Cirrhosis - Science topic

Hi Khadija,

I wish this email finds you well , what is your project about ?

Hi Dr Fazleh Mahomed . Yes it should be banned because it sometimes lead to big crimes at least car accidents .

When the amount of sugar in a person’s blood is too low to provide their body with sufficient energy, it can lead to something called hypoglycemia. Hypoglycemia is defined as a blood sugar level under 70 mg/dl (3.9 mmol/l) and can result in irritability, confusion, and even seizures and unconsciousness during extreme lows.

Isolated B-cells were stimulated with anti-CD40 antibodies and TLR9 agonist to assess costimulation marker expression, cytokine production, immunoglobulin production, and CD4+ T-cell allostimulatory capacity.

Hi Bingqian

I would suggest you refer to these articles.

https://pubmed.ncbi.nlm.nih.gov/20512987/

Best

The prognosis of liver cirrhosis is determined by presence of portal hypertension.

As cirrhosis progressed from compensated to decompensated cirrhosis, portal hypertension worsen and prognosis worsen.

In cirrhosis without varices and ascites, the annual risk of death is 1%

In cirrhosis with varices alone without other complications, the annual risk of death is 3.4%

In cirrhosis with ascites, with or without varices, the annual risk of death is 20%

In cirrhosis with variceal bleeding, the annual risk of death is 57%

(D'Amico , J Hepatol 2006)

Yes it is useful, cryptogenic means we had evaluated the disease thoroughly but unable to find a cause. So it's an entity we compare with known etiology to find a prognosis.

When evaluating laboratory tests included in the non-invasive fibrosis diagnosis kits, it must be remembered that they were validated to diagnose fibrosis in chronic viral or alcoholic hepatitis.

In addition, the potential effect of metortexate on laboratory tests must be considered in order to avoid false positive and false negative results.

A liver biopsy is of course the gold standard. But it is very curious from the execution technique.

Elastography , in my opinion, may well be an alternative.

Sincerely,

Metabolic syndrome is a constellation of problems including obesity, dyslipidemia, diabetes, and insulin resistance These diseases are associated with both increased risk for, and worsened outcomes of many types of cancer. In the liver, inflammatory and angiogenic changes due to underlying insulin resistance and fatty liver disease will likely lead to increased numbers of patients with HCC in the near future. Much work needs to be done to define more clearly the risks for development of HCC in those with underlying metabolic syndrome, the best methods of screening those at risk, and ultimately, the best treatments targeting the underlying mechanisms of pathogenesis.

The left hepatic vein can sometimes be harder to profile if the liver is echogenic and the patient is large. But no difference in the middle and right that I am aware of.

The pathogenesis of how the accumulated hepatic fat causes liver damage is a complicated issue.

According to “ 2 or multiple hits hypothesis”, the accumulated hepatic fat in some people causes injury to liver cells (nonalcoholic steatohepatitis or NASH) through direct lipotoxicity from free fatty acids (FFAs), oxidative stress, mitochondrial dysfunction, gut microbiota/LPS, activation of fibrogenesis, etc.

Data on the matter in question may relate to many factors e.g. magnitude of alcohol related problems in a country [data from countries where alcohol is social or religious taboo will be very different from those that are not], alcohol related diseases [psychiatric, injuries, liver etc] alcohol related liver disease [which further include decompensated liver disease, acute on chronic liver failure, alcoholic hepatitis etc] and each of which will be different in different regions of the world. Added to this it must remembered that the above mentioned points may occur in unison which also affect outcomes depending on the multidisciplinary medical infrastructure in a country devoted to diagnosing and treating alcohol related problems [which is dismal in India] Alcohol problems are also under reported most times.

Considering liver disease, data in meagre in India [for relapse rates check article: Narendra S. Choudhary, Naveen Kumar, Sanjiv Saigal,⁎ Rahul Rai, Neeraj Saraf, and Arvinder S. Soin. Liver Transplantation for Alcohol-Related Liver Disease. J Clin Exp Hepatol. 2016 Mar; 6(1): 47–53.] Data will vary according to nature of alcohol related liver disease that is being treated. I also personally feel that much of these data are biased in favour of selection of patients who have chance of better outcome on pretransplant check up. Also the follow up period is very variable and most studies do not report long term outcome.

Dear Puja According to the information you provided, there are two possibilities:

1 - The images in a different planes refer to a specific sample liver, then you can use the 3D segmentation instead of the 2D segmentation,specially when 3D volume measurement is required . Of course, this requires image fusion. The whole process can be done both manually and (semi-)automated. thesis [1] has a suitable review about them. if your goal is to segment the particular part of the liver, then the algorithm should be directed in that context.

There are several software that performs it semi-automatically, like 3D-Doctor and ...

2. The images in different planes refer to multiple samples , in which case two-dimensional segmentation methods can work(manual/automated). texture-based Approaches were reviewed in[2].

In this case, the auxiliary softwares can do this process (semi-)automatically.

but, nowadays manually and semi-automated framework are more reliable in clinical used( [1] ).

[1] Childs, Jessie. "Development of a simple technique of measuring liver volume using 2D ultrasound including development of a reference range." (2016).

[2] Rathore, Saima, et al. "Texture analysis for liver segmentation and classification: a survey." Frontiers of Information Technology (FIT), 2011. IEEE, 2011.

I hope it can be useful.

Regards

Yes can you help me regarding how to do it using SPSS??? Any presentation or booklet??

Thank!

(I hope you will find the correct answers in the appendix section of the manuscript we are writing!)

@Fahimeh Kazemi

Thank you for your suggestion

Dear Mohd Saleem Itoo

The accumulation of fats in the liver (liver steatosis "LS") causes variable damage in hepatocytes

The most common cause of LS is metabolic syndrome (MS), simple obesity or associated MS and DM2.

LS causes alteration in the function of hepatocytes and visualization under microscope and within the hepatocytes, of fat microvesicles in a nearby area and around the perivenular veins and minimal degree of inflammation:

regards

Jose Luis

Estimado Mohd Saleem Itoo

La acumulación de grasas en el hígado (esteatosis hepática "EH") ocasionan daño variable en los hepatocitos

La causa más común de EH es el síndrome metabólico (SM), la obesidad simple o asociada el SM y DM2.

La EH ocasiona alteración en la función de los hepatocitos y visualización bajo microscopio y dentro de los hepatocitos, de microvesículas de grasa en una área cercana y alrededor de las vénulas (perivenular) y grado mínimo de inflamación: 

Saludos

José Luis

Please look for disorders of muscle (heart, skeletal) by estimating CPK, aldolase and those of RBC by parameters of hemolysis like LDH, bilirubin (direct/indirect), hemoglobin and of course kidney function tests. Regards  

Nice question very practical-- before remedies first step must be to stop alcohol intake.

this the answer that I was looking for, I thought it might be helpful:

weight loss is associated with rapid, yet transient recruitment of macrophages into AT. However, in this case, an increase in the number of macrophages does not promote inflammation but rather regulates lipolysis.

Very difficult. How is HCV-RNA? 

Zhao, M.Q.; Han, D.W.; Ma, X.H.; Zhao, Y.C.; Yin, L.; Li, C.M. Preventive and therapeutic actions of glycyrrhizin, glycyrrhetic acid and crude saikosides on experimental liver cirrhosis in rats. Acta Pharm. Sin. 1983, 18, 325–331.

 Wang, J.; Guo, J.; Liu, S. [inhibitory effect of glycyrrhizin on nf-kappa b binding activity in ccl4 plus ethanol induced liver cirrhosis in rats]. Chin. J. Hepatol. 1999, 7, 42–43.

 Guo, C.; Xu, L.; He, Q.; Liang, T.; Duan, X.; Li, R. Anti-fibrotic effects of puerarin on ccl4-induced hepatic fibrosis in rats possibly through the regulation of ppar-gamma expression and inhibition of pi3k/akt pathway. Food Chem. Toxicol. An Int. J. Publ. Br. Ind. Biol. Res. Assoc. 2013, 56, 436–442.

 Qu, Y.; Zong, L.; Xu, M.; Dong, Y.; Lu, L. Effects of 18alpha-glycyrrhizin on tgf-beta1/smad signaling pathway in rats with carbon tetrachloride-induced liver fibrosis. Int. J. Clin. Exp. Pathol. 2015, 8, 1292–1301.

Zhang, B.J.; Xu, D.; Guo, Y.; Ping, J.; Chen, L.B.; Wang, H. Protection by and anti-oxidant mechanism of berberine against rat liver fibrosis induced by multiple hepatotoxic factors. Clin. Exp. Pharmacol. Physiol.

2008, 35, 303–309.

Li, J.; Pan, Y.; Kan, M.; Xiao, X.; Wang, Y.; Guan, F.; Zhang, X.; Chen, L. Hepatoprotective effects of berberine on liver fibrosis via activation of amp-activated protein kinase. Life Sci. 2014, 98, 24–30.

Wang, N.; Feng, Y.; Cheung, F.; Chow, O.Y.; Wang, X.; Su, W.; Tong, Y. A comparative study on the hepatoprotective action of bear bile and coptidis rhizoma aqueous extract on experimental liver fibrosis in rats. BMC Complement. Altern. Med. 2012, 12, 239.

Li, R.; Xu, L.; Liang, T.; Li, Y.; Zhang, S.; Duan, X. Puerarin mediates  hepatoprotection against ccl4-induced hepatic fibrosis rats through attenuation of inflammation response and amelioration of metabolic function. Food Chem. Toxicol. An Int. J. Publ. Br. Ind. Biol. Res. Assoc. 2013, 52, 69–75.

Yen, M.H.; Weng, T.C.; Liu, S.Y.; Chai, C.Y.; Lin, C.C. The hepatoprotective effect of bupleurum kaoi, an endemic plant to taiwan, against dimethylnitrosamine-induced hepatic fibrosis in rats. Biol. Pharm. Bull.

2005, 28, 442–448.

Dear Sezin,

The important issue is the time point of injection. Please try to do your experiment at late afternoon, if you work on rodents. You will get considerable results depending on the experimental time or you have to fasten the animals at least 8 hours before the injection.

Non-alcoholic fatty liver disease (NAFLD) is a tissue-clinico-pathological entity with histological characteristics similar to those caused by alcohol use in the hepatic parenchyma, but concerns patients with short or no history of alcohol abuse.

The NAFLD is characterized by makronodular hepatic steatosis histologically distinguishable as simple fat accumulation in hepatocytes (steatosis-fatty liver) and steatosis accompanied by necroinflammatory reaction with or without fibrosis. The form of the disease accompanied by fibrosis defined as nonalcoholic steatohepatitis (NASH).

FLHS is a non human fatal accumulation of fat in the liver of the female chickens.

So NAFLD is steatosis to cirrhosis and FLHS is Hepatocyte Damaged resulting in severe bleeding

Actually with this new imformation, Prof. Marcel Machado gave a good answer.

Bacterial infections occur in one third of hospitalized cirrhotic patients and in approximately half of those admitted with gastrointestinal bleeding. C-reactive protein (CRP) and procalcitonin (PCT) are two plasma biomarkers included among the inflammatory variables in the diagnosis of sepsis. Based on a serum PCT cut-off value of 0.5 ng/mL for the diagnosis of infections, the sensitivity and specificity were reported as 92.5% and 77%, respectively. Some studies suggested serum PCT levels with WBC/PLT ratios can be used as diagnostic biomarkers of cirrhotic patients with infections.

Elevation of PCT could be due to

1.Localized mild-to-moderate bacterial infection

2.Noninfectious systemic inflammatory response

3.Untreated end-stage renal failure

PCT levels may be elevated in patients who do not have sepsis. The plasma levels usually are not very high (<2 ng/mL), but they may increase significantly in certain conditions, e.g. following liver transplantation, during severe and prolonged cardiogenic shock, in patients with severe pancreatitis, and rhabdomyolysis (>2-10 ng/mL). In addition, certain types of autoimmune disorders may induce significant amounts of PCT. Therefore, the etiology of that patient's liver cirrhosis should be learnt.

There is a very detailed description on UpToDate. ACE inhibitors could cause renal failure (hypoperfusion) when the perfusion pressure cannot be sustained because of decrease in arterial pressure or when it is highly angiotensin II dependent.

Thank you, Dr Luis.

Do NOT use canagliflozin if:

you are allergic to any ingredient in canagliflozin

you have type 1 diabetes

you have high blood or urine ketone levels (diabetic ketoacidosis)

you have severe liver problems or severe kidney problems, or if you are on dialysis

... It does not give in liver cirrhosis...

You may find it useful to look at the relevant info in these EASL practice guidelines-

The only way to determine whether this is cirrhosis or some other alteration (inflammation, etc.) is by having a pathologist evaluate this liver histologically.

Interesting senario...

First at all, may I know why the Ig levels were offered to her? Do you worried of Autoimmune hepatitis? Does she has any other immunocompromised illness, such as HIV and Epstein-Barr virus? Haemophilic status?

Pathophysiology of hypogammaglobulinemia:

(a)Conditions that cause an abnormal loss or increased catabolism of Ig:

Nephrotic syndrome and other severe renal diseases

Severe burns

Sepsis

Protein-losing enteropathy

Intestinal lymphangiectasia

(b)Conditions/factors affecting Ig production

Nutritional due to malnutrition or alcoholism

Drugs e.g. phenytoin, carbamazepine, immunosuppressive drugs

Malignancies, especially haemato malignancies

Rheumatological disease, e.g. rheumatoid arthritis or SLE

Viruses including HIV, Epstein-Barr virus, rubella, cytomegalovirus

HCV with low Ig levels - we should think of:

-HCV Related Cryoglobulinemia

-HCV Related Lymphoproliferation

-Drug induced, e.g. rituximab

Few articles did mentioned about the relationship between low Ig levels with Hepatitis C:

IgA deficiency is a risk factor for HCV infection in some patients - IgA deficiency associated with chronic hepatitis C virus infection. A cause or an effect?

by Ilan Y et al. Arch Intern Med. 1993 Jul 12;153(13):1588-92.

Hi Florent,

looking at your pictures, the second analysis is much closer to what I would expect than the first one. If you are in doubt which of the staining is really collagen, looking at your PSR-stained slides using polarized light microscopy might help. Collagen bundles will light up brightly. In our hand imageanalysis in these kind of slides with ImageJ works best by making a RGB-stack and threshold the green slice using the Yen method. It looks like your pictures are slightly underexposed which makes things harder as well.

good luck,

Reinout

According to this article, the AST/ALT ratio can decrease when uremia sets in. Any idea if your research subjects began experiencing uremia when these readings were taken?

Dear Dr Rosas,

thank you for your very pertinent idea.

eventhough, in our patient we didn't observed, lymphadenopathy, pancreatitis, tubbulointertitial nephritis, nor retropetoneal fibrosis, and that there was no storiform pattern in the histology of major salivary glands biopsy, and also that PBC ARE VERY RARELY REPORTED in IG4 related disease...we will look for Ig4 elevation in our case.

thank you again. 

L-carnitine for Muscle Cramps in Patients with Cirrhosis

Nakanishi H et al. Clin Gastroenterol Hepatol 2015 Aug.

Another point to remember is the infection of the ascitic fluid itself [spontaneous bacterial peritonitis] which is quite common in decompensated chronic liver disease and may be the source of sepsis. Other less common variants called monomicrobial non neutrocytic bacterascites [earlier stage in development of SBP] and culture negative neutrocytic bacterascites [where organisms cannot be grown in culture as Dr Biddulph mentioned] also occur and can be the source of SIRS. Even fungal infections are common in late stages of the disease

Thanks dear Dr Nader, 

That is good,

and to know the basic nutrients that honey contains I will do so, and results will be discussed with you and all other researchers who are interested in this topic

thanks. .

 I think manual cell counter is a best method. I was see sometimes strong difference betwen this 2 methods and in my experience normally the manual method y more consistent with the others clinical and laboratories parameters

It is a very interesting question, Zmicer. Actually, spider angiomas also called as telangiectasias, are not specific to liver cirrhosis or portal hypertension. Nevertheless, they are frequent (not exclusive) in liver cirrhosis and located on skin and mucosa of superior vena cava territory. It is certain that hyper estrogenic theory of genesis is the most mentioned, however it has never been proved. We can see them all the long of GI tract from mouth to rectum without relation to liver cirrhosis, neither plasma estrogen high levels nor portal hypertension. In these locations they are frequent cause of bleeding and risk factors are genetics, advanced age and renal insufficiency.

Luisa, the most likely reasons are 1) Tissue is differentially homogenized, some being more completely homogenized than others (i.e., TUBA levels are reflective of degree of homogenization, 2) Tissue composition is different for each sample, some with more cells than others (i.e., TUBA levels is reflective of cellular content in tissue), and 3) TUBA expression is impacted by the disease conditions (i.e., TUBA levels reflect degree of pathology.

Other possible reasons are you have loaded an unequal amount of total protein, not likely assuming you have performed a good protein quantitation assay. If the protein levels vary widely between your samples, this could be a source of your variation, even with appropriate quantitation. Ideally, your lysates should have protein at a concentration of about 1-3ug/uL. Much less or more can result in some issues. Depending on what you are attempting to detect (very low abundant protein?), I don't know that 50ug of total protein is necessary. 10-20ug is sufficient for most tissues, and I go down as low as 5 ug for cells from culture. At or above 50ug you start to run into problems with protein migration, especially in mini-gels with 12+ wells.

To determine if you have loaded grossly different amounts of total protein then consider staining your gel with commassie blue, or your membrane with Ponceu S. These will show whether or not your loaded equal protein. I bet you have, so then you may consider the more likely reasons I've stated above for future tissue processing.

Best of luck.

Just to add some suggestions when we have cirrhosis of unknown origin we always check for non alcoholic steatohepatitis (metabolic syndrome, overweight/obesity, insulin resistance...), iron overload (genetic or secondary), Wilson Disease and alpha1antitripsin. Furthermore a number of cirrhosis in India might depend from vascular disease causing macro or micro thrombosis in the liver (Budd Chiari ...) 

Hormon replacement, as well as oral contraceptives remain as two-edged  sword, since sexual hormones are capable of inducing protective or deleterious effects on liver diseases, depending on several factors, the very disease, age, estrogens or progestins type administered to women, genetic propensity, etc. Given the complexity of primary billiary cirrhosis, as it has been recognized as an autoimmune injury; I invite you to read my last article wherein you may find any further information which perhaps helps you. You will please find it attached.

Dear Adrian and Dear Zmicer

Adrian, I agree with your last comment.  Then, one can conclude that HRS is a prerenal, non responding to vascular volume expanders and non renal parenchimal condition,  exclusive of cirrhotic patients ,occurring spontaneously or secondary to a precipitating factor. Right?

It leads to answer  Zmicer´s question :Type 1 hepatorenal syndrome (HRS) does not  lead to acute tubular necrosis (ATN) in the absence of other insult.

Best regards both

Dear Dr.Strebel,

I agree with what you have pointed out. With reference to the  discussion, I have mentioned that there is no role of the drugs in cirrhosis. The other point is that NASH by itself is not a fully curable disease and hence both UDCA and Vitamin E are given for short time periods [may 6m - 1 year] for normalisation of liver enzymes if found elevated. There is no question of giving both drugs for years together. At least I have found it extremely useful in my patients. 

I thank all for the responses.

I think, that rapid deterioration or “critically ill cirrhotic” could be regarded as acute decompensation and as acute-on-chronic liver failure (ACLF).

ACLF is potentially reversible, but acute decompensation could also be potentially reversible condition. ACLF usually results following a precipitating event (bacterial infection, GI bleeding, HBV etc.), and the AD develops because of the same events.

It is important to know, why one patient is tolerant to accelerating events, but others are not.

Excellent research CANONIC has given us the tool for stratification of risk for critically ill cirrhotic (CLIF-SOFA score).

Identification of risk defines early specific treatments and intensive management.

Here are a few things that I’ve learned from my experience using CCl4 injections to induce liver inflammation and fibrosis in mice.

For the experiments that I was doing, the goal was to induce chronic inflammation/fibrosis – the dosage and injection regimen will be different (namely, a higher dose with fewer injections) if the goal is to induce acute liver damage.

Starting at 8 weeks of age, I injected male C57BL/6J mice intraperitoneally with a solution of 10% CCl4 in mineral oil. Mice were injected with ~2.5ul per gram body weight twice a week for 12 weeks. This protocol was sufficient to induce chronic liver inflammation, steatosis, and fibrosis that was maintained until at least 65 weeks of age.

I’ve tried both corn oil and mineral oil. In either case, with repeated IP injection the oil ends up forming small white inclusion bodies attached to the exterior of the peritoneal organs (liver, intestines, etc.). This is likely because the amount of oil injected is too much for the animals to completely process, so the excess gets sequestered in these inclusion bodies. (They are also formed with repeated injection of oil alone, so this is not an effect of the CCl4). In my experience, corn oil induced a stronger reaction in the mice, leading to a larger number and size of these inclusion bodies, as compared to mineral oil. As they are likely to affect the animals’ physiology in some way, my conclusion was that mineral oil was a more appropriate vehicle for delivery.

I would suggest using sterile oil – it may not be absolutely necessary, but its minimal expense is justified by the enhanced experimental control it provides. Sterile mineral oil is available from Sigma (product #M5310).

Given CCl4’s high volatility, I think it would be harder to maintain a consistent effective dose without mixing it into some sort of delivery vehicle.

I’d be happy to send a more detailed protocol and/or example images of what I described if you’re interested.

Good luck!

Jesse

Thank you Huy. It will help me greatly. Sincere thanks.

common sense

hyperdynamic changes are related to the severity of the liver disease, therefore ... 

Window concept for beta blocker is new in portal hypertension. So window period for beta blocker is very short from primary prophylaxis to decompensated cirrhosis without the risk factors (I have already mentioned). Recent studies have shown increased renal failure (HRS) and mortality with beta blocker in refractory ascites, MAP < 82 mm hg, CI < 1.5. In these high risk group endoscopic vareceal ligation is the best alternative

Of course!

There is a decrease of several coagulation factors, but also an umpaired anticoagulation proteins realease and cleavage!, and a fbrinolysis disbalance, with a trend to hyperfibrinolisis and disfibrinogenemia!

Unnecessary plasma transfusion (with citrate as anticoagulant) could modify this fragil balance

Dear Alexandra

I totally agree with the previous answer (Thomas Riley)

According to ACSM's guidelines("ACSM's exercise management for persons with chronic diseases and disabilities" by Durstine JL, Moore GE), patients with liver failure have reduced VO2 peak, decrease in muscle mass & strength and alcoholic myopathy. Special considertions during exercise: avoid Valsalva (d/t esophageal or gastric varices), and be aware of potential bleeding (d/t coagulation disorders - so avoid contact exercise, and ensure safe environment). Exercise intensity - fatigue dependent so monitor RPE.

Another resource: the group at Inova Health Systems (Fairfax, VA) reported its analysis of chronic liver disease trends using data from National Health and Nutrition Examination Surveys. You might give Dr Younossi a call about how to access that database. Article: "Changes in the Prevalence of the Most Common Causes of Chronic Liver Diseases in the United States From 1988 to 2008" Clinical Gastroenterology and Hepatology Vol 9, No 6 (June 2011) pp 524-530

See full text at:

In stable patients without signs of metabolic decompesation, there is no need to reduce protein intake. In patients with hyperammoniemia or clinical signs of encephalopathy it is opportune to reduce proteins in the diet, which could been supplemented by branched chain amyno-acids.

Dear Ahad,

there are reports on liver injury by statins, yet this adverse event is relatively rare in the general population. In fact, drug-induced liver injury does not occur more often in patients with cirrhosis or other liver diseases, but its consequences might be more severe due to a lower functional reserve in the already impaired liver.

The problem of statins and liver disease was reviewed by Russo and Jacobson quite comprehensively (http://ccjm.org/content/71/1/58.short) as well as Tandra and Vuppalanchi (http://www.ncbi.nlm.nih.gov/pubmed/19627660). These papers conclude that close monitoring can protect from unintended toxicity and recommend strategies for dose adjustment to minimize risks for hepatotoxicity.

In terms of drug-induced liver injury you are never completely save, but in the case of statins there seems to be compelling evidence, that the benefit outweighs the risks by far.

... at least in children and adolescents there seems to be an association of age/ pubertal stage with surrogate markers of steatosis and steatohepatitis. For more in-depth information, I'd like to refer to our paper "Gender-specific prevalences of fatty liver in obese children and adolescents: roles of body fat distribution, sex steroids, and insulin resistance" (The Journal of clinical endocrinology and metabolism 09/2009; 94(10):3872-81).

Look at the brief summary of liver functions:

1. Synthetic: albumin, coagulation proteins, some binding proteins etc.

2. Metabolic/homeostatis: glucose, lipids etc.

3. Storage: glycogen, iron, copper, lipid etc.

4. Catabolic: ammonia/urea, hormones, detoxification of drugs, chemicals etc.

5. Excretory: bile excretion

Why you are focusing on AST and ALT? You should define what exactly you want to know/study and further build very accurately your questions.

Generally speaking – you should read classical hepatology textbooks.

Atta, excellent question. In biliary disorders, the literature suggests a cholangiocyte origin of increased serum GGT. However, in non-biliary chronic alcohol liver disorder, the origini of increased serum GGT is more likely the injured hepatocyte, disruption and extrusion of GGT into the canalicular region, and eventual absorption into the bloodstream. See excellent study by Irie et al:

"Hepatic expression of gamma-glutamyltranspeptidase in the human liver of patients with alcoholic liver disease" Hepatology Research (Nov 2007) 37(11):966-973. Abstract at: http://www.ncbi.nlm.nih.gov/pubmed/17854466

I cannot find a weblink for the full article. Here is Abstract:

Background: Gamma-glutamyltranspeptidase (GGT) has been recognized as an enzyme that converts glutathione into cysteine, and it is localized predominantly within the liver. Serum GGT is clinically recognized as the most useful marker for diagnosis of alcoholic liver disease (ALD). Methods: GGT localization within the liver was examined immunohistochemically using an anti-GGT antibody and was visualized by confocal laser scanning microscopy in ALD and normal livers. Double immunostaining for GGT and dipeptidylpeptidase-IV (DPP-IV) was carried out to evaluate GGT localization in greater detail. Results: Expression of GGT protein and mRNA was studied with immunoblot analysis and in situ hybridization, respectively. Immunohistochemically, the expression of GGT in the normal liver was faintly demonstrated in the bile canaliculi of hepatocytes and in biliary epithelial cells. In ALD livers, GGT was clearly demonstrated at the same sites. Double immunostaining demonstrated that GGT and DPP-IV were colocalized in hepatocytes in the ALD liver. In situ hybridization clearly demonstrated GGT-mRNA within the cytoplasm of hepatocytes and biliary epithelial cells. Immunoblot analysis revealed that GGT protein expression was increased in the ALD livers compared with that seen in the normal livers. Conclusion: These findings indicate that GGT in control and alcoholic livers is synthesized in hepatocytes and biliary epithelial cells, and is localized within the bile canalicular membrane and the luminal membrane in those cells, respectively. In conclusion, GGT synthesis and protein expression are increased in ALD livers, leading to the elevation of serum levels of GGT that are commonly noted in patients with the disease

For source of increased serum GGT in biliary cholestasis disorder, see Bulle at:

"Mechanism of gamma-glutamyl transpeptidase release in serum during intrahepatic and extrahepatic cholestasis in the rat: a histochemical, biochemical and molecular approach." in Hepatology. 1990 Apr;11(4):545-50 Abstract on web at:

Thanks for very useful information Dr Mooney.

Thank you

There are some crucial questions in such cases: which organ exactly is incarcerated, and wheter the incarcerated content is vital or not, and is there an infection? So in my opinion laparoscopy is the most reliable option – you can reduce the hernia, can see what is incarcerated and wheter there are signs of necrosis, and also take fluid for culture. If there is a bowel necrosis the need of resection is clear. But if it is not the problem is always whether there is an infected ascites, as there is never been a good idea to place a mech in infected conditions. So better reduce the hernia, apply external pressure of the sac, for example with gauzes and fix them with adhesive bands or folio drape. Start antibiotics keeping the guidelines for the treatment of bacterial peritonitis in cirrhosis. Do not remove ascites if not visibly purulent, no drains, as they usually caused nearly uncontrollable homeostatic disturbances due to huge amount of fluid losed. When the patient is stable and infection is controlled by antibiotics you can move back to OR and do that what you prefer. I think the laparoscopic repair is better. So the philosophy is that there is absolutely no need to address both problems – incarceration and hernia itself in one stage in a patient that is usually not fit for surgery and had severe comorbidities. The exception might be the patients requiring bowel resection.

There are 2 widely used ones in the UK:

1. Maddrey's discriminate function

2. Glasgow Score

HI

You can find your answer by reading this paper: Cardiovascular Diseases and the Liver

Clinics in Liver Disease - Volume 15, Issue 1 (February 2011) written by: Ilan S. Weisberg, and Ira M. Jacobson, The paper is attached

I hope it helps

Hossein