Hypertensive disorders in pregnancy complicated by liver rupture or hematoma: a systematic review of 391 reported cases

SHRP is an exceedingly rare complication of pregnancy. Probably it is underreported due to high maternal and fetal mortality. Preeclampsia and HELLP syndrome are common in young primigravid women, while multiparous and older preeclamptic women are at higher risk of SHRP [7]. The reported incidence of SHRP is between 1/45,000 and 1/225,000 overall deliveries, whereas the incidence of SHRP in patients with HELLP syndrome is 0.4–1.8 % [8, 9]. The exact pathophysiology of SHRP is not entirely understood. Liver histology shows periportal hemorrhage and intravascular fibrin deposition. This can lead to hepatic sinusoidal obstruction, intrahepatic vascular congestion, and hepatic ischemia/infarction. Intraparenchymal and subcapsular hemorrhages may result in capsular rupture [10]. Thrombocytopenia from HELLP syndrome further enhances (uncontrolled) liver hemorrhage enhancing the risk of coagulopathy [11], making a vicious cycle.

We did not compare our results with previous reviews because these had fewer cases collected. Darby et al., in 2013, analyzed the relation of classes of HELLP syndrome with hepatic rupture and included ‘’only’’ 87 cases [12]. Vigil-de Gracia and Ortega-Paz, from 2012, collected ‘’only’’ 163 cases [13], while we have collected 391. Also, they have concentrated on the relation of HELLP syndrome, SHRP and mortality in general. We tried to extract more specific interrelations. Two recent reviews collected cases from 2000. One had 93 [11], while the other had 35 cases [14]. All these reviews had no definitive conclusions.

In our review, almost all patients presented in the third trimester or early postpartum. Most women had preeclampsia, and most women with SHRP had HELLP syndrome. This interrelation of SHRP and HELLP syndrome could be inaccurate due to variable definitions used. More women with HELLP syndrome survived. One of the reasons may be the severity of diagnosis with immediate antenatal care leading to earlier recognition of complications. Association with preeclampsia/eclampsia or HELLP syndrome is very high, almost a prerequisite for SHRP. Higher percentages of preeclampsia/eclampsia were diagnosed before 1990, while after 1990, HELLP syndrome was almost universal. This is probably due to more accurate diagnostics of HELLP syndrome. HELLP Class 2 was most common with SHRP, although SHRP can occur in all classes of HELLP syndrome.

There is a wide variation of the clinical presentations and the severity of symptoms and signs of SHRP. Some present with very mild symptoms before the sudden and massive circulatory collapse. The upper abdominal pain was the most frequent (83.3%), followed by hemodynamic instability (62.4%), nausea/vomiting (24.5%), and shoulder pain (13.2%). Almost half (46.1%) of patients had at least one, 34.5% at least two, and 6.5% at least three symptoms or signs. However, 12.9% of women were asymptomatic. Therefore, a lack of specific symptoms or signs leads to diagnostic dilemmas and delays in definitive diagnosis and management.

Most hemodynamically unstable women (majority with liver rupture) or those who developed eclampsia died. Both conditions were the only predictors of mortality. Also, these conditions remain frequent in both analyzed periods. Over 96% of hemodynamically unstable women died in both periods. Hemodynamic instability is highly lethal despite modern diagnostics and treatment options. Less than 10% become hemodynamically unstable more than 24 hours from delivery. Hemodynamical instability was not associated with the difference in number or liver lobe involvement. Fetal mortality was associated with the same conditions, or to be more precise, it is associated with maternal mortality. Fetal survival rises with gestational age.

Most pregnancies were completed by CS, with a higher incidence in the second period (53.3% vs. 81.2%). The higher incidence of CS in the second period resulted from the earlier use and more accurate diagnostic modalities, while the fetus was still alive. Also, better interdisciplinary support, more primiparous women, advancements in obstetrics, intrapartum monitoring, and neonatal care during the last decades lead to successful CS and fetal outcomes. A relatively high rate of vaginal delivery results from intrapartum or postpartum SHRP. Increased intra-abdominal pressure during vaginal delivery, sometimes accompanied with Kristeller’s maneuver (forbidden after 2007), can result in SHRP.

Imaging modalities were more frequent during the second period. During the first period, the diagnosis was made mainly by laparotomy (62.2%), while the second period had an equal ratio of surgical and radiological diagnoses (ultrasound 22.7%, CT 13.3%, and combined 12.7%).

Maternal hemodynamic status dictates the diagnostic protocol. Extended focused abdominal sonography for trauma (E-FAST) immediately detects free intra-abdominal fluid. However, an abdominal ultrasound may be false-negative due to clotted blood or suboptimal quality views [15]. CT with iv. contrast is the gold standard in hemodynamically stable or stabilized patients (Fig. 3) [16]. Selective angiography can identify the bleeding site and stop the active hemorrhage [17, 18].

Fig. 3figure 3

Therapeutic algorithm for spontaneous hepatic rupture in pregnancy

Preeclampsia was more common in the first period and HELLP syndrome in the second. Although HELLP syndrome is associated with higher mortality, due to more frequent use of diagnostic imaging, efficient modern treatment options, and advancements in intensive care, mortality was lower in the second period. This is confirmed by fewer hemodynamically unstable women in the second period.

Compared to the first period, maternal and fetal mortality after 1990 was 20% and 23.6% lower, respectively. Better survival could be partly explained by early imaging with correct diagnosis and adequate early intervention before the fetus died from maternal hemorrhagic shock.

The appropriate management varied from conservative with supportive therapy to surgical treatment with supportive therapy. Surgical options included liver packing, omental patch, hepatic artery ligation or percutaneous embolization, and liver transplantation. Liver packing was the most frequent, followed by hepatorrhaphy/omentoplasty, hepatic artery ligation, and liver resection. Laparoscopy was never used. However, those procedures did not influence maternal survival. Liver packing was sometimes combined with other procedures depending on the surgeon's preferences/skills, so it is difficult to evaluate the effectiveness of these treatment options and strategies for SHRP (Fig. 3).

Percutaneous hepatic artery embolization, a procedure increasingly used after 1990 [19], increases maternal survival, resulting in maternal mortality of 3.0%. The bias could be that stable patients underwent embolization while hemodynamically unstable were operated. Unfortunately, hepatic artery embolization was performed mainly in tertiary centers, so surgery was still the first option in many cases.

Factor VIIa was not analyzed in our review due to a small number of cases where its use was noted. It has been successfully used in several patients as an adjunct measure to main treatment for bleeding control [11], such as completed hepatic artery embolization with concomitant use of Factor VIIa [14]. Failure of conventional therapies and intolerability of massive blood transfusions are the circumstances where Factor VIIa may be considered although nonavailability, high cost, and risk of thromboembolism confine its use [11].

The only published article with an algorithm [20] is obsolete. In the meantime, many treatment options for SHRP during pregnancy were implemented, aside from surgical treatment. Guided by the WSES guidelines for liver trauma in the general population [16] and our results, we proposed an algorithm for SHRP in pregnancy (Fig. 1). Nonoperative management should be the initial treatment of hemodynamically stable patients with a subcapsular liver hematoma confirmed by a CT with iv. contrast. Monitoring in the intensive care unit with serial clinical examinations and laboratory testing is mandatory to detect further bleeding. Angiography with hepatic artery embolization may be a first-line intervention in hemodynamically stable patients with an arterial blush on CT. It results in a high bleeding control rate and high maternal survival.

Hemodynamically unstable and nonresponders to nonoperative management should undergo surgical exploration. The primary goal is the control of hemorrhage and bile leak and damage control resuscitation. Without major bleeding, digital compression with gauze, the use of electrocautery, bipolar devices, argon beam coagulation, topical hemostatic agents, simple suture of the hepatic parenchyma, or omental patching may stop the bleeding [16]. In cases of major hemorrhage, aggressive procedures include manual compression and hepatic packing, ligation of vessels, balloon tamponade, shunting procedures, or hepatic vascular isolation and exclusion [21]. Techniques vary significantly, especially between high- and low-income countries, leading to different mortality rates and trends in mortality. Major hepatic resections should be avoided during the initial operation. Resections should be considered in subsequent operations as a “resectional debridement” of large areas of devitalized liver done by a hepatobiliary surgeon.

’The final option for the successful treatment and maternal survival was liver transplantation. Most cases had a bilobar liver rupture or necrosis or complete right lobe rupture that extended to the left liver lobe, found at a series of laparotomies due to unsuccessful repeated liver packing. In the advanced stage, commonly only the left lateral liver segment appeared macroscopically normal. Most cases presented during or immediately after delivery. In one scenario, the most common surgical management included several laparotomies with unsuccessful liver packings with the addition of other unsuccessful hemostatic surgical techniques or liver resections. The other scenario included again one or more (un)successful liver packing, but the main indication for liver transplantation was not uncontrollable bleeding but irreversible or progressive liver failure. In both scenarios, the best strategy was to put a patient in Status One (high priority for the liver) of the liver transplant program in the early phase of the SHRP. In more fulminant cases, total hepatectomy was performed due to uncontrollable bleeding or liver failure with complete liver destruction along with multiorgan failure. The only option was to enroll a patient on the emergent liver transplant list as Status One priority and complete the operation with a temporary portacaval shunt until the receipt of the liver. In all cases, the anhepatic phase was less than 20 hours, and all patients survived.

Although the algorithm we propose is based on results, it is not binding, nor are the recommendations of many medical professional societies. The decision to terminate the pregnancy should be made in agreement with the informed patient, taking into account the ethical norms and rights of the patient.

Strengths and limitations

The main strength of this study is the most extensive worldwide collection of SHRP during pregnancy. Limitations include nonstructured case descriptions and retrospective design. Some risk factors might be present but were not reported or measured. Therefore, the most important risk factor in our study, HELLP syndrome, could be falsely lower in the first period analyzed (before the year 1990), resulting in inaccurate comparison and conclusions. Accurate maternal and fetal survival rates are unmeasurable because many fatal cases are probably not published. The next issue is the accurate definition of the antepartum or postpartum SHRP. In some patients with preterm delivery, the diagnosis is made postpartum, but the rupture occurred in pregnancy or delivery, not puerperium although recognized in the puerperium. In this regard, the number of claimed cases during the puerperium could be objectively smaller. Also, SHRP detected during or after emergent CS is not always postpartum. Moreover, it is difficult to determine the exact times of the vital sign and laboratory measurements or imaging diagnostics for each case to make a particular conclusion.

In women with no symptoms reported, the question is whether these were hemodynamically unstable and therefore incapable of communicating and was the medical history adequate. Regarding the latter, there is a concern of whether these clinical presentations were objectively recorded. Nevertheless, the number of cases with missing data was not significant. Also, most patients had hypertensive disease as the cause of SHRP. Unfortunately, many of them had their last blood pressure measured before rupture. Therefore, the values do not correlate with blood pressure values that developed during rupture. Finally, the objective correlates of blood pressures and outcomes cannot be made. Also, there are no data about adjunct therapy for minimizing postoperative or postprocedural complications. For example, iv. magnesium can lower maternal blood pressure and also serve as a tocolytic. In HELLP syndrome management, dexamethasone is often used for fetal respiratory distress syndrome prophylaxis, but it is unclear whether it can reduce postoperative or postprocedural bleeding, minimizing surgical reinterventions.

Conclusions and implications

This systematic review provided the most extensive findings on SHRP with the largest collection of patients. Hepatic involvement in patients with preeclampsia or HELLP syndrome is a life-threatening complication of pregnancy. Due to increased awareness, better diagnostic imaging, early fetal monitoring, and fetal and maternal supportive care, mortality has been reduced since the first described cases in the past century. Due to its rarity, most obstetricians are still not familiar with the SHRP. Patients with severe preeclampsia, eclampsia, or HELLP syndrome should be closely observed and treated to prevent such complications. Patients with hepatic involvement should be transferred to tertiary centers prepared for maternal/fetal complications. In cases with SHRP, a multidisciplinary approach provides the best outcome. Protocols should be determined for treating patients with hepatic involvement in pregnancy to prevent catastrophic complications.

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