Acetylcysteine to Treat Severe Hepatic Injury Caused by a Dietary Fitness Supplement. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy 2015;35:e96-e101. https://doi.org/10.1002/phar.1572

In the absence of adequate premarketing efficacy and safety evaluations, adverse events from over‐the‐counter supplements are emerging as a public health concern. Specifically, bodybuilding products are being identified as a frequent cause of drug‐induced liver injury.

We present a case of a 20‐year‐old Hispanic male who presented with acute nausea and vomiting accompanied by severe right upper quadrant abdominal pain, shivering, and shortness of breath. Laboratory data pointed to mixed cholestatic and hepatocellular damage, and after exclusion of known alternate etiologies, the patient was diagnosed with acute drug‐induced liver injury secondary to the use of “Friction,” a bodybuilding supplement.

Treatment with N‐acetylcysteine (NAC) 20% oral solution was initiated empirically at a dose of 400 mg (70 mg/kg) every 4 hours and was continued once the diagnosis was made. Within 48 hours of admission to our hospital, the patient began to show clinical resolution of right abdominal pain and tolerance to oral diet associated with a significant decline toward normal in his liver function tests and coagulopathy.

The WHO‐UMC causality assessment system suggested a “certain causality” between exposure to the supplement and the acute liver injury. In the event of suspected drug‐induced liver injury, treatment with NAC should be considered given its favorable risk‐benefit profile.

 

[Michael Scally MD]

Shalaby AM, Bahey NG. Reversal of the hepatic damage induced by the supraphysiological dose of nandrolone decanoate after its withdrawal in the adult male rat. Tissue and Cell 2018;53:44-52. Reversal of the hepatic damage induced by the supraphysiological dose of nandrolone decanoate after its withdrawal in the adult male rat - ScienceDirect

Highlights
· Nandrolone decanoate encourages a significant increase in the rat body weight gain and the level of serum transaminases.
· Nandrolone decanoate induces dilatation and congestion of intrahepatic blood vessels with excessive inflammatory cellular infiltration.
· Vacuolar degeneration in the hepatocytes with partial loss of mitochondrial cristae are observed after nandrolone decanoate administration.
· Nandrolone decanoate induces a significant increase in the hepatic fibrosis, apoptosis and the area percentage of the hepatic stellate cells.
· Withdrawal of nandrolone promotes a significant improvement in the hepatic function and structure.

Nandrolone decanoate is an anabolic-androgenic steroid that is frequently used at a very high dose to improve the physical performance. Recently, this drug has been abused by athletes to augment their muscle mass and improve their physical performance. However, this could have an impact on other body systems with the potential increase in its harmful effect. Therefore, the aim of this study was to evaluate the effect of administering a supraphysiological dose of nandrolone decanoate on the hepatic functions and structure of the adult rat and to test the potential reversibility after nandrolone withdrawal.

Thirty adult male rats were equally divided into;
· control group,
· nandrolone-treated group (10 mg/kg/IM/weekly) for four weeks and
· recovery group (received nandrolone for four weeks followed by four weeks recovery).

The results showed that nandrolone treatment led to a significant increase in the body weight gain and in the levels of serum alanine and aspartate transaminases. Moreover, the liver sections from nandrolone-treated rat showed; dilatation and congestion in the blood vessels, inflammatory cellular infiltration with hepatic fibrosis, severe vacuolar cytoplasmic degeneration, apoptotic hyperchromatic nuclei and partial loss of mitochondrial cristae in the hepatocytes.

In addition, nandrolone treatment resulted in significant increase in the apoptotic index and the area percentage of GFAP positive stellate cells in the liver tissues. Importantly, withdrawal of nandrolone for 4 weeks rescued these biochemical and histological changes.

In conclusion, our results showed that supraphysiological dose of nandrolone has hepatotoxic effects in the adult rat and showed that these toxic effects are reversible after treatment withdrawal.

 

[Michael Scally MD]

Acute Pancreatitis Secondary to The Use of The Anabolic Steroid Trenbolone Acetate

Background: The use of performance-enhancing drugs has increased dramatically in the last decade with high prevalence reported among the young athlete population. Many of these drugs contain anabolic steroids and may carry potential significant side effects and health risks.

We report a case of anabolic steroid-induced acute pancreatitis (AP) that recurred after the reuse of the same drug by the patient, confirming the causative relationship.

Case report: A 24 year-old male presented with severe epigastric pain. His past medical history was significant for two hospitalizations during the last year with AP. During his hospital admissions, extensive workup was performed ruling out the common and uncommon causes of AP.

Upon further pressing, the patient admitted to a history of past and current anabolic steroid use for athletic performance enhancement. He began this use four years ago and most recently started using trenbolone acetate (TA).

The correlation between the timing of the anabolic steroids administration and the attacks of AP, along with ruling out other causes, confirmed TA as the cause of pancreatitis.

Discussion: The side effects associated with the use of these increasingly prevalent drugs are difficult to study in clinical trials due to the unethical nature of their consumption. In addition, these medications are difficult to study due to the varied usage cycles and patterns, unknown origin and source, as well as often high dose ingestion. Physicians and body builders need to be aware of the possible serious consequences of their use.

Kumar V, Issa D, Smallfield G, Bouhaidar D. Acute pancreatitis secondary to the use of the anabolic steroid trenbolone acetate. Clinical Toxicology 2018:1-3. https://doi.org/10.1080/15563650.2018.1491983

 

[Saitama]

Hi, this is my first post here, please don't be mean to me, English is not my native language, hope it's not off topic but since you've been talking about liver damage, I would like to share my experience hoping that you could give me some good advices.

I started cycling last January and before that I took some blood exams.

ASAT(GOT) 42 UI/l 38 is the maximum
ALAT (GPT) 77 UI/l 41 is the maximum

Total Bilirubin 2.05 mg/dl 1.0 is the maximum
Direct Bilirubin 0.41 mg/dl 0.2 is the maximum
Indirect Bilirubin 1.64 mg/dl between 0.0 and 0.75

So I decided not to take any orals and I started with a 10 weeks cycle, 500mg of testo enanthate and 160mg of parabolan for the first 8 weeks and 200mg for the last two. 0.5 AI each day.

I took another blood exam in February:

ASAT(GOT) 36 UI/l 38 is the maximum
ALAT (GPT) 65 UI/l 41 is the maximum

Total Bilirubin 1.2 mg/dl 1.0 is the maximum
Direct Bilirubin 0.3 mg/dl 0.2 is the maximum
Indirect Bilirubin 0.9 mg/dl between 0.0 and 0.75

Then I ran my TRT for 10 weeks and I started another cycle in June, 8 weeks this time with same testo and increasing tren to 250mg. I increased AI to 1 per day because I had some kind of gyno issues.

I repeated blood exams in April:

ASAT(GOT) 45 UI/l 38 is the maximum
ALAT (GPT) 74 UI/l 41 is the maximum

Total Bilirubin 1.45 mg/dl 1.0 is the maximum

At the moment I'm going to finish my 8 weeks TRT and in the meantime I took an abdominal scan. Everything is alright, there is no sing of enlarged liver or obstruction of biliar ducts. Kidneys are fine, everything is fine according to the doctor. He told me it's very unusual 'cause I haven't any other syntoms.

He also showed me three possible scenarios:

A temporary virus;
Blood test machine failure;
Gilbert Syndrome.

Sorry for the long post, please share your opinions.

 

[Saitama]

I forgot to mention I've been taking NAC since January, 3600mg a day on the first cycle along with liver 52, then I dropped NAC to 1,800mg a day and I stopped liver 52. Now I'm trying with DEURSIL 300mg until the next blood exams.

 

[Michael Scally MD]

Squarza S, Rossi UG, Torcia P, Cariati M. Association between cholesterol gallstones and testosterone replacement therapy in a patient with primary hypogonadism. Revista de gastroenterologia de Mexico 2018;83:205-7. https://www.sciencedirect.com/science/article/pii/S037509061830082X?via=ihub

A 16-year-old boy had a past medical history of primary hypogonadism, due to bilateral anorchia. He presented with gallstones located in the gallbladder and a mild dilatation of the intrahepatic biliary tree. The histology study reported cholesterol gallstones.

The patient had been treated with testosterone replacement therapy since infancy. We suggest a possible correlation between testosterone replacement therapy and the presence of cholesterol gallstones.

 

[Dr JIM]

Squarza S, Rossi UG, Torcia P, Cariati M. Association between cholesterol gallstones and testosterone replacement therapy in a patient with primary hypogonadism. Revista de gastroenterologia de Mexico 2018;83:205-7. https://www.sciencedirect.com/science/article/pii/S037509061830082X?via=ihub

A 16-year-old boy had a past medical history of primary hypogonadism, due to bilateral anorchia. He presented with gallstones located in the gallbladder and a mild dilatation of the intrahepatic biliary tree. The histology study reported cholesterol gallstones.

The patient had been treated with testosterone replacement therapy since infancy. We suggest a possible correlation between testosterone replacement therapy and the presence of cholesterol gallstones.

Bc Hispanics already have a very high incidence of Biliary Tract Disease, the association of Gallstones to TRT, requires much more than a single case study.

Jim

 

[Michael Scally MD]

Novartis announces clinical collaboration with Pfizer to advance the treatment of NASH
Novartis announces clinical collaboration with Pfizer to advance the treatment of NASH | Novartis

• Agreement includes a clinical trial to evaluate a combination of tropifexor (LJN452) and one or more Pfizer compounds for the treatment of non-alcoholic steatohepatitis (NASH)
• Novartis has a leading development portfolio in non-viral liver diseases, including NASH
• There are currently no approved treatments for NASH, a progressive form of non-alcoholic fatty liver disease, which affects up to 6.5% of the population worldwide

 

[Bigboy727]

Novartis announces clinical collaboration with Pfizer to advance the treatment of NASH
Novartis announces clinical collaboration with Pfizer to advance the treatment of NASH | Novartis

• Agreement includes a clinical trial to evaluate a combination of tropifexor (LJN452) and one or more Pfizer compounds for the treatment of non-alcoholic steatohepatitis (NASH)
• Novartis has a leading development portfolio in non-viral liver diseases, including NASH
• There are currently no approved treatments for NASH, a progressive form of non-alcoholic fatty liver disease, which affects up to 6.5% of the population worldwide

RePosting studies and other stuff is great and all, but writing a conclusion to these would be much more beneficial to everyone here. I am in the commercial development business, not the medical field. It would be great to get your opinion on some of these if you think they’re accurate or misleading. Just my .2. Thanks

 

[Michael Scally MD]

 

[Bigboy727]

So there is a cure! Blast away boys!

 

[Munky]

Are orals the worst for the liver , is testosterone enthanante tough on the liver?

 

[Bigboy727]

Are orals the worst for the liver , is testosterone enthanante tough on the liver?

Orals are devastating to your liver and yes any AAS is hard on the liver. Tren is terrible.

 

[Munky]

Thank-you

 

[Michael Scally MD]

Liver Supplements Are Worthless ..

Kiracofe B, Coffey R, Jones LM, et al. Incidence of oxandrolone induced hepatic transaminitis in patients with burn injury. Burns 2018. https://www.sciencedirect.com/science/article/abs/pii/S0305417918302870?via=ihub

Highlights
· 42% patients developed transaminitis, significantly higher than ever reported.
· Transaminitis group used a higher number of other concomitant medications.
· No differences in length of stay or liver dysfunction were found between groups.

The benefits of oxandrolone in burn patients has led to its accepted use in the burn care community, however details regarding the most common adverse effect, transaminitis, remains unclear. The purpose of this study was to determine the incidence of transaminitis in patients with burn injury and identify risk factors associated with the development of transaminitis.

This single-center, retrospective risk factor analysis compared burn patients on oxandrolone with and without the development of transaminitis, defined as any aspartate aminotransferase or alanine aminotransferase value >100mg/dL. Patient demographics, past medical history, lab values, and burn characteristics were recorded.

Overall 28 out of 66 (42%) patients developed transaminitis. The transaminitis group had a significantly higher proportion of other concomitant medications with a transaminitis risk (p=0.045). No significant difference in liver dysfunction or length of stay was observed between the two groups.

Oxandrolone induced transaminitis is occurring in patients significantly more frequently than previously reported warranting further research to guide monitoring requirements, use of concomitant medications, and to determine if rechallenging after resolution should be considered.

 

[Bigboy727]

Liver Supplements Are Worthless ..

Kiracofe B, Coffey R, Jones LM, et al. Incidence of oxandrolone induced hepatic transaminitis in patients with burn injury. Burns 2018. https://www.sciencedirect.com/science/article/abs/pii/S0305417918302870?via=ihub

Highlights
· 42% patients developed transaminitis, significantly higher than ever reported.
· Transaminitis group used a higher number of other concomitant medications.
· No differences in length of stay or liver dysfunction were found between groups.

The benefits of oxandrolone in burn patients has led to its accepted use in the burn care community, however details regarding the most common adverse effect, transaminitis, remains unclear. The purpose of this study was to determine the incidence of transaminitis in patients with burn injury and identify risk factors associated with the development of transaminitis.

This single-center, retrospective risk factor analysis compared burn patients on oxandrolone with and without the development of transaminitis, defined as any aspartate aminotransferase or alanine aminotransferase value >100mg/dL. Patient demographics, past medical history, lab values, and burn characteristics were recorded.

Overall 28 out of 66 (42%) patients developed transaminitis. The transaminitis group had a significantly higher proportion of other concomitant medications with a transaminitis risk (p=0.045). No significant difference in liver dysfunction or length of stay was observed between the two groups.

Oxandrolone induced transaminitis is occurring in patients significantly more frequently than previously reported warranting further research to guide monitoring requirements, use of concomitant medications, and to determine if rechallenging after resolution should be considered.

@Roger rabbit intresting read

 

[Michael Scally MD]

USP Labs' sales pitch got customers' attention: The Dallas company sold products developed by "the world's top pharmacists & scientists;" dietary supplements that were derived from natural ingredients like geraniums.

But they were in fact dangerous synthetic stimulants made in Chinese chemical factories, according to prosecutors. Nevertheless, the company's executives marketed their products as safe, even though in private they talked about the dangers. The CEO referred privately to one of their controversial ingredients — known as DMAA — as a "questionable powder," court records show.

The products flew off the shelves and netted the owners over $230 million, the feds say.

USP Labs and its owners were charged in 2015 in an 11-count indictment. On the eve of trial last week, the last of seven defendants pleaded guilty. Cyril Willson, 38, of Ralston, Neb., and Matthew Hebert, 40, of Dallas, admitted to introducing misbranded food into interstate commerce with the intent to defraud or mislead.

The recent plea agreements came after U.S. District Judge Sam A. Lindsay denied defense motions seeking to suppress some government evidence. It is unclear whether the pleas might also have had something to do with new evidence the government said in court documents it planned to introduce. Prosecutors said it showed that some of the defendants have a history of smuggling illegal substances and tried to intimidate witnesses.

Patrick R. Runkle, a trial attorney with the Justice Department's consumer protection branch, said in a February court filing that evidence of the defendants' prior bad acts was relevant because it showed their "knowledge, plan and absence of mistake" in the USP Labs case.

...

USP Labs' top-selling products from 2009 to 2013 — Jack3d and OxyElite Pro — contained DMAA, which authorities said resulted in a rash of liver injuries. At least one other person died after taking the products. When the "outbreak of injuries" was reported in 2013, the company rushed to sell its remaining inventory before substituting DMAA with different ingredients, prosecutors said.

 

[Deleted member 59947]

What is the degree of liver toxicity of Exemestane at 12.5mg twice a week?

I’ve seen studies stating liver toxicity in women cancer patients, but that’s using 25mg/day.

 

[Michael Scally MD]

[OA] A Missense Variant in Mitochondrial Amidoxime Reducing Component 1 Gene and Protection Against Liver Disease

Analyzing 5770 all-cause cirrhosis cases and 572,850 controls from seven cohorts, we identify a missense variant in the Mitochondrial Amidoxime Reducing Component 1 gene (MARC1 p.A165T) that associates with protection from all-cause cirrhosis (OR 0.88, p=2.1*10-8).

This same variant also associates with lower levels of hepatic fat on computed tomographic imaging and lower odds of physician-diagnosed fatty liver as well as lower blood levels of alanine transaminase (-0.012 SD, 1.4*10-8), alkaline phosphatase (-0.019 SD, 6.6*10-9), total cholesterol (-0.037 SD, p=1*10-18) and LDL cholesterol (-0.035 SD, p=7.3*10-16).

Carriers of rare protein-truncating variants in MARC1 had lower liver enzyme levels, cholesterol levels, and reduced odds of liver disease (OR 0.19, p= 0.04) suggesting that deficiency of the MARC1 enzyme protects against cirrhosis.

Emdin CA, Haas M, Khera AV, et al. A missense variant in Mitochondrial Amidoxime Reducing Component 1 gene and protection against liver disease. bioRxiv 2019:594523. A missense variant in Mitochondrial Amidoxime Reducing Component 1 gene and protection against liver disease

 

[Michael Scally MD]

[OA] A Missense Variant in Mitochondrial Amidoxime Reducing Component 1 Gene and Protection Against Liver Disease

Analyzing 5770 all-cause cirrhosis cases and 572,850 controls from seven cohorts, we identify a missense variant in the Mitochondrial Amidoxime Reducing Component 1 gene (MARC1 p.A165T) that associates with protection from all-cause cirrhosis (OR 0.88, p=2.1*10-8).

This same variant also associates with lower levels of hepatic fat on computed tomographic imaging and lower odds of physician-diagnosed fatty liver as well as lower blood levels of alanine transaminase (-0.012 SD, 1.4*10-8), alkaline phosphatase (-0.019 SD, 6.6*10-9), total cholesterol (-0.037 SD, p=1*10-18) and LDL cholesterol (-0.035 SD, p=7.3*10-16).

Carriers of rare protein-truncating variants in MARC1 had lower liver enzyme levels, cholesterol levels, and reduced odds of liver disease (OR 0.19, p= 0.04) suggesting that deficiency of the MARC1 enzyme protects against cirrhosis.

Emdin CA, Haas M, Khera AV, et al. A missense variant in Mitochondrial Amidoxime Reducing Component 1 gene and protection against liver disease. bioRxiv 2019:594523. A missense variant in Mitochondrial Amidoxime Reducing Component 1 gene and protection against liver disease

Sek Kathiresan MD, a physician scientist and a human geneticist, is the Director of the Center for Genomic Medicine (CGM) at Massachusetts General Hospital (MGH), Ofer and Shelly Nemirovsky MGH Research Scholar, Director of the Cardiovascular Disease Initiative at the Broad institute, and a Professor of Medicine at Harvard Medical School. http://www.kathiresanlab.org/about-sek/

[Thread] what I hope will be our most impactful discovery to date. An enzyme whose loss of function lowers blood cholesterol & *protects* against fatty liver & cirrhosis.

…

So, in summary MARC1:
1. enzyme
2. loss of function protects against cirrhosis
3. loss of function lowers blood cholesterol, ALT, lower fatty liver
4. expressed in liver and adipocytes

What is the function of MARC1? Let's all figure this out!