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26 Shah et al. | Journal of Clinical and Translational Research 2024; 10(1): 25-32
making the diagnostic procedure challenging and necessitating 3. Results and Case Descriptions
differential diagnosis to rule out other liver diseases. In India,
the combination of anti-tuberculosis (TB) drugs (46.4%), CAMs 3.1. Results
(13.9%), anti-epileptic drugs (8.1%), non-anti-TB antimicrobials The mean age of the enrolled patients was 28.8 years, and the
(6.5%), anti-metabolites (3.8%), anti-retroviral drugs (3.5%), majority were males (80%). The median duration from the onset
non-steroidal anti-inflammatory drugs (2.6%), hormones (2.5%), of symptoms to the presentation at our hospital was approximately
and statins (1.4%) represents the most common cause of DILI [2]. 4 weeks. Case 1 had polycystic ovarian disease for which she took
Management of DILI includes discontinuation of the culprit drug CAMs, and Case 3 took dapsone for leprosy. Cases 2a, 2b, and
and administration of supportive care. However, in many patients, 4 had no underlying comorbidities. RUCAM scores were 5 for
long after discontinuation of the culprit drug and implementation Case 1, 7 for case 2b, and 6 for each of the other three patients.
of supportive care, the injury fails to improve and progresses R-values were 4.0, 3.6, 7.0, 2.4, and 2.5 for Cases 1, 2a, 2b, 3, and
instead. Unfortunately, definitive management for such patients 4, respectively. Although these patients had severe DILI, none had
has not been developed. The role of steroids in the management acute liver failure. Mean durations for pruritus improvement and
of patients with DILI, except for those with immune checkpoint complete biochemical improvement after steroid treatment were
inhibitors [3] and drug-induced auto-immune hepatitis [4], 3.2 weeks and 11.2 weeks, respectively. All patients had good
remains doubtful. In other forms of DILI, the therapeutic effect tolerance with corticosteroids without presenting any conspicuous
of steroids has not been proven, especially when the injury is side effects. Extended follow-up was done for a mean duration
accompanied by pruritus. In the present study, we assessed the role of 29.6 weeks from the presentation, and none of the patients
of corticosteroids in five patients with DILI induced by different had recurrence of liver injury after discontinuation of steroids
medications who had intractable pruritus and did not respond to (Table 2). Figure 1 depicts values of bilirubin, ALP, and ALT at
conventional management. different time points in all cases.
2. Materials and Methods 3.2. Case descriptions

Five patients were recruited in the Department of 3.2.1. Case 1 - CAM-induced liver injury with intractable
Gastroenterology, Banaras Hindu University, Varanasi, Uttar pruritus in the background of doubtful choledocholithiasis
Pradesh, India, from January 2022 to December 2022. Patients A 26-year-old female patient complained of abdominal pain,
were diagnosed with DILI secondary to CAMs (1), anabolic jaundice, and itching all over the body for 6 months before
steroids (2), dapsone (1), and itraconazole (1). All these patients seeking medical consultation in our hospital. Her symptoms
failed not respond adequately to the discontinuation of the worsened at night, severely diminishing quality of sleep and life.
offending agents and the supportive care and their condition even On general examination, she had excoriating maculopapular skin
exacerbated. This case series depicts the etiology, clinical profile, lesions all over the body, with a few lesions showing oozing of
management, and outcomes of patients with DILI and HILI. blood (Figure 2A). Two weeks before presentation to our hospital,
The R-value was calculated to define the patterns of liver injury. she underwent endoscopic retrograde cholangiopancreatography
R-value was calculated by dividing alanine aminotransferase (ERCP) for biliary stone extraction and biliary stenting at another
(ALT) by alkaline phosphatase (ALP), using multiples of the hospital. Her symptoms worsened, and she was admitted to our
upper limit of normal (ULN) for both. R-value of >5 defines hospital and thoroughly investigated (Table 3). The biliary system
hepatocellular; <2, cholestatic; and between 2 and 5, a mixed was not dilated on imaging post-ERCP. Because there was no
pattern of liver injury. Patients were thoroughly evaluated to definitive diagnosis, a liver biopsy was performed. The results
identify the alternative causes of liver injury, such as hepatotropic unveiled portal tract neutrophilic and eosinophilic infiltrates with
viruses, autoimmune liver diseases, Wilson’s disease, and biliary hepatocellular and canalicular cholestasis with cholestatic rosettes
obstruction by imaging. A liver biopsy was performed in all cases predominantly in zone 3, suggesting mixed hepatocellular and
for histopathological examinations. We used the updated (2016) cholestatic pathology (Figure 3, Case 1); DILI was considered
version of the Roussel UCLAF Causality Assessment Method a probable diagnosis. On re-inquiring, she admitted to having
(RUCAM) for causality assessment [5] (Table 1). For cases of consumed CAMs for polycystic ovarian disease, which she
non-response or worsening of liver injury and pruritus despite started a few weeks before the onset of jaundice and stopped
discontinuation of the offending agents, both corticosteroids and 15 days before presentation at our hospital. Her RUCAM score
supportive care were administered to the patients. Prednisolone was five points, which suggests a possible DILI/HILI. The patient
was started either at a dose of 40 mg/day (cases 1, 2a, and 3) or was given ursodeoxycholic acid (UDCA) 10 mg/kg/day. For
1 mg/kg/day (cases 2b and 4) depending on the choice of treating treating pruritus, she received topical emollients, anti-histaminic,
hepatologist. Patients were followed to observe the outcomes in cholestyramine, and naltrexone; however, these medications were
terms of improvement in pruritus, normalization of liver enzymes, not therapeutically effective as her symptoms persisted during her
intolerance or adverse effects of corticosteroids, and recurrence of hospital stay. She was started on prednisolone 40 mg/day which
liver injury. Informed consent was obtained from all patients or was slowly tapered later as her pruritus, jaundice, and skin lesions
their nearest kin. This work is reported as per the CARE guidelines. improved drastically at 3 weeks of follow-up (Figure 2B). Over
DOI: https://doi.org/10.36922/jctr.00104