Kessarin Thanapirom

The Learning Curve of Gastric Intestinal Metaplasia Interpretation on the Images Obtained by Probe-Based Confocal Laser Endomicroscopy

Background. Reading the results of gastric intestinal metaplasia (GIM) with probe-based confocal laser endomicroscopy (pCLE) by the expert was excellent. There is a lack of study on the learning curve for GIM interpretation. Therefore, we conducted a study to explore the learning curve in the beginners. Material and Method. Five GI fellows who had no experience in GIM interpretation had been trained with a set of 10 pCLE video clips of GIM and non-GIM until they were able to interpret correctly. Then they were asked to interpret another 80 video clips of GIM and non-GIM. The sensitivity, specificity, accuracy, PPV, NPV, and interobserver agreement on each session were analyzed. Results. Within 2 sessions, all beginners can achieve 80% accuracy with substantial to almost perfect level of interobserver agreement. The sensitivities and specificities among all interpreters were not different statistically. Four out of five interpreters can maintain their high quality of reading skill. Conclusion. After a short session of training on GIM interpretation of pCLE images, the beginners can achieve a high level of reading accuracy with at least substantial level of interobserver agreement. Once they achieve the high reading accuracy, almost all can maintain their high quality of reading skill.

Aloe vera attenuated liver injury in mice with acetaminophen-induced hepatitis

BackgroundAn overdose of the acetaminophen causes liver injury. This study aims to examine the anti-oxidative, anti-inflammatory effects of Aloe vera in mice with acetaminophen induced hepatitis.MethodsMale mice were randomly divided into three groups (n = 8 each). Control group were given orally distilled water (DW). APAP group were given orally N-acetyl-P-aminophenol (APAP) 400 mg/kg suspended in DW. Aloe vera-treated group were given orally APAP and Aloe vera (150 mg/kg) suspended in DW. Twenty-four hours later, the liver was removed to determine hepatic malondialdehyde (MDA), hepatic glutathione (GSH), the number of interleukin (IL)-12 and IL-18 positive stained cells (%) by immunohistochemistry method, and histopathological examination. Then, the serum was collected to determine transaminase (ALT).ResultsIn APAP group, ALT, hepatic MDA and the number of IL-12 and IL-18 positive stained cells were significantly increased when compared to control group (1210.50 ± 533.86 vs 85.28 ± 28.27 U/L, 3.60 ± 1.50 vs 1.38 ± 0.15 nmol/mg protein, 12.18 ± 1.10 vs 1.84 ± 1.29%, and 13.26 ± 0.90 vs 2.54 ± 1.29%, P = 0.000, respectively), whereas hepatic GSH was significantly decreased when compared to control group (5.98 ± 0.30 vs 11.65 ± 0.43 nmol/mg protein, P = 0.000). The mean level of ALT, hepatic MDA, the number of IL-12 and IL-18 positive stained cells, and hepatic GSH in Aloe vera-treated group were improved as compared with APAP group (606.38 ± 495.45 vs 1210.50 ± 533.86 U/L, P = 0.024; 1.49 ± 0.64 vs 3.60 ± 1.50 nmol/mg protein, P = 0.001; 5.56 ± 1.25 vs 12.18 ± 1.10%, P = 0.000; 6.23 ± 0.94 vs 13.26 ± 0.90%, P = 0.000; and 10.02 ± 0.20 vs 5.98 ± 0.30 nmol/mg protein, P = 0.000, respectively). Moreover, in the APAP group, the liver showed extensive hemorrhagic hepatic necrosis at all zones while in Aloe vera-treated group, the liver architecture was improved histopathology.ConclusionsAPAP overdose can cause liver injury. Our result indicate that Aloe vera attenuate APAP-induced hepatitis through the improvement of liver histopathology by decreased oxidative stress, reduced liver injury, and restored hepatic GSH.

Genetic variation in the vitamin D pathway CYP2R1 gene predicts sustained HBeAg seroconversion in chronic hepatitis B patients treated with pegylated interferon: A multicenter study

Evidence of a role of vitamin D in the immune system is increasing. Low serum vitamin D is associated with increased hepatitis B virus replication. Genome-wide association study (GWAS) data has revealed a number of the single nucleotide polymorphisms (SNPs) within the vitamin D synthetic pathway that affect vitamin D functions. We aimed to determine the association between SNPs in the vitamin D gene cascade and response to pegylated interferon (PegIFN) therapy in hepatitis B e-antigen (HBeAg)-positive patients. One hundred and eleven patients treated for 48 weeks with PegIFN-alfa 2a at 13 hospitals were retrospectively evaluated. Thirteen SNPs derived from vitamin D cascade-related genes, including DHCR7 (rs12785878), CYP27B1 (rs10877012), CYP2R1 (rs2060793, rs12794714), GC (rs4588, rs7041, rs222020, rs2282679), and VDR (FokI, BsmI, Tru9I, ApaI, TaqI), were genotyped. Thirty-one patients (27.9%) seroconverted to HBeAg after 24 weeks of treatment. Multivariate analysis found pretreatment qHBsAg <10,000 IU/mL (OR = 7.73, 95% CI: 2.36–25.31, P = 0.001), CYP2R1 rs12794714 TT genotype (OR = 4.16, 95% CI: 1.07–16.25, P = 0.04), and baseline ALT >2 times the upper limit of normal (OR = 3.83, 95% CI: 1.31–11.22, P = 0.014) predicted sustained HBeAg seroconversion after completion of PegIFN treatment. HBV DNA during study period tended to be lower with the rs12794714 CYP2R1 TT than the non-TT genotype. The rs12794714 CYP2R1 polymorphism may be a useful pretreatment factor predictive of sustained HBeAg seroconversion after PegIFN therapy. This study provides evidence that not only vitamin D level but also genetic variation of CYP2R1 in the vitamin D cascade influences host immune response in chronic HBV infection.

Association between CXCL10 and DPP4 Gene Polymorphisms and a Complementary Role for Unfavorable IL28B Genotype in Prediction of Treatment Response in Thai Patients with Chronic Hepatitis C Virus Infection.

Pretreatment serum levels of interferon-γ-inducible protein-10 (IP-10, CXCL10) and dipeptidyl peptidase-4 (DPP IV) predict treatment response in chronic hepatitis C (CHC). The association between functional genetic polymorphisms of CXCL10 and DPP4 and treatment outcome has not previously been studied. This study aimed to determine the association between genetic variations of CXCL10 and DPP4 and the outcome of treatment with pegylated interferon-α (PEG-IFN-α) based therapy in Thai patients with CHC. 602 Thai patients with CHC treated using a PEG-IFN-α based regimen were genotyped for CXCL10 rs56061981 G>A and IL28B rs12979860 C>T. In addition, in patients infected with CHC genotype 1, DPP4 (rs13015258 A>C, rs17848916 T>C, rs41268649 G>A, and rs 17574 T>C) were genotyped. Correlations between single nucleotide polymorphisms, genotype, and treatment response were analyzed. The rate of sustained virologic response (SVR) was higher for the CC genotype of IL28B rs12979860 polymorphisms than for non-CC in both genotype 1 (60.6% vs. 29.4%, P < 0.001) and non-genotype 1 (69.4% vs. 49.1%, P < 0.05) CHC. SVR was not associated with the CXCL10 gene variant in all viral genotypes or DPP4 gene polymorphisms in viral genotype1. Multivariate analysis revealed IL28B rs12979860 CC genotype (OR = 3.12; 95% CI, 1.72–5.67; P < 0.001), hepatitis C virus RNA < 400,000 IU/ml (OR = 2.21; 95% CI, 1.22–3.99, P < 0.05), age < 45 years (OR = 2.03; 95% CI, 1.11–3.68; P < 0.05), and liver fibrosis stage 0–1 (OR = 1.64; 95% CI, 1.01–2.65, P < 0.05) were independent factors for SVR. Unfavorable IL28B rs12979860 CT or TT genotypes with the CXCL10 rs56061981 non-GG genotype were associated with a higher SVR than GG genotype (66.7% vs. 33.0%, P = 0.004) in viral genotype 1. In Thai CHC genotype 1 infected patients with an unfavorable IL28B rs12979860 CT/TT genotype, the complementary CXCL10 polymorphism strongly enhances prediction of treatment response.

Polymyositis Associated with Hepatitis B Virus Cirrhosis and Advanced Hepatocellular Carcinoma

Polymyositis (PM) is an inflammatory condition of skeletal muscle and is believed to be a paraneoplastic syndrome associated with various types of cancer. PM associated with chronic hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is very rare. We report a case of advanced HCC with chronic HBV cirrhosis that presented with proximal muscle weakness. Further investigation showed elevation of muscle enzymes, myopathic pattern of electromyography (EMG), and evidence of myositis compatible with PM. Lamivudine and 1 mg/kg of oral prednisolone were given. Two sessions of transcatheter arterial chemoembolization (TACE) were performed and sorafenib was started. Muscle enzymes normalized after 6 weeks of treatment. Unfortunately, 5 months after treatment, patient was readmitted and died of severe bacterial pneumonia.

Vitamin D supplementation improves serum markers associated with hepatic fibrogenesis in chronic hepatitis C patients: A randomized, double-blind, placebo-controlled study

Hepatic fibrosis is the net accumulation of matrix tissue components which controlled by pro-fibrolytic enzymes, matrix metalloproteinases (MMPs), and pro-fibrotic cytokine, TGF-β1, and enzymes, tissue inhibitors of MMPs (TIMPs). Vitamin D (VD) supplementation has been shown to reverse these processes in vitro and in vivo. This study sought to determine the effect of VD supplementation on serum fibrotic markers in chronic hepatitis C (CHC) patients. Fifty-four CHC patients with VD deficiency were randomized into two groups, a VD group (n = 29) and a placebo group (n = 29). The serum levels of 25-hydroxy VD, TGF-β1, TIMP-1, MMP2 and MMP9 were measured at baseline and at the end of the 6-week study period. Upon correction of VD levels, TGF-β1 and TIMP-1 levels were decreased, and the MMP2 and MMP9 levels were significantly increased in the VD group. A comparison of the mean changes (delta) in the markers between groups showed that TGF-β1 and TIMP-1 levels were significantly decreased and the MMP2 and MMP9 were significantly higher in the VD group than in the placebo group. By using CHC patients as a model, this study provides additional evidence that VD plays an important role in the reversal of hepatic fibrogenesis.

Gastrointestinal: Splenic abscesses-related gastrosplenic fistula: Unusual complication of melioidosis: Gastrointestinal: Splenic abscesses-related gastrosplenic fistula: Unusual complication of melioidosis

A 52-year-old man with uncontrolled diabetes mellitus presented with fever, abdominal pain associated with melena and jaundice for 2 weeks. Physical examination revealed body temperature of 40 °C, marked pale conjunctiva, and mild icteric sclera. Abdominal examination showed hepatomegaly (liver span 13 cm) without splenic enlargement. He had localized pain and marked tenderness at the upper left quadrant of the abdomen. Laboratory investigations showed a white blood cell count of 12 300 × 10/L with neutrophil predominance, hemoglobin of 6.8 g/dL. Liver function test revealed total bilirubin 3.4 mg/dL, direct bilirubin 1.9 mg/dL, aspartate aminotransferase 94 IU/L, alanine aminotransferase 69 IU/L, alkaline phosphatase 234 IU/L, and creatinine 0.72 mg/dL. Gastroscopy showed focal thickening folds at the greater curve of the stomach and a 0.7-cm ulcer with purulent discharge (Fig. 1). Computed tomography of abdomen revealed multiple rim-enhancing hypodense lesions in the spleen with hyperdense fluid content in the gastrosplenic region and multiple areas of erosion through serosal surface of the adjacent gastric fundus (Fig. 2). Percutaneous aspiration of splenic abscesses was performed. Pus culture and hemoculture revealed Burkholderia pseudomallei. Serum melioidosis antibodies were positive at a dilution of >1:320 as tested by indirect hemagglutination. Melioidosis splenic abscesses-related gastrosplenic fistula was diagnosed. Ceftazidime at the dose of 6 g/day was given. However, he still had persistent fever and developed septic shock after 10 days of therapy. Splenectomy with repairing of gastrosplenic fistula was performed. After surgery, he was well and discharged with oral trimethoprim/sulfamethoxazole for 3 months. Subsequently, he has been doing well without recurrent diseases. Gastrosplenic fistula is a rare complication of malignant or benign diseases of the stomach or spleen. Splenic abscess-related gastrosplenic fistula is a very unusual condition, and, in most cases, lymphoma is the major cause. The differential etiologies are a complication of peptic ulcer, gastric adenocarcinoma, and Crohn’s disease. Gastrosplenic fistula associated with splenic abscess due to melioidosis is extremely uncommon; only one case has been reported. Melioidosis is endemic in North Australia and Southeast Asia including Thailand. The causative organism is B. pseudomallei. The usual clinical presentations are pneumonia, genitourinary infection, skin infection, and visceral organ abscess, particularly lung, spleen, and liver. Risk factors of melioidosis are diabetes, excess alcohol consumption, chronic lung diseases, and chronic renal diseases. Serologic testing alone is not a reliable method of diagnosis. The culture and isolation of B. pseudomallei from clinical samples are crucial tests for diagnosis. Prolonged antibiotic therapy is needed for the treatment of visceral melioidosis abscesses and prevention of relapse. Several antibiotic regimens have been recommended. Therapies generally began with an intravenous antibiotic such as ceftazidime or carbapenems for 10–14 days and followed by oral antibiotics, for example, trimethoprim/sulfamethoxazole for a minimum of 3 months. Percutaneous drainage or surgery might be considered in patients with uncontrolled infection or treatment failure.

Correction of vitamin D deficiency facilitated suppression of IP-10 and DPP IV levels in patients with chronic hepatitis C: A randomised double-blinded, placebo-control trial

Vitamin D deficiency was common among patients with chronic hepatitis C (CHC) and had negative influence on treatment outcome. Correction of vitamin D deficiency improved treatment response. Interferon gamma-induced protein 10 (IP-10) and enzyme dipeptidyl peptidase-4 (DPP IV) involved in inflammatory responses in CHC. Their higher levels at pretreatment of CHC could predict poorer responses. Vitamin D suppressed expression of IP-10 from monocytes in vitro. In CHC patients, DPP IV involved in IP-10 regulation. We hypothesized that correction of vitamin D insufficiency or deficiency in CHC patients might restore immune dysregulation through a pathway linked to the TH1/Th2 cytokines, IP-10 or DPP IV. We conducted a double-blind, placebo-controlled trial. 80 CHC patients with vitamin D levels less than 30 ng/mL were assigned to receive vitamin D (40) or placebo (40) supplements for 6 weeks. The levels of 25-hydroxyvitamin D [25(OH)D], Th1/Th2 cytokines, IP-10 and DPP IV were measured at baseline and at the 6th week. At the end of study, the mean 25(OH)D level in vitamin D group was significantly increased and normalised. There were no changes in the level of Th1/Th2 cytokines. Our important finding revealed that upon correction of vitamin D insufficiency or deficiency, the serum IP-10 and DPP IV levels were decreased significantly as compare to the placebo group (delta changes; 83.27 vs -133.80; 95% CI [-326.910, -40.758], p = 0.0125, and 271.04 vs -518.69; 95% CI [-1179,15, -59.781], p = 0.0305, respectively. As previous evidences suggested that each factor individually influenced and predicted outcome of CHC treatment. Our results offer a new insight and help to piece the puzzle of vitamin D deficiency, IP-10 and DPP IV together in CHC. Trial registration: Thai Clinical Trials Registry TCTR20160429001

Hepatobiliary and Pancreatic: Epstein-Barr virus-associated smooth muscle tumors: Unusual cause of hepatic mass in AIDS patient

A 33-year-old man presented with chronic watery diarrhea, fever, and weight reduction of 9 kg in 6months. On physical examination, body temperature was 37.5 °C. Abdominal examination revealed hepatomegaly without splenomegaly. Liver function test was normal except for elevated alkaline phosphatase (371 IU/L) with normal alpha-fetoprotein (0.76 IU/ml). Through work-up, he was first diagnosed with acquired immunodeficiency syndrome (AIDS) with mycobacterium avium complex enteritis. His CD4 count was 4 cells/mm. Epstein–Barr virus (EBV) serology was negative for anti-EBV viral capsid antigen IgM and positive for anti-EBV viral capsid antigen IgG and anti-EBV nuclear antigen. Plasma EBV viral load was 661 copies/mL. Tests for hepatitis B and C virus were negative. Abdominal magnetic resonance imaging showed multiple well-defined hyposignals in T1/intermediate in T2 with rim enhancing on arterial, portovenous, and delayed phase lesions (Fig. 1a,b) scattering at both lobes, and innumerable intra-abdominal lymph nodes. Liver biopsy of the largest lesion. Histological examination demonstrated neoplastic spindle cell arranged in short fascicles. Scattered tumor cell process mild to moderate pleomorphic, hyperchromatic tapering-end nuclei, and mitosis were noted (Fig. 1c). Immunohistochemistry study showed positive result for smooth muscle actin (Fig. 1d) and negative for CD117, DOG1, CD34, Desmin, and S-100, which is compatible for smooth muscle cell tumor (SMT). The tumor showed strong nuclear staining for EBV-encoded small RNA-1 in situ hybridization (Fig. 1e). Indicating that these are EBV-associated SMTs. Following treatment of Mycobacterium avium complex (MAC) infection with clarithromycin, ethambutol, and levofloxacin, he was administered antiretroviral drugs, consisting of efavirenz, emtricitabine, tenofovir. Surgery was planned for management hepatic lesions. EBV-associated SMTs are rare hepatic tumors in immunocompromised patients, such as those with AIDS or organ transplant. Unique clinical features are multicentric involvement, a preference for central nervous system involvement both cranial and spinal epidura, but extra-central nervous system lesions especially liver involvement as in this patient are unusual. Brain imaging was not performed on this patient because of a completely normal neurological exam. The imaging features of hepatic EBV-SMT is non-specific, mostly contrast-enhancing mass(es), which is difficult to differentiate from other primary or metastatic liver tumors. Test of plasma EBV viral load is less helpful for diagnosis because of low sensitivity; thus, tissue diagnosis is an important issue. The differential diagnosis of hepatic spindle cell neoplasms in HIV infection includes mycobacterial spindle cell pseudo-tumor and Kaposi sarcoma. Tissue smooth muscle actin immunohistochemistry and EBV-encoded small RNA-1 in situ hybridization are the most helpful tools for diagnosis. At present, there is no standard treatment for EBV-SMT. Case series of hepatic EBV-SMT suggested complete surgical resection showed satisfactory results. In contrast, chemotherapy and radiotherapy appear to be ineffective in these tumors.

Hepatopleural Fistula with Empyema Thoracis: A Rare Complication of Autosomal Dominant Polycystic Kidney Disease

We report a 70-year-old man with autosomal dominant polycystic kidney disease (ADPKD) who presented with right-sided extended-spectrum beta-lactamases Escherichia coli empyema thoracis. Chest and abdominal computed tomography showed hepatopleural fistula. The patient refused a surgical operation and was treated with tube thoracotomy, percutaneous drainage of dominant liver cyst, and intravenous antibiotics. His symptoms improved after 2 months of nonsurgical treatment.