A Case of Primary Biliary Cirrhosis That Progressed Rapidly after Treatment Involving Rituximab
A 66-year-old woman was referred to our hospital for treatment of a gastric tumor. She had been diagnosed with PBC at the age of 60 years and had been treated with ursodeoxycholic acid. Although she had been stable and asymptomatic for several years, a gastric tumor was detected on upper gastric endoscopy performed due to abdominal discomfort after meals a month before visiting a local hospital. Abdominal computed tomography (CT) and 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) showed the localized stage of malignant lymphoma in her stomach. Endoscopic biopsy examination confirmed diffuse large B-cell lymphoma (DLBCL). She showed good performance status (PS1) and normal serum lactate dehydrogenase level (189 IU/l, normal range 121–220 IU/l). She had been diagnosed with gastric DLBCL with stage II1 in the Lugano classification and showed low international prognostic index (IPI, 1 point) []. With regard to PBC status, she had no jaundice (serum total bilirubin 1.0 mg/dl, normal range 0.2–1.3 mg/dl) and showed well-preserved liver function (serum albumin 4.0 g/dl, normal range 4.0–5.0 g/dl; PT% 100%, normal range 80–120%), although biliary enzyme levels were slightly elevated (gamma-glutamyl transpeptidase 214 U/l, normal range 10–47 U/l; ALP 826 U/l, normal range 115–359 U/l). Her serum IgM and AMA-M2 titers were high (IgM 615 mg/dl, normal range 57–288 mg/dl; AMA-M2 70, normal index <7), reflecting PBC.\nPrior to treatment for DLBCL, we performed a biopsy on the right lobe of the liver and found chronic non-suppurative destructive cholangitis with interface hepatitis consistent with PBC at Scheuer's histological stage II (fig. ). According to the risk score of PBC, her risk score before treatment of DLBCL was calculated as 5.5 and the estimated probability of survival for 24 months was >99% []. Thereafter, she was treated with chemotherapy, including rituximab (R-CHOP – cyclophosphamide/hydroxydaunorubicin/oncovin/prednisone, rituximab 375 mg/m2) plus radiation 40 Gy as shown in figure . After treatment with 8 doses of rituximab, her biliary enzyme and serum IgM levels decreased gradually and the AMA titer also decreased (fig. ). Moreover, we found that portal inflammation had decreased after rituximab treatment (fig. ). She finished R-CHOP plus radiation therapy and achieved complete remission of DLBCL. Thereafter, she was observed and remained in a stable condition for 24 months after diagnosis of DLBCL. She was asymptomatic and her PBC Mayo risk scores remained low for 24 months after diagnosis of DLBCL (fig. ). However, she showed marked jaundice and ascites without elevation of serum AMA titer 30 months after diagnosis of DLBCL. CT scan showed bile duct cancer at the bottom of the common bile duct in addition to cirrhotic changes such as ascites. Percutaneous drainage of the bile duct was immediately and successfully performed and her jaundice was partially decreased, but surgical resection or chemotherapy could not be done due to decreased liver function. Hepatobiliary scintigraphy using 99mTc-PMT showed disturbance of hepatocellular excretion of bile (data not shown). Therefore, her cirrhosis was estimated to be already established at the time when jaundice developed. She received the best supportive care and died from liver failure 3 years after diagnosis of DLBCL. Autopsy showed bridged fibrosis formation of the liver (fig. , Scheuer's histological stage IV) and lower bile duct cancer. Prominent infiltration of inflammatory cells was not found in the liver (fig. ).