Re: hepatitis c and PSC

[Guest guest]

Hi " mistystarla " ;

I'm so sorry to hear about your husband's hepatitis C and PSC

diagnosis. This is a pretty rare combination, and I don't know of any

others in the group who have both. It has been reported in the

literature occassionally, and I thought I would pass on one report

that appeared in 2007:

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J. Gastrointestin. Liver Dis. June 2007 Vol.16 No 2, 222-223

Primary sclerosing cholangitis lesions in a patient with Crohn's

disease and HCV infection.

To the Editor,

It is well known that patients with chronic inflammatory bowel

disease (IBD) have a higher incidence of primary sclerosing

cholangitis (PSC) that varies from 2.5 to 7.5%. This association is

more obvious for PSC ailing patients; a significant percentage, that

varies from 50 to 75%, of these patients will develop IBD (1).

The etiology of PSC remains unknown. Bacteria, toxins, viral

infections, immunological and genetic factors have all been proposed

as etiological agents. Patients with PSC may have elevated levels of

circulating immune complexes and autoantibodies (2). On the other

hand, an etiopathological link between hepatitis C virus (HCV) and

autoimmune liver disease has been suggested, as it is well known that

autoantibodies, as well as autoimmune extrahepatic manifestations are

often observed during the course of viral C hepatitis (3).

A smoker, 26-year-old female was admitted to our department with

abdominal colicky pain, 4-5 diarrheic stools per day, weight loss and

fever of 3 weeks duration. She mentioned appendectomy 20 years ago.

Abdominal examination revealed hepatomegaly and right lower quadrant

and periumbilical tenderness.

Initial laboratory studies showed: Ht 42%, Hb 13.7g/dl, MCV 89fl, PLT

300K/ul, WBC 14.6K/ul, ESR 35mm/h, C reactive protein 2.03mg/dl

(normal value <0.8mg/dl), alkaline phosphatase 381u/l (90-270), AST

79u/l (9-48), ALT 148u/l (5-49), g-GT 179u/l (0-53), BUN, serum

creatinine, total bilirubin normal, serum amylase 143u/l (0-96),

urine amylase 658u/l (0-350), serum protein 7.5 g/dl, albumin 3g/dl,

INR 1.03, aPTT 36.1''. Autoantibodies (ANA, anti-dsDNA, AMA, ASMA,

c/p ANCA) were negative. HCV: positive, HBsAg: negative, HIV 1/2 :

negative, HCV-RNA: 1,324 000 IU/ml (Versant HCV RNA 3.0 Assay).

Urinalysis revealed plenty of oxalic calcium crystals. Stool analysis

revealed numerous leukocytes and no ova or parasites.

Barium contrast small-intestinal radiologic examination

revealed diffuse mural edema of terminal ileum. Ultrasonography of

the liver, gallbladder, intra- and extrahepatic bile ducts revealed

no abnormalities. Abdominal CT scan identified mural thickening of

terminal ileum without adenopathy. Colonoscopy demonstrated confluent

eruption of the mucosa without ulcers, in a segmentary pattern, from

the anal verge to the terminal ileum. Biopsy from terminal ileum

during colonoscopy was compatible with Crohn's disease (CD). The

mucosa showed architectural changes such as irregularity and focal

shortening of the villi with inflammatory infiltrate consisting of

histiocytes, lymphocytes, eosinophilic and neutrophilic leukocytes.

The inflammation process involved also submucosa. Furthermore,

granulomas were found supporting the diagnosis of CD.

Treatment was started with metronidazole and ofloxacin. The patient

became afebrile with a significant decrease of the number of stools.

She was in good general condition but mentioned mild colicky

abdominal pain.

Laboratory findings of increased AST, ALT, ã-GT, alkaline

phosphatase, serum and urine amylase persisted, serum bilirubin

increased. ERCP revealed two stenoses of the bile duct - in both the

initial and terminal segment - with mild dilatation of pancreatic and

hepatic duct. No gallstones were observed in the gallbladder.

A liver biopsy showed histological features of non specific portal

tract changes (mild inflammation with lymphocytes and few

neutrophiles), interlobular bile duct epithelial changes with

inflammatory infiltration of their walls surrounded by a ring of

oedematous or hyaline fibrosis (periductular fibrosis), and no

granulomas were detected (Fig.1).

Mesalazine and ursodeoxycholic acid (UDCA) were added to treatment.

The patient was discharged 8 days later without symptoms. After two

months she was free of symptoms and laboratory findings were normal.

Hepatobiliary disorders are well known complications in patients with

IBD. Histological findings at liver biopsies were unrelated to either

activity or extent of colitis, except for the onion lesions which

were seen exclusively in biopsies of patients with involvement of the

total colon (4). Cholangiography and liver biopsy are both needed to

evaluate the extent of the disease. The close association between PSC

and IBD remains unexplained and both groups of patients have a high

prevalence of autoantibodies.

Possible triggers of liver autoimmunity have been explored and

several sequences shared in common between autoantigenes and

hepatotropic viruses, namely hepatitis B, C and cytomegalovirus have

been identified (5). It has been hypothesized that HCV antigens could

enhance immune cell sensitization and cytotoxicity by being

homologous with host antigens or by molecular mimicry (6). Findings

suggesting cross-reactivity between homologous sequences, especially

between HCV and cytochromes, support the possibility that molecular

mimicry plays a role in the induction of autoantibodies and

autoreactive cytotoxic T cells.

To summarize, in the reported case, although a mere coexistence of

PSC and HCV infection is probable, we hypothesize that HCV may be

related, as a trigger of autoimmunity, to PSC type lesions of

intrahepatic and possibly extrahepatic bile ducts.

Constantinos Goritsas1

Nikolaos Papadopoulos1

Rodoula Trigidou2

Haris Tzathas3

1) Internal Medicine Department

2) Pathology Department, " Sotiria " General Hospital

3) Gastroenterology Department " Evaggelismos " General Hospital

Athens, Greece

References

1. Raj V, Lichtentein DR: Hepatobiliary manifestations of

inflammatory bowel disease. Gastroenterol Clin North Am 1999;28:491-

513.

2. Narayanan Menon KV, Wiesner RH. Etiology and natural history of

primary sclerosing cholangitis. J Hepatobiliary Pancreat Surg

1996;4:343-351.

3. Mans MP, Rambush E.G. Autoimmunity and extrahepatic manifestations

in HCV infection. J Hepatology 1999;31 (suppl.1):39-42

4. Broome U, Glaumann H, Hultcrantz R. Liver histology and follow up

of 68 patients with ulcerative colitis and normal liver function

tests. Gut 1990;31:468-472.

5. Lohse AM, Gerken G, Mohr H, et al. Relation between autoimmune

liver disease and viral hepatitis: clinical and serological

characteristics in 859 patients. Z Gastroenterol 1995:33:527-533

6. Lunel F. HCV and autoimmunity: fortuitous association or reality?

Gastroenterology 1994; 107:1550-1555

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Basically, they cannot rule out that this association is coincidence,

but they speculate that the hepatitis C virus may contain proteins

that may trigger autoimmune disease (PSC) in certain individuals.

I have always wondered whether my son's PSC may have been triggered

by a hepatitis B vaccination.

Sorry, but I have no experience or knowledge of interferon therapy.

Best regards,

Dave

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