Acute kidney injury after platinum-based transcatheter arterial chemoembolization and transarterial infusion chemotherapy in patients with hepatocellular carcinoma.

BACKGROUNDS: The incidence of acute kidney injury and the association between acute kidney injury and prognosis have been reported about transcatheter arterial chemoembolization using anthracycline. However, the incidence of acute kidney injury after platinum-based transarterial chemoembolization or transarterial infusion chemotherapy remains unclear. The aim of this study was to investigate association between acute kidney injury after platinum-based transcatheter arterial chemoembolization/transarterial infusion chemotherapy and prognosis in patients with hepatocellular carcinoma. METHODS: We retrospectively analysed 270 sessions in 129 patients who underwent platinum-based transcatheter arterial chemoembolization/transarterial infusion chemotherapy. Acute kidney injury was diagnosed according to the criteria established by the International Club of Ascites. The incidence of acute kidney injury, risk factors for serum creatinine elevation and association between acute kidney injury and prognosis were assessed. RESULTS: Fifteen cases of acute kidney injury (5.6%, 15/270) developed in 14 patients (10.8%, 14/129). Ascites (coefficient: 0.059, P = 0.006), low estimated glomerular filtration rate (coefficient: -0.008, P = 0.029), diabetes (coefficient: 0.072, P < 0.001) and high albumin-bilirubin grade (albumin-bilirubin grade 2: coefficient: 0.053, P = 0.004; and albumin-bilirubin grade 3: coefficient: 0.103, P < 0.001) were significantly associated with an elevation in serum creatinine levels after transcatheter arterial chemoembolization/transarterial infusion chemotherapy. The development of acute kidney injury was associated with poor prognosis (hazard ratio: 3.18, 95%CI: 1.411-7.171, P = 0.005). Patients with acute kidney injury had a significantly lower survival rate than patients without acute kidney injury (log-rank test; P = 0.034). CONCLUSIONS: The incidence of acute kidney injury after platinum-based transcatheter arterial chemoembolization/transarterial infusion chemotherapy was consistent with that after transcatheter arterial chemoembolization using anthracycline, and the development of acute kidney injury was associated with poor prognosis. Ascites, diabetes, low estimated glomerular filtration rate and high albumin-bilirubin grade were risk factors for serum creatinine elevation after platinum-based transcatheter arterial chemoembolization/transarterial infusion chemotherapy.

Endogenous Endophthalmitis Associated with Pyogenic Liver Abscess Caused by Klebsiella pneumoniae.

We report 2 cases of endogenous endophthalmitis associated with pyogenic liver abscess caused by Klebsiella pneumoniae. Case 1 involved a 70-year-old woman and case 2 involved a 50-year-old man who were admitted to our hospital with diagnoses of liver abscess and endogenous endophthalmitis, respectively. The liver abscess resolved with antibiotics and percutaneous transhepatic drainage in case 1 and with antibiotics alone in case 2. Even though both cases underwent ophthalmic surgery, they were discharged from our hospital without the recovery of their eyesight. An earlier diagnosis and treatment are needed to improve the prognosis of endophthalmitis.

Skeletal muscle volume loss during transarterial chemoembolization predicts poor prognosis in patients with hepatocellular carcinoma.

AIM: Sarcopenia has a negative impact on the prognosis of patients with hepatocellular carcinoma (HCC). We investigated the significance of skeletal muscle volume and its changes in HCC patients receiving transarterial chemoembolization (TACE). METHODS: We retrospectively analyzed 179 HCC patients receiving TACE from 2006 to 2017. Skeletal mass index was calculated as the left-right sum of the major × minor axis of the psoas muscle at the third lumbar vertebra, divided by height squared (psoas muscle index [PMI]). Patients were classified into two groups (low and normal PMI) depending on an index <6.0 and <3.4 cm2 /m2 for men and women, respectively. We assessed overall survival (OS) and TACE period (between the first TACE [Pre] and the time of TACE refractoriness [Post]). Changes in PMI per month during the TACE period (CPMI; (PMI [Pre] - PMI [Post]) / TACE period) were calculated as an index of progressive muscle atrophy. RESULTS: There were no significant differences in OS between groups with low and normal PMI at Pre. Multivariate analysis showed that CPMI was significantly associated with poor OS (hazard ratio, 1.884; P = 0.001). Patients with severe muscle atrophy (CPMI above the upper quartile) had a significantly lower OS than those with mild muscle atrophy (CPMI below the upper quartile). Compared with patients with mild muscle atrophy, patients with severe muscle atrophy had a significant loss of liver function reserves at Post. CONCLUSION: Progressive loss of skeletal muscle volume is an important predictor of poor prognosis in HCC patients treated with TACE.

Huge Hepatocellular Carcinoma Treated with Radical Hepatectomy after Drug-eluting Bead Transarterial Chemoembolization.

We performed split drug-eluting bead transarterial chemoembolization (DEB-TACE) in a patient with huge unresectable hepatocellular carcinoma and multiple intrahepatic metastases. However, TACE was discontinued at the fourth application because the tumor was fed by the cholecystic artery. As most intrahepatic metastases disappeared following DEB-TACE, the patient was able to undergo radical hepatectomy, and has maintained a complete response. DEB-TACE enables cancer treatment without reducing the liver or renal function. However, it is associated with a risk of ischemia in other organs in patients whose arteries feed both tumors and other organs; thus appropriate selection is required.

Changes in serum levels of leucine-rich α2-glycoprotein predict prognosis in primary biliary cholangitis.

AIMS: A non-invasive biomarker for patients with primary biliary cholangitis (PBC) is needed. The association between leucine-rich α2 glycoprotein (LRG) and PBC has not been investigated. We aimed to assess the predictive value of LRG for the development of cirrhosis-related conditions in PBC. METHODS: We retrospectively reviewed clinical data of 129 individuals with biopsy-confirmed PBC. Leucine-rich α2 glycoprotein was analyzed by enzyme-linked immunosorbent assays using stored sera at biopsy (n = 129) and after treatment (n = 80). RESULTS: Levels of LRG decreased significantly after treatment (55.8 µg/mL vs. 39.8 µg/mL, P < 0.001). Neither LRG nor delta-LRG was associated with transaminase or histological findings. Delta-LRG >0 (hazard ratio [HR] 4.61, P = 0.013), delta-LRG >0 and an aspartate aminotransferase/platelet ratio index (APRI) >0.76 (HR 458, P < 0.001) were associated with the development of a cirrhosis-related condition. Patients with a delta-LRG >0 and an APRI >0.76 had a significantly increased rate of developing cirrhosis-related conditions (P < 0.001). CONCLUSIONS: Changes in LRG levels after treatment predicted PBC prognosis but were not associated with histological stage. Changes in LRG in addition to the APRI could be a useful combination of tools for clinicians as a non-invasive biomarker.

Hepatitis B Virus Reactivation in a Patient with Nonalcoholic Steatohepatitis 41 Months after Rituximab-containing Chemotherapy.

Hepatitis B virus (HBV) reactivation occasionally occurs long after immunosuppressive therapy. The characteristics of late HBV reactivation remain unclear. We herein present a case of HBV reactivation in a patient with nonalcoholic steatohepatitis (NASH) more than 3 years after rituximab-containing chemotherapy for diffuse large B-cell lymphoma. Increased transaminase levels, which were induced by NASH, were observed after chemotherapy and were alleviated with statin treatment. HBV reactivation was identified incidentally. The patient developed hepatitis that improved with entecavir therapy. Our case might indicate that the presence of NASH is associated with HBV reactivation long after treatment and that statins, as immune-modulatory agents, affect HBV reactivation.

Dysbiosis of oral microbiota and its association with salivary immunological biomarkers in autoimmune liver disease.

The gut microbiota has recently been recognized to play a role in the pathogenesis of autoimmune liver disease (AILD), mainly primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH). This study aimed to analyze and compare the composition of the oral microbiota of 56 patients with AILD and 15 healthy controls (HCs) and to evaluate its association with salivary immunological biomarkers and gut microbiota. The subjects included 39 patients with PBC and 17 patients with AIH diagnosed at our hospital. The control population comprised 15 matched HCs. Salivary and fecal samples were collected for analysis of the microbiome by terminal restriction fragment length polymorphism of 16S rDNA. Correlations between immunological biomarkers measured by Bio-Plex assay (Bio-Rad) and the oral microbiomes of patients with PBC and AIH were assessed. Patients with AIH showed a significant increase in Veillonella with a concurrent decrease in Streptococcus in the oral microbiota compared with the HCs. Patients with PBC showed significant increases in Eubacterium and Veillonella and a significant decrease in Fusobacterium in the oral microbiota compared with the HCs. Immunological biomarker analysis showed elevated levels of inflammatory cytokines (IL-1ß, IFN-γ, TNF-α, IL-8) and immunoglobulin A in the saliva of patients with AILD. The relative abundance of Veillonella was positively correlated with the levels of IL-1ß, IL-8 and immunoglobulin A in saliva and the relative abundance of Lactobacillales in feces. Dysbiosis of the oral microbiota is associated with inflammatory responses and reflects changes in the gut microbiota of patients with AILD. Dysbiosis may play an important role in the pathogenesis of AILD.

Contrast uptake in primary hepatic angiosarcoma on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging in the hepatobiliary phase.

Primary hepatic angiosarcoma is the most common malignant mesenchymal tumor of the liver. It has a poor prognosis and various appearances on magnetic resonance (MR) images. We report a case of hepatic angiosarcoma with a characteristic appearance on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MR imaging in the hepatobiliary phase. A 72-year-old man was admitted with a complaint of abdominal pain. Gd-EOB-DTPA-enhanced MR imaging revealed a liver tumor that showed slight hyperintensity in the hepatobiliary phase. These findings suggested Gd-EOB-DTPA uptake in the tumor. An autopsy revealed the solid proliferation and sinusoidal spreading of hepatic angiosarcoma cells. Immunohistochemistry indicated that the tumor was negative for OATP1B3. Gd-EOB-DTPA uptake in the liver tumor in the hepatobiliary phase suggested sinusoidal tumor invasion with residual normal hepatocytes.

Serum levels of a cell death biomarker predict the development of cirrhosis-related conditions in primary biliary cholangitis.

Non-invasive predictors for the development of cirrhosis-related conditions are needed for patients with primary biliary cholangitis (PBC). We investigated the association between cytokeratin-18 fragments (M30 and M65) and liver histology, treatment response and the development of cirrhosis-related conditions in patients with PBC. We retrospectively reviewed the clinical data of 111 individuals with biopsy-proven PBC. Serum M30 and M65 levels were measured using stored sera. M30 were significantly decreased after treatment, but there was no significant change in the M65 levels. M65 was significantly higher in non-responders according to the Paris-I and Paris-II definitions. In the multivariate analysis, high levels of M65 were significantly associated with advanced Scheuer stage (odds ratio 5.86; 95% confidence interval 0.55-22.2; P = 0.009) and with the development of cirrhosis-related conditions (hazard ratio 3.94; 95% confidence interval: 1.06-14.5, P = 0.039). Among PBC patients without cirrhosis, those with high serum M65 levels at baseline were at higher risk of developing cirrhosis-related conditions (log-rank test; P = 0.001). High levels of serum M65 may be a non-invasive and early predictor of the development of cirrhosis-related conditions in PBC patients. Our findings may help initiate therapies earlier for those at risk for cirrhosis.

Drug-induced liver injury with autoimmune features complicated with hemophagocytic syndrome.

A 60-year-old woman was admitted to our hospital with non-coma acute liver failure. Based on a 1-month history of supplement use, negative viral hepatitis markers, positive antinuclear antibody test, high IgG level, positive HLA-DR4, liver biopsy findings of centrizonal necrosis, and inflammatory cell infiltration in the portal area, she was diagnosed with drug-induced liver injury (DILI) with autoimmune features or the acute hepatitis phase of autoimmune hepatitis (AIH). Although her liver disorder was ameliorated by administration of prednisolone and plasma exchange, anemia and thrombocytopenia were observed during the course of treatment. A bone marrow examination showed hemophagocytosis. Therefore, with no other evidence suggesting infection or malignancy, we determined that the patient had DILI complicated by hemophagocytic syndrome (HPS). Although HPS is very rarely seen in patients with DILI with autoimmune features or the acute hepatitis phase of AIH, this condition should be considered if cytopenia is observed in a patient with DILI.

Paralytic Ileus due to Superior Mesenteric Venous Thrombosis after Transarterial Injection for Hepatocellular Carcinoma.

A 69-year-old man was admitted to hospital with abdominal pain. In the four years prior to his presentation, he had undergone repeated transarterial chemoembolizations and injections for hepatocellular carcinoma. He underwent his 8th transcatheter arterial therapy one month prior to admission. Abdominal X-rays and contrast-enhanced computed tomography showed large amounts of small intestinal gas and venous thrombosis from the portal vein to the superior mesenteric vein, respectively. The thrombosis was reduced after anticoagulation therapy (heparin, antithrombin III, danaparoid sodium and warfarin). This is the first case report of paralytic ileus due to superior mesenteric venous thrombosis after transcatheter arterial therapy for hepatocellular carcinoma with an arterioportal shunt.

[A case of methotrexate-associated lymphoproliferative disorder diagnosed by liver biopsy].

In 1998, a 68-year-old woman was diagnosed with rheumatoid arthritis. She was treated with prednisolone, nonsteroidal anti-inflammatory drugs, methotrexate (MTX), and biological drugs. Retroperitoneal lymph node swelling and hepatosplenomegaly appeared but spontaneously disappeared after drug withdrawal. Anorexia and general fatigue occurred in March 2012. She was admitted to our hospital with retroperitoneal, periaortic, and mediastinal lymph node swelling and was found to have multiple liver tumors. Based on the results of aspiration biopsy of a liver tumor, she was diagnosed with malignant lymphoma (Hodgkin lymphoma). She died from liver failure and disseminated intravascular coagulation before chemotherapy. We present this case of MTX-associated lymphoproliferative disorder, which caused formation of a liver tumor.

Case of idiopathic portal hypertension complicated with autoimmune hepatitis.

We report a case of idiopathic portal hypertension (IPH) complicated with autoimmune hepatitis. A 60-year-old woman was admitted to our hospital with esophageal and gastric varices in February 2010. Abdominal ultrasonography and computed tomography showed splenomegaly and collateral veins without evidence of liver cirrhosis. Laboratory examinations and liver biopsy indicated that the esophageal and gastric varices were caused by IPH. She underwent endoscopic injection sclerotherapy and partial splenic embolization. Two years after these therapies, laboratory examinations showed liver dysfunction with elevated levels of aspartate aminotransferase (180 IU/L), alanine aminotransferase (190 IU/L), γ-glutamyl transpeptidase (159 IU/L) and immunoglobulin G (2609 mg/dL). The titer of antinuclear antibodies was 1:320 and its pattern was homogeneous and speckled. Histological examination revealed plasma cell/lymphocyte infiltration and interface hepatitis in the portal tract. Based on these findings, a diagnosis of autoimmune hepatitis accompanied by IPH was made. After treatment with prednisolone (20 mg/day), liver functions were normalized immediately. Overlapping of IPH and AIH is extremely rare, but the present case is interesting considering the etiology of IPH because an autoimmune mechanism is thought to be involved in the pathogenesis of IPH.

Centrilobular necrosis in acute presentation of Japanese patients with type 1 autoimmune hepatitis.

AIM: To compare clinicopathological features of acute presentation of type 1 autoimmune hepatitis (AIH) with or without centrilobular necrosis (CN). METHODS: Our study comprised 41 patients with biopsy-proven acute presentation (acute exacerbation phase 36, acute hepatitis phase 5) of type 1 AIH at our hospital from 1975 to 2009. Elevated serum alanine aminotransferase (ALT) (> 5x upper limit of normal) identified acute presentation of the disease. We compared clinicopathological features of these AIH patients with or without CN. The data used for analysis included patient background (age, sex, type of disease, presence of complications with other autoimmune diseases, human leukocyte antigen, and International Autoimmune Hepatitis Group score), clinical parameters at presentation (ALT, alkaline phosphatase, IgG, anti-nuclear antibodies, and anti-smooth muscle antibodies), histology and therapy. RESULTS: CN was found in 13 (31.7%) patients with acute presentation (acute exacerbation phase 10, acute hepatitis phase 3) of AIH. Serum IgG levels of patients with CN were significantly lower than those of patients without CN (mean: 2307 mg/dL vs 3126 mg/dL, P < 0.05), while antinuclear antibody-negative rates were significantly higher (30.7% vs 3.5%, P < 0.05). However, other clinical features were similar between the two groups. The frequency of advanced fibrosis in patients with CN was significantly lower than in patients without CN (F0-2: 84.6% vs 35.7%, F3-4: 15.4% vs 64.3%, P < 0.05). Other histological features were similar between the two groups. Although there was no significant difference between groups when evaluated using the revised original score (12 vs 14), the simplified AIH score of patients with CN was significantly lower (6 vs 7, P < 0.05). Frequency of DR4 was similar between patients with and without CN. CONCLUSION: CN is observed in both Japanese patients with acute hepatitis phase and acute exacerbation phase of type 1 AIH, although AIH with CN often shows clinical features of the genuine acute form.

Hepatocellular carcinoma that relapsed 54 months after living donor liver transplantation.

We report the case of a 41-year-old woman with hepatocellular carcinoma (HCC). She received living donor liver transplantation (LDLT) from her husband for HCC at 36 years of age. She had few risk factors for HCC recurrence, such as elevated alpha-fetoprotein (AFP), protein induced by vitamin K absence (PIVKA) II, vascular invasion, and number, size of tumors. However, recurrent tumors were found in the graft at 54 months after LDLT. Although we examined the sex chromosomes of the HCC by fluorescence in situ hybridization (FISH) methods, the origin of the HCC was unclear. This is a very rare case of recurrent HCC appearing more than 4 years after LDLT in the absence of risk factors for recurrence.