aMAP score prediction of hepatocellular carcinoma occurrence and incidence-free rate after a sustained virologic response in chronic hepatitis C.

AIMS: Hepatocellular carcinoma (HCC) can still occur in hepatitis C virus (HCV) patients who have achieved a sustained virologic response (SVR), which remains an important clinical issue in the direct-acting antivirals era. The current study investigated the clinical utility of the aMAP score (consisting of age, male, albumin-bilirubin, and platelets) for predicting HCC occurrence in HCV patients achieving an SVR by direct-acting antivirals. METHODS: A total of 1113 HCV patients without HCC history, all of whom achieved an SVR, were enrolled for clinical comparisons. RESULTS: Hepatocellular carcinoma was recorded in 50 patients during a median follow-up period of 3.7 years. The aMAP score was significantly higher in the HCC occurrence group than in the HCC-free group (53 vs. 47, p < 0.001). According to risk stratification based on aMAP score, the cumulative incidence of HCC occurrence for the low-, medium-, and high-risk groups was 0.14%, 4.49%, and 9.89%, respectively, at 1 year and 1.56%, 6.87%, and 16.17%, respectively, at 3 years (low vs. medium, low vs. high, and medium vs. high: all p < 0.01). Cox proportional hazard analysis confirmed aMAP ≥ 50 (hazard ratio [HR]: 2.78, p = 0.014), age≥ 70 years (HR: 2.41, p = 0.028), ALT ≥ 17 U/L (HR: 2.14, p < 0.001), and AFP ≥ 10 ng/mL (HR: 2.89, p = 0.005) as independent risk factors of HCC occurrence. Interestingly, all but one patient (99.5%) with aMAP less than 40 was HCC-free following an SVR. CONCLUSION: The aMAP score could have clinical utility for predicting HCC occurrence in HCV patients achieving an SVR.

Serum sodium concentration is associated with increased risk of mortality in patients with compensated liver cirrhosis.

AIM: Although hyponatremia is associated with a poor prognosis in liver cirrhosis, little is known about the clinical significance of serum sodium concentration in cirrhosis in Japan. This study investigated associations of mortality in Japanese cirrhosis patients taking conventional diuretics with serum sodium concentration and other clinical characteristics. METHODS: A total of 171 consecutive patients with cirrhosis who were taking diuretic medication were enrolled retrospectively. We determined the prevalence of low serum sodium concentration and searched for associations with age, sex, etiology, complications of cirrhosis, liver function tests and Model for End-Stage Liver Disease (MELD) and MELD-Na scores. The predictive ability of sodium level on mortality was also investigated. RESULTS: Median serum sodium concentration was 139 mEq/L (interquartile range, 137-141). Only eight of 171 (4.7%) patients had low serum sodium (<130 mEq/L). Median MELD-Na score was 10.5 (interquartile range, 8.0-14.3). Cumulative survival rates were significantly lower in patients with Na of less than 139 mEq/L or MELD-Na score of 10.5 or more (log-rank test, P = 0.017 and P = 0.0002, respectively). Several liver function tests, MELD and MELD-Na scores, and the incidence of ascites were all significantly associated with patients having Na of less than 139 mEq/L. CONCLUSION: Serum sodium concentration below 139 mEq/L and MELD-Na score above 10.5 may be predictive markers for mortality in patients with cirrhosis despite being within normal ranges. These markers may help to better assess and manage the prognosis of patients with cirrhosis in Japan.

Eosinophilic gastroenteritis complicated with Helicobacter pylori infection unresponsive to eradication therapy.

An adolescent girl presented with inappetence. Upper gastrointestinal endoscopy showed rough and cracked mucosa at the gastric antrum with a scarred duodenal ulcer, and a biopsy sample demonstrated abundant eosinophils. We therefore diagnosed the patient as having eosinophilic gastroenteritis. Eradication therapy for Helicobacter pylori (H. pylori) did not improve her symptoms; however, proton pump inhibitor therapy was effective in resolving her chief complaints. There are several reports of eosinophilic gastroenteritis complicated with H. pylori infection in which the association between eradication therapy and the patient's symptoms is unclear. In the present case, the patient's symptoms did not improve with eradication therapy, and there appeared to be no relationship between the two.

KIR3DL1-HLA-Bw4 combination and IL28B polymorphism predict response to Peg-IFN and ribavirin with and without telaprevir in chronic hepatitis C.

Natural killer cells play a key role in the immune control of viral infections. Killer immunoglobulin-like receptors (KIRs) regulate natural killer cell activation and inhibition through the recognition of their cognate HLA class I ligands. We assessed the predictive factors of a sustained virological response (SVR) in 200 Japanese patients with chronic genotype 1b hepatitis C who were treated with telaprevir (TVR), pegylated-interferon-α2b (PEG-IFN), and ribavirin (RBV) triple therapy (92 patients) or PEG-IFN/RBV therapy alone (108 patients). Sixteen KIR genotypes, HLA-A, -B and -C ligands, and an interleukin (IL) 28B polymorphism (rs8099917) were analyzed. We observed that triple therapy, white blood cell count, hemoglobin value, hepatitis C viral load, a rapid virological response (RVR), IL28B TT genotype, and KIR3DL1-HLA-Bw4 genotype were associated with an SVR. In multivariate regression analysis, we identified an RVR (P < 0.000001; odds ratio [OR] = 20.95), the IL28B TT genotype (P = 0.00014; OR = 5.53), and KIR3DL1-HLA-Bw4 (P = 0.004, OR = 3.42) as significant independent predictive factors of an SVR. In conclusion, IL28B and KIR3DL1/HLA-Bw4 are independent predictors of an SVR in Japanese patients infected with genotype 1b HCV receiving TVR/PEG-IFN/RBV or PEG-IFN/RBV therapy.

KIR, HLA, and IL28B variant predict response to antiviral therapy in genotype 1 chronic hepatitis C patients in Japan.

Natural killer cell responses play a crucial role in virus clearance by the innate immune system. Although the killer immunoglobulin-like receptor (KIR) in combination with its cognate human leukocyte antigen (HLA) ligand, especially KIR2DL3-HLA-C1, is associated with both treatment-induced and spontaneous clearance of hepatitis C virus (HCV) infection in Caucasians, these innate immunity genes have not been fully clarified in Japanese patients. We therefore investigated 16 KIR genotypes along with HLA-B and -C ligands and a genetic variant of interleukin (IL) 28B (rs8099917) in 115 chronic hepatitis C genotype 1 patients who underwent pegylated-interferon-α2b (PEG-IFN) and ribavirin therapy. HLA-Bw4 was significantly associated with a sustained virological response (SVR) to treatment (P = 0.017; odds ratio [OR] = 2.50, ), as was the centromeric A/A haplotype of KIR (P = 0.015; OR 3.37). In contrast, SVR rates were significantly decreased in patients with KIR2DL2 or KIR2DS2 (P = 0.015; OR = 0.30, and P = 0.025; OR = 0.32, respectively). Multivariate logistic regression analysis subsequently identified the IL28B TT genotype (P = 0.00009; OR = 6.87, 95% confidence interval [CI] = 2.62 - 18.01), KIR2DL2/HLA-C1 (P = 0.014; OR = 0.24, 95% CI = 0.08 - 0.75), KIR3DL1/HLA-Bw4 (P = 0.008, OR = 3.32, 95% CI = 1.37 - 8.05), and white blood cell count at baseline (P = 0.009; OR = 3.32, 95% CI = 1.35 - 8.16) as independent predictive factors of an SVR. We observed a significant association between the combination of IL28B TT genotype and KIR3DL1-HLA-Bw4 in responders (P = 0.0019), whereas IL28B TT along with KIR2DL2-HLA-C1 was related to a non-response (P = 0.0067). In conclusion, combinations of KIR3DL1/HLA-Bw4, KIR2DL2/HLA-C1, and a genetic variant of the IL28B gene are predictive of the response to PEG-IFN and ribavirin therapy in Japanese patients infected with genotype 1b HCV.

A case of pyogenic liver abscess infected with Fusobacterium necrophorum depicted by microscopy and confirmed by tissue culture.

A 40-year-old man was admitted with a continuous high grade fever accompanying a relatively large solitary liver abscess with septations. A puncture of the abscess revealed gram-negative rods that could be identified histologically as Fusobacterium necrophorum, which was later confirmed by tissue culture. The patient was switched to meropenem and penicillin, and cured of the infection. Fusobacterium necrophorum is a rare bacterium causing potentially fatal liver abscesses in humans. Clinicians should bear Fusobacterium necrophorum in mind when treating patients with an enlarged solitary liver abscess.

Ileocecal collision tumor composed of adenocarcinoma and primary malignant lymphoma.

Collision tumor means that two kinds of histologically distinct tumors coexist and neighbor without histological interminglement. This report describes a rare case of an ileocecal collision tumor composed of adenocarcinoma and primary malignant lymphoma. A 76-year-old woman was referred to our institute with anemia and a right lower quadrant mass. Colonoscopy revealed type 2 advanced colon cancer in the cecum accompanied by a submucosal mound neighboring this cancer, which appeared different from the usual shape of colon cancer. A barium enema study manifested the typical apple-core sign in the cecum with a smooth semicircular line appearing in the shadow of the apple-core sign. Biopsy specimens showed adenocarcinoma, so a right hemicolectomy was performed. The gross resected specimen presented a mass measuring 64 × 58 × 28 mm at the ileocecal portion. The half of this mass on the colonic side had a crater-like appearance, whereas the remaining part of the mass on the ileal side had an aspect with a smooth surface. Microscopic examination disclosed that the mass was composed of adenocarcinoma and malignant lymphoma bordering on each other and mediated by a thin layer of connective tissue. Cases of colon tumors with an unusual epithelial and submucosal appearance may be instances of collision tumors composed of cancer and malignant lymphoma.

[A case of acute pancreatitis after extracorporeal shock wave lithotripsy for renal pelvic calculus].

A 62-year-old man was admitted to receive extracorporeal shock wave lithotripsy (ESWL) for a right renal pelvic calculus. During the operation, the patient complained of right upper quadrant pain. Later in the day, laboratory data showed elevated serum amylase levels, and abdominal CT revealed an enlarged pancreas. These findings led to a diagnosis of acute pancreatitis. The following day, urine output had decreased, and pleural and ascitic fluid had accumulated. For these reasons, the patient was transferred to our hospital to receive combination therapy, including arterial infusion therapy with protease inhibitors, antibiotics and continuous hemodiafiltration. The condition of the patient improved, and he was discharged on day 30. Acute pancreatitis should be considered as an early complication after ESWL for urinary tract calculus.