Metabonomics and pharmacodynamics studies of Gentiana radix and wine-processed Gentiana radix in damp-heat jaundice syndrome rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Gentiana radix (GR) and wine-processed Gentiana radix (WGR) have been commonly used in folk medicine for the treatment of bile or liver disorders, including jaundice, hepatitis, swelling and inflammation for thousands of years. However, the therapeutic effects of gentian root (GR) and wine-made gentian root (WGR) treatment on damp-heat jaundice syndrome (DHJS) have not been studied in animal experiments. AIM OF THE STUDY: This study aimed to investigate the protective effects and mechanisms of GR and WGR on DHJS in rats. MATERIALS AND METHODS: In a high-fat and high-sugar diet in a humidified hot environment, hepatic injury induced by giving alpha-naphthalene isothiocyanate (ANIT) in rats were used as a DHJS model. Histological analysis, enzyme-linked immunosorbent assay (ELISA), PCR analysis, and metabolomics were used to elucidate the mechanism of GR and WGR for DHJS. RESULTS: The results indicated that GR and WGR affected DHJS by inhibiting the release of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), direct bilirubin (D-BIL), total bilirubin (TBIL), total bile acid (TBA), malondialdehyde (MDA), glutathione S-transferase (GST) (P < 0.05). In addition, they significantly reduced the gene expression levels of Na+/taurocholate cotransporting polypeptide (NTCP), bile salt export pump (BESP), multidrug resistance-associated protein 2 (MRP2) and multidrug resistance-associated protein 3 (MRP3) (P < 0.05). The WGR group improved the above function indicators better than the GR group. GR and WGR could restore 11 potential biomarkers in rats with DHJS tended to return to normal levels, these biomarkers were involved in arachidonic acid metabolism, steroid hormone biosynthesis, biosynthesis of unsaturated fatty acids, porphyrin and chlorophyll metabolism, retinol metabolism, arginine biosynthesis. The results of the metabolic pathway showed that WGR was significantly better than GR in the improvement of porphyrin and chlorophyll metabolism. CONCLUSIONS: These findings suggest that treatment with GR and WGR has a beneficial effect on DHJS in rats, the major mechanisms may be involved in improving functional indicators of the body and endogenous metabolism, and WGR is more effective than GR. It provides important evidence for the clinical application of GR and WGR in the treatment of DHJS.

A study for quality evaluation of Lysimachiae herba from different origins based on fingerprint-activity relationship modeling and multi-component content determination.

ETHNOPHARMACOLOGICAL RELEVANCE: Lysimachiae Herba (LH), called Jinqiancao in Chinese, is a commonly used traditional Chinese medicine in clinical practice. Doctors in the Qing Dynasty recorded that it tastes bitter, sour, and slightly cold, and it belongs to the liver, gallbladder, kidney, and bladder meridians. It has the effects of removing dampness and jaundice, eliminating gallstones, and reducing blood stasis. Because of its potent pharmacological effects, it is extensively utilized in the treatment of hepatobiliary and urinary system stones, jaundice, hepatitis, and cholecystitis. Although LH is included in "Sichuan authentic Chinese herbal medicine records", the quality of it from different origins still lacks reliable evaluation methods, which is difficult to reflect the high quality of LH from Sichuan. AIMS OF THE STUDY: This study aimed to establish a fingerprint-activity relationship model between the fingerprint of LH and its protective effect on cholestatic liver injury, and to evaluate the quality of LH from Sichuan and Guizhou by multivariate statistical analysis. MATERIALS AND METHODS: 20 batches of LH samples were collected from Sichuan and Guizhou. Characteristic fingerprints of samples were established by UHPLC-Triple TOF-MS/MS and the chemical pattern recognition analysis was carried out by HCA. Then, a rat model of cholestatic liver injury was established by intragastric administration of ANIT. Combined with the common peak information of fingerprint and pharmacodynamic index results, GCA and BCA were used to screen the efficacy markers. Finally, based on UHPLC-QTRAP-MS/MS, the content of efficacy markers was simultaneously determined, and the overall quality of LH from two origins was evaluated by PCA and TOPSIS. RESULTS: In the fingerprint of 20 batches of LH, 15 common peaks were identified in the negative ion mode, and the similarity was between 0.887 and 0.981. Pharmacological results showed that, compared with the control group, the content of AST, ALT, ALP, TBA, TBIL, and MDA in serum increased, and the content of GSH and SOD activity decreased after 48 h of ANIT administration. In addition, compared to the model group, different doses of LH from the two origins could decrease the serum levels of AST, ALT, ALP, TBA, TBIL, and MDA, raise the levels of GSH and SOD activity, reduce the infiltration range of inflammatory cells, and improve the cholestatic liver injury in rats. Among them, the pharmacodynamic indices of the SCHD group were significantly better. GCA and BCA showed that a total of 7 constituents related to the efficacy were screened, which were proanthocyanidin B1, ferulic acid, hyperoside, astragalin, nicotiflorin, afzelin, and kaempferol. Besides, the content of 7 active constituents in samples from Sichuan was higher than that from Guizhou, indicating that the quality of samples from Sichuan may be better, consistent with the result of the pharmacological experiment. CONCLUSION: The quality and efficacy of LH from different origins were stable, and all of them had protective effects on cholestatic liver injury in rats. The method established in this study is accurate and reliable, and it can be used to comprehensively evaluate the internal quality of LH.

Immune checkpoint inhibitor use and the incidence of hepatitis B virus reactivation or immune-related hepatitis in non-small cell lung cancer patients with chronic hepatitis B.

BACKGROUND: The safety of immune-checkpoint inhibitors (ICIs) has not been thoroughly investigated in non-small cell lung cancer (NSCLC) patients with chronic hepatitis B (CHB) or occult hepatitis B infection (OBI). The authors analyzed the incidence of hepatitis B virus (HBV) reactivation, immune-related hepatitis and jaundice in NSCLC patients in a real-world setting. METHODS: A total of 1277 NSCLC patients treated with ICIs were analyzed. Among them, 52 patients were hepatitis B surface antigen (HBsAg) (+) (group A, CHB), 759 patients were HBsAg (-)/hepatitis B core antibody immunoglobulin G (anti-HBc IgG) (+) (group B, OBI), and 466 patients were HBsAg (-)/anti-HBc IgG (-) (group C). Among the 52 patients with CHB, 38 (73.1%) were receiving antiviral therapy. The primary end point was HBV reactivation, immune-related hepatitis, and jaundice. The secondary end points included other immune-related adverse events and efficacy. RESULTS: HBV reactivation was observed in two patients (0.2%) who were both in group A (CHB). Among CHB patients who were not receiving antiviral therapy, HBV reactivation was observed in 14.3% (2 of 14 patients). The incidences of immune-related hepatitis and jaundice were comparable among the three groups. The incidence of ≥grade 3 other immune-related adverse events and efficacy were all comparable among the three groups (p > .05 for all comparisons). CONCLUSIONS: In this large, real-world cohort study, the safety and efficacy of ICIs were comparable in patients with CHB and OBI. HBV reactivation was observed in patients with CHB without antiviral therapy indicating antiviral prophylaxis should be required for them. For patients with OBI, the risk of HBV reactivation was minimal.

Immunoglobulin for hemolytic jaundice in Japan: A retrospective survey.

BACKGROUND: Intravenous immunoglobulin G (IVIG) is used to treat blood-type incompatibility hemolytic disease of newborns (BTHDN). Although IVIG's efficacy for treating BTHDN has been challenged, as an updated systematic review suggests, IVIG could significantly reduce exchange transfusions. We conducted a mail-in questionnaire survey to ascertain actual use of IVIG for BTHDN in Japan. METHODS: The survey, conducted in 2014, included infants born between January 1, 2009, and December 31, 2013. Questionnaires were sent to the heads of neonatal intensive care units (NICUs) at perinatal centers of the Japan Neonatologist Association. RESULTS: A total of 195 centers (64.6%) responded to the questionnaire. During the study period, 170 centers (87.2%) reported incidences of BTHDN. Among these centers, there were 1726 diagnosed cases of BTHDN in neonates. Of these cases, 419 infants were treated with IVIG in 127 centers, representing approximately 74.7% of all centers. After the exclusion of cases with missing data and those where consent for data usage was not obtained, a total 916 infants were included in this study. Of these, 219 (23.9%) were treated with IVIG after phototherapy, and 187 (20.4%) of these infants did not require further blood exchange transfusion. The IVIG dosages ranged from 40 to 1200 mg/kg/dose, but the majority were between 500 and 1000 mg/kg/dose, with a median of 800 mg/kg/dose. About 20% of the infants treated with IVIG showed late-onset anemia and required treatment. Adverse events were reported in less than 1% of infants. CONCLUSIONS: For the treatment of BTHDN, IVIG administration was widely used in NICUs in Japan without severe adverse events.

[Effect of soil moisture on efficacy to eliminate dampness and relieve jaundice and flavonoid content of Sedum sarmentosum].

The growth environment of medicinal plants plays an important role in the formation of their medicinal quality. However, there is a lack of combined analysis studying the close relationship between the growth environment, chemical components, and related biological activities of medicinal plants. Therefore, this study investigated the effect of different soil moisture treatments on the efficacy to eliminate dampness and relieve jaundice and the flavonoid content of Sedum sarmentosum, and explored their correlation. The flavonoid content in the decoction of S. sarmentosum growing under field conditions with soil moisture levels of 35%-40%(T1), 55%-60%(T2), 75%-80%(T3), and 95%-100%(T4) was compared. The effects of these treatments on liver function parameters, liver inflammation, and oxidative damage in mice with dampness-heat jaundice were evaluated, and the correlation between pharmacological indicators and flavonoid content was analyzed. The results showed that the total flavonoid and total phenolic acid content in the decoction of S. sarmentosum were highest in the T1 treatment, followed by the T3 treatment. The content of quercetin, kaempferol, and isorhamnetin was highest in the T2, T1, and T3 treatments, respectively. Among the different moisture treatments, the T3 group of S. sarmentosum effectively reduced the levels of serum ALT, AKP, TBIL, DBIL, TBA, as well as hepatic TNF-α and IL-6 in mice with jaundice, followed by T2 treatment, especially in reducing AST level. The T4 treatment had the poorest effect. Correlation analysis showed a significant negative correlation between AST, ALT, AKP levels in mice and the total content of quercetin and the three flavonoids. MDA showed a significant negative correlation with the total flavonoid content and kaempferol. TNF-α exhibited a significant negative correlation with the content of isorhamnetin. In conclusion, S. sarmentosum growing under field conditions with a soil moisture level of 75%-80% exhibited the best efficacy to eliminate dampness and relieve jaundice. This study provides insights for optimizing the cultivation mode of medicinal plants guided by pharmacological experiments.

An evaluation of ursodeoxycholic acid treatment in prolonged unconjugated hyperbilirubinemia due to breast milk.

Background/Aim: Prolonged jaundice is one of the most common problems during neonatal period. The aim of this study was to evaluate the efficiency of ursodeoxycholic acid (UDCA) treatment in newborn infants with prolonged unconjugated hyperbilirubinemia. Materials and Methods: The present study included 27 patients who were fed by breast milk and followed up in the outpatient clinic due to prolonged jaundice without any underlying etiological factor; 10 mg/kg/day UDCA was administrated in two doses for 7 days. Furthermore, 20 newborns diagnosed with prolonged jaundice with same characteristics were enrolled as the control group. The control group was also given a placebo; demographic characteristics, liver functions tests before and after the treatment, bilirubin decrease rates, and hemogram parameters of groups were compared. Results: Total bilirubin levels in the study and control groups before the treatment were 16.02 ± 1.41 mg/dL and 15.93 ± 1.66 mg/dL, respectively (P = 0.84). Total bilirubin levels in the study and control groups at day 7 after UDCA treatment were detected 8.18 ± 2.31 mg/dL and 13.92 ± 2.66 mg/dL, respectively (P < 0.001), and at day 14 after the treatment were 5.45 ± 2.59 mg/dL and 11.91 ± 2.83 mg/dL, respectively (P < 0.001). Furthermore, serum aspartate aminotransferase (AST) was detected <21 U/L in the ROC analysis after UDCA treatment (P = 0.04). Conclusion: The study outcomes indicated that an efficient reduction in total bilirubin levels may be achieved, and outpatient clinic follow-up period may be reduced in patients whom UDCA was administrated. Moreover, it may be speculated that AST can be used to evaluate the efficacy after treatment. However, studies with larger sample sizes are needed for the routine use of UDCA in the treatment of prolonged jaundice.

Integration of pharmacodynamics, network pharmacology and metabolomics to elucidate effect and mechanism of Artemisia capillaris Thunb. in the treatment of jaundice.

ETHNOPHARMACOLOGICAL RELEVANCE: As one of the most commonly used herbs, Artemisia capillaris Thunb. (ACT) display favorable effect in the treatment of jaundice. However, mechanism of ACT in the treatment of jaundice remains unclear at present, which limits its development and application. AIM OF THE STUDY: To investigate effect and mechanism of Artemisia capillaris Thunb. (ACT) in the treatment of jaundice using pharmacodynamics, network pharmacology and metabolomics. METHODS: Effect of ACT in treating jaundice was evaluated by biochemical assays and pathological observation using the α-naphthyl isothiocyanate (ANIT)-induced mice. Jaundice-relieving mechanism of ACT was investigated by integration of network pharmacology and metabolomics. RESULTS: After the mice with jaundice were administrated ACT extract for 9 days, compared to that of the model group, serum D-BIL, T-BIL and ALP levels of the mice in the low, medium, high dose of ACT group decreased by 39.81%, 15.30% and 16.92%; 48.06%, 42.54% and 36.91%; 26.90%, 12.34% and 16.90%, respectively. The pathologic study indicated that ACT improved the symptoms of liver injury of the mice with jaundice. The network of herb (i.e., ACT)-components-targets-disease (i.e., jaundice) was established, which consisted of 17 components classified in flavonoids, chromones, organic acids, terpenoids, and 234 targets related to treatment of jaundice. Metabolomics analysis showed that, compared to that in the model group, level of 8 differential metabolites were upregulated and level of 29 differential metabolites were downregulated in the mice liver in the ACT group, respectively. The main metabolic pathways involved in treatment of jaundice by ACT were pantothenate and CoA biosynthesis, glutathione metabolism, biosynthesis of unsaturated fatty acids, primary bile acid biosynthesis in the liver, respectively. The integrated analysis of network pharmacology and metabolomics showed that 3α,7α,12α a-Trihydroxy-5ß-cholanate, glycocholate, taurocholate, pantetheine 4'-phosphate, and d-4'-phosphopantothenate were the potential biomarkers for treatment of jaundice, and AKR1C4, ALDH2 and HSD11B were the potential drug targets in the treatment of jaundice by ACT. CONCLUSION: The study based on metabolomics and network pharmacology indicated that ACT can display favorable jaundice-relieving effect by its multiple components regulating multiple biomarkers, multiple targets and multiple pathways, and may be a rational therapy for the treatment of jaundice.

Effect of soil moisture on efficacy to eliminate dampness and relieve jaundice and flavonoid content of Sedum sarmentosum / 中国中药杂志

The growth environment of medicinal plants plays an important role in the formation of their medicinal quality. However, there is a lack of combined analysis studying the close relationship between the growth environment, chemical components, and related biological activities of medicinal plants. Therefore, this study investigated the effect of different soil moisture treatments on the efficacy to eliminate dampness and relieve jaundice and the flavonoid content of Sedum sarmentosum, and explored their correlation. The flavonoid content in the decoction of S. sarmentosum growing under field conditions with soil moisture levels of 35%-40%(T1), 55%-60%(T2), 75%-80%(T3), and 95%-100%(T4) was compared. The effects of these treatments on liver function parameters, liver inflammation, and oxidative damage in mice with dampness-heat jaundice were evaluated, and the correlation between pharmacological indicators and flavonoid content was analyzed. The results showed that the total flavonoid and total phenolic acid content in the decoction of S. sarmentosum were highest in the T1 treatment, followed by the T3 treatment. The content of quercetin, kaempferol, and isorhamnetin was highest in the T2, T1, and T3 treatments, respectively. Among the different moisture treatments, the T3 group of S. sarmentosum effectively reduced the levels of serum ALT, AKP, TBIL, DBIL, TBA, as well as hepatic TNF-α and IL-6 in mice with jaundice, followed by T2 treatment, especially in reducing AST level. The T4 treatment had the poorest effect. Correlation analysis showed a significant negative correlation between AST, ALT, AKP levels in mice and the total content of quercetin and the three flavonoids. MDA showed a significant negative correlation with the total flavonoid content and kaempferol. TNF-α exhibited a significant negative correlation with the content of isorhamnetin. In conclusion, S. sarmentosum growing under field conditions with a soil moisture level of 75%-80% exhibited the best efficacy to eliminate dampness and relieve jaundice. This study provides insights for optimizing the cultivation mode of medicinal plants guided by pharmacological experiments.

Clinical and genetic characterization of pediatric patients with progressive familial intrahepatic cholestasis type 3 (PFIC3): identification of 14 novel ABCB4 variants and review of the literatures.

BACKGROUND: Progressive familial intrahepatic cholestasis type 3 (PFIC3) is an autosomal recessive disease caused by pathogenic variants of the gene ABCB4. This study aimed to investigate the ABCB4 genotypic and the clinical phenotypic features of PFIC3 patients. METHODS: The clinical and molecular genetic data of 13 new pediatric patients with PFIC3 as well as 82 reported ones in the PubMed and CNKI databases were collected and analyzed. RESULTS: The 13 new PFIC3 patients included six females and seven males, and the main presentations were hepatomegaly, splenomegaly, jaundice, and pruritus, as well as increased levels of gamma-glutamyl transpeptidase (GGT). Fourteen new ABCB4 variants were detected, including eight diagnosed to be likely-pathogenic and six, pathogenic. Among all the 95 PFIC3 cases, hepatomegaly was observed in 85.3% (81/95), pruritus in 67.4% (64/95), splenomegaly in 52.6% (50/95), jaundice in 48.4% (46/95), portal hypertension in 34.7% (33/95) and GGT elevation in 100% (88/88) of the patients. Positive responses at varied degrees to oral ursodeoxycholic acid (UDCA) treatment were observed in 66.1% (39/59) of the patients, among whom 38.5% (15/39) fully recovered in terms of the laboratory changes. Although the condition remained stable in 53 patients (58.9%, 53/90), the clinical outcomes were not promising in the rest 37 cases (41.1%, 37/90), including 7 died, 27 having undergone while another 3 waiting for liver transplantation. A total of 96 ABCB4 variants were detected in the 95 patients. PFIC3 patients with biallelic null variants exhibited earlier onset ages [10.5 (2, 18) vs. 19 (8, 60) months, p = 0.007], lower UDCA response rate [18.2% (2/11) vs. 77.1% (37/48), p = 0.001], and more unpromising clinical outcomes [80% (12/15) vs. 33.3% (25/75), p = 0.001], compared with those with non-biallelic null variants. CONCLUSIONS: PFIC3 presented with hepatomegaly, pruritus, splenomegaly and jaundice with increased serum GGT level as a biochemistry hallmark. Although varying degrees of improvement in response to UDCA therapy were observed, 41.1% of PFIC3 patients exhibited unfavorable prognosis. ABCB4 genotypes of biallelic null variants were associated with severer PFIC3 phenotypes. Moreover, the 14 novel variants in this study expanded the ABCB4 mutation spectrum, and provided novel molecular biomarkers for diagnosis of PFIC3 patients.

Indirect hyperbilirubinemia and jaundice during chronic hepatitis C in an HIV-infected patient treated with glecaprevir/pibrentasvir (GLE/PIB) and antiretroviral therapy (ART). The first reported case in Italy.

Glecaprevir (GLE)/pibrentasvir (PIB) is a pangenotypic direct-acting antiviral regimen approved for treating chronic hepatitis C virus. Primary treatment and re-treatment with GLE/PIB are effective and safe for patients without decompensated liver cirrhosis and chronic hepatitis C in a real-world clinical setting. However, in the context of compensated cirrhosis and concomitant administration of inhibitors of cytochromes, a careful monitoring of liver biomarkers, as well as therapeutic drug monitoring (TDM), may be advisable during GLE/PIB therapy. The GLE / PIB combination is very effective and safe in achieving a sustained virological response, but it can be associated with the development of severe hepatic adverse events, which require virological and serum concentration monitoring of the two drugs to prevent a serious liver damage. The possible onset of hyperbilirubinemia must not necessarily lead to the suspension of therapy, because the phenomenon may be transient. We report what is likely the first known case of severe jaundice after treatment with GLE/PIB in Italy in a patient with compensated chronic hepatitis in the context of HIV disease.

Therapeutic efficacy and safety of Yinzhihuang granules with phototherapy in neonatal pathologic jaundice: An updated systematic review and meta-analysis.

BACKGROUND: Yinzhihuang granule, consisting of extracts of Artemisia capillaris Thunb., Gardenia jasminoides Ellis, Lonicera japonica Thunb., and Scutellaria baicalensis Georgi is a well-known traditional Chinese patent medicine for patients with liver injury in China. However, the effects and safety of its use for pathologic jaundice in newborns require further systematic evaluation. PURPOSE: To systematically evaluate the efficacy and safety of Yinzhihuang granules for the treatment of neonatal pathologic jaundice and to provide clinical evidence. METHODS: Chinese databases (China Network Knowledge Infrastructure, Wan Fang Database, and VIP Database) and English databases (PubMed, EmBase, and the Cochrane Library) were thoroughly investigated through screening randomized controlled trials on Yinzhihuang granules for neonatal pathologic jaundice from the establishment of all databases to November 18, 2021. A meta-analysis was performed for selected data using STATA software. TSA software was used for trial sequential analyses of the total effective rate and adverse reactions. RESULTS: A total of 19 trials and 2,221 newborns with pathologic jaundice were included in this study. Outcome measures of clinical efficacy in the experimental group were higher than in controls, including total bilirubin (WMD = -30.34, 95% CI = -35.44 to -25.23, p < 0.001), direct bilirubin (WMD = -15.03, 95% CI = -23.54 to -6.52, p < 0.001), indirect bilirubin (WMD = -11.22, 95% CI = -17.50 to -4.95, p < 0.001), recovery time (WMD = -2.96, 95% CI = -3.92 to -2.00, p < 0.001), hospitalization time (WMD = -3.83, 95% CI = -4.89 to -2.76, p < 0.001), and liver function indices. There were statistically significant differences between the two groups. Likewise, the incidence of adverse reactions, including diarrhea, erythra, and fever decreased remarkably in the trial group (RR = 0.44, 95% CI =  0.33 to 0.59, p < 0.001). Publication bias did not exist. We verified the efficacy and safety of Yinzhihuang granules with phototherapy for pathologic jaundice in newborns according using TSA analysis. CONCLUSION: Yinzhihuang granules with phototherapy for neonatal pathologic jaundice are more effective than phototherapy alone. The incidence of ADRs does not increase with the application of Yinzhihuang granules. Due to the heterogeneity across the included studies, additional multicenter clinical trials with follow-ups are needed to confirm our findings.

Disseminated Carcinomatosis of Bone Marrow as the Initial Presentation of Intrahepatic Cholangiocarcinoma without Jaundice: An Autopsy Case Report.

Disseminated carcinomatosis of the bone marrow (DCBM) is often accompanied by disseminated intravascular coagulation (DIC) and has a poor prognosis. DCBM develops most frequently in gastric cancer and is rarely associated with intrahepatic cholangiocarcinoma. A 41-year-old man was incidentally found to have DIC on his regular visit for ulcerative colitis and was diagnosed with DCBM with intrahepatic cholangiocarcinoma. He received intensive care, including chemotherapy, but died suddenly from hyperkalemia, possibly due to tumor lysis syndrome (TLS). The autopsy showed the periductal infiltrating type of intrahepatic cholangiocarcinoma and tumor necrosis, possibly due to chemotherapy, indicating the effectiveness of chemotherapy for DCBM with intrahepatic cholangiocarcinoma.

Primary tubercular granulomatous hepatitis presenting as fluctuating jaundice.

Granulomatous hepatitis is an uncommon presentation of tuberculosis (TB). It is even more peculiar to have TB confined to the liver alone with no pulmonary or a disseminated form. In either form, there is the usual presentation of nonprogressive cholestatic jaundice, but no documented case with fluctuating jaundice in the literature was found. In order to highlight this rare presentation aiding the right diagnosis, we present one such case of a 46-year-old woman with no known comorbidities, who complained of fluctuating and painless type of jaundice, associated with fatiguability, pruritus, and weight loss. Preliminary blood investigations showed anemia and cholestatic pattern of jaundice. Ultrasonography and computed tomography imaging showed hepatomegaly with heterogeneous texture. Magnetic resonance cholangiopancreatography further revealed features of cholecystitis with hepatic ducts near proximal common bile duct showing postinflammatory change. The periampullary region was normal. Sputum acid-fast staining and cartridge-based nucleic acid amplification test were negative. Eventually, liver biopsy was done which showed caseating granulomas with Langhans giant cells. The tissue was abundant in acid-fast bacilli. The patient was started on a 9-month course of first-line Antitubercular treatment (ATT) and responded well. Fluctuating jaundice is a rare and undocumented presentation of primary hepatic TB and can cause diagnostic dilemmas.

Acute Kidney Injury and Jaundice in a Patient With Concurrent Severe Malaria and Acute Exacerbation of Hepatitis B.

Patients chronically infected with hepatitis B virus (HBV) may travel to areas with high endemicity of malaria. The overlap between malaria and HBV infection can be clinically severe and present a diagnostic challenge as both diseases manifest similar symptoms. This case describes a fatal case of a 43-year-old man with chronic HBV infected with Plasmodium falciparum malaria that presents as acute kidney injury (AKI) and jaundice following a trip to malaria-endemic region. Despite administering antimalarial and 6 courses of renal replacement therapy, the patient's clinical condition did not improve, leading to septic shock, multi-organ dysfunction, and eventually, death. AKI and jaundice are commonly seen in severe P. falciparum malaria, as well as acute exacerbation of chronic HBV. This case emphasizes the importance to consider malarial screening when evaluating sick returning travelers, even in those with underlying chronic HBV. Given the severity of coinfection, prompt identification of this overlap can avert the rapid deterioration of severe malaria by early administration of intravenous artesunate and renal replacement therapy.

An unusual cause of fever and jaundice.

A 52 year old previously healthy woman from Mumbai presented with fever and jaundice of 10 days duration. At admission, she was jaundiced with tachycardia, tachypnea, hypoxia, hypotension, conjunctival congestion and mild erythematous flush over the skin. She had very high WBC counts and CRP's with direct hyperbilirubinemia and azotemia. Investigations for infectious causes of fever were negative. RT-PCR for SARS-CoV-2 in the nasopharynx was negative. However her SARS-CoV-2 antibodies were reactive. She also had echocardiographic and biochemical evidence of cardiac dysfunction. The diagnosis of Multisystem inflammatory syndrome-Adult (MIS-A) was thus established. She rapidly improved with intravenous immunoglobulin (2 gm/kg) and high dose steroids.

Characterization of gut microbiota and short-chain fatty acid in breastfed infants with or without breast milk jaundice.

This study aims to investigate the gut microbiota and metabolites in breastfed infants with breast milk jaundice (BMJ) using gut microbiome-metabolomics. Breastfed newborns diagnosed with BMJ and those without BMJ (control group) were enrolled. Faecal samples were collected from the participants and subjected to high-throughput sequencing of the 16s rDNA V3 and V4 regions of the gut flora and metabolomics of short-chain fatty acids (SCFAs). Proteobacteria, Fimicutes and Actinobacteria were the main bacteria at the phylum level. Eshcerichia-Shigella and Enterobacteriacea were the main bacteria at the genus level. The difference between the two groups was compared. Compared to the control group, the amount of Streptococcus was significantly increased while the amount of Enterococcus was significantly decreased in the faeces from infants with BMJ. Functional prediction analysis of 16S found that biosynthesis of penicillin and cephalosporin significantly increased in the BMJ group. Gas chromatography-mass spectrometry detection of SCFAs revealed that levels of acetic acid and propionic acid were significantly lower in the BMJ group than in the control group. The reduced levels of acetic acid and propionic acid may be related to the increase in Streptococcus and decrease in Enterococcus, both of which may contribute to BMJ.

Efficacy of and prognosis after steroid pulse therapy in patients with poor reduction of jaundice after laparoscopic Kasai portoenterostomy.

PURPOSE: High-dose postoperative steroid therapy after Kasai portoenterostomy is reported to improve jaundice clearance and a strong anti-inflammatory activity might prevent fibrous tissue formation which is often observed at the porta hepatis in revision surgery. We started steroid pulse therapy for the patients with cessation of decrease in jaundice and aimed to evaluate the efficacy in this study. METHODS: The demographics and outcomes of patients who underwent laparoscopic Kasai portoenterostomy and received steroid pulse therapy within 2 months postoperatively between September 2014 and December 2018 were retrospectively reviewed; the therapy was determined successful when the serum total bilirubin level decreased to or below two-thirds of the pre-therapy level after 2 weeks. Patient data in the successful group were compared with those in the unsuccessful group. RESULTS: Steroid pulse therapy was successful in seven of 16 patients (43.8%). The percentage of patients whose serum total bilirubin level decreased to normal was significantly higher in the successful group at 3 months (85.7% vs. 11.1%, P = 0.0028) and after all (100% vs. 33.3%, P = 0.011). CONCLUSIONS: Steroid pulse therapy was effective for some patients. Unsuccessful cases may have little chances of jaundice clearance; revision Kasai portoenterostomy would be a good option.

Autoimmune pancreatitis not otherwise specified (NOS): Clinical features and outcomes of the forgotten type.

BACKGROUND: Autoimmune pancreatitis (AIP) is a well-recognized fibroinflammatory disease of the pancreas. Despite the significant number of studies published on AIP type 1 and 2, no studies have been focused on AIP type not otherwise specified (NOS) and therefore very little is known about clinical features and long-term outcomes of these patients. The aim of this study was to investigate clinical and radiological features of AIP type NOS-patients. METHODS: Patients classified as AIP type NOS at clinical onset included in our database prospectively maintained since 1995 were evaluated. Epidemiological, clinical data were collected and analyzed. RESULTS: Forty-six patients were included in the study. The clinical onset was mainly characterized by weight loss, jaundice and acute pancreatitis. Eight patients (17.4%) were reclassified as AIP type 2 during follow-up because of the development of ulcerative colitis. Seven patients (15.2%) experienced relapse after steroid treatment but only one (2.2%) needed immunosuppressive drugs because of recurrent relapses. CONCLUSIONS: AIP type NOS shares clinical features similar to AIP type 2 and a relevant proportion of patients was reclassified as AIP type 2 during follow-up because of the development of ulcerative colitis. The risk of relapse is low but not irrelevant.

Pembrolizumab-induced Autoimmune Hemolytic Anemia and Hemophagocytic Lymphohistiocytosis in Non-small Cell Lung Cancer.

We herein report a 78-year old man with squamous cell carcinoma of the lungs treated with pembrolizumab. At 10 days after the administration of pembrolizumab, he showed progressive anemia and increased levels of bilirubin. Because the findings of a direct coombs test and cold hemagglutinin were positive, we diagnosed the patient with autoimmune hemolytic anemia and treated him with prednisolone. Subsequently, he was admitted to our hospital owing to fatigue, a high fever, and jaundice. His clinical findings met the diagnostic criteria of hemophagocytic lymphohistiocytosis, and he was rescued with a high dose of glucocorticoids. Marked tumor regression was obtained and has been maintained since then.