BACKGROUND Immune checkpoint inhibitors (ICIs) can lead to immune-related hepatitis (IRH) and severe liver damage, which is life-threatening in the absence of specific treatment. CASE SUMMARY A 75-year-old man was admitted to our hospital complaining of loss of appetite, yellow urine, and abnormal liver function for the past 2 wk. Three months prior to admission, he was treated with two rounds of capecitabine in combination with camrelizumab for lymph node metastasis of esophageal cancer. Although liver function was normal before treatment, abnormal liver function appeared at week 5. Capecitabine and camrelizumab were discontinued. Ursodeoxycholic acid and methylprednisolone 40 mg daily were administered. Liver function continued to deteriorate. Prothrombin time and international normalized ratio were 19 s and 1.8, respectively. The patient was diagnosed with acute liver failure. A pathological analysis of liver biopsy indicated a strongly positive immunohistochemical staining of T8 + cells, thereby suggesting that drug-induced liver injury was related to IRH caused by camrelizumab. Subsequently, we performed sequential dual-molecule plasma adsorption system (DPMAS) treatment with plasma exchange (PE). After two rounds of treatment, the patient's appetite significantly improved, the yellow color of urine reduced, and liver function improved (total bilirubin level decreased) after five rounds of treatment. Liver function normalized 4 wk after discharge. CONCLUSION The use of sequential DPMAS with PE can reduce liver injury and systemic toxic reactions by clearing inflammatory mediators and harmful substances from blood, and regulate immune cell activity, which may be effective in the treatment of severe ICI-induced IRH.

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Introduction: Nilotinib is a selective inhibitor of the BCR-ABL tyrosine kinase receptor and is used in the management of chronic myelogenous leukemia (CML). Nilotinib therapy at high doses is associated with elevated serum bilirubin levels. If the serum bilirubin level exceeds 3 times the upper limit of normal, the recommendation is to either adjust nilotinib dosage or temporarily discontinue the treatment. However, it is unclear whether hyperbilirubinemia indicates obvious liver histology damage. Patient concerns: A 24-year-old man with confirmed CML was treated with nilotinib therapy and developed hyperbilirubinemia after the treatment. Although the first remission of the hyperbilirubinemia was achieved after dose adjustment, the hematological parameters deteriorated. Thus, we initiated an antineoplastic therapy (at the standard dose) until complete remission of the CML was achieved. The pathogenic mechanism of hyperbilirubinemia may be related to the inhibition of uridine diphosphate-glucuronosyltransferase (UGT1A1) activity. Liver histological analysis revealed no significant liver damage. In addition, the patient had no family history of hyperbilirubinemia and liver disease. Diagnosis: The patient was admitted to our hospital under the diagnosis of hyperbilirubinemia, and histopathology by liver biopsy showed no obvious damage. We also detected a UGT1A1 mutation [ex1 c.686C > A (p.Pro229Gln)] in the patient and his mother. Interventions: When the nilotinib dose was decreased to 300 mg daily, the total bilirubin (TBIL) level decreased to 30 to 50 μmol/L for 1 month. However, because the Bcr-Abl/Abl IS ratio did not correspond to the major molecular response (MMR; <0.1%), the nilotinib dose was readjusted to 400 mg daily. One week later, the TBIL and indirect bilirubin levels increased to 89 and 79 μmol/L, respectively. The levels of alanine transaminase and other liver functional indicators were normal. Outcomes: A Naranjo Adverse Drug Reaction (ADR) Probability Scale score of 13 indicates that hyperbilirubinemia is attributed to ADR caused by nilotinib rather than by drug-induced liver injury. Conclusion: Although reducing the nilotinib dose can alleviate the occurrence of hyperbilirubinemia, the effect of MMR is also reduced. Treatment of CML without dose adjustment or discontinuation of nilotinib therapy may be more advantageous.

Chronic infection with hepatitis B virus (CHB) affects as many as 350-400 million people worldwide and 93 million people in China. 1 Moreover, elderly patients with CHB are increasing. Hence, the treatment of elderly patients with CHB is an important issue. However, to our knowledge, there is no report about the efficacy of Entecavir (ETV) treatment on elderly patients (≥60 years) with CHB.A retrospective cohort study was conducted between February 2006 and March 2008; 40 consecutive Chinese patients aged ≥60 years were enrolled in this study at Zhenjiang No. 3 Hospital. We also selected 40 patients aged <60 years with CHB on ETV therapy at same time, who were matched to the ≥60 age group with respect to sex, alanine aminotransferase (ALT), HBV-DNA level, HBV genotype, and HBeAg status and duration of therapy. The study protocol was approved by the ethics committees of the hospital. All patients were treated with Entecavir at a dose of 0.5 mg/day peroral. Table 1 shows the rates of normalization of ALT level and non-detection of HBV-DNA, among patients aged ≥60 years and <60 years after six months and three years on ETV therapy. The rates of ALT normalization of and of non-detection of HBV-DNA in the two groups were similar (p > 0.05 for the two comparisons). Thirteen aged ≥60 years and nine patients aged less than 60 years underwent long-term liver biopsy (median time: 23 months, range: 12-39 months). Histological improvement (over 2-point decrease in the Knodell necroinflammatory Table 1 -Rates of ALT normalization and of non-detection of HBV-DNA in patients aged ≥60 years and <60 years. n ALT normalization rates (%) HBV-DNA non-detection rates (%) 6 months 12 months 24 months 36 months 6 months 12 months 24 months 36 months Age ≥60 years 40 87.5 87.5 90 87.5 82.5 87.5 87.5 92.5 Aged <60 years 40 85 87.5 85 82.5 80 90 85 90score and no worsening of the Knodell fibrosis score) were 76.9% (10/13) versus 77.8% (7/9) and fibrosis improvement (the Ishak fibrosis score ≥1-point decrease) were 38.5% (5/13) versus 44.4%(4/9) in two groups, respectively (p > 0.05 for the two comparisons). The cumulative emergence rates of ETV resistance in patients aged ≥60 years and in those <60 years were 0% and 0% at one year, 2.5% and 0% at two years, and 2.5% and 2.5% at three years, respectively. The emergence rates of ETV resistance in patients aged ≥60 years were similar to those of patients aged <60 years at all three time intervals. The cumulative rates of breakthrough hepatitis in patients aged ≥60 and <60 years were 0% and 0% at one year, 2.5% and 0% at two years, and 2.5% and 2.5% at three years, respectively (not significant). The mutation clusters were rtI169T + rtL180M + rtM204V + rtM250 V and rtL180M + rtT184G + rtS202I, and rtM204 V, respectively. After emergence of the HBV mutant, we added adefovir dipivoxil (ADV) to ongoing ETV therapy.The benefits of ETV in patients with compensated HBVrelated liver disease have been suggested by several groups. [2][3][4][5] Our study is the first to show long-term efficacy of ETV m...

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