Anabolic Steroids & Liver [GI]

[Bigunitny]

Everything's got a price.....injectables have their own set of issues, especially relating to increasing the chances of diabetes later in life, renal issues, blood sepsis, etc. There are no freebies when tinkering with the human body. Like any prescription drug---no matter how supposedly "safe" it is, you can read a whole assload of potential side-effects on the bottle. Shit, just read the back of a Tylenol bottle and see what it says not only about the liver, but potential effects on your kidneys and eyes as well. There is a give and take in life, but in the end, life has to end for us all....how you want to spend it is up to you. Hopefully, a person can lead a productive and happy life without it being at the expense of others

What diabetes later in life? What injectables are those ?

 

[Nattyboomba]

Some say that orals are safer. I don't know why, just prefer injection anyway.

I don't think anyone says orals are safer. If they do, I think they may want to reconsider giving advice on the subject.

 

[Dr JIM]

Is Trenbolone liver toxic?

Any drug metabolized by the liver, and that's most, may result
in enzyme changes.

However based on existing evidence unlike oral agents parenteral anabolics appear to be relatively "non-toxic".

Of course toxicity in this case would largely depend upon WHAT AAS is actually in that UGL vial!

 

[solo47]

Right, DJ, but injectables bypass the original passage through the liver, unlike digestibles. Still, I realize that anything injected is likely to pass through the liver and kidneys on later circulations, but injectables, used wisely, are still much safer. Dbol used to wreck my stomach too.

 

[Dr JIM]

Right, DJ, but injectables bypass the original passage through the liver, unlike digestibles. Still, I realize that anything injected is likely to pass through the liver and kidneys on later circulations, but injectables, used wisely, are still much safer. Dbol used to wreck my stomach too.

Good points @solo47!

I hope you're doing well mate.

 

[Michael Scally MD]

Tapper EB, Lok ASF. Use of Liver Imaging and Biopsy in Clinical Practice. New England Journal of Medicine 2017;377(8):756-68. http://www.nejm.org/doi/full/10.1056/NEJMra1610570

Liver biopsies are traditionally performed to determine the cause and stage of liver disease, as well as to inform treatment decisions and determine prognosis. In 2001, Bravo et al. observed that “liver biopsy is usually the most specific test to assess the nature and severity of liver diseases.” During the past 16 years, however, the clinical use of liver biopsies has undergone a profound transformation.

Validated alternatives to liver biopsy have proliferated, spurred by concerns about the costs of biopsy and the risk of complications. Furthermore, research has brought a new understanding of the limitations of liver biopsy.

In this review, we discuss the role of liver biopsy in the current era, as well as the accuracy of noninvasive evaluations and their use in clinical practice for determining the cause of liver disease and focal liver lesions and for detecting advanced fibrosis and cirrhosis.

Advances in imaging techniques such as vibration-controlled transient elastography and magnetic resonance elastography have reduced the need for liver biopsy as a means of diagnosing liver disease.

 

[Dr JIM]

Tapper EB, Lok ASF. Use of Liver Imaging and Biopsy in Clinical Practice. New England Journal of Medicine 2017;377(8):756-68. http://www.nejm.org/doi/full/10.1056/NEJMra1610570

Liver biopsies are traditionally performed to determine the cause and stage of liver disease, as well as to inform treatment decisions and determine prognosis. In 2001, Bravo et al. observed that “liver biopsy is usually the most specific test to assess the nature and severity of liver diseases.” During the past 16 years, however, the clinical use of liver biopsies has undergone a profound transformation.

Validated alternatives to liver biopsy have proliferated, spurred by concerns about the costs of biopsy and the risk of complications. Furthermore, research has brought a new understanding of the limitations of liver biopsy.

In this review, we discuss the role of liver biopsy in the current era, as well as the accuracy of noninvasive evaluations and their use in clinical practice for determining the cause of liver disease and focal liver lesions and for detecting advanced fibrosis and cirrhosis.

Advances in imaging techniques such as vibration-controlled transient elastography and magnetic resonance elastography have reduced the need for liver biopsy as a means of diagnosing liver disease.

Although advances in imaging have had a considerable impact on the "need" for liver BX, it's difficult to argue with pathological evidence of disease.

Great review THX @Michael Scally MD

 

[nextstepgainzzz]

Vilella AL, Limsuwat C, Williams DR, Seifert CF. Cholestatic Jaundice as a Result of Combination Designer Supplement Ingestion (July/August). Ann Pharmacother. http://www.theannals.com/content/early/2013/06/11/aph.1R405.abstract

OBJECTIVE: To report a case of cholestatic jaundice as a result of combination herbal and designer supplement use.

CASE SUMMARY: A 50-year-old Hispanic male presented to the hospital with a 1-week history of significant painless jaundice; total bilirubin on admission was 29.4 mg/dL. He reported use of both herbal (creatine and whey protein) and designer (Incredible Bulk and Spartan 45) supplements concurrently for approximately 2 months. Upon admission, all supplements were discontinued and multiple laboratory and diagnostic tests were ordered. On day 6 of his hospital admission, a liver biopsy was performed, the results of which indicated drug-induced hepatotoxicity. On day 9 he was discharged with prescriptions for ursodeoxycholic acid and hydroxyzine. Three months post hospital discharge, the patient continued to be supplement-free and bilirubin had decreased substantially.

DISCUSSION: Anabolic-androgenic steroids are capable of causing hepatotoxicity, and multiple cases reported in the literature support this. A case report described hepatotoxicity secondary to both creatine and whey protein consumption, and several reports have described liver damage secondary to designer supplement use. To our knowledge, this is the first case to describe hepatotoxicity as a result of combination herbal and designer supplement use. The Roussel Uclaf Causality Assessment Method (RUCAM) score for drug-induced hepatotoxicity indicated a highly probable correlation between the use of combination supplements and cholestatic jaundice.

CONCLUSIONS: Health care professionals need to be aware of complications associated with designer supplement use and should be able to identify patients who would benefit from education on herbal and designer supplement use.

 

[nextstepgainzzz]

I would have to agree. Liver damage, then stay away from orals!

 

[Dr JIM]

Although oral are associated with an increased incidence of hepatic "toxicity", the user defines the relative risk of these
and most other AAS.

 

[marco11]

Last time I ran tren my stool was yellow and watery because I guess my liver and gallbladder were messed up so my bile couldn't break down the fats in my stomach which in turn caused the watery yellow stool. Same thing happened to me when I increased the dosages on my anadrol. Never had issues with test or deca though.

 

[Michael Scally MD]

[WTF!!! Mice weigh at most 100g, probably less. And, they were administered 25 mg twice a week for a period of 90 days. Or, 250 mg/kg. Even at 25 mg/kg, a high dose!]

[Mice] Analysis of Elevated levels of Nandrolone Decanoate Induced Cytochrome-P450 Alterations

BACKGROUND: Frequent non-medicated use of anabolic androgenic steroids (AAS) is an instance of substance abuse which mimics the status of a natural hormone and upon prolonged exposure may lead to adverse drug reactions. These adverse drug reactions proceed in a manner so as to alter the normal metabolism of an enzyme mediated pathway such as the cytochrome P450 (CYP) family of enzymes.

OBJECTIVE: The present study was conducted to investigate the impact of overuse of Nandrolone Decanoate (ND), an AAS, upon CYP enzyme activity and a CYP gene, belonging to CYP1 family.

METHOD: The study was carried out using normal and ND treated male albino mice. Genetic analysis was conducted using normalized and treated cDNA and reverse transcriptase polymerase chain reaction based assays. For enzyme assay, 0.1ml of 25 mg ND was administered to the animals twice a week for a period of 90 days. Genetic analysis was carried out with the same dose but administered for a period of 360 days.

RESULT: CYP enzyme activity increased significantly (p<0.01) in the ND treated group of animals compared to that in the normal group. However, no noticeable alteration was observed at the molecular level.

CONCLUSION: From the present study it could be inferred that, at elevated doses, ND has the potential to alter hepatic CYP enzyme activity without any modification in the CYP gene. This could be due to a possible adaptive response of the living system to such drugs.

Chowdhury P, Mahantab R. Analysis of Elevated levels of Nandrolone Decanoate Induced Cytochrome-P450 Alterations in Mice. Drug Metab Lett. Analysis of Elevated levels of Nandrolone Decanoate Induced Cytochrome-P450 Alterations in Mice. - PubMed - NCBI

 

[Michael Scally MD]

Diehl AM, Day C. Cause, Pathogenesis, and Treatment of Nonalcoholic Steatohepatitis. New England Journal of Medicine 2017;377(21):2063-72. http://www.nejm.org/doi/full/10.1056/NEJMra1503519

Nonalcoholic steatohepatitis is a major cause of cirrhosis and liver cancer. It is associated with visceral adiposity and the metabolic syndrome and is nearly as common as type 2 diabetes. Metabolic stress, inflammation, and fibrosis are the primary pathogenic mechanisms.

 

[Michael Scally MD]

Parisinos CA, Hingorani AD. Is a fatty liver (always or ever) bad for the heart? European Heart Journal 2017:ehx718-ehx. http://dx.doi.org/10.1093/eurheartj/ehx718

Non-alcoholic fatty liver disease (NAFLD), a condition associated with the metabolic syndrome, has become common in an era of poor diet and reduced physical activity, affecting up to one in four adults.1 Patients exhibit variability in the rate of liver disease progression but only a relative minority progress to cirrhosis and liver-related death. However, NAFLD is also associated with increased morbidity and mortality from coronary heart disease (CHD), with emerging evidence implicating hepatic fibrosis (a progressive feature of NAFLD) in other vascular disorders such as ischaemic stroke.2,3 Therefore, an important research question in the past decade has been to tease apart whether NAFLD independently increases the risk of CHD.


Lauridsen BK, Stender S, Kristensen TS, et al. Liver fat content, non-alcoholic fatty liver disease, and ischaemic heart disease: Mendelian randomization and meta-analysis of 279 013 individuals. European Heart Journal 2017:ehx662-ehx. http://dx.doi.org/10.1093/eurheartj/ehx662

Aims - In observational studies, non-alcoholic fatty liver disease (NAFLD) is associated with high risk of ischaemic heart disease (IHD). We tested the hypothesis that a high liver fat content or a diagnosis of NAFLD is a causal risk factor for IHD.

Methods and results - In a cohort study of the Danish general population (n = 94 708/IHD = 10 897), we first tested whether a high liver fat content or a diagnosis of NAFLD was associated observationally with IHD. Subsequently, using Mendelian randomization, we tested whether a genetic variant in the gene encoding the protein patatin-like phospholipase domain containing 3 protein (PNPLA3), I148M (rs738409), a strong and specific cause of high liver fat content and NAFLD, was causally associated with the risk of IHD. We found that the risk of IHD increased stepwise with increasing liver fat content (in quartiles) up to an odds ratio (OR) of 2.41 (1.28–4.51)(P-trend = 0.004). The corresponding OR for IHD in individuals with vs. without NAFLD was 1.65 (1.34–2.04)(P = 3×10−6). PNPLA3 I148M was associated with a stepwise increase in liver fat content of up to 28% in MM vs. II-homozygotes (P-trend = 0.0001) and with ORs of 2.03 (1.52–2.70) for NAFLD (P = 3×10−7), 3.28 (2.37–4.54) for cirrhosis (P = 4×10−12), and 0.95 (0.86–1.04) for IHD (P = 0.46). In agreement, in meta-analysis (N = 279 013/IHD = 71 698), the OR for IHD was 0.98 (0.96–1.00) per M-allele vs. I-allele. The OR for IHD per M-allele higher genetically determined liver fat content was 0.98 (0.94–1.03) vs. an observational estimate of 1.05 (1.02–1.09)(P for comparison = 0.02).

Conclusion - Despite confirming the known observational association of liver fat content and NAFLD with IHD, lifelong, genetically high liver fat content was not causally associated with risk of IHD. These results suggest that the observational association is due to confounding or reverse causation.

 

[Michael Scally MD]

Heavy Consumption of Alcohol is Not Associated With Worse Outcomes in Patients With Idiosyncratic Drug-induced Liver Injury Compared to Non-Drinkers

BACKGROUND & AIMS: The relationship between alcohol consumption and idiosyncratic drug induced liver injury (DILI) is not well understood. We investigated the relationship between heavy consumption of alcohol and characteristics and outcomes of patients with DILI enrolled in the Drug-induced Liver Injury Network (DILIN) prospective study.

METHODS: We collected data from 1198 individuals with definite, highly likely, or probable DILI enrolled in the DILIN study from September 2004 through April 2016. At enrollment, all participants were asked about alcohol consumption; those with any alcohol consumption during previous 12 months were asked to complete the Skinner questionnaire to assess drinking history. Heavy consumption of alcohol was defined as more than 3 drinks, on average, per day by men or more than 2 drinks, on average, per day by women.

RESULTS: Of the 601 persons who reported consuming at least 1 alcoholic drink in the preceding 12 months, 348 completed the Skinner questionnaire and 80 reported heavy consumption of alcohol. Heavy drinkers were younger (average age, 42 years) than non-drinkers (average age, 49 years) and a higher proportion were men (63% of heavy drinkers vs 35% of nondrinkers) (P<.01 for each comparison).

ANABOLIC STEROIDS WERE THE MOST COMMON CAUSE OF DILI AMONG HEAVY DRINKERS (in 13% vs 2% in non-drinkers) (P<.001).

Heavy drinkers had significantly higher peak serum levels of alanine aminotransferase (1323 U/L) than non-drinkers (754 U/L) (P=.02) and higher levels of bilirubin (16.1 mg/dL vs 12.7 mg/dL in non-drinkers) (P=.03) but there was no significant difference in liver-related death or liver transplantation between heavy drinkers (occurred in 10%) vs non-drinkers (occurred in 6%) (P=.18).

CONCLUSION: IN AN ANALYSIS OF DATA FROM THE DILIN, WE FOUND ANABOLIC STEROIDS TO BE THE MOST COMMON CAUSE OF DILI IN INDIVIDUALS WHO ARE HEAVY CONSUMERS OF ALCOHOL. Compared to non-drinkers, DILI was not associated with a greater proportion of liver-related deaths or liver transplantation in heavy drinkers.

Dakhoul L, Ghabril M, Gu J, Navarro V, Chalasani N, Serrano J. Heavy Consumption of Alcohol is Not Associated With Worse Outcomes in Patients With Idiosyncratic Drug-induced Liver Injury Compared to Non-Drinkers. Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 2018. http://www.cghjournal.org/article/S1542-3565(17)31534-3/pdf

 

[Dr JIM]

Considering the authors used two rather extreme outcome measures, DEATH and/or LIVER TRANSPLANTATION I'm not surprised by the results.

However bc the study was not designed to determine the hepatotoxic impact of AAS and ETOH, their simultaneous use is best avoided altogether.

 

[focussvt]

I thought this topic would be of interest. I will go through Meso to find posts relevant to this thread and copy/paste. If anyone knows of a post that should be included, let me know. In the meantime, for a first post.

El Sherrif Y, Potts JR, Howard MR, et al. Hepatotoxicity from anabolic androgenic steroids marketed as dietary supplements: contribution from ATP8B1/ABCB11 mutations? Liver Int. Hepatotoxicity from anabolic androgenic steroids marketed as dietary supplements: contribution from ATP8B1/ABCB11 mutations? - El Sherrif - 2013 - Liver International - Wiley Online Library

BACKGROUND: Though possession of androgenic anabolic steroids (AAS) is illegal, non-prescription use of AAS persists.

METHODS: We describe two Caucasian males (aged 25 and 45 years) with cholestatic hepatitis following ingestion of the dietary supplement Mass-Drol ('Celtic Dragon') containing the AAS 2alpha-17alpha-dimethyl-etiocholan-3-one,17beta-ol.

RESULTS: Despite substantial hyperbilirubinaemia peak gamma-glutamyl transferase (GGT) remained normal. Besides 'bland' intralobular cholestasis, liver biopsy in both found deficiency of canalicular expression of ectoenzymes as seen in ATP8B1 disease. In the older patient, bile salt export pump marking (encoded by ABCB11) was focally diminished. We hypothesized that AAS had either induced inhibition of normal ATP8B1/ABCB11 expression or triggered initial episodes of benign recurrent intrahepatic cholestasis (BRIC) type 1/or 2. On sequencing, ATP8B1 was normal in both patients although the younger was heterozygous for the c.2093G>A mutation in ABCB11, a polymorphism previously encountered in drug-induced liver injury.

CONCLUSION: AAS marketed as dietary supplements continue to cause hepatotoxicity in the UK; underlying mechanisms may include unmasking of genetic cholestatic syndromes.

 

[focussvt]

These Pro-Hormones have been known for a long time as being very harsh on the liver, and the body in general. Sure they are easily accessible and pretty cheap, but there is a price to pay. I stopped all forms of orals long ago and have never looked back. My blood tests have thanked me ever since.

 

[Michael Scally MD]

Eapen J, Ayoola R, Subramanian RM. 'The efficacy of extracorporeal liver support with molecular adsorbent recirculating system in severe drug-induced liver injury'. Oxford medical case reports 2018;2018mx077. ‘The efficacy of extracorporeal liver support with molecular adsorbent recirculating system in severe drug-induced liver injury’ | Oxford Medical Case Reports | Oxford Academic

We report a case of a 26-year-old man with no significant medical history, who presented with fatigue, pruritus, jaundice, dark urine and clay colored stool for one month. He had been taking methyl-1-etiochoenolol-epietiocholanolone, an androgenic anabolic steroid (AAS). He was initially found to have a total bilirubin (Tbili) of 6 mg/dL. He discontinued the AAS but the patients' symptoms worsened and Tbili increased to 36 mg/d. This prompted inpatient management of his drug-induced liver injury (DILI). Molecular adsorbent recirculating system (MARS) is an extracorporeal liver support system that replaces the detoxification function of the liver. The patient was initiated on a 4-day trial of MARS therapy. Over the course of his therapy, he clinically improved and his Tbili decreased to 20.7 mg/dL. At follow-up, his symptoms resolved and Tbili was 3.3 mg/dl. This case demonstrates the efficacy of MARS in treating severe cholestatic DILI refractory to standard medical therapy.



A 26-year-old Caucasian male with no significant past medical history presented with fatigue, pruritus, jaundice, dark urine and clay colored stools for 1 month. The patient had been taking methyl-1-etiochoenolol-epietiocholanolone, an androgenic anabolic steroid (AAS).

Initially, at an outpatient clinic he was found to have a total bilirubin (Tbili) of 6 mg/dl. He was advised to discontinue the AAS. He discontinued the AAS but the patients’ symptoms worsened. Repeat blood work 2 weeks later showed a Tbili of 32.5 mg/d, which prompted inpatient management.

The patient denied use of other hepatotoxic drugs, herbal supplements, tobacco, illicit drugs or alcohol. He had a similar episode 5 years ago; he had been taking a similar AAS and developed mild jaundice, which resolved spontaneously once he discontinued the AAS.

On exam, his vital signs were normal. He was extensively jaundiced, had a normal mental status without asterixis, and normal cardio-respiratory and abdominal exam without ascites or hepatomegaly. Liver biochemistries revealed aspartate aminotransferase (AST) 67 U/l, alanine transaminase (ALT) 106 U/L, alkaline phosphatase 166 U/l, Tbili 36 mg/dl, and international normalized ratio (INR) 0.95. Complete blood cell count (CBC) and Renal Function Panel (RFP) were normal. An extensive infectious, autoimmune, and metabolic work was negative. His abdominal ultrasound was normal.

At this stage, he was initiated on a 4-day trial of MARS therapy due to refractory hyperbilirubinemia after standard medical therapy (SMT). By day 3 of MARS therapy his pruritus, fatigue, hemoglobinuria and jaundice improved. Liver biochemistries at that time revealed AST 95 U/l, ALT 147 U/l, alkaline phosphatase 166 U/l, Tbili 24.3 mg/dl and INR 1.01. CBC and RFP remained normal.

Over the course of his therapy, he remained hemodynamically stable, clinically improved and his Tbili decreased to 20.7 mg/dl. A percutaneous liver biopsy was performed showing severe cholestasis with bile duct injury/inflammation and hepatocyte injury without steatosis (Fig. 1), consistent with DILI. Patient was discharge with outpatient follow-up.

 

[Michael Scally MD]

Mascagni P, Melandro F, Larghi Laureiro Z, Mennini G, Rossi M. Spontaneous hepatic rupture in a bodybuilder: a case report and review of the literature. Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva 2018;110. REED - Revista Española de Enfermedades Digestivas

This article is the first description of a spontaneous hepatic rupture in a young bodybuilder with a history of clenbuterol and ephedrine alkaloid use. The patient presented with a sudden mid-epigastric pain and vomiting. Hemoglobin levels decreased a few hours later and a computed tomography scan was performed which revealed a rupture of the right liver capsule and hemoperitoneum. Two attempts at transarterial embolization did not control the bleeding and a right hemihepatectomy was performed. The pathological report identified a hepatic adenoma, a capsular tear and diffuse peliosis hepatis. The patient was discharged in a good condition after eleven days. Spontaneous hepatic ruptures are rare and life-threatening and are usually described in association with tumors, connective tissue diseases and gestosis. This article is a review of the available literature with regard to this condition, with a focus on its relation to peliosis hepatis and banned substance used by body image fanatics. The present case highlights the challenging diagnosis of this potentially fatal liver complication in a healthy appearing male, the risk associated with the online trade of performance enhancing drugs and its relation with peliosis hepatis.