Pathology Journals

Hepatitis C virus core protein induces fibrogenic actions of hepatic stellate cells via toll-like receptor 2.
Coenen M, Nischalke HD, Krämer B, Langhans B, Glässner A, Schulte D, Körner C, Sauerbruch T, Nattermann J, Spengler U. Lab Invest. 2011 Sep;91(9):1375-82. (CUMC Full Text PDF)

Recurrent hepatitis C and acute allograft rejection: clinicopathologic features with emphasis on the differential diagnosis between these entities.
Moreira RK. Adv Anat Pathol. 2011 Sep;18(5):393-405. (CUMC Full Text PDF)

Increasing hepatic arteriole wall thickness and decreased luminal diameter occur with increasing age in normal livers.

Fiel MI, Deniz K, Elmali F, Schiano TD. J Hepatol. 2011 Sep;55(3):582-6. Epub 2011 Jan 12. (CUMC Full Text PDF)

Liver pathology in Malawian children with fatal encephalopathy.
Whitten R, Milner DA Jr, Yeh MM, Kamiza S, Molyneux ME, Taylor TE. Hum Pathol. 2011 Sep;42(9):1230-9. (CUMC Full Text PDF)

Rate of Progression of Hepatic Fibrosis in Patients With Chronic Hepatitis C: Results From the HALT-C Trial.

Hoefs JC, Shiffman ML, Goodman ZD, Kleiner DE, Dienstag JL, Stoddard AM; HALT-C Trial Group. Gastroenterology. 2011 Sep;141(3):900-908. (CUMC Full Text PDF)

Hepatology and Gastroenterology Journals:

Presence and significance of microvesicular steatosis in nonalcoholic fatty liver disease.
Tandra S, Yeh MM, Brunt EM, Vuppalanchi R, Cummings OW, Unalp-Arida A, Wilson LA, Chalasani N; for the NASH Clinical Research Network (NASH CRN). J Hepatol. 2011 Sep;55(3):654-659. (CUMC Full Text PDF)

The use of liver biopsy evaluation in discrimination of idiopathic autoimmune hepatitis versus drug-induced liver injury.

Suzuki A, Brunt EM, Kleiner DE, Miquel R, Smyrk TC, Andrade RJ, Isabel Lucena M, Castiella A, Lindor K, Björnsson E. Hepatology. 2011 Sept 54;931-939 (CUMC Full Text PDF)

Idiopathic noncirrhotic portal hypertension.

Schouten JN, Garcia-Pagan JC, Valla DC, Janssen HL. Hepatology. 2011 May 13. (CUMC Full Text PDF)

Pathology Journals

Mucinous cystic neoplasms of the liver: a clinicopathological study and comparison with intraductal papillary neoplasms of the bile duct.
Zen Y, Pedica F, Patcha VR, Capelli P, Zamboni G, Casaril A, Quaglia A, Nakanuma Y, Heaton N, Portmann B. Mod Pathol 2011 Aug;24(8):1079-89.

OATP 1B1/1B3 expression in hepatocellular carcinomas treated with orthotopic liver transplantation.
Vasuri F, Golfieri R, Fiorentino M, Capizzi E, Renzulli M, Pinna AD, Grigioni WF, D'Errico-Grigioni A.
Virchows Arch. 2011 Aug;459(2):141-6. (CUMC Full Text PDF)

Liver histology as predictor of outcome in patients with acute-on-chronic liver failure (ACLF).
Rastogi A, Kumar A, Sakhuja P, Bihari C, Gondal R, Hissar S, Garg H, Sarin SK. Virchows Arch. 2011 Aug;459(2):121-7. (CUMC Full Text PDF)

Gastroenterology and Hepatology Journals:

A prospective study of the rate of progression in compensated, histologically advanced chronic hepatitis C.
Dienstag JL, Ghany MG, Morgan TR, Di Bisceglie AM, Bonkovsky HL, Kim HY, Seeff LB, Szabo G, Wright EC, Sterling RK, Everson GT, Lindsay KL, Lee WM, Lok AS, Morishima C, Stoddard AM, Everhart JE; HALT-C Trial Group. Hepatology. 2011 Aug;54(2):396-405. (CUMC Full Text PDF)

Pathology Journals

Primary hepatolithiasis, recurrent pyogenic cholangitis, and oriental cholangiohepatitis-a tale of 3 countries.
Tsui WM, Lam PW, Lee WK, Chan YK. Adv Anat Pathol. 2011 Jul;18(4):318-28. (CUMC Full Text PDF)

Update on Fatty liver disease and steatohepatitis.
Aly FZ, Kleiner DE. Adv Anat Pathol. 2011 Jul;18(4):294-300. (CUMC Full Text PDF)

Claudin-18 in biliary neoplasms. Its significance in the classification of intrahepatic cholangiocarcinoma.
Shinozaki A, Shibahara J, Noda N, Tanaka M, Aoki T, Kokudo N, Fukayama M. Virchows Arch. 2011 Jul;459(1):73-80. (CUMC Full Text PDF)

Iron in the liver: a review for surgical pathologists.
Torbenson M. Adv Anat Pathol. 2011 Jul;18(4):306-17. (CUMC Full Text PDF)

Gastroenterology and Hepatology Journals

Risk factors for cholangiocarcinoma.
Tyson GL, El-Serag HB. Hepatology. 2011 Jul;54(1):173-84. (CUMC Full Text PDF) 

Diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases.
Bacon BR, Adams PC, Kowdley KV, Powell LW, Tavill AS; American Association for the Study of Liver Diseases. Hepatology. 2011 Jul;54(1):328-43. (CUMC Full Text PDF)

Pathology Journals

Effect of Tumor Heterogeneity on the Assessment of Ki67 Labeling Index in Well-differentiated Neuroendocrine Tumors Metastatic to the Liver: Implications for Prognostic Stratification.
Yang Z, Tang LH, Klimstra DS. Am J Surg Pathol. 2011 Jun;35(6):853-60.

Hyperplastic luschka ducts: a mimic of adenocarcinoma in the gallbladder fossa.
Singhi AD, Adsay NV, Swierczynski SL, Torbenson M, Anders RA, Hruban RH, Argani P. Am J Surg Pathol. 2011 Jun;35(6):883-90.

Hepatocellular Carcinoma Arising in a Pigmented Telangiectatic Adenoma With Nuclear β-catenin and Glutamine Synthetase Positivity: Case Report and Review of the Literature.
Hechtman JF, Raoufi M, Fiel MI, Taouli B, Facciuto M, Schiano TD, Blouin AG, Thung SN. Am J Surg Pathol. 2011 Jun;35(6):927-32.

Viral hepatitis is associated with intrahepatic cholangiocarcinoma with cholangiolar differentiation and N-cadherin expression.
Yu TH, Yuan RH, Chen YL, Yang WC, Hsu HC, Jeng YM. Mod Pathol. 2011 Jun;24(6):810-9. (CUMC Full Text PDF)

Insulin-like growth factor I receptor β expression in hepatocellular carcinoma.
Liu X, Jiang W, Aucejo F, Kim R, Miller C, Byrne M, Lopez R, Yerian L. Hum Pathol. 2011 Jun;42(6):882-91. (CUMC Full Text PDF)

Update on precursor and early lesions of hepatocellular carcinomas.
Park YN. Arch Pathol Lab Med. 2011 Jun;135(6):704-15. (CUMC Full Text PDF)

OATP 1B1/1B3 expression in hepatocellular carcinomas treated with orthotopic liver transplantation.
Vasuri F, Golfieri R, Fiorentino M, Capizzi E, Renzulli M, Pinna AD, Grigioni WF, D'Errico-Grigioni A. Virchows Arch. 2011 Jun 21. [Epub ahead of print]. (CUMC Full Text PDF)

Gastroenterology and Hepatology Journals:

Changes in the prevalence of the most common causes of chronic liver diseases in the United States from 1988 to 2008.
Younossi ZM, Stepanova M, Afendy M, Fang Y, Younossi Y, Mir H, Srishord M. Clin Gastroenterol Hepatol. 2011 Jun;9(6):524-530. (CUMC Full Text PDF).

Clinical and histopathologic features of fluoroquinolone-induced liver injury.
Orman ES, Conjeevaram HS, Vuppalanchi R, Freston JW, Rochon J, Kleiner DE, Hayashi PH; DILIN Research Group. Clin Gastroenterol Hepatol. 2011 Jun;9(6):517-523. (CUMC Full Text PDF).

Acute presentation of autoimmune hepatitis: Does it exist? A published work review.
Takahashi H, Zeniya M. Hepatol Res. 2011 Jun;41(6):498-504. (CUMC Full Text PDF).

Focal nodular hyperplasia or focal nodular hyperplasia-like lesions of the liver: A special emphasis on diagnosis.
Choi JY, Lee HC, Yim JH, Shim JH, Lim YS, Shin YM, Yu ES, Suh DJ. J Gastroenterol Hepatol. 2011 Jun;26(6):1004-9. (CUMC Full Text PDF).

Polycystic liver diseases: congenital disorders of cholangiocyte signaling.
Strazzabosco M, Somlo S. Gastroenterology. 2011 Jun;140(7):1855-1859. (CUMC Full Text PDF).

An apoptosis panel for nonalcoholic steatohepatitis diagnosis.
Tamimi TI, Elgouhari HM, Alkhouri N, Yerian LM, Berk MP, Lopez R, Schauer PR, Zein NN, Feldstein AE. J Hepatol. 2011 Jun;54(6):1224-9. (CUMC Full Text PDF).

Association of caffeine intake and histological features of chronic hepatitis C.
Costentin CE, Roudot-Thoraval F, Zafrani ES, Medkour F, Pawlotsky JM, Mallat A, Hézode C. J Hepatol. 2011 Jun;54(6):1123-9. (CUMC Full Text PDF).

A classification of ductal plate malformations based on distinct pathogenic mechanisms of biliary dysmorphogenesis.
Raynaud P, Tate J, Callens C, Cordi S, Vandersmissen P, Carpentier R, Sempoux C, Devuyst O, Pierreux CE, Courtoy P, Dahan K, Delbecque K, Lepreux S, Pontoglio M, Guay-Woodford LM, Lemaigre FP. Hepatology. 2011 Jun;53(6):1959-66. (CUMC Full Text PDF).

Pathologic criteria for nonalcoholic steatohepatitis: Interprotocol agreement and ability to predict liver-related mortality.
Younossi ZM, Stepanova M, Rafiq N, Makhlouf H, Younoszai Z, Agrawal R, Goodman Z. Hepatology. 2011 Jun;53(6):1874-82. (CUMC Full Text PDF).

Surgery and Liver Transplantation Journals:

Noninvasive diagnosis of acute cellular rejection in liver transplant recipients: A proteomic signature validated by enzyme-linked immunosorbent assay.
Massoud O, Heimbach J, Viker K, Krishnan A, Poterucha J, Sanchez W, Watt K, Wiesner R, Charlton M. Liver Transpl. 2011 Jun;17(6):723-32. (CUMC Full Text).
A serum proteome signature was identified in a group of patients with histology-proven ACR. Differentially expressed proteins included serum amyloid A, complement component 4 (C4), fibrinogen, complement component 1q (C1q), complement component 3, heat shock protein 60 (HSP60), and HSP70. Immunohistochemical markers for several of these proteins are available and it would be interesting if tissue samples would also reflect the increased expression of these proteins observed in serum in this study.

Explanted liver inflammatory grade predicts fibrosis progression in hepatitis C recurrence.
Ghabril M, Dickson RC, Krishna M, Machicao V, Aranda-Michel J, Bonatti H, Nguyen JH. Liver Transpl. 2011 Jun;17(6):685-94. (CUMC PDF Full Text).

Pathology Journals

Hepatocellular carcinoma arising in a pigmented telangiectatic adenoma with nuclear β-catenin and glutamine synthetase positivity: case report and review of the literature.
Hechtman JF, Raoufi M, Fiel MI, Taouli B, Facciuto M, Schiano TD, Blouin AG, Thung SN. Am J Surg Pathol. 2011 Jun;35(6):927-32.

Pathology Journals

Claudins and tricellulin in fibrolamellar hepatocellular carcinoma.
Patonai A, Erdélyi-Belle B, Korompay A, Somorácz A, Straub BK, Schirmacher P, Kovalszky I, Lotz G, Kiss A, Schaff Z. Virchows Arch. 2011 Apr 19. [Epub ahead of print]. (CUMC Full Text PDF).
The histogenesis of fibrolamellar HCC has long been debated. With emerging evidence for 'stem cell' carcinomas and tumors with divergent/bilineal differentiation, some of the morphologic, immunohistochemical, and molecular features of FL-HCC have been re-examined in this context. The authors of this study detected a claudin expression pattern in FL-HCC that is more similar to conventional HCC's than to cholangiocarcinomas. However, tight junction protein expression is qualitatively and quantitatively different from both conventional HCCs and cholangiocarcinomas.

Advanced histology and impaired liver regeneration are associated with disease severity in acute-onset autoimmune hepatitis.
Fujiwara K, Nakano M, Yasui S, Okitsu K, Yonemitsu Y, Yokosuka O. Histopathology. 2011 Apr;58(5):693-704. (CUMC Full Text PDF).
Semiquantitative evaluation of ductular reaction, intermediate hepatocytes and hepatic progenitor cells, as assessed by cytokeratin 7 immunostaining was used by the authors to study patients presenting with autoimmune hepatitis of different severities. The authors conclude that the above features reflect impaired liver regeneration and may represent useful prognostic markers in this setting. It would have been interesting if the authors had also studied the expression of p21, a known marker of replicative arrest, in these patients.

Gastroenterology and Hepatology Journals

Histopathological stages of nonalcoholic fatty liver disease in type 2 diabetes: prevalences and correlated factors.
Leite NC, Villela-Nogueira CA, Pannain VL, Bottino AC, Rezende GF, Cardoso CR, Salles GF. Liver Int. 2011 May;31(5):700-6. (CUMC Full Text PDF).
The reported prevalence of NAFLD and NASH in type-2 diabetic patients with either ultrasonographic evidence of fatty liver or abnormal transaminase levels and negative work-up for other liver diseases was 94% and 78%, respectively. The authors suggest that liver biopsy should be considered for all type-2 diabetic patients in this setting.

Review of liver injury associated with dietary supplements.
Stickel F, Kessebohm K, Weimann R, Seitz HK. Liver Int. 2011 May;31(5):595-605. (CUMC Full Text PDF).
This is a comprehensive review of the literature regarding hepatotoxicity associated with various dietary supplements, various teas and herbal remedies, anabolic steroids, and other compounds. Clinical suspicion for hepatotoxicity by substances belonging to one of the above groups is not uncommon in practice; however, finding information in literature about these supplement and medications is often challenging. I found this review to be a very useful guide.  

Morphologic classification of microvessels in hepatocellular carcinoma is associated with the prognosis after resection.
Chen ZY, Wei W, Guo ZX, Lin JR, Shi M, Guo RP. J Gastroenterol Hepatol. 2011 May;26(5):866-74. (CUMC Full Text PDF). (also see editorial [CUMC Full Text PDF])

Liver transplantation using fatty livers: Always feasible?
McCormack L, Dutkowski P, El-Badry AM, Clavien PA. J Hepatol. 2011 May;54(5):1055-62. (CUMC Full Text PDF).
The authors review the available data about utilizing steatotic grafts in liver transplantation. As the authors point out, different methods of assessing steatosis (gross assessment, frozen H&E section, permanent H&E sections, oil-red-O, sudan black, digital analysis, chemical quantitation methods in tissue etc), evaluation of macro vs micro steatosis, and pathologists's interobserver variability are among the various problems that may contribute to the widely variable outcomes seen in different studies according to the degree of steatosis. In general, a mild degree of macrovesicular steatosis (<30%) is associated with relatively low rates of complications (prolonged ICU time, primary graft non function etc.) while severe macrovesicular steatosis (>60%) is associated with increased rates of complications. The risk associated with moderate steatosis (30-60%), however, is highly variable and the risk conferred by microvesicular steatosis is not well-established.

Massive Hepatic Echinococcosis.
Sweetser S, Loftus, CG. Hepatology 2011 May;53(5):1771-2. (CUMC Full Text PDF).

Hepatitis C virus receptors claudin-1 and occludin after liver transplantation and influence on early viral kinetics.
Mensa L, Crespo G, Gastinger MJ, Kabat J, Pérez-Del-Pulgar S, Miquel R, Emerson SU, Purcell RH, Forns X. Hepatology. 2011 May;53(5):1436-45. (CUMC Full Text PDF).

Constitutional telomerase mutations are genetic risk factors for cirrhosis.
Calado RT, Brudno J, Mehta P, Kovacs JJ, Wu C, Zago MA, Chanock SJ, Boyer TD, Young NS. Hepatology. 2011 May;53(5):1600-7. (CUMC Full Text PDF).

Telomerase gene mutations are associated with cirrhosis formation.
Hartmann D, Srivastava U, Thaler M, Kleinhans KN, N'kontchou G, Scheffold A, Bauer K, Kratzer RF, Kloos N, Katz SF, Song Z, Begus-Nahrmann Y, Kleger A, von Figura G, Strnad P, Lechel A, Günes C, Potthoff A, Deterding K, Wedemeyer H, Ju Z, Song G, Xiao F, Gillen S, Schrezenmeier H, Mertens T, Ziol M, Friess H, Jarek M, Manns MP, Beaugrand M, Rudolph KL. Hepatology. 2011 May;53(5):1608-17. (CUMC Full Text PDF).

These two remarkably similar publications in this month's issue of Hepatology investigate the role of telomerase mutations as potential risk factors for development of cirrhosis in the setting of chronic liver disease of various types.

Incidence of primary sclerosing cholangitis: A systematic review and meta-analysis.
Molodecky NA, Kareemi H, Parab R, Barkema HW, Quan H, Myers RP, Kaplan GG. Hepatology. 2011 May;53(5):1590-9. (CUMC Full Text PDF).
The authors review the evidence for an increasing incidence of PSC in the US and European countries.

Lineage tracing demonstrates no evidence of cholangiocyte epithelial-to-mesenchymal transition in murine models of hepatic fibrosis.
Chu AS, Diaz R, Hui JJ, Yanger K, Zong Y, Alpini G, Stanger BZ, Wells RG. Hepatology. 2011 May;53(5):1685-95. (CUMC Full Text PDF) (also see editorial [CUMC Full Text PDF]).

Diagnostic accuracy of clathrin heavy chain staining in a marker panel for the diagnosis of small hepatocellular carcinoma.
Di Tommaso L, Destro A, Fabbris V, Spagnuolo G, Laura Fracanzani A, Fargion S, Maggioni M, Patriarca C, Maria Macchi R, Quagliuolo M, Borzio M, Iavarone M, Sangiovanni A, Colombo M, Roncalli M. Hepatology. 2011 May;53(5):1549-57. (CUMC Full Text PDF). (also see editorial [CUMC Full Text]).
Di Tommaso et al investigate the contribution of clathrin heavy chain (in addition to glypican-3, glutamine synthetase, and heat-shock protein 70) in the diagnosis of HCC on needly biopsy. The addition of CHC to the panel increased the diagnostic accuracy for small HCCs from 76.9% to 84.3%, and there was an increase in sensitivity from 46.8% to 63.8%.

General Medicine Journals

Primary biliary cirrhosis.
Selmi C, Bowlus CL, Gershwin ME, Coppel RL. Lancet. 2011 May 7;377(9777):1600-9. (CUMC Full Text PDF).

Surgery and Liver Transplantation Journals

Liver and portal histopathological correlation with age and survival in extra hepatic biliary atresia.

Sharma S, Das P, Dattagupta S, Kumar L, Gupta DK. Pediatr Surg Int. 2011 May;27(5):451-61. (CUMC full text PDF)

Pathology Journals

Different roles of S100P Overexpression in Intrahepatic Cholangiocarcinoma: Carcinogenesis of Perihilar Type and Aggressive Behavior of Peripheral Type.
Aishima S, Fujita N, Mano Y, Kubo Y, Tanaka Y, Taketomi A, Shirabe K, Maehara Y, Oda Y. Am J Surg Pathol. 2011 Apr;35(4):590-8.
S100P is a member of the S100 family of calcium-binding proteins that has previously been shown to be overexpressed in pancreatic ductal adenocarcinoma. This group has studied the expression of S100P in cases of biliary intraepithelial neoplasia (BilIN) and cholangiocarcinoma. S100P is expressed more often in perihilar-type (68%) than in peripheral-type (12%) chCA. S100P+ peripheral chCA had a more aggressive behavior than S100P- tumors in this study.

Similarities and differences between intraductal papillary tumors of the bile duct with and without macroscopically visible mucin secretion.
Ohtsuka M, Kimura F, Shimizu H, Yoshidome H, Kato A, Yoshitomi H, Furukawa K, Takeuchi D, Takayashiki T, Suda K, Takano S, Kondo Y, Miyazaki M. Am J Surg Pathol. 2011 Apr;35(4):512-21.

What is expected from the pathologist in the diagnosis of viral hepatitis?
Denk H. Virchows Arch. 2011 Apr;458(4):377-92.

Gastroenterology and Hepatology Journals

Investigation of primary cilia in the pathogenesis of biliary atresia.
Hartley JL, O'callaghan C, Rossetti S, Consugar M, Ward CJ, Kelly DA, Harris PC. J Pediatr Gastroenterol Nutr. 2011 Apr;52(4):485-8.
This is an interesting article discussing the possible role of primary ciliary abnormalities in the pathogenesis of biliary atresia. Can biliary atresia, in particular the "embryonic"/prenatal/syndromic subgroup, in which numerous congenital maformations (including polysplenia, pre-duodenal portal vein, situs inversus etc) be part of the spectrum of "ciliopathies", which currently include ADPKD, ARPKD, congenital hepatic fibrosis, Caroli's disease, Caroli's syndrome, and polycystic liver disease? In this study, 9 of 355 children with BA developed renal cysts on follow-up (all of whom had the perinatal/nonsyndromic form). In one of seven cases (among the nine children who developed renal cysts) undergoing genetic testing, one child was a compound heterozygote for a mutation involving the PKHD1 gene. No functional ciliary abnormalities were identified in two children whose nasal cilia were studied. Interestingly, however, the bile duct epithelium in BA cases (with or without renal cysts) was uniformly negative for fibrocystin by immunohistochemistry, in contrast to strong expression in normal livers and livers with various other inflammatory/genetic/metabolic diseases


A- Autosomal recessive polycystic kidney disease with associated congenital hepatic fibrosis. Note the presence of splenomegaly secondary to portal hypertension.
B- Autosomal dominant polycystic kidney disease with associated liver cysts. In this setting, liver cysts are isolated and usually do not communicate with the biliary tree.



Normal portal tract development (left) compared to plate malformation (right) with persistence of embryonal duct plate configuration.
Reference: Gunay-Aygun M. Liver and kidney disease in ciliopathies. Am J Med Genet C Semin Genet 2009;151C(4):296-306.

Design and validation of the biliary atresia research consortium histologic assessment system for cholestasis in infancy.
Russo P, Magee JC, Boitnott J, Bove KE, Raghunathan T, Finegold M, Haas J, Jaffe R, Kim GE, Magid M, Melin-Aldana H, White F, Whitington PF, Sokol RJ; Biliary Atresia Research Consortium. Clin Gastroenterol Hepatol. 2011 Apr;9(4):357-362. (CUMC Full Text PDF)
In this study, BARC researchers evaluated 97 liver biopsy specimens from 49 cases of BA, 17 cases of idiopathic neonatal hepatitis, and 31 cases of other neonatal cholestatic diseases (including TPN-induced liver disease, alpha1-antitrypsin deficiency, Alagille's syndrome, PFIC and others). Numerous important observations were reported in this study that are of practical utility for those who evaluate liver biopsies from cholestatic newborns. The overall sensitivity for the diagnosis of BA (including the "favor BA" and "favor obstruction other than BA" groups) was 86% (among 464 biopsies from 49 patients) . Inadequate samples (small and fragmented specimens) and very early biopsies (one patient was biopsied at 2-weeks after birth, an age at which the features of BA may not be sufficiently developed for diagnosis) were identified as causes for false negative interpretations. The investigators, therefore, suggest that samples should be at least 2 cm long, 0.2 cm wide, and contain at least 10 portal tracts to be considered adequate. Among patients with idiopathic neonatal hepatitis, on the other hand, 21% of biopsies (among 156 samples from 17 patients) were incorrectly interpreted as either "favor BA" or "favor obstruction other than BA". The error rate, therefore is was approximately 14% for BA cases and 21% fo INH cases. Biopsies from the third category of patients ("other") were classified as BA or "obstruction other than BA" 50% of the time, including nearly all cases of TPN liver disease and alpha1-antitrypsin deficiency.
Among the 16 individual histologic features investigated, the most useful ones in distinguishing BA from non-BA cases on logistic regression were 1- ductular reaction, 2- portal fibrosis, and 3- lack of sinusoidal fibrosis. Bile duct and canalicular cholestasis and portal edema were also seen more commonly in BA. Interestingly, several features considered useful by many pathologists in this setting, including hepatocellular changes (swelling, necrosis) giant-cell transformation/multinucleation, pseudorosette formation, and EMH were seen as frequently in BA as in non-BA cases.

Hepatic sinusoidal obstruction syndrome associated with consumption of Gynura segetum.
Lin G, Wang JY, Li N, Li M, Gao H, Ji Y, Zhang F, Wang H, Zhou Y, Ye Y, Xu HX, Zheng J. J Hepatol. 2011 Apr;54(4):666-73. (CUMC Full Text PDF)

Aberrant DNA methylation distinguishes hepatocellular carcinoma associated with HBV and HCV infection and alcohol intake.
Lambert MP, Paliwal A, Vaissière T, Chemin I, Zoulim F, Tommasino M, Hainaut P, Sylla B, Scoazec JY, Tost J, Herceg Z. J Hepatol. 2011 Apr;54(4):705-15. (CUMC Full Text PDF) (also see editorial PDF)

Endoplasmic reticulum stress in liver disease.
Malhi H, Kaufman RJ. J Hepatol. 2011 Apr;54(4):795-809. (CUMC Full Text PDF)

Liver transplantation as a model to better understand the cell entry of hepatitis C virus.
Féray C. J Hepatol. 2011 Apr;54(4):825-6. (CUMC Full Text PDF)

Nuclear receptors as new perspective for the management of liver diseases.
Trauner M, Halilbasic E. Gastroenterology. 2011 Apr;140(4):1120-1125. (CUMC Full Text PDF)

Clinicopathological features of severe and fulminant forms of autoimmune hepatitis.
Yasui S, Fujiwara K, Yonemitsu Y, Oda S, Nakano M, Yokosuka O. J Gastroenterol. 2011 Mar;46(3):378-90. (CUMC Full Text PDF)

GB virus C infection among young, HIV-negative injection drug users with and without hepatitis C virus infection.
Boodram B, Hershow RC, Klinzman D, Stapleton JT. J Viral Hepat. 2011 Apr;18(4):e153-9. (CUMC Full Text PDF)

Hepatic steatosis and insulin resistance are associated with severe fibrosis in patients with chronic hepatitis caused by HBV or HCV infection.
Petta S, Cammà C, Marco VD, Macaluso FS, Maida M, Pizzolanti G, Belmonte B, Cabibi D, Stefano RD, Ferraro D, Guarnotta C, Venezia G, Craxì A. Liver Int. 2011 Apr;31(4):507-15. (CUMC Full Text PDF)

A novel and comprehensive mouse model of human non-alcoholic steatohepatitis with the full range of dysmetabolic and histological abnormalities induced by gold thioglucose and a high-fat diet.
Ogasawara M, Hirose A, Ono M, Aritake K, Nozaki Y, Takahashi M, Okamoto N, Sakamoto S, Iwasaki S, Asanuma T, Taniguchi T, Urade Y, Onishi S, Saibara T, Oben JA. Liver Int. 2011 Apr;31(4):542-51. (CUMC Full Text PDF) (also see editorial PDF)

Clinical characterization of patients developing histologically-proven fibrosing cholestatic hepatitis C post-liver transplantation.
Satapathy SK, Sclair S, Fiel MI, Del Rio Martin J, Schiano T. Hepatol Res. 2011 Apr;41(4):328-39. (CUMC Full Text PDF)

Utility of simplified criteria for the diagnosis of autoimmune hepatitis in children.
Hiejima E, Komatsu H, Sogo T, Inui A, Fujisawa T. J Pediatr Gastroenterol Nutr. 2011 Apr;52(4):470-3.

Simplified criteria for AIH have been shown to be a reliable alternative to the more complex original criteria proposed by the IAIHG in 1998, with >90% doagnostic specificity and sensitivity. This Japanese group, however, draws attention to the fact that the simplified criteria may be significantly less accurate in the pediatric population.

General Medicine Journals

A new era of hepatitis C therapy begins.
Jensen DM. N Engl J Med. 2011 Mar 31;364(13):1272-4. (CUMC Full Text PDF)

Surgery and Liver Transplantation Journals

Visceral Leishmaniasis in Liver Transplant Recipients From an Endemic Area.
Clemente WT, Faria LC, Romanelli RM, Lima SS, Cortes JR, Oliveira AP, Carvalho AL, Ferreira AR, Lima AS. Transplantation. 2011 Apr 15;91(7):806-808. 

The importance of portal venous blood flow in ischemic-type biliary lesions after liver transplantation.
Farid WR, de Jonge J, Slieker JC, Zondervan PE, Thomeer MG, Metselaar HJ, de Bruin RW, Kazemier G. Am J Transplant. 2011 Apr;11(4):857-62. (CUMC Full Text PDF)

Characterization of HCV-Specific CD4+Th17 Immunity in Recurrent Hepatitis C-Induced Liver Allograft Fibrosis.
Basha HI, Subramanian V, Seetharam A, Nath DS, Ramachandran S, Anderson CD, Shenoy S, Chapman WC, Crippin JS, Mohanakumar T. Am J Transplant. 2011 Apr;11(4):775-85. (CUMC Full Text PDF)

Characterization of the cross-neutralizing antibody response against hepatitis C virus in the liver transplantation setting.
Dragun J, Pérez-Del-Pulgar S, Crespo G, Ramírez S, Coto-Llerena M, Mensa L, García-Valdecasas JC, Navasa M, Forns X. Am J Transplant. 2011 Apr;11(4):767-74. (CUMC Full Text PDF)

Liver allograft antibody-mediated rejection with demonstration of sinusoidal C4d staining and circulating donor-specific antibodies.
Kozlowski T, Rubinas T, Nickeleit V, Woosley J, Schmitz J, Collins D, Hayashi P, Passannante A, Andreoni K. Liver Transpl. 2011 Apr;17(4):357-68. (CUMC Full Text PDF)

Pathology Journals

Segmental atrophy of the liver: a distinctive pseudotumor of the liver with variable histologic appearances.
Singhi AD, Maklouf HR, Mehrotra AK, Goodman ZD, Drebber U, Dienes HP, Torbenson M.  Am J Surg Pathol. 2011 Mar;35(3):364-71. (CUMC Full Text PDF)

Singhi et al describe the clinical and pathologic features of a group of 18 patients presenting with a pseudotumor secondary to segmental atrophy of the liver. The authors conclude that these pseudotumors occur in the setting of of an intralesional abnormal and/or thrombosed vessel and, histologically, may progress through several "stages": from areas of parenchymal collapse with brisk ductular proliferation (early lesions), nodular elastosis (more advanced lesions), and finally nodular fibrosis (end-stage lesion).

 Prevalence and clinical significance of Küpffer cell hyperplasia with hemophagocytosis in liver biopsies.
Prendki V, Stirnemann J, Lemoine M, Lohez M, Aras N, Ganne-Carrié N, Larroche C, Roulot D, Tengher-Barna I, Fain O, Ziol M. Am J Surg Pathol. 2011 Mar;35(3):337-45. (CUMC Full Text PDF)

Prendki and colleagues discuss the prevalence and clinical significance of Kupffer cell hyperplasia with accompanying hemophagocytosis in liver biopsy samples. The authors identified hemophagocytosis in 69 of 5194 liver biopsies (1.3%) obtained over a 6-year period. Complete hemophagocytic syndrome (fever, splenomegaly, bicytopenia, hypertriglyceridemia, hyperferritinemia, and/or hypofibrinogenemia) was seen in 36% of patients in which hemophagocytosis was identified. Almost all patients had at least one of the following conditions: HIV infection, hematologic malignancy, autoimmune diseases, or an ongoing infectious process, including tuberculosis, CMV, or EBV. A decreased perforin to CD3+ lymphocyte ratio was associated with hemophagocytosis in this study.

This is a case we had in our service a couple of weeks ago. This young female presented with complete hemophagocytic syndrome and underwent liver biopsy for severe hepatic dysfunction. Decreased perforin to CD3 lymphocytes is seen in this case, as described in the study above.

The concept of hepatic artery-bile duct parallelism in the diagnosis of ductopenia in liver biopsy samples.
Moreira RK, Chopp W, Washington MK. Am J Surg Pathol. 2011 Mar;35(3):392-403. (CUMC Full Text PDF)

In this paper, my colleagues and I essentially apply the concept of hepatic artery-bile duct parallelism (i.e. parallel arrangement of these two structures within portal tracts) to propose specific diagnostic criteria for the diagnosis of bile duct loss (ductopenia) in liver biopsy samples. The final set of proposed criteria is relatively simple: two or more portal tracts containing an unpaired hepatic artery (representing at least 10% of all portal tracts in a given sample) is indicative of bile duct loss. The article is definitely information-heavy and may best be appreciated with a couple of glasses of fine wine.

 This liver biopsy from a patient with stage 1 PBC illustrates the application of the "unpaired hepatic artery" method for evaluation of ductopenia (click on image to enlarge). A total of seven portal tracts are present in the sample below, five of which contain an interlobular bile duct (BD+). Therefore, the speciment is not diagnostic for bile duct loss. However, two of seven portal tracts contain an unpaired hepatic artery (UHA+), which is indicative of bile duct loss according to the data presented in this study.

Fibrolamellar carcinomas are positive for CD68.
Ross HM, Daniel HD, Vivekanandan P, Kannangai R, Yeh MM, Wu TT, Makhlouf HR, Torbenson M. Mod Pathol. 2011 Mar;24(3):390-5. (CUMC Full Text PDF)

This is one of a series of articles by Michael Torbenson's group on the subject of fibrolamellar HCC (see other links below). In this study, the authors demonstrate a generally strong CD68 expression in a granular or dot-like pattern in 31/32 FL-HCCs. CD68 was also expressed by a minority of conventional HCCs, especially those arising in non-cirrhotic livers (overall sensitivity of 96% and specificity of 80%).
(see also: Mod Pathol 2010;23(6):790-8; Mod Pathol 2008;21(6):670-5; Adv Anat Pathol 2007;14(3):217-23; Hum Pathol 2007;38(4):639-44).

Comparing morphometric, biochemical, and visual measurements of macrovesicular steatosis of liver.
Li M, Song J, Mirkov S, Xiao SY, Hart J, Liu W. Hum Pathol. 2011 Mar;42(3):356-60. (CUMC Full Text PDF)

The authors measure the degree of steatosis in liver samples by biochemical measure of fat content (weight percentage of fat) and digital morphometric analysis (percentage of areas occupied by fat) and compare these with traditional ("visual") pathologic evaluation. Biochemical and digital analyses generated similar results, while "visual" estimates systematically yielded values approximately four times higher than the other two methods (but with highly reproducible values among 3 pathologists).  The fact that different methods yield different absolute values and percentages for "fat content" should come at no surprise. In this study, for instance, the visual assessment evaluated the "proportion of hepatocytes involved by macrovesicular steatosis". This is in sharp contrast with what is being measured biochemically (i.e. total fat content, regardless of cellular location or droplet size, using the entire tissue fragment - portal tracts and fibrous septa included - as denominator). As for digital analysis, it is generally just as accurate as the individual selecting the fields and operating the software. The excellent intra- and interobserver agreement among the three study pathologist is noteworthy as it contradicts previous studies (see Ann Surg 2009;250(5):691-7).

Gastroenterology and Hepatology Journals

"Pardon the interruption": Comments on the International Liver Cancer Association Fourth Annual Conference, 2010. Is there really no role for liver biopsy interpretation in liver cancer?
Brunt EM, Gores G. Hepatology. 2011 Mar;53(3):721-2. (CUMC Full Text PDF)

The authors question the widespread belief among clinicians and surgeons that liver biopsies have a very limited role in the era of -omics, gene array, micro-RNA, and other molecular markers. Also, are liver pathologists a dying breed?

Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: distinct clinicopathologic meanings. 
Brunt EM, Kleiner DE, Wilson LA, Belt P, Neuschwander-Tetri BA; for the NASH Clinical Research Network (CRN). Hepatology. 2011 Mar;53(3):810-820. (CUMC Full Text PDF)

In this issue of Hepatology, Elizabeth Brunt and colleagues from the NASH Clinical Research Network (CRN) reiterate the fact that the NAFLD activity score (NAS) - a scoring system originally designed to serve a similar purpose as the various chronic hepatitis grading systems, or the Banff scoring system for rejection - is not an efficient substitute to traditional diagnostic criteria for NASH. As the authors point out, the composite NAS above a certain value (usually >5) has been adopted by some investigators as the basis for a diagnosis of NASH, although the validity of this approach is unproven. In this regard, the authors show that only 75% of biopsies with definite SH had an NAS >5 and that among biopsies with NAS >5, 86% had SH. They conclude that the diagnosis of NASH does not always correlate with specific threshold values of the semiquantitative NAS.

Epithelial cell adhesion molecule (EpCAM) marks hepatocytes newly derived from stem/progenitor cells in humans. Yoon SM, Gerasimidou D, Kuwahara R, Hytiroglou P, Yoo JE, Park YN, Theise ND. Hepatology. 2011 Mar;53(3):964-73. (CUMC Full Text PDF)

The expression of EpCAM as a marker of hepatic stem/progenitor cells is studied in the setting of hepatitis B and C in various stages. EpCAM expression in hepatocytes is reported to become more prominent in later stages of chronic hepatitis, accompanied by development of ductular reaction (CK19+, w/ high proliferation) and, on a molecular level, presence of telomeres of longer length. The data support the concept that EpCAM+ hepatocytes represent a population of newly-formed hepatocytes from hepatobiliary stem/progenitor cells.

Management of hepatocellular carcinoma: An update.
Bruix J, Sherman M. Hepatology. 2011 Mar;53(3):1020-2. (CUMC Full Text PDF)

Human hepatic stem cell and maturational liver lineage biology.
Turner R, Lozoya O, Wang Y, Cardinale V, Gaudio E, Alpini G, Mendel G, Wauthier E, Barbier C, Alvaro D, Reid LM. Hepatology. 2011 Mar;53(3):1035-45. (CUMC Full Text PDF)
A detailed review of the histogenesis and development of the liver with excellent illustrations.

Obliterative portal venopathy: Portal hypertension is not always present at diagnosis.
Cazals-Hatem D, Hillaire S, Rudler M, Plessier A, Paradis V, Condat B, Francoz C, Denninger MH, Durand F, Bedossa P, Valla DC. J Hepatol. 2011 Mar;54(3):455-61. (CUMC Full Text PDF)

Intratumoral neutrophils: A poor prognostic factor for hepatocellular carcinoma following resection.
Li YW, Qiu SJ, Fan J, Zhou J, Gao Q, Xiao YS, Xu YF. J Hepatol. 2011 Mar;54(3):497-505. (CUMC Full Text PDF)

Anabolic-androgenic steroids: a possible new risk factor of toxicant-associated fatty liver disease.
PA, Cotrim HP, Salles BR, Almeida CE, dos Santos CR Jr, Nachef B, Andrade AR, Zoppi CC.

Liver Int. 2011 Mar;31(3):348-53. (CUMC Full Text PDF)
It's all about looking good for Canaval. Forget about your liver! This group from Salvador, Brazil studied the prevalence of fatty liver disease in asymptomatic non-competitive male bodybuilders with a history of anabolic-androgenic steroid use. In this case-control study, 12.6% of these athletes met criteria for fatty liver disease, as defined in this study, compared to 2.4% of controls (bodybuilders with no history of anabolic steroid use) (OR=6.0, 95% CI: 1.3-27.6). The authors include anabolic steroid-induced liver disease as a cause of what has been referred to as TAFLD (toxicant-associated fatty liver disease) and TASH (toxicant-associated steatohepatitis).

Surgery and transplantation journals

The Significance of Donor-Specific HLA Antibodies in Rejection and Ductopenia Development in ABO Compatible Liver Transplantation.
Musat AI, Agni RM, Wai PY, Pirsch JD, Lorentzen DF, Powell A, Leverson GE, Bellingham JM, Fernandez LA, Foley DP, Mezrich JD, D'Alessandro AM, Lucey MR. Am J Transplant. 2011 Mar;11(3):500-10. (CUMC Full Text PDF)
This is the latest addition to a rapidly increasing number of articles showing a possible important role for humoral rejection in cases of liver allograft rejection. Applying the currently used strategy for detection of antibody-mediated rejection in other solid organs (using C4d staining and presence of donor-specific HLA antibodies), the authors conclude that humoral alloreactivity is frequently present in cases of "cellular" rejection in ABO-compatible liver allografts.

Immunohistochemical study of hepatocyte, cholangiocyte and stem cell markers of hepatocellular carcinoma.
Shibuya M, Kondo F, Sano K, Takada T, Asano T. J Hepatobiliary Pancreat Sci. 2011 Jan 14. (CUMC Full Text PDF)
The authors identify expression of cholangiocyte markers in the majority of HCC cases included in this study, while hepatic stem/progenitor cell marker (C-kit) was present in a small minorit y of cases.

The clinicopathological significance of heat shock protein 70 and glutamine synthetase expression in hepatocellular carcinoma.
Shin E, Ryu HS, Kim SH, Jung H, Jang JJ, Lee K. J Hepatobiliary Pancreat Sci. 2011 Jan 14. [Epub ahead of print] (CUMC Full Text PDF)
HSP-70 was expressed by the majority of HCCs in this study (71.9%) and correlated with microscopic vascular invasion, larger tumor size, higher Edmondson-Steiner grade, and lower disease-free survival.