Abstract
Background and aims
Hepatic infarcts are uncommon vascular lesions due to dual vascular supply of the liver characterized by the peripherally-located wedge-shaped large zones of necrosis in the hepatic parenchyma. They are commonly seen as a complication of liver transplant.
Material and methods
The cases of hepatic infarcts of the native liver detected in medical autopsies were searched in the archives and their clinical, biochemical, gross, and histomorphological details were retrieved.
Results
Three cases of hepatic infarct of the native liver were detected from among 1865 consecutive cases of adult and pediatric autopsies (0.2%). These cases were caused by hornet stings, acute pancreatitis, and hemolysis, elevated liver enzymes, low platelet syndrome (HELLP) in a 24-year-old male, 19-year-old male, and a 28-year-old postpartum female, respectively. The first two cases showed 50–150 times elevated transaminases and conjugated hyperbilirubinemia. All cases showed hyperemic to pale subcapsular infarcts. The HELLP syndrome case showed intrasinusoidal fibrin-rich microthrombi, while the other two cases showed the presence of fibrin-rich/organized microthrombi involving variable-sized portal and central venous radicles. Two of these cases (hornet sting and HELLP syndrome) did not show any macroscopic thrombi in the portal vein, hepatic artery, or hepatic veins.
Conclusion
Hepatic infarcts are rare vascular lesions found in the nontransplant liver. The gross and histomorphology of these lesions depend on the age of these lesions. They can occur in the presence of vascular microthrombi in the absence of any documented macroscopic thrombus.
Keywords: Hepatic infarct, hornet sting, HELLP syndrome, acute pancreatitis
Hepatic infarcts are uncommon vascular lesions of the liver. These lesions are usually peripherally located and wedge-shaped. They are uncommon due to the vascular protection of the liver by its dual vascular supply and complex intrahepatic microcirculation. Hepatic arterial occlusion following liver transplants is the most common cause of hepatic infarct in the modern era.1 Other iatrogenic causes, especially trans-arterial chemoembolization (TACE) for the treatment of hepatocellular carcinoma are also seen in a few cases.1 In contrast, various uncommon causes of hepatic infarcts can be found in the autopsies. The cases of hepatic infarcts of the native liver detected in medical autopsies were searched in the archives and their clinical, biochemical, gross, and histomorphological details were retrieved.
Materials and methods
The departmental archives were screened for the cases of hepatic infarcts, and three cases were found among 1865 consecutive adult and pediatric autopsies (0.2%). The clinical features of these cases along with the gross morphology and histomorphology of the liver were reviewed.
Approximately 15 slides of liver were examined per case (range 12–18), including sections from the lesional and nonlesional areas. The sections were stained with routine hematoxylin and eosin stains, and the relevant sections were stained with various special stains, including Masson trichrome, reticulin, orcein, rhodanine, diastase-PAS, Perls, Martius scarlet blue, and elastic van Gieson. CK7 immunostain (Cell marque, OV-TL 12/30, Mouse Monoclonal Antibody, 1:300 dilution) was performed in all cases.
Case discussion
Three cases of hepatic infarcts were found. The details of these cases are discussed below.
Case 1
A 24-year-old young male individual presented with severe pain, redness, and swelling of the face, bilateral upper limbs, and lower limbs, following multiple (∼30–35) hornet stings (diagnosed as hornets following the description of the species and their nests by the patient and onlookers). These local changes were associated with abdominal pain and frequent vomiting followed by an episode of hematemesis and passage of cola-colored urine without any decrease in urine output. He was referred to our institute by a local hospital. His hematological and biochemical parameters at admission are depicted in Table 1. His peripheral blood smear showed mild anisopoikilocytosis and <1% schistocytes. His urinalysis was positive for myoglobin and RBCs. The upper GI endoscopy showed two linear esophago-gastric ulcers (Forrest class 1B). The electrocardiogram was normal, although the bedside echocardiogram showed global left ventricular hypokinesia with an ejection fraction of 25%. Abdominal ultrasonography (USG) did not reveal any hepatic infarct, though the clinical presentation and the biochemical profile highlighted an ischemic hepatitis.
Table 1.
Various Clinical, Hematological, and Biochemical Parameters of all Three Cases at Admission.
| Parameters (Normal range) | Case 1 | Case 2 | Case 3 (post-LSCS) |
|---|---|---|---|
| Age/sex | 24/M | 19/M | 28/F |
| Hemoglobin (12-14 gm/dl) | 10.5 → 5.4 | 10.1 | 10.6 |
| Total leukocyte count (4000–11000/μl) | 32,100 → 35,200 | 19,200 | 8500 |
| Platelet (1,50,000–4,50,000/μL) | 57,000 → 48,000 | 78,000 | 59,000 |
| PT/aPTT/INR (11–13.5 s/25–35 s/0.8–1.1) | 17.3/>120/1.65 | 14.5/21.5/1.2 | NP |
| Fibrinogen (2.0–4.0 g/L) | 3.1 | 3.2 | NP |
| D-dimer (220–500 ng/mL) | 859 | 27,894 | NP |
| Urea (10–50 mg/dL) | 151 | 92 | 50 |
| Creatinine (0.5–1.2 mg/dL) | 5.9 | 6.4 | 1.8 |
| Sodium (135–145 mEq/L) | 136 | 133 | NP |
| Potassium (3.6–5.2 mmol/L) | 6.6 | 5.7 | NP |
| Total bilirubin (0.1–1.2 mg/dL) | 16.4 | 4.64 | NP |
| Direct bilirubin (<0.3 mg/dL) | 8.6 | 3.4 | NP |
| AST (2–40 U/L) | 6620 | 4110 | 83 (pre-LSCS) |
| ALT (2–41 U/L) | 2230 | 3280 | 124 (pre-LSCS) |
| ALP (42–128 IU/L) | 155 | 134 | 198 (pre-LSCS) |
| Total protein (6.4–8.3 g/dL) | 4.2 | 5.6 | NP |
| Albumin (3.4–4.8 g/dL) | 3.1 | 3.45 | NP |
| Amylase (30–110 U/L) | 457 | 2207 | NP |
| Lipase (0–160 U/L) | 270 | 2778 | NP |
| CKNAC (10–120 μg/L) | 11,087 | NP | NP |
| LDH (140–280 U/L) | 555 | 2256 | NP |
| Trop T (≤22 ng/L) | 3343 | 204 | NP |
| Pro-BNP (<125 pg/mL) | 124,964 | 20,702 | NP |
ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; aPTT: activated partial thromboplastin time; AST: Aspartate aminotransferase; BNP: Brain natriuretic peptide; CKNAC: Creatine kinase with N-acetylcysteine; INR: International normalized ratio; LDH: Lactate dehydrogenase; LSCS: Lower segment caesarean section; NP: Not performed; PT: Prothrombin time.
The individual succumbed on the 3rd day of his admission with the diagnosis of hornet sting-related multiorgan dysfunction syndrome (MODS) despite receiving standard hemodialysis followed by sustained low-efficiency dialysis (SLED), antihyperkalemic measures along with intravenous fluids, mechanical ventilation with lung-protective ventilation, infusion of proton pump inhibitors, and packed RBCs followed by hemoclip application over the ulcers and achievement of hemostasis, N-acetyl cysteine infusion, and broad-spectrum antibiotics.
A complete autopsy following his demise showed a soft to firm bile-stained liver weighing 1500 gm. The capsular surface was smooth. There was no nodularity of the surface. The extrahepatic biliary tree, portal veins, and the hepatic veins were patent and normal. The cut surface showed an occasional vague and ill-defined subcapsular area obscured by the diffuse biliary staining of the liver (Figure 1a). This pale-yellow subcapsular area was more sharply demarcated in histomorphology due to the presence of coagulative necrosis of the hepatocytes giving rise to a contrasting pale eosinophilic tinctorial character of the infarcted zone compared to the viable area with deeper eosinophilia (Figures 1b-1c). This wedge-shaped peripheral area of infarct did not show any peripheral zone of hyperemia and had multiacinar and panacinar confluent hepatocellular coagulative-type of necrosis. The periportal areas were relatively spared, and there was occasional centrilobular reticulin condensation within the infarcted zone (Figure 1d). The relative lack of reticulin collapse and hyperemic margin suggested a relatively recent-onset hepatic infarct. Multiple adjacent central venous and portal venous radicles showed fibrin-rich thrombi, highlighted by the Martius scarlet blue stain (Figures 1e–1f). No intrasinusoidal thrombi were identified. The rest of the hepatic parenchyma showed multiacinar confluent centrilobular ischemic necrosis with reticulin collapse and cholestasis.
Figure 1.
Gross morphology and histopathology of Case 1: The slice of the liver showed bile-stained cut surface with barely discernible infarct (a); the hepatic infarct (thick white arrow) highlighted by a pale subcapsular geographic zone (b, Hematoxylin and eosin, 40x) (c, Masson trichrome, 40x); occasional perivenular zone showed reticulin collapse (d, Reticulin, 200x); fibrin thrombi (black arrowhead) within the portal (e) and central venous radicles (f) (Martius scarlet blue, 200x).
Thus, the liver showed hepatic infarct in its acute stage in the background of centrizonal hemorrhagic necrosis as a complication of toxin-mediated injury. The rest of the organs at autopsy showed a local sting reaction in the form of epidermal and dermal necrosis with panniculitis and vasculopathy, and systemic features of toxin-mediated injury in the form of necrotizing rhabdomyopathy, cardiac microinfarcts, acute necrotizing pancreatitis, glottic and epiglottic edema, and subarachnoid hemorrhage. This was further complicated by pigment cast nephropathy resulting from rhabdomyolysis, acute tubulointerstitial nephritis, and severe acute tubular injury along with bronchopneumonia.
Case 2
A 19-year-old adolescent obese (BMI: 34 kg/m2) male individual presented with sudden onset of severe abdominal pain with distension for one day. The pain was epigastric in location, severe in intensity, and radiated to the back. It was associated with generalized distension, obstipation, multiple episodes of non-projectile, non-bilious, non-bloody vomiting, and reduced urine output. His hematological and biochemical parameters at admission are depicted in Table 1. Noncontrast computed tomography (NCCT) abdomen revealed acute necrotizing pancreatitis with peripancreatic collections, hepatosplenomegaly with hepatic steatosis, and left mild pleural effusion with mild ascites. Biphasic contrast enhanced CT (CECT) highlighted portal vein, superior mesenteric vein, and splenic vein thrombosis along with ill-defined hypodense areas of the liver. Ultrasonography did not reveal any gallstone or parathyroid adenoma. The upper GI endoscopy showed multiple linear superficial erosions in the esophagus with sloughed off black-colored mucosa. The urine microscopic examination showed 2+ proteinuria and 2+ hematuria and grew yeast. There was growth of Acinetobacter baumannii and yeast in the blood culture. Serum Anti-nuclear antibody (ANA) and Anti-neutrophil cytoplasmic antibody (ANCA) were negative.
Autopsy showed multiple subcapsular well-defined wedge-shaped pale zones of hepatic infarcts variably rimmed by darker ill-defined zones of hyperemia in the right lobe of the liver (Figure 2a). The liver weighed 1640 gms and showed a smooth capsular and cut surface. It was firm to feel and had pale-yellow to pale-green mottled cut surface. The portal vein, hepatic vein, and the extrahepatic biliary tree at the time of autopsy were patent. Histopathology of the liver revealed diffuse macrovesicular steatosis of the liver without any evidence of steatohepatitic/steatofibrotic changes in the form of ballooning, Mallory hyaline, or perivenular/pericellular fibrosis. The portal tracts did not reveal any significant fibrosis, inflammation, interface activity, plasmacytosis, or cholangiopathy. There were multiple hepatic infarcts highlighted by large areas of multiacinar confluent coagulative hepatocellular necrosis. These zones of necrosis were panacinar and centrilobular with periportal sparing. The periportal sparing was especially seen at the edge of the infarct while the central part of the infarct appeared to have panacinar involvement (Figures 2b-2c). These areas of infarct showed reticulin condensation and variable vascular changes chiefly involving the central venous radicles/sublobular hepatic veins. Portal veins of variable size were also involved. These veins showed predominantly organized thrombi with/without recanalization along with occasional fibrin-rich thrombi (Figures 2d-2e). A few veins also showed the presence of steatotic droplets in the proliferated intima or within their lumina (Figure 2f). Moderate ductular reaction around the zones of necrosis and in the portal tracts and ductular cholestasis was also seen.
Figure 2.
Gross morphology and histopathology of Case 2: Gross morphology of hepatic infarct (black arrow), pale yellow in color bordered by erythema (a); the hepatic infarct (thick white arrow) with periportal sparing and occlusive fibrin thrombi within the portal venous radicle (black arrowhead) (b, hematoxylin and eosin, 40x) (c, Masson trichrome, 20x); occlusive organized thrombi in the central venous radicle (d, Masson trichrome, 400x) and sublobular hepatic vein (e, elastic van Gieson, 200x); Presence of fat droplets within the intima of the portal vein (black star) (f, Masson trichrome, 200x).
Thus, the liver showed hepatic infarct in the background of centrizonal hemorrhagic necrosis and diffuse macrovesicular steatosis in conjunction with acute necrotizing pancreatitis (nonalcoholic fatty steato-pancreatitis) with noninfected peri-pancreatic and serosal fat necrosis, fibrocongestive spleen with splenic infarct, pulmonary thromboembolism, edema, and hemorrhage, and acute interstitial nephritis, pigment cast nephropathy, and renal vein thrombi.
Case 3
A 28-year-old G2P1001 lady presented with breathlessness and palpitation on climbing upstairs (NYHAII) at the 4th month of her pregnancy and hypertension detected at the 6th month of her pregnancy. Her hypertension was controlled by oral labetalol 200 mg three times a day. She was routinely followed up in an outside institute, and her first trimester was uncomplicated. She had a history of pre-eclampsia in the previous pregnancy requiring emergency preterm lower segment caesarean section (LSCS) at 34 + 3 weeks period of gestation that occurred seven years ago. She was hypertensive in the interconceptional period for which she was on irregular medications. She was referred to the index institute at 34 + 2 weeks as outside echocardiography suggested concentric left ventricular hypertrophy and moderate mitral regurgitation. The patient underwent emergency LSCS on her third day of admission as she developed increased blood pressure and headache. She developed palpitations 10 h post-LSCS and abdominal distension with dyspnea, hypotension (blood pressure 84/56 mm of Hg), and tachycardia (pulse rate 110/min) with decrease in the urine output at 20 h post-LSCS. Her post-LSCS hematological and biochemical parameters are depicted in Table 1. Patient was managed with a propped-up position, intubation, and intravenous fluids. However, the patient developed multiple cardiac arrests in the following hours and could not be resuscitated. She was declared dead at 27 h post-LSCS.
The liver at the time of autopsy weighed 1650 gm. It showed smooth capsular surface and a firm cut surface. The cut surface showed multiple subcapsular wedge-shaped hemorrhagic infarcts involving both lobes (Figure 3a). The rest of the cut surface showed focal mottling. No capsular wrinkling, nodularity, or any mass lesion was identified. The portal vein (Figure 3b) and hepatic veins did not lodge any thrombi. The extrahepatic biliary tree was patent. Microscopy of the liver showed maintained lobular architecture. The infarcted area showed multiacinar panacinar hemorrhagic necrosis (Figures 3c-3d) with focal centrilobular sparing at places. There was no reticulin collapse at the zones of hepatic infarct. The presinusoidal portal venules and the periportal sinusoids showed abundant fibrin-rich thrombi (Figures 3e-3f) with focal endothelial swelling of the hepatic arteries. The portal veins and the central veins appeared to be normal. The portal tracts and the hepatic lobules were otherwise normal.
Figure 3.
Gross morphology and histopathology of Case 3: Gross morphology showing Zahn-like hemorrhagic wedge-shaped infarct (black arrow) (a) and patent portal vein (white arrowhead) (b); Microscopic features of the infarcts (white arrows) highlight sinusoidal congestion (b and c, hematoxylin and eosin, 40x); multiple fibrin-thrombi in the presinusoidal portal venules and the periportal sinusoids (black arrowheads) (Martius scarlet blue) (e, 100x) (f, 200x). Also note the periportal necrosis (white arrow) with sparing of the perivenular area in e.
Thus, the liver showed hepatic infarct in its acute stage, likely as a result of eclampsia-associated endothelial injury. Other organs show acute cortical necrosis in the kidneys and adrenal hemorrhage along with pulmonary edema and diffuse alveolar damage in its early exudative phase. The heart showed concentric left ventricular hypertrophy with moderate arteriosclerotic changes of the aorta and medium-sized vessels. Table 2 highlighted the comparison and contrast of the gross and microscopic features of the hepatic infarct in all three cases.
Table 2.
Comparison and Contrast of the Gross Morphology and Histopathological Features of the Hepatic Infarct in all Three Cases.
| Parameters | Case 1 | Case 2 | Case 3 |
|---|---|---|---|
| Gross morphology | |||
| Likely etiology | Toxin-associated (hornet sting) | Acute pancreatitis and hepatic steatosis-associated | Eclampsia-associated endothelial injury |
| Weight of liver (gm) | 1500 | 1640 | 1650 |
| Location of the infarct | Subcapsular geographic (a nearly quadrangular-shaped area with map-like irregular border) | Subcapsular wedge (a triangular area with base toward the capsular surface) | Subcapsular wedge (a triangular area with base toward the capsular surface) |
| Color of the infarct | Vague, pale yellow, obscured by the background liver color | Pale yellow with hemorrhagic border | Hemorrhagic |
| Number | Single | Multiple | Multiple |
| Maximum dimension | 12 × 4 mm | 35 × 30mm (largest) | 15 × 5mm |
| Laterality | Right lobe | Right lobe | Both lobes |
| Portal vein | No thrombus | No thrombus postmortem (radiologically detected antemortem) | No thrombus |
| Hepatic veins | No thrombus | No thrombus | No thrombus |
| Background liver | Biliary mottling without nodularity | Steatotic without nodularity | Normal |
| Microscopy | |||
| Patterns and zone of necrosis | Multiacinar panacinar with periportal sparing | Multiacinar panacinar with periportal sparing | Multiacinar panacinar with focal centrilobular sparing |
| Reticulin stain | No/minimal condensation | Condensation present | No condensation |
| Portal veins | Fibrin-rich thrombi |
|
Normal (presinusoidal portal venules showed fibrin-rich thrombi) |
| Central veins | -Do- | -Do- | Normal |
| Hepatic arteries | Normal | Normal | Endotheliosis |
| Sinusoids |
|
|
|
| Size of the vessels involved | 100–400 μm | 100–1000 μm | <15 μm |
| Timeline of injury | Acute; 2–4 days | Acute-subacute; 10–14 days | Acute; 24–48 h |
| Background liver | Centrizonal hemorrhagic necrosis |
|
Normal |
Discussion
Hepatic infarct is an uncommon form of ischemic liver disease characterized by large, well-demarcated, peripherally located wedge-shaped regions of multiacinar hepatocellular necrosis. The rarity of the lesion is due to the unique blood supply of the liver described below. The large majority of cases of hepatic infarct in the modern era are detected radiologically and are the consequence of hepatic arterial occlusion following chemoembolization, liver transplant, trauma, or iatrogenic procedures. However, other uncommon causes can be detected during autopsy. We describe three uncommon causes of hepatic infarct detected during autopsy with detailed clinical profile, gross morphology, and histomorphology.
The liver has an arterial and a venous supply approximately contributing 20–30% and 70–80% of the blood flow. Therefore, the low-flow portal venous system carries the dominant amount of blood to the liver. The low-flow portal venous and high-flow systemic arterial systems show multiple intrahepatic communications (trans-sinusoidal, peribiliary, perivenous) before draining into a single hepatic venous outflow system. Besides, multiple intrahepatic and extrahepatic, subdiaphragmatic and supradiaphragmatic accessory, and collateral arteries also supply the liver and become dominant following occlusion of the hepatic artery. This dual vascular supply, complex vascular microanatomy, and well-regulated hepatic microcirculation prevent the occurrence of hepatic infarction.1,2 Thus, the occurrence of hepatic infarct may require a combinatorial circulatory compromise and the occlusion of only the hepatic artery or portal vein or hepatic vein may be insufficient to cause hepatic infarct. A few cases of hepatic infarct can occur without any obvious occlusion of the hepatic vasculature at the macro- and/or the micro-level chiefly as a consequence of global ischemia, background cardiovascular disease, septicemia, drugs, or surgical intervention.1, 2, 3 The individuals with hepatic infarct usually show a biochemical pattern of ischemic hepatitis (transaminase levels >1000 IU/L). This biochemical pattern is nonspecific indicator of hepatic infarct, which is usually detected on radiology. The index cases also showed a similar increase in the transaminases. The occurrence of collaterals was not documented in the index cases.
The hepatic infarct in the first case in the series was caused by hornet sting-associated toxins. Hornets, wasps, and yellow jackets (family: Vespoidea) belong to the order Hymenoptera along with bees (family: Apoidea), and ants (family: Formicidea).4 The hornets, wasps, yellow jackets, and bees contain numerous toxins in their sting, including various amines (histamine, serotonin, acetylcholine, apamine), peptides (melittin, mastoparan), and enzymes (phospholipase A2, hyaluronidase) in variable proportions.4,5 These vasoactive amines, peptides, and enzymes can elicit an IgE-mediated anaphylactic reaction along with local and systemic tissue destruction leading to multisystemic injury depending upon the dose of envenomation.6 The occurrence of hepatic infarct following hornet sting is not documented in the literature, although the derangement of the liver function test (elevation of serum bilirubin and transaminases) occurs in approximately 30% of cases.7 The biochemical parameters in the index case corroborate with the available literature. Although, there was no gross evidence of vascular thrombosis in the index case, the presence of fibrin-rich microthrombi in both portal and hepatic venous radicles documents the prothrombotic milieu caused by these toxins.
The second case in the index series occurred in association with acute pancreatitis. Acute pancreatitis causes local vascular stasis, mass effect due to the edema of the pancreatic parenchyma, vasospasm, and vascular endothelial injury due to the liberation of the tissue digestive/proteolytic enzymes and a proinflammatory and prothrombotic milieu.3,8 The index case also showed the presence of portal and hepatic venous microthrombi with evidence of organization along with occasional fibrin-rich microthrombi. Acute/chronic pancreatitis causes both local and systemic alterations required for the precipitation of hepatic infarct. Despite the occurrence of hepatic infarct following acute/chronic pancreatitis is limited to only a few anecdotes.1,3,8,9 The cause of acute pancreatitis in the index case is likely hyperlipidemic steato-pancreatitis. The other important and unique observation in the index case was the presence of fat globules within the hepatic vascular lumina as well as within the wall of organized hepatic microthrombi. This phenomenon can be explained by fat embolism following the ischemic injury to the hepatocytes following acute pancreatitis. Alternately, acute pancreatitis can cause fat embolism leading to mechanical obstruction of the sinusoids by the fat globules, depletion of glycogen and mitochondrial damage, and make the hepatocytes prone to oxidative injury.
The third case was caused by eclampsia and hypertension-associated endothelial injury in the immediate postpartum period. This may represent HELLP syndrome (hemolytic anemia (could not be ascertained in the index case), elevated liver enzymes (AST>70 U/L), and low platelet (<1 x 106/μL)) with fibrin-rich microthrombi in the presinusoidal portal venules and sinusoids.10 This potentially fatal complication of pregnancy often causes systemic endothelial dysfunction, precipitating disseminated intravascular coagulation. Subsequent hypoxic liver damage with hepatocellular necrosis ensues rarely portending to hepatic infarcts.1,2 Importantly, this case represents a hepatic infarct in its early form with a wedge-shaped subcapsular hemorrhagic zone. This lesion grossly mimics the description of Zahn “infarct” characterized by a sharply delineated area of hyperemia.2,11 Microscopically, Zahn “infarcts” are not true infarcts with centrilobular congestion and hepatocellular atrophy with only exceptional cases of hepatocellular necrosis.2,11 In contrast, this case shows an early stage of hepatocellular necrosis in a multiacinar and panacinar distribution. This case also shows a focal centrilobular sparing unlike the previous two cases due to portal venular, hepatic arteriolar, and sinusoidal involvement.
The hepatic infarcts in the index series showed different gross morphology. The third case (HELLP syndrome-associated) showed multiple bilobar hyperemic/dark infarcts and represents the hepatic infarct in its earliest phase. Consequently, this case did not show any significant inflammatory cell influx in the infarcted areas and showed retention of the reticulin framework. The first case (hornet sting toxin-associated) showed a single zone of infarct in the right lobe that was grossly difficult to identify, although it showed a vague pale-yellow color. The difficulty in its gross identification could be due to extensive biliary staining of the index case. Microscopically, this case showed well-demarcated zones of coagulative necrosis with foci of reticulin collapse. The second case (acute pancreatitis-associated) showed the classical gross morphology of hepatic infarct with a central area of pallor surrounded by a hyperemic zone. Microscopically, this lesion appeared to be nearly two-weeks old as there was reticulin condensation and organization of the vascular thrombi. The chronology of the hepatic infarcts in these three cases was also highlighted by the presence of fibrin-rich thrombi in the third and first case, signifying early infarct, while the second case highlighted occasional fibrin-rich thrombi along with many organized thrombi suggesting older age. Another important observation was the absence of any macro-thrombus in Case 1 and Case 3 signifying the fact that the documentation of macro-thrombus is not essential for the occurrence of hepatic infarct and microthrombi in the hepatic microcirculation are sufficient to cause hepatic infarcts. The presence of antemortem macrothrombi in Case 2 was documented radiologically. Antiphospholipid antibody (APLA) work-up was not performed in any case as it was not indicated.
Hepatic infarcts are uncommon vascular lesions of the liver. Various autopsy series had reported a frequency of 0–2% similar to our observation (0.2%). The main reason of hepatic infarct in the modern era is iatrogenic, especially as a complication of liver transplant, trans-arterial chemoembolization (TACE), various surgical interventions, and drugs.1,2 Other important causes are uncommon and include hemolysis, elevated liver enzymes, low platelet syndrome (HELLP), malignancies, pancreatitis, thromboembolism, procoagulant state, cardiovascular disorder, sepsis, and shock. In a series of 34 cases of HELLP syndrome, only one case developed hepatic infarction (approximately 3%) while hepatic infarcts following pancreatitis are anecodotal.1,3,8,9,12 The occurrence of hepatic infarction in association with hornet sting is not reported in the literature. Most liver infarcts occur due to obstruction of a branch of the hepatic artery (may occur even with acute portal vein thrombosis). Obstruction of an intra-hepatic branch of the portal vein does not, under normal circumstances, cause true infarction. Most often these would cause atrophy of hepatic cords, causing compensatory sinusoidal dilatation and congestion. This can result in the macroscopic appearance of a “red infarct” of the liver. None of the cases in the index series showed hepatic arterial occlusion though portal vein occlusion was noted in the case with acute pancreatitis. This case also showed multiple infarcts and global ischemia. The other two cases showed involvement of the small vessels (venules and/or sinusoids) along with evidence of global ischemia. Therefore, these cases highlight the occurrence of hepatic infarcts in the absence of macrovascular occlusion, provided the ischemia affects the liver globally and/or there is microvascular occlusion at multiple levels (both influx and efflux vessels).
Hepatic infarcts are usually radiologically detected by CT scan. They usually portend a poor prognosis and can be associated with fatality if not adequately managed. The index cases showed diffuse ischemic involvement of the liver as highlighted by the centrizonal necrosis of the hepatocytes with systemic manifestations of hemodynamic instability in the form of shock. Thus, these infarcts, though seemingly incidental autopsy findings, are in fact, the culmination of an ischemic hepatic injury with poor prognosis.
We report three uncommon cases of hepatic infarcts with variable etiology, clinical features, biochemical parameters, gross morphology, and histomorphology among nearly 2000 autopsy cases. This case series provides the detailed etiological, clinical, and histopathological features of hepatic infarct in the modern era at its various stages of evolution and substantiates the necessity of its identification. The prognosis in the index series is uniformly grim due to the selection of the cases from the autopsy population.
Credit authorship contribution statement
DB collected and analyzed the data and prepared the first draft of the manuscript. SM and RN were involved in the gross and histopathological analysis and diagnosis of the cases along with the evaluation of the special stains and immunohistochemistry. RN critically reviewed the manuscript. AB, SKS, VS, and AD were involvement in the clinical diagnosis and management of the cases, and critically reviewed the manuscript. SM conceptualized the idea, was involved in the final tabulation and analysis, and prepared the final draft of the manuscript.
Funding
The authors received no funds for this study.
Declaration of competing interest
The authors declare no conflict of interest.
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