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ver the last several years significant progress has beenmade in improving the noninvasive assessment of liver

brosis. Increased sensitivity and specificity of serum biomarkeresting and the improved expertise in the performance andnterpretation of Fibroscan imaging, as well as the develop-

ent of magnetic resonance elastography have all decreasedhe need for liver biopsy in the assessment of hepatic fibro-is.1–3 Knowledge of the stage of fibrosis is extremely impor-ant in the management of patients having hepatitis CHCV), hepatitis B (HBV), and nonalcoholic steatohepatitisNASH). The attendant risks of liver biopsy along with theotential for sampling error with regard to fibrosis stagingupport the use of such noninvasive modalities.1–3

With comprehensive serologic testing, an experienced gastro-nterologist can diagnose the etiology of abnormal liver chem-stry tests in the great majority of patients. However, in chole-tatic liver diseases such as early stage primary biliary cirrhosisPBC) and primary sclerosing cholangitis (PSC), granulomatousepatitis, cystic fibrosis, and congenital hepatic fibrosis, theerformance of a liver biopsy is essential in helping establishhe diagnosis. The diagnosis of drug-induced liver injury (DILI)

ay be difficult to make without liver histology. More cases ofoncirrhotic portal hypertension such as from nodular regen-rative hyperplasia and hepatoportal sclerosis are increasinglyeing recognized and are most reliably diagnosed via liveriopsy.4 Liver biopsy still plays a role in making the diagnosis inpatient having hepatosplenomegaly of unknown etiology and

or identifying the presence of concurrent liver diseases, ie,lcoholic liver disease with alpha-1-antitrypsin deficiency, andverlap syndromes of PBC and autoimmune hepatitis (AIH)nd PSC-AIH overlap. It is also important to determine theegree of concurrent steatosis or steatohepatitis in patientsith hepatitis C (HCV). Although radiological studies can ap-roximate the degree of hepatic steatosis, they do not have thebility to differentiate between NASH and simple steatosis.5

iver biopsy is important in making this distinction and inelping guide clinical management as to whether patients pur-ue life style modification versus more aggressive medical ther-py. Finally, post liver transplantation there is a broad differ-ntial diagnosis for abnormal liver chemistry tests, so a liveriopsy remains essential.

In this issue, Björnsson et al sought to determine whetheriver biopsy is necessary to establish the diagnosis of AIH inatients having typical biochemical and serologic features.6

hey studied 257 patients who were identified via a databaseearch as having AIH and retrospectively reviewed the med-cal charts and histologic features as described in the liveriopsy reports. Patients transplanted for AIH, and thoseaving decompensated liver disease at presentation, as wells pediatric patients were excluded. Patients with PBC, PSC,nd those with clinical suspicion of overlap syndromes werelso excluded. The investigators found that in 95% of theirohort, the histology was compatible with AIH whereas 5%14 cases) showed an atypical histology. In these cases, 77%

et the simplified diagnostic criteria for having probable or

efinite AIH.7 The patients having atypical histology had t

imilar serologic profiles as those having compatible histol-gy, and a majority were treated with immunosuppressiveherapy. Overall, in 83 patients a second liver biopsy waserformed at least 1 year after treatment was initiated with0% showing no inflammation. Interestingly, of 16 patientsho were initially diagnosed with cirrhosis, 50% showed

egression of cirrhosis on follow-up biopsy.The investigators concluded that among patients with a

iagnosis of AIH very few had atypical histology and that theresence of an atypical histology had little impact anyway onatient management. Once a viral etiology for the liver dis-ase was excluded, no unexpected histologic findings wereoted, except in 1 patient. These results led the authors toonclude that diagnostic liver biopsy may not be necessary inatients who meet clinical criteria for AIH. Some shortcom-

ngs of the study are that the investigators themselves didot review the biopsy nor were the biopsies uniformly re-iewed by a single experienced pathologist. In addition, manyatients may have had low titer antineutrophil antibody orntismooth muscle antibody and in this setting the clinicaliagnosis of AIH may not be so obvious.

It is encouraging to know that in the great majority of casesn the appropriate clinical setting and with compatible serolo-ies and biochemistries, patients can be reliably diagnosed withIH in the absence of having histology available. This is ex-

remely important in patients presenting with significant liverysfunction and coagulopathy, or those having a contraindica-ion to the performance of a liver biopsy. Thus, timely cortico-teroid therapy can be initiated which at times may be life-aving. However, we feel strongly that whenever possible, a liveriopsy should be performed prior to initiating immunosup-ressive therapy in patients with AIH for the following reasons.he investigators excluded patients having overlap syndromes

n their analysis. It may be difficult without histology to in factiagnose an overlap syndrome, and it is important to know thisrior to initiating steroid therapy. Autoimmune markers mayave varied profiles in patients who have other immunologiciseases, as well as collagen vascular diseases and other auto-

mmune conditions. It may not be so easy to diagnose anverlap syndrome without a liver biopsy. Knowing the morerominent histologic component will be helpful in guidinganagement as to whether ursodiol should also be started and

s to the timing of the addition of a steroid-sparing agent.Because corticosteroids have so many untoward side effects,

atients are often resistant to therapy and are quite proactive inanting to be weaned from it. Knowledge of their underlyingistology is important in educating the patient about theirisease and in fact may promote compliance with therapy. Weisagree with the conclusions of Björnsson et al regardingaseline histology not influencing one’s management decisions.f patients have more advanced fibrosis and inflammation, weould choose to pursue a slower steroid-tapering regimen be-

ause of the fear and danger of disease reactivation and result-nt liver failure. In the setting of advanced histologic damage,he addition of azathioprine potentially should be delayed ashe development of pancreatitis or other DILI might also con-

ribute to hepatic decompensation.

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2011;9:3–4

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4 SCHIANO AND FIEL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 9, No. 1

We find very interesting the authors’ description of 8/16atients having regression of their cirrhosis. This information

n itself would be enough to encourage patients to continueith therapy if found to have advanced fibrosis on initial liveriopsy. Furthermore, in patients who have a suboptimal or slow

nitial response, it may be difficult to have them continueorticosteroids without definitive histology especially if they areaving steroid-induced adverse effects. Patients may developther liver diseases while using immunosuppressive therapy forIH, such as NASH due to steroid-induced weight gain, aza-

hioprine-induced cholestatic hepatitis or other DILI, as well asther liver conditions. Knowing baseline histology would makeuture management decisions clearer in these settings.

We agree with the investigators’ findings that it is possible tonitiate immunosuppressive therapy in patients having the typ-cal serologic and biochemical profile of AIH. However, weelieve that histologic confirmation of the diagnosis of AIHrior to therapy will facilitate treatment decisions, and that

iver biopsy should be performed whenever possible. This isupported by the recently published American Association forhe Study of Liver Disease Practice Guidelines for Autoimmuneepatitis.8

The discipline of hepatology has evolved over the years inarge part due to better understanding of hepatic pathophysi-logy, that has stemmed from the study of liver histology. Closeollaboration between liver pathologist, hepatologist, and hepa-obiliary/transplant surgeon remains a vital part of the man-gement of patients having acute and chronic liver disease.lthough technologic advances have obviated the need for liveriopsy in many situations, liver biopsy will remain the foremostiagnostic tool in the field of hepatology for many years toome. Tissue sampling and histologic assessment will remainital as a tool in translational research pursuits, to diagnoseILI in drug research trials and drug development, as well as in

enomic and proteomic studies. With an adequate biopsy spec-men, supported by appropriate clinical and laboratory infor-

ation and close communication between clinician and pathol-

gist, liver biopsy will always yield helpful information. If posed

he question, “To biopsy or not to biopsy. . .,” we favor theormer as it is always better to have as much data at hand tossist in the management of our patients, and with which toelp educate them regarding their disease.

THOMAS D. SCHIANO, MDM. ISABEL FIEL, MD

The Mount Sinai Medical CenterNew York, New York

References

. Talwalkar JA, Yin M, Fidler JL, et al. Magnetic resonance imaging ofhepatic fibrosis: emerging clinical applications. J Hepatol 2008;47:332–342.

. Friedrich-Rust M, Ong MF, Martens S, et al. Performance of tran-sient elastography for the staging of liver fibrosis: a meta-analysis.Gastroenterology 2008;134:960–974.

. Castera L, Vergniol J, Foucher J, et al. Prospective comparison oftransient elastography, Fibrotest, Apri, and liver biopsy for theassessment of fibrosis in chronic hepatitis C. Gastroenterology2005;128:343–350.

. Schiano TD, Kotler DP, Ferran E, et al. Hepatoportal sclerosis as acause of noncirrhotic portal hypertension in patients with HIV. Am JGastroenterol 2007;102:2536–2540.

. Browning JD. New imaging techniques for non-alcoholic steato-hepatitis. Clin Liver Dis 2009;13:607–619.

. Björnsson E, Talwalkar J, Treeparsertsuk S, et al. Patients with typicallaboratory features of autoimmune hepatitis rarely need a liver biopsyfor diagnosis. Clin Gastroenterol Hepatol 2011;9:57–63.

. Hennes EM, Zenia M, Czaja AJ, et al. Simplified criteria for thediagnosis of autoimmune hepatitis. J Hepatol 2008;48:169–176.

. Manns MP, Czaja AJ, Gorham JD, et al. Diagnosis and manage-ment of autoimmune hepatitis. Hepatology 2010;51:2193–2213.

onflicts of interestThe authors disclose no conflicts.

doi:10.1016/j.cgh.2010.09.027