Re: Any ideas would be appreciated.

[Guest guest]

Hi Cathy;

Liver biochemistry improvement on treatment with Imuran (azathioprine) is

suggestive of autoimmune hepatitis, and so an AIH/PSC overlap (AIH/sclerosing

cholangitis overlap syndrome (autoimmune sclerosing cholangitis, ASC) might be

possible:

_____________________________

World J. Gastroenterol. 14: 3360-3367 (2008)

Autoimmune paediatric liver disease.

Mieli-Vergani G, Vergani D.

Institute of Liver Studies, King's College Hospital, Denmark Hill, London SE5

9RS, UK. giorgina.vergani@...

Liver disorders with a likely autoimmune pathogenesis in childhood include

autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and de novo

AIH after liver transplantation. AIH is divided into two subtypes according to

seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1)

or liver kidney microsomal antibody (LKM1, type 2). There is a female

predominance in both. LKM1 positive patients tend to present more acutely, at a

younger age, and commonly have partial IgA deficiency, while duration of

symptoms before diagnosis, clinical signs, family history of autoimmunity,

presence of associated autoimmune disorders, response to treatment, and

long-term prognosis are similar in both groups. The most common type of

paediatric sclerosing cholangitis is ASC. The clinical, biochemical,

immunological, and histological presentation of ASC is often indistinguishable

from that of AIH type 1. In both, there are high IgG, non-organ specific

autoantibodies, and interface hepatitis. Diagnosis is made by cholangiography.

Children with ASC respond to immunosuppression satisfactorily and similarly to

AIH in respect to remission and relapse rates, times to normalization of

biochemical parameters, and decreased inflammatory activity on follow up liver

biopsies. However, the cholangiopathy can progress. There may be evolution from

AIH to ASC over the years, despite treatment. De novo AIH after liver

transplantation affects patients not transplanted for autoimmune disorders and

is strikingly reminiscent of classical AIH, including elevated titres of serum

antibodies, hypergammaglobulinaemia, and histological findings of interface

hepatitis, bridging fibrosis, and collapse. Like classical AIH, it responds to

treatment with prednisolone and azathioprine. De novo AIH post liver

transplantation may derive from interference by calcineurin inhibitors with the

intrathymic physiological mechanisms of T-cell maturation and selection. Whether

this condition is a distinct entity or a form of atypical rejection in

individuals susceptible to the development of autoimmune phenomena is unclear.

Whatever its etiology, the recognition of this potentially life-threatening

syndrome is important since its management differs from that of standard

anti-rejection therapy. PMID: 18528933.

full test available at:

http://www.wjgnet.com/1007-9327/14/3360.pdf

_____________________________

Best regards,

Dave

(father of (23); PSC 07/03; UC 08/03)

[Guest guest]

Hi Cathy;

Liver biochemistry improvement on treatment with Imuran (azathioprine) is

suggestive of autoimmune hepatitis, and so an AIH/PSC overlap (AIH/sclerosing

cholangitis overlap syndrome (autoimmune sclerosing cholangitis, ASC) might be

possible:

_____________________________

World J. Gastroenterol. 14: 3360-3367 (2008)

Autoimmune paediatric liver disease.

Mieli-Vergani G, Vergani D.

Institute of Liver Studies, King's College Hospital, Denmark Hill, London SE5

9RS, UK. giorgina.vergani@...

Liver disorders with a likely autoimmune pathogenesis in childhood include

autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and de novo

AIH after liver transplantation. AIH is divided into two subtypes according to

seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1)

or liver kidney microsomal antibody (LKM1, type 2). There is a female

predominance in both. LKM1 positive patients tend to present more acutely, at a

younger age, and commonly have partial IgA deficiency, while duration of

symptoms before diagnosis, clinical signs, family history of autoimmunity,

presence of associated autoimmune disorders, response to treatment, and

long-term prognosis are similar in both groups. The most common type of

paediatric sclerosing cholangitis is ASC. The clinical, biochemical,

immunological, and histological presentation of ASC is often indistinguishable

from that of AIH type 1. In both, there are high IgG, non-organ specific

autoantibodies, and interface hepatitis. Diagnosis is made by cholangiography.

Children with ASC respond to immunosuppression satisfactorily and similarly to

AIH in respect to remission and relapse rates, times to normalization of

biochemical parameters, and decreased inflammatory activity on follow up liver

biopsies. However, the cholangiopathy can progress. There may be evolution from

AIH to ASC over the years, despite treatment. De novo AIH after liver

transplantation affects patients not transplanted for autoimmune disorders and

is strikingly reminiscent of classical AIH, including elevated titres of serum

antibodies, hypergammaglobulinaemia, and histological findings of interface

hepatitis, bridging fibrosis, and collapse. Like classical AIH, it responds to

treatment with prednisolone and azathioprine. De novo AIH post liver

transplantation may derive from interference by calcineurin inhibitors with the

intrathymic physiological mechanisms of T-cell maturation and selection. Whether

this condition is a distinct entity or a form of atypical rejection in

individuals susceptible to the development of autoimmune phenomena is unclear.

Whatever its etiology, the recognition of this potentially life-threatening

syndrome is important since its management differs from that of standard

anti-rejection therapy. PMID: 18528933.

full test available at:

http://www.wjgnet.com/1007-9327/14/3360.pdf

_____________________________

Best regards,

Dave

(father of (23); PSC 07/03; UC 08/03)

[Guest guest]

Thank you ,

I appreciate the information. What is throwing me off is 's liver biopsy

came in negative for AIH. Do you know how reliable liver biopsies normally

are? It was preformed at a good transplant center so I assumed it was done, and

read correctly.

I will take this study to her next appointment and discuss it. She recently was

tested for celiac and carries the gene, but she does not have celiac. From this

article it looks like needs to be tested for the IgA deficiency. I am

grateful her gastro doctor put her on the Imuran for her colitis. It felt like

she was on a runaway train leading to transplant. Hopefully this will buy her

time, and her numbers will continue to improve. I am cautiously optimistic,

but more hopeful then before.

Cathy

[Guest guest]

Thank you ,

I appreciate the information. What is throwing me off is 's liver biopsy

came in negative for AIH. Do you know how reliable liver biopsies normally

are? It was preformed at a good transplant center so I assumed it was done, and

read correctly.

I will take this study to her next appointment and discuss it. She recently was

tested for celiac and carries the gene, but she does not have celiac. From this

article it looks like needs to be tested for the IgA deficiency. I am

grateful her gastro doctor put her on the Imuran for her colitis. It felt like

she was on a runaway train leading to transplant. Hopefully this will buy her

time, and her numbers will continue to improve. I am cautiously optimistic,

but more hopeful then before.

Cathy

[Guest guest]

Dear Cathy;

I am not an expert on liver biopsies, and I honestly don't know how reliable

they are for AIH. I've heard that for PSC they are not always reliable for

staging because the disease may not be uniform throughout the liver, and because

the biopsy can sample from only a small part of the liver.

But according to this article, it is the most important diagnostic procedure for

AIH:

Autoimmune Hepatitis: Differential Diagnoses & Workup

Author: C Wolf, MD, FACP, FACG, AGAF, Medical Director of Liver

Transplantation, Westchester Medical Center, Professor of Clinical Medicine,

Division of Gastroenterology and Hepatobiliary Diseases, Department of Medicine,

New York Medical College

Coauthor(s): Unnithan V Raghuraman, MD, FRCP, FACG, FACP, Consulting Staff,

Department of Gastroenterology, St Medical Center

Updated: Jul 31, 2008

Overview

http://emedicine.medscape.com/article/172356-overview

Differential Diagnoses & Workup

http://emedicine.medscape.com/article/172356-diagnosis

Treatment & Medication

http://emedicine.medscape.com/article/172356-treatment

Follow-up

http://emedicine.medscape.com/article/172356-followup

(Sorry, but I am not sure whether or not you will need to register on this site

to gain access to this 5-part article?)

Perhaps some of the laboratory test results listed here may help you in your

quest?

Best regards,

Dave R.

> Do you know how reliable liver biopsies normally are? It was preformed at a

good transplant center so I assumed it was done, and read correctly.

[Guest guest]

Dear Cathy;

I am not an expert on liver biopsies, and I honestly don't know how reliable

they are for AIH. I've heard that for PSC they are not always reliable for

staging because the disease may not be uniform throughout the liver, and because

the biopsy can sample from only a small part of the liver.

But according to this article, it is the most important diagnostic procedure for

AIH:

Autoimmune Hepatitis: Differential Diagnoses & Workup

Author: C Wolf, MD, FACP, FACG, AGAF, Medical Director of Liver

Transplantation, Westchester Medical Center, Professor of Clinical Medicine,

Division of Gastroenterology and Hepatobiliary Diseases, Department of Medicine,

New York Medical College

Coauthor(s): Unnithan V Raghuraman, MD, FRCP, FACG, FACP, Consulting Staff,

Department of Gastroenterology, St Medical Center

Updated: Jul 31, 2008

Overview

http://emedicine.medscape.com/article/172356-overview

Differential Diagnoses & Workup

http://emedicine.medscape.com/article/172356-diagnosis

Treatment & Medication

http://emedicine.medscape.com/article/172356-treatment

Follow-up

http://emedicine.medscape.com/article/172356-followup

(Sorry, but I am not sure whether or not you will need to register on this site

to gain access to this 5-part article?)

Perhaps some of the laboratory test results listed here may help you in your

quest?

Best regards,

Dave R.

> Do you know how reliable liver biopsies normally are? It was preformed at a

good transplant center so I assumed it was done, and read correctly.

[Guest guest]

,

I am very grateful for your help, thank you. I would not normally ask, but this

is important, and I don't want to miss something. switched transplant

centers recently due to insurance, and I feel there have been some gaps because

of that. She has been through alot the last couple of years. She had 20% of her

liver removed because of a CC scare, which was quiet the ordeal. Then this new

problem came up. Thanks you again, Cathy

[Guest guest]

Dear Cathy;

I think that you are well aware that AIH often comes first and then AIH/PSC can

follow, or both can be found at the same time. It is rare that PSC can come

first and AIH second, but here is one report where this sequence was found:

____________________________

Eur J Gastroenterol Hepatol. 2008 Mar;20(3):232-6.

Autoimmune hepatitis 2 years after the diagnosis of primary sclerosing

cholangitis: an unusual overlap syndrome in a 17-year-old adolescent.

Mueller T, Bianchi L, Menges M

Department of Internal Medicine, Diakonie-Hospital Schwaebisch Hall, Germany.

A 15-year-old girl was admitted in April 2004 owing to fatigue and loss of

appetite. Her paediatrician had found elevated serum levels for alkaline

phosphatase. The endoscopic retrograde cholangiography documented typical signs

of primary sclerosing cholangitis with involvement of the small and large ducts.

The liver biopsy revealed extensive septal and portal fibrosis. No evidence of

inflammatory bowel disease was present. She was started on ursodeoxycholic acid

therapy and improved clinically. After 22 months she presented again with rising

transaminase levels up to 600 U/l. The second liver biopsy was strongly

suggestive for autoimmune hepatitis besides the already known features of

primary sclerosing cholangitis. Elevated levels of IgG, and elevated titres for

ANA and antismooth muscle antibodies (ASMA) were also found. The duct

irregularities seen on re-endoscopic retrograde cholangiography were slightly

regredient as compared with the first investigation. We added prednisolone and

azathioprine to the ursodeoxycholic acid and the transaminase levels dropped

together with clinical improvement. PMID: 18301306.

____________________________

This sounds like a little bit like the sequence you are describing for ?

So sorry to hear about 's CC scare! That must have been tough on both her

and you.

Best regards,

Dave R.

[Guest guest]

pANCA positive is consistent with PSC (as well as with UC- and I believe with AIH, as well). , Mom to 18 yo daughter UC 6/95, PSC 3/09Could this possibly be PSC/ Autoimmune Cholagitis overlap given her P ANCA is positive?

[Guest guest]

pANCA positive is consistent with PSC (as well as with UC- and I believe with AIH, as well). , Mom to 18 yo daughter UC 6/95, PSC 3/09Could this possibly be PSC/ Autoimmune Cholagitis overlap given her P ANCA is positive?