The albumin-bilirubin score as a predictor of outcomes in Japanese patients with PBC: an analysis using time-dependent ROC.

The albumin-bilirubin (ALBI) score is calculated using only serum albumin and bilirubin levels, and was developed as a simple method to assess hepatic function. In this study, a total of 409 patients with primary biliary cholangitis (PBC) were enrolled between March 1990 and October 2018. The predictive performances of the ALBI score and other well-established prognostic scores were compared using time-dependent receiver operating characteristic (ROC) analysis. During the follow-up period, 60 patients died, 45 due to liver-related diseases and 15 due to non-liver-related diseases, and 16 patients underwent liver transplantation. Time-dependent ROC analysis showed that the ALBI score has higher the areas under the ROC curves (AUROCs) than the Child-Pugh (C-P) score at each time point; AUROCs at 3, 5, and 10 years after the start of follow-up were 0.94, 0.91, and 0.90 for the ALBI score, and 0.89, 0.88, and 0.82 for the C-P score, respectively. The ALBI score showed the highest AUROCs within 2 years after the start of observation; beyond 2 years, however, the Mayo score had better prognostic ability for mortality and liver transplantation. The ALBI score/grade, derived from objective blood tests, and the Mayo score were superior prognostic tools in PBC patients.

Utility and limitations of noninvasive fibrosis markers for predicting prognosis in biopsy-proven Japanese non-alcoholic fatty liver disease patients.

BACKGROUND AND AIM: The fibrosis stage of non-alcoholic fatty liver disease (NAFLD) is closely associated with long-term prognosis, including liver-related mortality. However, it is not yet clear whether noninvasive fibrosis markers can predict the incidence of non-liver-related complications in Japanese NAFLD. In this study, we clarified the prognosis of NAFLD patients, including non-liver-related diseases, based on hepatic pathology and noninvasive fibrosis markers. METHODS: A total of 246 Japanese patients with NAFLD diagnosed by liver biopsy were enrolled. We investigated their prognosis based on hepatic pathology and noninvasive fibrosis markers. RESULTS: When these patients were categorized based on the severity of liver fibrosis as F0-2 (n = 196) and F3-4 (n = 50), the patients with F3-4 had significantly poorer prognosis in overall survival rates and all complications (P < 0.05). The fibrosis-4 (FIB-4) index was useful to predict overall survival and the incidence of hepatocellular carcinoma and liver cirrhosis (LC)-related complications but not extrahepatic malignancies. Multiple logistic regression analyses revealed the following risk factors: total bilirubin ≥ 1.2 (hazard ratio [HR] 6.362, 95% confidence interval [CI] 1.393-29.052) and severe liver fibrosis (HR 6.512, 95% CI 1.433-29.592) for overall survival; liver fibrosis (F3-4) (HR 13.370, 95% CI 2.775-64.427) for hepatocellular carcinoma; FIB-4 index (HR 26.560, 95% CI 3.320-212.494) for LC-related complications, and liver inflammation (A2-3) (HR 4.214, 95% CI 1.354-13.116) for extrahepatic malignancies. CONCLUSIONS: Severe liver fibrosis was associated not only with the hepatocarcinogenesis and LC-related complications but also with extrahepatic malignancies. The FIB-4 index was useful for predicting liver-related diseases but had limitations in predicting extrahepatic malignancies.

A case of acute hepatitis B in a chronic hepatitis C patient after daclatasvir and asunaprevir combination therapy: hepatitis B virus reactivation or acute self-limited hepatitis?

Reactivation of hepatitis B virus (HBV) in HBV surface antigen (HBsAg)-positive patients treated with cytotoxic chemotherapy is well known. HBV reactivation in patients with HBV and hepatitis C virus (HCV) coinfection caused by direct-acting antiviral (DAA) therapy has also recently been reported. We report a case of acute hepatitis B in a patient with HCV infection after DAA therapy. An 83-year-old woman was referred for chronic hepatitis C. She was infected with HCV genotype 1b and negative for HBsAg at baseline. She received daclatasvir and asunaprevir therapy, and HCV became negative at 4 weeks and remained negative until 6 months after the end of DAA therapy. Acute hepatitis B developed 5 months after ending DAA therapy. Genome sequencing revealed the subgenotype as B1, and the serological subtype as adr. T118 K mutation at the S region as an immune escape mutant was identified. These virologic features led to HBV reactivation. The presence of hepatitis B core antibody or HBs antibody was not determined before DAA therapy, so prior HBV infection status was unclear. This case is speculated to represent HBV reactivation in a patient with previously resolved HBV induced by DAA therapy, based on virologic analysis and clinical status. The risk might be very low, but DAA therapy can cause HBV reactivation in chronic hepatitis C patients with prior HBV infection. When acute hepatitis emerges in patients who have received DAA therapy for HCV, HBV reactivation should be considered to allow early initiation of anti-HBV therapy.

[An autopsy case of penetration of a sigmoid colon diverticulum with septic shock during the treatment of lung cancer-related pain].

A 70-year-old man presented with septic shock and abdominal pain during treatment of pain caused by stage IV lung adenocarcinoma. CT revealed air collection from the retroperitoneum to the muscle around the thigh. Septic shock due to retroperitoneal penetration from the digestive tract was suspected. Despite treatment attempts, the patient died. The autopsy diagnosis was penetration of a sigmoid colon diverticulum under the serosa. When a diverticulum is located near the mesenterium and the size of penetration is small, the air collection rather than fecal matter is likely to extend retroperitoneally. Abdominal pain is little manifest in the penetration in contrast to perforation into abdominal cavity, and the attention is needed.

[Subcutaneous continuous injection of octreotide decreased the tumor marker levels and induced cystic necrosis of the tumors in a case of pancreatic neuroendocrine tumor with multiple hepatic metastases].

For symptom alleviation, subcutaneous continuous injection of octreotide was administered to a patient with pancreatic neuroendocrine tumor (NET) accompanied by multiple hepatic metastases and ascites. The level of the tumor marker neuron-specific enolase decreased to the normal range and cystic necrosis of the tumors was confirmed. There have been some reports on the antineoplastic effects of octreotide on pancreatic NET; therefore, octreotide appears to be a valid option as a therapeutic agent in patients with highly advanced pancreatic NET, in whom administration of molecular targeted or anticancer agents is difficult because of a poor general status.

[Effectiveness of mirtazapine for digestive symptoms in palliative care - retrospective study of 50 cases].

BACKGROUND: Previous research has reported that mirtazapine, a 5-HT3 antagonist, is effective for alleviation of digestive symptoms. PURPOSE: To elucidate the effect of low-dose mirtazapine on digestive symptoms. PATIENTS AND METHODS: Mirtazapine was administered to 50 cancer patients with digestive symptoms in palliative care, and the data were retrospectively examined. The initial doses ranged from 1.875 to 7.5 mg, and were increased to a maintenance dose according to its effects and the degree of somnolence. RESULTS: The cases were divided into 2 groups based on the cause of the digestive symptoms, including unknown causes(27 cases)and chemotherapy and/or opioid treatment(23 cases). At the initial dose, the efficacy rate was 74.4%, and the effectiveness was significantly higher in patients whose symptoms were due to chemotherapy and/ or opioid use than in those with symptoms of unknown cause(p=0.008). The rate of somnolence was 29.5%. Discontinuation of treatment within 1 week occurred in 10 cases. In 40 cases that continued administration of the maintenance dose, the efficacy rate was 82.5%, and the increased doses provided relief in the patient group with digestive symptoms of unknown cause. CONCLUSIONS: Low-dose mirtazapine showed different effects depending on the cause of digestive symptoms; therefore, the dose should be increased in patients whose symptoms are of unknown cause. Somnolence often appeared even at a low-dose, and this should be taken into consideration in the palliative care setting.

[An autopsy of G-CSF-producing anaplastic carcinoma of the pancreas with impaired accumulation on FDG-PET after S-1 chemotherapy].

This paper presents a woman in her 70's with G-CSF producing anaplastic carcinoma of the pancreas(Stage IVb)who underwent chemotherapy by S-1 alone. On FDG-PET after the first course, accumulation of FDG was impaired remarkably. After the second course, the patient died of carcinomatous pleuritis and peritonitis on the 88th day after initiation of treatment. G-CSF producing anaplastic carcinoma of the pancreas is extremely rare and there are no reports with regard to response evaluation by FDG-PET. Thus, this case has significant clinical value.

[A case of successful treatment of granulocyte colony-stimulating factor producing hepatocellular carcinoma accompanying type B hepatitis with tegafur-uracil].

A 37-year-old man underwent lobectomy of the right liver for granulocyte colony-stimulating factor (G-CSF) producing hepatocellular carcinoma accompanying type B hepatitis. Within two months after the surgery, lung metastases were revealed and administration of sorafenib was begun, however, the lung metastases continued to enlarge. Changing the patient's medication to tegafur-uracil provided remarkable reduction of the lung metastases. The patient is alive two years after diagnosis and receives outpatient chemotherapy. We concluded that this case is valuable with regard to the extreme rarity of G-CSF producing hepatocellular carcinoma and its successful treatment in this case.

[Medical treatment including pregabalin and radiation therapy provided remarkable relief for neuropathic pain by brachial plexus invasion in a patient with esophageal cancer].

This paper presents the case of a man in his 60's with advanced esophageal cancer after the first course of 5-FU/CDDP therapy during follow-up visit, who had pain and numbness from right scapula to upper arm. MRI revealed bone metastasis in the first thoracic vertebra and lymph node metastasis to be diagnosed as neuropathic pain by brachial plexus invasion. Radiation therapy and medical treatment with lornoxicam and controlled-release oxycodone started. However, breakthrough pain in the night was remarkably severe and numerical rating scale was 9-10/10. Pregabalin as analgesic adjuvant was administrated from dose of 75mg/day to 300mg/day and the breakthrough pain in the night disappeared completely. The patient underwent the second course of 5-FU/CDDP therapy without the pain. In the present case, the combined therapy of medical treatment and radiation therapy provided complete relief of the neuropathic pain. We conclude that it is an option to select pregabalin as effective agent for neuropathic pain in medical treatment.

[Low-dose mirtazapine improved nausea and appetite loss during S-1 therapy].

This paper presents a man in his 80's with pancreatic cancer(cStage IV). He suffered from nausea duringS -1 therapy, and therefore, prochlorperazine maleate at a daily dose of 15 mgwas administered. However, refractory nausea was diagnosed because it did not improve, and mirtazapine at a daily dose of 7. 5 mgbefore bedtime was started. Nausea was improved in the next morning, and the patient ate almost all of his breakfast. After that, no nausea appeared, and his food intake was robust. Mirtazapine is a new antidepressant called noradrenergic and specific serotonergic antidepressant(NaSSA)and blocks 5-HT3 receptors to improve nausea. Mirtazapine is usually started at a daily dose of 15 mg, but this dose induces somnolence. Therefore, mirtazapine was administered at a low daily dose of 7. 5 mgin the present case. No somnolence or disturbance of daily life was seen, and administration was safely continued. We conclude that low-dose mirtazapine is one effective option for refractory nausea duringS -1 therapy.

[Oxycodone and pregabalin using transdermal fentanyl patch provided relief of symptoms for postherpetic neuropathic pain in a patient with non-small cell lung cancer].

This paper presents a man in his 70's with non-small cell lung cancer (cT3N2M0, Stage III A) after chemoradiation therapy during follow-up visits. He was referred to the department of palliative care 1 month after the occurrence of herpes zoster, because of pain. Opioids (transdermal fentanyl patch and rapid-release oxycodone) were administered for his cancer pain previously. Additionally, gabapentin was given for neuropathic pain uncontrolled by opioids. However, this was replaced by pregabalin because he experienced somnolence. Although numbing improved remarkably with pregabalin, the pain was only slightly improved. The dose of rapid-release oxycodone was increased and controlled-release oxycodone was added. This provided for marked pain relief. We conclude that administration of pregabalin as an analgesic adjuvant, and oxycodone, which is an opioid, should be considered in the treatment of cancer patients without improvement of neuropathic pain from herpes zoster through use of the transdermal fentanyl patch.

Characteristics and prognosis of hepatocellular carcinoma detected in sustained responders to interferon therapy for chronic hepatitis C.

Interferon (IFN) therapy allows the eradication of hepatitis C virus (HCV) in some part of patients with chronic hepatitis C which is major cause of hepatocellular carcinoma (HCC). To clarify characteristics and prognoses of HCC detected in these patients (sustained responders to IFN), we compared HCC in sustained responders with HCC detected in patients without a sustained response (non-sustained responders). Characteristics and prognoses were compared in nine cases of HCC detected in sustained responders after IFN therapy and 61 cases of HCC detected in non-sustained responders at one of five our institutions. HCC in sustained responders often were larger (P=0.0051), less differentiated tumor (P=0.0084) than HCC in non-sustained responders when it was detected. No differences were observed in overall survival rate between sustained responders and non-sustained responders, but disease-free survival was higher in cases of HCC in sustained responders (P=0.0494). HCC detected in sustained responders often appear more advanced when detected than HCC in non-sustained responders, but recurrence seems to be less frequent when the initial HCC is treated sufficiently.

Prevalence and characterization of hepatitis C virus genotype 4 in Japanese hepatitis C carriers.

Hepatitis C virus (HCV) can be classified into six major genotypes, the prevalences of which differ around the world. In Japan, the main genotypes are HCV 1 and HCV 2; others are found only rarely. Little is known about the prevalence in Japan of HCV genotype 4 which, is found frequently in North and Central Africa and the Middle East. Thus, we conducted a study to clarify distribution of HCV genotype 4 and the clinical demographics of patients with HCV genotype 4 in Japan. We examined HCV genotypes in 899 Japanese individuals with HCV viremia living in Aichi Prefecture, including 63 hemophiliacs. Four patients (0.4%) were infected with HCV genotype 4. All four of these patients were male hemophiliacs who had received clotting factors from foreign countries. Three patients were co-infected with human immunodeficiency virus (HIV); none were co-infected with GB virus-C/hepatitis G virus. Phylogenetic analysis of the El region indicated that all four patients were infected with subtype 4a. This subtype is related genetically to a subtype previously reported in Japanese and Italian hemophiliacs. HCV genotype 4 is indeed rare in Japan and may be detected only among hemophiliacs who have received inactivated clotting factor concentrates from foreign countries.