www.elsevier.com/locate/jhep

Journal of Hepatology 49 (2008) 930–935

Pregnancy-associated acute liver disease and acute viral hepatitis:Differentiation, course and outcomeq

Harshad Devarbhavi1,2,*, Walter K Kremers3, Ross Dierkhising3, Lakshmi Padmanabhan4

1Department of Gastroenterology, St. John’s Medical College Hospital, Bangalore, India2William J. Von Liebig Transplant Center and Division of Gastroenterology, Department of Internal Medicine,

Mayo Clinic and Mayo Clinic College of Medicine, Rochester, MN 55905, USA3William J. Von Liebig Transplant Center and Department of Health Sciences Research, Mayo Clinic and Mayo Clinic College of Medicine,

Rochester, MN 55905, USA4Department of Obstetrics and Gynecology, St. John’s Medical College Hospital, Bangalore, India

Background/Aims: Pregnant women with acute viral hepatitis (VH) and those with pregnancy associated acute liver dis-

ease (PAALD) including acute fatty liver disease of pregnancy, hemolysis elevated liver enzyme and low platelet syndrome

present with similar clinical features and liver tests abnormalities. Accurate differentiation between the two groups is crit-ical to expedite early delivery in the latter and prevent progressive liver damage. There is scant data in the literature to

differentiate between PAALD and VH.

Methods: We studied the clinical variables, hematological, biochemical and viral serological tests of 87 consecutive preg-

nant patients with jaundice from 2000 to 2003.

Results: There were 46 and 41 patients in PAALD and VH group, respectively. Two-thirds in VH group were due to

hepatitis E. Univariate analysis identified hypertension, encephalopathy, oliguria, ascites, serum creatinine, and low plate-

lets as significantly more common in the PAALD group. Multivariate analysis and recursive partitioning identified hyper-

tension and ascites as predictors of PAALD with excellent predictive ability and c value of 0.92. Mortality was 41% inPAALD and 7.5% in VH. Increased bilirubin and oliguria were predictors of mortality in PAALD.

Conclusions: Presence of ascites and hypertension differentiates PAALD from VH and should prompt early delivery.

Mortality due to hepatitis E is low.

� 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Keywords: Preeclampsia; Liver failure; Ascites; Hypertension; HELLP; Hepatitis E

1. Introduction

Liver test abnormalities and jaundice are rare in preg-nant women and are seen in 0.3–3% of pregnancies [1,2].A majority of them are either due to pregnancy-associ-

0168-8278/$34.00 � 2008 European Association for the Study of the Liver.

doi:10.1016/j.jhep.2008.07.030

Received 3 February 2008; received in revised form 12 July 2008;

accepted 22 July 2008; available online 1 October 2008

Associate Editor: M.P. Mannsq The authors declare that they do not have anything to disclose

regarding funding from industries or conflict of interest with respect tothis manuscript.

* Corresponding author. Tel.: +91 80 22065239; fax: +91 80 25530070.E-mail address: harshad.devarbhavi@gmail.com (H. Devarbhavi).

ated acute liver diseases (PAALD) such as preeclamp-sia-associated liver disease, acute fatty liver ofpregnancy (AFLP) and hemolysis elevated liver enzymesand low platelet syndrome (HELLP) or acute viral hep-atitis (VH). Diagnosing these diseases and accurate dif-ferentiation between PAALD vs VH is extremely criticalnot only for prevention of progressive liver disease andexpediting prompt delivery, in the former but also con-tinue supportive treatment in the latter [3–5]. Distinctionbetween the two is often difficult resulting in patientswith viral hepatitis being operated with the mistakendiagnosis of PAALD. Gastroenterologists and internistsare very often called upon to help make the distinctionbetween the two which may be difficult [3,4]. Clinical

Published by Elsevier B.V. All rights reserved.

H. Devarbhavi et al. / Journal of Hepatology 49 (2008) 930–935 931

features are non-specific with considerable overlapbetween the clinical and laboratory features. For exam-ple hyperbilirubinemia and elevated transaminases arepresent in both groups and is not always helpful [6].Serological tests for viral hepatitis that help make thisdistinction may not be readily available, take time [4]and therefore may delay definitive therapy. Liver biopsywhich is the gold standard for distinction is invasive andis not routinely recommended especially in such sickpregnant women with a compromised coagulation pro-file. There are no studies comparing PAALD vs VH tohelp make the distinction. Even in the PAALD group,distinction is often made between the various subtypes.preeclampsia-associated liver disease, HELLP andAFLP, with AFLP generally considered the most severeform of liver disease in the PAALD spectrum.

The presence of substantial overlap in the clinical andbiochemical features between the various subtypesmakes a specific diagnosis difficult [7–9]. Regardless ofthe subtypes of PAALD, early delivery followed by sup-portive care is recommended. Therefore, there is need,especially in developing countries where acute viral hep-atitis is common, to help make this distinction betweenthe two groups in an expedited manner.

The aims of this study were: (1) to differentiatebetween pregnancy associated acute liver disease(PAALD) and acute viral hepatitis in pregnancy (VH)based on clinical, biochemical, and hematological fea-tures, (2) to derive a model based upon readily availableparameters predictive of PAALD vs VH to help makethis distinction, and [3] to determine predictors of mor-tality in PAALD.

2. Patients and methods

2.1. Patient groups

The study protocol conforms to the ethical guidelines of the 1975declaration of Helsinki as reflected in a priori approval by the Institu-tion Review Board. We studied 87 consecutive patients admitted to St.John’s Medical College Hospital, Bangalore, which is a tertiary carereferral center, with jaundice during pregnancy from January 2000 toJuly 2003. Viral hepatitis was diagnosed by detection of IgM antibod-ies to hepatotropic virus in the serum in the presence of jaundice andabnormal liver biochemical tests in the absence of drugs, sepsis, AFLP,and HELLP. Pregnancy-associated acute liver disease (PAALD) wasdefined as the presence of jaundice secondary to AFLP, HELLP orpreeclampsia or eclampsia in the absence of IgM antibodies to hepato-tropic viruses in the serum. The diagnosis of pre-eclampsia was basedon standard criteria [10]. The diagnosis of HELLP was based on thepresence of thrombocytopenia (platelets less than 100,000/mm3) inthe presence of liver biochemical test abnormalities in pregnantwomen, whereas AFLP was based on the presence of elevated uricacid, elevated prothrombin time, hypoglycemia and liver test abnor-malities. As there were overlapping clinical and laboratory featuresbetween the subgroups in pregnancy-associated liver disease, all thesepatients were grouped under PAALD.

Other causes of jaundice and altered liver biochemical tests such asmalaria (n = 2), enteric fever (n = 1) and leptospirosis (n = 3) wereexcluded. Laboratory parameters assessed in all patients included thefollowing: hemoglobin, total and differential white blood count, plate-

let count, prothrombin time, uric acid, blood sugars, serum creatinine,blood urea nitrogen (BUN) and serum electrolytes. Blood samples ofall patients were screened by enzyme-linked immunosorbent assaysfor IgM antibodies to the hepatitis A virus, the hepatitis B virus coreantigen (IgM anti-HBc) and the hepatitis E virus. Blood serum wasalso screened for the hepatitis B surface antigen (HBsAg) and the hep-atitis C virus (anti-HCV). Ultrasonography of the abdomen and fetuswas carried out in all patients and CT (abdomen) was done wheneverindicated. Urine output of less than 400 ml per day or less than 20 ml/hour was considered as oliguria. Patients who were chronic inactivecarriers of HBsAg were excluded (n = 8). All patients received support-ive treatment. Three patients with stable viral hepatitis were conservedand carried till term. In women with a clinical diagnosis of PAALDinduction of labor was induced with intracervical application of Pros-taglandin E2 gel (PGE2) and accelerated with artificial rupture of mem-brane with or without oxytocin infusion. In women with establishedlabor acceleration was done with artificial rupture of membranes withor without oxytocin. Patients not responding to above measures orthose with deteriorating maternal conditions such as encephalopathy,eclampsia, renal failure and worsening coagulation profile or fetal dis-tress, non progression of labor underwent cesarean section. Packed redblood cells, platelet transfusions and fresh frozen plasma were trans-fused whenever required.

Socioeconomic status was assessed by standard criteria [11].Patients were followed up to 6 months or until death. Patients whodied were subjected to a liver biopsy whenever consent was availablefrom relatives.

2.1.1. Statistical analysisData were summarized using means ± standard deviation for

numeric variables, and percents and counts for categorical variables.Relevant clinical and laboratory variables were analyzed by univariatelogistic regression and those significant were included in a stepwisemultivariate logistic regression analysis to identify factors predictiveof PAALD vs VH. Concordance (C) was used to describe the predic-tive ability of the models. Roughly, selecting at random one patientfrom each of the two groups, concordance is the probability of themodel correctly placing these individuals into the two groups. Logisticregression was also used to compare 6-month survival rates betweenthe two groups, in addition to measuring how the clinical and labora-tory covariates were associated with survival. As an alternative strat-egy, recursive partitioning was investigated to see how clinical andlaboratory variables distinguish patients with PAALD from VH [12].We used t test and chi square test to compare normally distributeddata and discrete values between groups. A p-value 60.05 was consid-ered significant.

3. Results

3.1. Differentiation of VH and PAALD

There were 87 patients who presented with jaundicein pregnancy, of whom 46 had PAALD and 41 hadacute VH (32% due to hepatitis B and 68% due to hep-atitis E). There was no patient with intrahepatic chole-stasis of pregnancy. Hepatitis E genotype or subtypeanalysis was not available. Details regarding clinical fea-tures are summarized in Table 1. The two groups couldnot be differentiated in terms of age, gravid status, per-iod of gestation, and presence of abdominal pain. How-ever patients with hypertension, encephalopathy,oliguria, or ascites were more likely to have PAALD.The differences in the laboratory variables between the2 groups are detailed in Table 2. There was a significantincrease in BUN, serum creatinine, and uric acid in thePAALD group, while the transaminase elevation was

Table 1

Clinical features and mortality in patients with PAALD and VH (means ± SD, n (%))

Variable PAALD (N = 46) VH (N = 41) Odds ratio (95% CI)b p-Valueb

Features

Age (years) 23.9 ± 4.6 24.5 ± 4.9 1.03 (0.94, 1.13) 0.57Primigravida 22 (47.8%) 18 (43.9%) 0.85 (0.36, 1.99) 0.71Gestation weeks 32.3 ± 6.5 31.2 ± 6.3 0.97 (0.91, 1.04) 0.42Hypertension 30 (65.2%) 1 (2.4%) 0.01 (<0.001, 0.07) <.0001Encephalopathy 19 (42.2%)a 4 (9.8%) 0.15 (0.04, 0.45) 0.0004Abdominal pain 13 (28.3%) 8 (19.5%) 0.62 (0.22, 1.66) 0.34Oliguria 15 (34.1%)a 0 (0.0%) <0.001 (0.0, 0.10) <0.0001Ascites 35 (76.1%) 3 (7.3%) 0.03 (0.01, 0.09) <0.0001

Outcomes

Death 19 (41.3%) 3 (7.5%) 0.12 (0.03, 0.38)* 0.0002*

Fetal death 24 (53.3%) 4 (9.8%) 0.10 (0.03, 0.28)* <0.0001*

PAALD, pregnancy-associated acute liver disease; VH, viral hepatitis.a Missing values present.b from univariate logistic regression differentiating VH vs. PAALD.* From univariate logistic regression differentiating death/fetal death (years vs. n) using viral serology (VH vs. PAALD).

Table 2

Laboratory features of patients with PAALD and VH (means ± SD)

Variable PAALD (N = 46) VH (N = 41) Odds ratio (95% CI)a p-Valuea

Hemoglobin (g/dl) 10.30 ± 3.5 10.29 ± 2.3 1.00 (0.86, 1.15) 0.99WBC (109/L) 26 ± 35.2 15.7 ± 13.8 0.98 (0.93, 1.00) 0.05LDH (U/L) 1084.7 ± 1168 415.4 ± 255.8 0.997 (0.994, 0.999) 0.0003Serum creatinine (mg/dl) 2.43 ± 1.5 1.17 ± 1.25 0.39 (0.22, 0.63) <0.0001Blood urea nitrogen (mg/dl) 52 ± 30 25 ± 34 0.96 (0.94, 0.98) 0.0001Uric acid (mg/dl) 8.39 ± 2.9 5.82 ± 3.5 0.76 (0.60, 0.92) 0.0037Glucose mg/dl 70.8 ± 43.7 83.0 ± 57.9 1.005 (0.996, 1.016) 0.29FDP 941.8 ± 232.6 806.7 ± 400.5 0.999 (0.996, 1.001) 0.16Prothrombin time (s) 33.0 ± 22.5 21.0 ± 7.1 0.93 (0.88, 0.97) 0.0003aPTT (s) 55.2 ± 25.9 45.2 ± 27.1 0.982 (0.955, 1.003) 0.11Platelets (109/L) 79218 ± 58603 205189 ± 88621 1.024 (1.015, 1.036)* <0.0001Total proteins (mg.dl) 5.26 ± 0.98 6.07 ± 0.78 2.85 (1.67, 5.34) <0.0001Albumin (mg/dl) 2.34 ± 0.49 2.96 ± 0.56 14.81 (4.64, 63.29) <0.0001Total bilirubin (mg/dl) 9.88 ± 6.9 11.18 ± 5.5 1.03 (0.97, 1.11) 0.33Direct bilirubin (mg/dl) 6.78 ± 4.9 6.62 ± 2.8 0.99 (0.89, 1.10) 0.85AST (U/L) 268 ± 295 828 ± 1045 1.001 (1.001, 1.003) 0.0003ALT (U/L) 186 ± 138 576 ± 729 1.003 (1.001, 1.006) <0.0001

Abbreviations: PAALD, pregnancy-associated acute liver disease; VH, viral hepatitis; WBC, white blood cells; FDP, fraction degeneration products;aPTT, activated partial thromboplastin time; AST, aspartate aminotraminases; ALT, alanine amino transaminases.Note: Some missing values are present.

a From univariate logistic regression model differentiating VH vs. PAALD.* Odds ratio for an increase of 1000 units.

Table 3

Multivariate logistic regression model for differentiating VH vs. PAALD

Variable Odds ratio (95% CI) p-Value

Hypertension 0.009 (<0.001, 0.069) 0.0001Ascites 0.018 (0.003, 0.085) <0.0001

932 H. Devarbhavi et al. / Journal of Hepatology 49 (2008) 930–935

more pronounced in the VH group. Furthermore, theplatelet levels were significantly decreased in thePAALD group.

The multivariate analysis identified presence ofhypertension and ascites as significant independent fac-tors helpful in differentiating between PAALD vs VH(C = 0.95, see Table 3). The final model was the sameregardless of whether we considered clinical variablesonly, clinical and easily obtainable laboratory variables(hemoglobin and white blood cell count), or clinical andall laboratory variables. In addition, only one rule wasobtained using recursive partitioning. This rule classifiesa pregnant woman as having VH if she had neither asci-

tes nor hypertension, instead of having PAALD. Forthis rule C = 0.92, indicating excellent predictive ability.

3.2. Outcome: maternal and fetal mortality

Mortality in PAALD was 19/46 (41%) compared to3/41(7.5%) in the viral hepatitis group. The mean inter-

H. Devarbhavi et al. / Journal of Hepatology 49 (2008) 930–935 933

val between diagnosis and maternal death was 10.6 daysin the VH group and 5.8 days in the PAALD group(p = 0.13). The interval between admission and deliverywas 2.5 days in 38/41 patients with VH and 1.3 days inpatients with PAALD (p = 0.09). Three patients in theVH group who presented in second trimester and didnot have any complication were discharged and contin-ued their pregnancies without complications till term.

Obstetric complications: there were 7/41 patients withantepartum hemorrhage in the VH group and 12/46patients in the PAALD group (p = 0.44). Post partumhemorrhage was noted in 9/41 patients in the VH groupand 15/46 in the PAALD group (p = 0.34). Prematurerupture of membranes were seen in 4 patients with theVH group and 8 patients of PAALD group (p = 0.36)

The incidence of intrauterine death was also high,53% vs 10% (PAALD vs VH). Most of the maternaldeaths were due to multiorgan failure in the PAALDwhereas the three deaths in the VH group occurred asa result of sepsis. Table 4 shows the clinical and labora-tory variables that significantly impacted maternal mor-tality. However, a stepwise multivariate analysisidentified total bilirubin and oliguria as significant fac-tors when considering clinical variables and all labora-tory variables except viral serology (see Table 5).When restricting the predictors to clinical variables onlyor in combination with easily available laboratory vari-ables (hemoglobin and white blood cell count), abdom-inal pain, oliguria and ascites together demonstrated aC = 0.85.

Table 4

Univariate logistic regression models for clinical and laboratory variables

predicting maternal mortality

Variable OR (95% CI) P-value C

S. creatinine (mg/dl) 1.95 (1.33, 3.14) 0.0002 0.81Blood urea nitrogen (mg/dl) 1.021 (1.005, 1.040) 0.0075 0.74Uric acid 1.34 (1.10, 1.70) 0.0028 0.73PT 1.08 (1.04, 1.2) <0.0001 0.79aPTT 1.04 (1.01, 1.07) 0.0007 0.81Platelets 0.989 (0.981, 0.996)* 0.0010 0.72Total bilirubin 1.13 (1.04, 1.24) 0.0027 0.70Encephalopathy 5.67 (1.99, 16.94) 0.0011 0.69oliguria 10.54 (3.15, 39.92) 0.0001 0.70Ascites 6.96 (2.40, 23.59) 0.0002 0.72

* Odds ratio for an increase of 1000 units.

Table 5

Multivariate logistic regression models for clinical and laboratory variables pr

Model variable types considered Variable

Clinical variables only or clinical variables/easy labs Abdominal pOliguriaAscites

Clinical and all laboratories Total bilirubOliguria

Using recursive partitioning, the rule for predictingdeath (yes vs no) when only clinical features are consid-ered yielded only oliguria with C = 0.70, which indicatesfair to good predictive ability. The rule says if oliguria ispresent, then predict death, otherwise predict no death.If we consider the clinical and easily obtainable labora-tory variables, then we would predict someone to die ifthey either (1) had oliguria or (2) did not have oliguriaand had a white blood cell count of at least27.45 cells 109/L. This rule has good predictive abilitywith a C = 0.79. When considering all clinical and labo-ratory variables, the rule predicts mortality if the pro-thrombin time is at least 26.7 s and serum creatinine isat least 2.1 mg/dl. If this does not hold the rule predictsthem not to die. We have good predictive ability as C inthis case is 0.80.

4. Discussion

Our study demonstrates that pregnant women withviral hepatitis usually present with jaundice and liver testabnormalities without other organ system involvement.(Table 2) This is similar to the presentation of viral hep-atitis in non-pregnant women. Transaminases were ele-vated to a much higher level (more than 10 timesnormal) in VH compared to mild 2–3 fold elevation inthe PAALD group. In our study a majority of pregnantwomen with viral hepatitis had a good maternal andfetal outcome with only 3 patients, all with hepatitis E,dying from sepsis. The outcome in patients with viralhepatitis is at variance from reported series from otherplaces in the northern part of India where pregnantpatients with viral hepatitis uniformly had a poor out-come secondary to fulminant hepatic failure, particu-larly from hepatitis E. The poor outcome in terms ofmortality was seen reported both in an epidemic andsporadic setting [13–18]. In one report of sporadic viralhepatitis in pregnancy, 47/76 (61.8%) pregnant womendeveloped FHF, of whom 50% died, a majority withhepatitis E (69.2%) [18]. In an epidemic setting, anotherstudy showed an incidence of FHF of 25% [17]. The rea-sons for the high morbidity and mortality are not clearand have been ascribed to a shift in the Th1/Th2 balancetowards a TH2 response [19]. In contrast, the low mor-tality in our series is similar to the experience from

edicting mortality

Odds ratio (95% CI) p-Value C

ain 5.68 (1.52, 24.31) 0.0125 0.857.47 (1.77, 36.72) 0.00865.17 (1.36, 23.33) 0.0206

in 1.17 (1.06, 1.32) 0.0053 0.8314.09 (3.58, 67.60) 0.0003

934 H. Devarbhavi et al. / Journal of Hepatology 49 (2008) 930–935

western countries where the outcome of viral hepatitis inpregnancy is similar to the clinical course in nonpreg-nant women [6] and could be ascribed to the highersocioeconomic condition in Bangalore and its suburbs.However the socioeconomic status in both groups weresimilar (p = 0.99) suggesting that other unknown factorsmay play a role. Furthermore other recent series fromother parts of India have shown a similar result withlow mortality (5–6%), but significant morbidity.[20,21]. The reasons for the low mortality are unclear.In Europe and United States hepatitis E is not endemicand often considered a zoonotic disease. Both swine andhuman isolates belong to the same genotype IV. In con-trast hepatitis E is endemic in northern parts of Indiaand like hepatitis A is transmitted enterically with thehuman HEV isolates belonging to genotype I and swineisolates belonging to genotype IV[22–24]. Whether ornot genotypic heterogeneity plays a role in the low mor-tality in southern parts of India needs further study andevaluation.

In contrast to patients with VH, patients withPAALD had only a mild elevation of transaminasesand similar levels of bilirubin. Patients with PAALDoften have multisystem involvement resulting in oligu-ria, encephalopathy and ascites in addition to many fea-tures of preeclampsia such as hypertension andproteinuria. Despite the univariate analysis identifyingmany variables that were significant (Tables 1 and 2)our study identified a model with simple clinical and lab-oratory variables which aids in the differentiation ofPAALD from VH. In a multivariate analysis, the pres-ence of hypertension and ascites helped identify PAALDwith a concordance of 0.95 (Table 3). A high concor-dance of 0.92 was maintained by recursive partitioninganalysis which means that using hypertension and asci-tes patients from different groups can be classified cor-rectly 92% of the time. Both hypertension and ascitescan be easily determined at the bedside by clinical exam-ination and ascites corroborated by ultrasonography.Presence of these two findings will decrease the inadver-tent reliance on virological tests that are not readilyavailable and usually take time due to varying turn-around times often in days making it suboptimal forimmediate medical intervention. PAALD often carriessignificant morbidity and mortality to both motherand the fetus [25–28]. Therefore prompt diagnosis is crit-ical when making treatment decisions such as termina-tion of pregnancy. Future studies are required todetermine the impact of early diagnosis and deliveryon both morbidity and maternal and fetal mortalities.

Preeclampsia is a multisystem disorder involvingendothelial dysfunction and fibrin deposition[29] andtherefore contributes to the development of hyperten-sion, renal failure, hepatic dysfunction and ascites. Endo-thelial dysfunction and fibrin deposition in the sinusoidmay cause both hepatic insufficiency and ascites.

Our study showed a significantly high maternal mor-tality and intrauterine death in the PAALD group.Although the reasons are not entirely clear, this mayin part be due to the late presentation of patients tothe hospital as reflected by the high numbers of intra-uterine deaths during admission.

There is conflicting data regarding factors associatedwith the high morbidity and mortality in patients withPAALD. One study identified five significant risk factorsassociated with complications: ascites, thrombocytope-nia, increased uric acid, serum creatinine and proteinuria[30], whereas another study found no discriminatory fac-tors between those with or without adverse outcomes[31]. The present study demonstrated that total bilirubinand oliguria are good predictors for mortality with aconcordance of 0.83 whereas using only clinical featuressuch as abdominal pain, ascites and oliguria had a con-cordance of 0.85. Future studies will be needed to deter-mine whether early detection of the above clinicalfeatures will impact the intervention, complications andoutcome.

In patients with pregnancy associated liver diseasethere is a tendency to categorize cases into preeclampsiawith liver dysfunction, AFLP and HELLP. Such a dis-tinction is not always helpful. The diagnosis of HELLPrelies very heavily on the platelet levels <100,000 cells/ml3. Such low levels were seen overall in 71% of ourpatients, whereas in those with a clinical diagnosis ofAFLP low platelets were seen in 62%. This is consistentwith other reports where low platelets were seen in 91%of patients with AFLP at some point during the courseof the disease [26]. Similarly, features of preeclampsiahave been seen in over 50% of patients with AFLP[26] and in up to 100% of patients with HELLP [32]and in two thirds of the patients in our series. Therefore,differentiating patients into AFLP, HELLP and pre-eclampsia-associated jaundice may not always be help-ful. Regardless of the subtypes, patients should beevaluated for early delivery as soon as the diagnosis ofPAALD is made. Indeed there are suggestions that thesedisorders may in fact be different facets of the same dis-ease [33]. For example, microvesicular fat has been seennot only in patients with HELLP and AFLP, but also inpatients with preeclampsia [8,9,34].

The complications including preterm delivery (31.2weeks in VH group and 32.2 weeks in the PAALDgroup) were similar in both groups. Preterm deliverieseither spontaneous or induced occur due to maternalor fetal conditions complicated by hepatitis, cholestasis,any infection or stress which causes chorioamnionitis,increased cytokine release or disturbed hormonal state[35,36]. A recent study reported a mean gestation periodof 31 weeks in patients with hepatitis E, which is similarto our study [13].

A strength of this unique study is the simple clinicalcharacteristics that help in the differentiation between

H. Devarbhavi et al. / Journal of Hepatology 49 (2008) 930–935 935

PAALD vs VH in a fairly large number of consecutivepatients. A limitations is the retrospective data due towhich there were a few missing variables.

In conclusion, this unique study shows that in preg-nant women with jaundice and liver test abnormalities,regardless of the changes in the hematological and bio-chemical profile, the hypertension and ascites status willcorrectly distinguish 95% of patients with PAALD fromviral hepatitis. Patients with ascites and hypertensionshould be evaluated for delivery without delay. Furtherprospective studies are needed to determine whetherthese simple distinguishing clinical features will helpmake an early diagnosis and contribute to expediteddelivery and improved outcome.

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