|Year : 2018 | Volume
| Issue : 1 | Page : 41-47
Retrospective analysis of explants liver pathology: Experience from a tertiary care center in India
Nalini Bansal1, Vivek Vij2, Mukul Rastogi3, Manav Wadhawan4, Ajay Kumar5
1 Department of Histopathology, SRL Limited, Fortis Escorts, New Delhi, India
2 Department of Liver Transplant Surgery and Hepatology, Fortis Escorts, New Delhi, India
3 Department of Hepatology, Fortis, Noida, Uttar Pradesh, India
4 Department of Hepatology, Fortis Escorts, New Delhi, India
5 Department of Gastroenterology, Fortis Escorts, New Delhi, India
|Date of Web Publication||29-Mar-2018|
Dr. Nalini Bansal
SRL Limited, Fortis Escorts Heart Institute, Okhla Road, New Delhi
Source of Support: None, Conflict of Interest: None
Background: The histological spectrum of explant liver pathology and their prevalence has not previously been reported from the Indian subcontinent. (1) The study was performed to provide new insight into the prevalence of explant liver pathologies in this part of the world by retrospective analysis of the spectrum of histological changes, (2) to study the etiopathological association of cirrhosis, (3) to study the etiopathogenesis for development of hepatocellular carcinoma (HCC), and to analyze whether there is any association of macroregenerative and dysplastic nodule with HCC. Materials and Methods: Written records of all explant liver pathology service were entered into an electronic database. Retrospective analysis of the liver explants was performed from May 2015 to July 2016 at a tertiary-care center in India. Results: Maximum (97.2%) number of liver explants showed cirrhosis. Hepatitis C virus (HCV)-related chronic liver disease was the most common etiological factor for the development of cirrhosis in this part of the world followed by HBV and alcohol. The association between HCC and HBV was found to be statistically significant with a value of P = 0.009. The association between dysplastic nodules and HCC was also found to be significant. Conclusion: This is the first study to describe the histological spectrum of explant liver pathology from India. HCV forms the major disease burden for the chronic liver disease. There is a significant association of dysplastic nodules with HCC postulating their role as a precursor lesion in HCC.
Keywords: Alcohol, autoimmune liver, Echinococcus multilocularis, explant liver, hepatitis C, primary biliary cirrhosis
|How to cite this article:|
Bansal N, Vij V, Rastogi M, Wadhawan M, Kumar A. Retrospective analysis of explants liver pathology: Experience from a tertiary care center in India. Indian J Transplant 2018;12:41-7
|How to cite this URL:|
Bansal N, Vij V, Rastogi M, Wadhawan M, Kumar A. Retrospective analysis of explants liver pathology: Experience from a tertiary care center in India. Indian J Transplant [serial online] 2018 [cited 2019 Jul 21];12:41-7. Available from: http://www.ijtonline.in/text.asp?2018/12/1/41/228933
| Introduction|| |
Transplant pathology has now become an integral part of the surgical pathology. Studies on explant liver pathology are required for better understanding of the pathogenesis of various diseases. We undertook this study to evaluate the prevalence of various explant pathologies in South East Asian population and to gain new insight into the etiopathological association of cirrhosis and hepatocellular carcinoma (HCC).
| Materials and Methods|| |
The study was a retrospective observational study of 180 cases of explant liver specimen received at Histopathology Department of SRL Limited, Fortis Escort Heart Institute, Okhla, New Delhi from May 2015 to July 2016.
Details of all histopathology reports were retrieved using hospital information system and central laboratory information management system and computerized using a Microsoft ® Excel database. Each diagnosis was entered accompanied by the patient's age, gender, and clinical details. The data were sorted by pathology category, diagnosis, age, and gender which facilitated the calculation of the frequency of the disease, male-to-female ratio, mean age and age range, and the percentage of particular pathologies.
All cases of explant liver were included in the study. Cases of partial or segmental liver resections for HCC/hemangiomas/gallbladder carcinomas/cholangiocarcinomas were excluded from the study. The diagnosis was sorted into 20 categories [Table 1].
Association between HCC and various causative factors were analyzed using Chi-square test or Fischer's exact test with a P value of #60; 0.05 was taken as a statistically significant association. All analysis was performed using Epi-info software version 6.0 (Software developed by Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, USA).
| Results|| |
Diagnostic categories on explant liver histology
Hepatitis C virus-related liver disease
Of the total liver explant maximum cases were of hepatitis C virus (HCV)-related chronic liver disease (CLD) (72/180). The age of patient ranged from 24 to 72 years with a male:female ratio of 2:1. HCC was seen in 19 of these cases. Of these 19 HCC cases, four were of steatohepatitic HCC. Associated comorbidities noted in three cases – primary hepatic lymphoma one case, one case of hepatic amyloidosis, and one case of atrophy-hypertrophy complex.
Hepatitis C virus with primary hepatic lymphoma
A 53-year-old female, known case of HCV-related chronic liver disease for last 10 years, underwent liver transplant for cirrhosis. Explant liver showed multiple >30 nodules in all liver lobes with the fleshy whitish cut surface. Nodules ranged in size from 0.5 to 2.5 cm in diameter [Figure 1]a. Microscopy from whitish nodules showed the uniform population of large cells [Figure 1]b and [Figure 1]c that were LCA [Figure 1]d, CD10, CD 20, and Bcl6 positive; negative for Pan CK, S100, CD 3, Mum 1, CD 99, CyclinD1, and CA 125; and Ki 67 was 85%–90%. Cytogenetic testing done to rule out double/triple hit lymphoma for c-myc, bcl2, and bcl6 were negative. Bone marrow aspiration and positron emission tomography scan were negative. The case was diagnosed with primary hepatic lymphoma – diffuse large B-cell lymphoma, germinal center phenotype with associated HCV cirrhosis.
|Figure 1: (a) Gross showing multiple whitish nodules. (b) Microscopy showing diffuse sheets of large cells (H and E, ×20). (c) Masson's trichrome stain showing neoplasm with adjacent cirrhotic liver (MT, ×10). (d) Immunohistochemistry leukocyte common antigen diffusely positive.|
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Hepatitis C virus with amyloidosis
One case of Hepatic amyloidosis was seen in a 47-year-old female. Explant liver weighed 2.4 kg with a waxy surface [Figure 2]a. Microscopy showed deposition of amyloid noted in a globular pattern within sinusoids and focally within hepatic arteries and portal vein [Figure 2]b. The deposits were Congo red positive [Figure 2]c and showed apple-green birefringence [Figure 2]d on the polarizer.
|Figure 2: (a) Explant showing enlarged waxy liver. (b) Microscopy showing globular amyloid deposits (H and E, ×10). (c) Congo red stain positive in these deposits. (d) Apple green birefringes noted on polarizer|
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Hepatitis C virus cirrhosis with atrophy-hypertrophy complex
A 57-year-old female with a history of cholecystectomy 2 years back developed HCV-related cirrhosis. Explant liver showed marked atrophy of right lobe with associated left lobe hypertrophy [Figure 3]a. Microscopy showed florid bile ductular reaction at the hilar region [Figure 3]b around the duct profiles [Figure 3]c and [Figure 3]d. Hilar portal vein shows the presence of intraluminal fibrinous thrombus with specks of calcification.
|Figure 3: (a) Explant gross showing deformation with prominent left lobe hypertrophy. (b) Florid bile ductular reaction at porta (H and E, ×10). (c and d) Masson's trichrome stain showing florid bile ductular reaction (MT, ×10)|
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HBV-related liver disease
HBV-related liver disease constituted 15% (27/180) of total explant specimen. Age of patients ranged from 19 to 66 years with a male-to-female ratio of 6:1. Of these HCC was noted in 41% (11/27) cases. The association between HCC and HBV was found to be statistically significant with a value of P = 0.009.
HBV with Hydatid Liver Disease –There was one patient of hydatid disease of the liver with associated hepatitis B chronic liver disease. The patient was a 54-year-old male with two cysts in explant liver measuring 8.5 cm × 5.5 cm and 4.5 cm × 3.5 cm [Figure 4]a. Histology of cyst wall showed laminated membrane [Figure 4]b.
|Figure 4: (a) Explant liver large hepatic cysts. (b) Microscopy showing laminated hydatid membranes (H and E, ×10)|
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Alcohol liver disease
There were 12% (22/180) of cases of the alcoholic liver disease. Age of patients ranged from 35 to 60 years with all cases seen in males. Most cases presented with micronodular cirrhosis (20/21) and (1/21) as acute on chronic liver failure (ACLF).
Nonalcoholic steatohepatitis -related liver disease
There were 5% (9/180) cases of nonalcoholic steatohepatitis (NASH)-related cirrhosis. Age of patients ranged from 37 to 72 years with a male: female ratio of 4:1. HCC was noted in three cases of NASH-related cirrhosis.
Cryptogenic liver disease
There were 8% (15/180) cases of cryptogenic CLD. Age of patients ranged from 35 to 70 years and male: female ratio of 14: 1. HCC was found in 4/15 patients.
HVOTO constituted 3% (6/180) cases of total explant specimen studied. HCC was noted in one case. Age of patients ranged from 10 to 55 years with a male: female ratio of 3:3. Most cases show block of 2–3 major hepatic veins. Slicing of the liver in most of these explants showed more congestion of right lobe as compared to left lobe [Figure 5]a. Major hepatic veins mainly right were occluded in all cases. Accessory vein noted adjacent to middle hepatic vein in four cases. Microscopy showed near total to complete occlusion of major hepatic veins. Liver parenchymal tissue show reversal of zonation and central–central bridging fibrosis and thinning of hepatocyte cords [Figure 5]b. Cirrhosis noted in one 55-year-old male. One case in 38-year-old female showed associated HCC in explant liver.
|Figure 5: (a) Gross showing nutmeg appearance on slices of liver explant with greater congestion in right lobe. (b) Microscopy showing perivenular congestion (H and E, ×10)|
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There were 2.7% (5/180) cases of Wilson's disease associated CLD. Age of patients ranged from 9 to 21 years with all cases seen in males. Four cases presented with cirrhosis and one case in a 21-year-old male presented with ACLF.
Primary biliary cirrhosis
There were two cases of primary biliary cirrhosis in 47 and 48-year-old female. Explant liver specimen in both had greenish coarsely nodular external surface [Figure 6]a. The cut surface showed mixed cirrhotic nodules. Microscopy showed biliary cirrhosis with perinodular halo. Bile ducts were absent in septae with fibrous tissue laying down as highlighted by immunostains CK7 and Ck19 [Figure 6]b,[Figure 6]c,[Figure 6]d.
|Figure 6: (a) Explant showing greenish nodular liver. (b) Microscopy showing absence of bile duct (H and E, ×10). (c and d) Immunohistochemistry CK7 and CK19 showing absence of bile duct|
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Progressive familial intrahepatic cholestasis
There were two cases of progressive familial intrahepatic cholestasis-related CLD. Age of patients were 2 and 10 years with a male: female ratio of 1:1. Explant of 2-year-old had a smooth greenish cut surface with a soft whitish mass in right lobe measuring 1.5 cm × 1.5 cm × 1.4 cm [Figure 7]a. Microscopy from mass revealed a neoplasm composed of cells in sheets and macrotrabeculae with round vesicular nuclei and scanty basophilic cytoplasm [Figure 7]b. Foci of extramedullary hematopoiesis noted. Neoplastic cells were alpha-fetoprotein positive [Figure 7]c. Adjacent liver showed prominent cholestasis, mild bile ductular reaction, and bridging fibrosis on Masson's trichrome [Figure 7]d.
|Figure 7: (a) Explant showing whitish nodular mass in cholestatic liver. (b) Microscopy showing neoplastic cells in sheets and macrotrabeculae (H and E, ×10). (c) Immunohistochemistry alpha-fetoprotein diffusely positive in neoplastic cells. (d) Adjacent liver tissue showing bridging fibrosis (MT, ×10)|
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There were 2.2% (4/180) cases of autoimmune CLD. Age of patients ranged from 43- to 63-year-old with a male:female ratio of 1:3. Three cases showed cirrhosis with one case showing features of ACLF. One case of autoimmune-associated cirrhosis showed foci of calcification within the portal tracts indicative of healed schistosomiasis [Figure 8]a,[Figure 8]b,[Figure 8]c,[Figure 8]d Patient had a history of swimming in pools frequently.
|Figure 8: (a and b) Microscopy showing globules of calcification. (c and d) Masson's trichrome stain showing dense deposits|
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Primary sclerosing cholangitis
There were three cases of Sclerosing cholangitis with one case being undergone retransplant for PSC. Age of patient ranged from 46 to 59 with a male:female ratio of 2:1. There was a single case of retransplant for PSC in a 46-year-old female who underwent repeated ERCP for it, but without relief and finally, retransplant was performed [Figure 9]a and [Figure 9]b. There was also the presence of traumatic neuroma at the porta hepatis with bile infarcts [Figure 9]c and [Figure 9]d.
|Figure 9: (a and b) Retransplant specimen showing globular liver with cholestatic cut surface. (c and d) Microscopy showing bile infarcts and proliferated nerve fibres (H and E, ×10)|
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Combined HCV- and HBV-associated CLD
Seen in 2.2 (4/180) cases, the age of patient ranged from 41 to 54 years with all cases seen in males. One patient had associated HCC.
There was one case of Echinococcus multilocularis. The patient was 24-year-old female resident of Kyrgyzstan in Central Asia. She had two large lesions with creamish yellow cut surface and central areas of cystic degeneration. One in the right lobe measures 11 cm × 11 cm × 7 cm and another in the left lobe measures 8 cm × 6.5 cm × 5.5 cm [Figure 10]a and [Figure 10]b. Histology shows abundant granulomatous reaction around the laminated periodic acid–Schiff (PAS) positive parasitic membranes [Figure 10]c and [Figure 10]d. There are areas of coagulative necrosis with PAS-positive laminated membranes. The parasitic membranes are seen infiltrating the large nerve bundles [Figure 10]e and [Figure 10]f.
|Figure 10: (a and b) Explant showing two large masses. (c and d) Microscopy showing eosinophilic membranous deposits which are periodic acid–Schiff positive (H and E, ×10, periodic acid–Schiff, ×10). (e and f) Periodic acid–Schiff stain showing nerve infiltration by parasite. (e) IHC S100 showing similar findings (f)|
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Congenital hepatic fibrosis
There was one case of congenital hepatic fibrosis (CHF) in a 33-year-old male who underwent combined liver and kidney transplant. The patient was diagnosed with cirrhosis based on biopsy findings, which were performed outside. Explant liver showed features of the smooth shiny external surface [Figure 11]a and [Figure 11]b of CHF with ductal plate malformation [Figure 11]c and [Figure 11]d.
|Figure 11: (a and b) Explant showing enlarged liver with smooth shiny surface. (c) Bland fibrous bands with associated ductal plate malformation (H and E, ×10, MT, ×10)|
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A 9-year-old female explant liver showed hypertrophied left lobe with micro gallbladder [Figure 12]a and [Figure 12]b. Histology shows biliary cirrhosis with prominent bile ductular reaction and moderate-to-severe steatosis. The ductules are dilated with lumen contain pink to light orange masses (concretion) [Figure 12]c and [Figure 12]d.
|Figure 12: (a and b) Explant showing nodular liver. (c) Microscopy showing biliary concretions (H and E, ×10). (d) Masson's trichrome stain highlighting biliary fibrosis (MT, ×10)|
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There was one case of primary hyperoxaluria in a 23-year-old male. The patient underwent combined liver–kidney transplant. Explant liver showed smooth, shiny brownish external surface. Microscopy appears largely unremarkable.
Metabolic liver disease? Tyrosinemia
There was one case of metabolic liver disease - Tyrosinemia in a 2-year-old male. Explant liver showed mixed cirrhosis [Figure 13]a and [Figure 13]b. Histology of liver showed hepatocytes with the granular material in the cytoplasm [Figure 13]c and [Figure 13]d.
|Figure 13: (a and b) Explant showing macronodular liver. (c and d) Microscopy showing cirrhotic liver with granular hepatocytes (H and E, ×10)|
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Extrahepatic biliary atresia
There was one case of liver cirrhosis post-Kasai's operation for EHBA in a 1-year-old male. The liver showed micronodular cirrhosis with nodules ranging from 0.1 to 0.3 cm in diameter [Figure 14]a. Section show expanded tracts with edema, bile ductular reaction, and hypertrophy of hepatic artery [Figure 14]b.
|Figure 14: (a) Explant showing micronodular cirrhosis. (b) Microscopy showing expanded tracts with edema, bile ductular reaction and ductal plate malformations (H and E, ×10)|
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Overall explant liver pathology analysis helped in identifying a case of lymphoma in HCV-related cirrhosis. The nodules were preoperatively considered as macroregenerative nodules (MRN's). In another case of HCV CLD, amyloidosis was identified as additional comorbidity. A case of autoimmune hepatitis was identified based on explant liver pathology.
Etiopathogenesis of cirrhosis
Maximum cases of explants 97.2% (175/180) were performed for cirrhosis either compensated or decompensated. Most common etiology for cirrhosis was found to be HCV CLD (40%) cases followed by HBV (15%) and alcoholic (12%).
Etiopathogenesis of hepatocellular carcinoma
HCC –The distribution of HCC among various etiologies is discussed in [Table 2]. Maximum percentage of HCC was seen in cases of HBV and the association was found to be statistically significant with a P #60; 0.009. Association of HCC with HCV/NASH/HVOTO was not found to be statistically significant with a P value of 0.20, 0.40, and 1.0, respectively.
Association of hepatocellular carcinoma with macroregenerative nodule or dysplastic nodules
Abnormal nodules identified in the liver include 39 (21.6%) cases of HCC, 24 (13.3%) cases of MRN, 21 (11.6%) cases of dysplastic nodules, and 25 (13.8%) cases of necrotic nodules [Table 3]. Several cases of HCC were identified on explant pathology. In cases of HBV mostly multicentric nodules were noted with few being missed on radiology. Most cases (75%) of MRN are seen in HCV-related cirrhosis with only three cases having associated HCC. The association of MRN was not found to be significantly associated with HCC with a P value of 0.24. Of 20 dysplastic nodules, 18 were low-grade dysplastic nodules and two high-grade dysplastic nodules. 17/20 cases have associated HCC. The association between dysplastic nodules and HCC was found to be statistically significant with a P value of <0.001. No dysplastic changes were noted in any of the necrotic nodules identified.
| Discussion|| |
This study aimed to describe submitted explant liver pathology to a tertiary care center in India in an effort to provide insight on the prevalence of explant liver pathology among the South Asian population and to compare these to global reports. The population base for this study was mainly Pakistan, Middle East, separated Russian countries, and India.
The results showed cirrhosis as most common explant liver pathology. In this study, the most commonly encountered etiology of cirrhosis was HCV CLD followed by HBV and alcohol. This is the first comprehensive study to report the prevalence of explant pathology in India.
Studies from Malaysia and Japan stated hepatitis B as the most common etiological factor for cirrhosis.,, Our series on previous 50 explants also showed HCV as the most common postulated cause of cirrhosis. Silva et al. also showed similar findings from African subcontinent. Multicenter studies from Mexico have postulated alcohol as the most common etiology for liver disease.
The etiological association between HBV and HCC was found to be statistically significant with a P #60; 0.009. HBV has been implicated as a major cause of HCC. The results are in concordance with most series published earlier emphasizing the etiological role of HBV in causing HCC.,,
The association of macroregenerative nodules with HCC was not found to be significant. Dysplastic nodules were significantly found to be associated with HCC. Various other authors have reported the association of dysplastic nodules with HCC previously. Silva et al. also found a similar association between MRN and dysplastic nodules with HCC. Other groups have postulated the possible role of MRN in hepatic carcinogenesis.,,
Necrotic nodules in concordance with previous studies no dysplastic changes were noted in any of the necrotic nodules. Most of these nodules are seen in cases of alcoholics and HCV CLD.
Nerve infiltrating E. multilocularis have not been reported previously. In our case, the parasite was seen infiltrating the nerve fibers as was also highlighted by immunostains. The findings indicate the tumorous nature of these parasites. Scattered case reports of lymphovascular invasion by Echinococcus have been reported previously in the literature.,
Association between HCV and PHL has been found in several case reports and case series on a smaller group of patients. The possible role of HCV causing clonal B cell proliferation has been reported. Similar association in our patient may give way for further research studies in this direction.,
Steatohepititic carcinomas as a recently described type of HCC usually seen in cases of metabolic syndrome, HCV and rarely in other etiologies. We report cases of SH-HCC in association with HCV CLD.
| Conclusion|| |
The study of the morphological spectrum of explant liver pathology will aid in better understanding of hepatic pathologies in this part of the world. The association of dysplastic nodules with HCC has been reported in several series across different groups of the population.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12], [Figure 13], [Figure 14]
[Table 1], [Table 2], [Table 3]