Normalization Of Liver Enzymes Research Articles

Chronic Hepatitis E Virus Manifesting as Elevated Transaminases in a Heart Transplant Patient

ABSTRACT Hepatitis E virus (HEV) is a common cause of viral hepatitis worldwide. Genotypes 1 and 2 cause acute hepatitis in endemic regions (Asia and Africa), whereas genotypes 3 and 4 (America and Europe) result in sporadic acute or chronic hepatitis, specifically in certain groups. HEV infections are rising because of increased transplantation rates and immunosuppression. We report a 75-year-old heart transplant patient with nonspecific symptoms, diagnosed with HEV chronic hepatitis. Despite ribavirin-induced hemolytic anemia, the patient achieved sustained virological response and normalization of liver enzymes.

Characteristics, clinical laboratory, histopathology, and outcomes of glycogenic hepatopathy in children.

Glycogenic hepatopathy (GH) is a rare complication of type I diabetes mellitus (DM1), resulting in abnormal deposition of glycogen in the liver due to poor glycemic control. Clinical characteristics and natural history of GH are not completely understood in children. In this study, we investigated clinical, biochemical, histologic parameters and outcomes in children with GH. This was a retrospective review of patients less than 18 years old diagnosed with GH and DM. GH was confirmed on liver biopsy. Medical records were reviewed for clinical presentation, laboratory tests, and clinical outcomes. Liver biopsy findings were reviewed by a pediatric pathologist (I. A. G.). Nine children were diagnosed with GH and type 1 DM. The median age at diagnosis of GH was 16 (IQR 14.5-17) years. Duration of diagnosis of DM until GH diagnosis was 7 (IQR 5-11) years. The median frequency of diabetic ketoacidosis before GH diagnosis was three times (IQR 2-5.25). Peak Aspartate transaminase (AST) and Alanine transaminase (ALT) ranged from 115 to 797, and 83-389 units/L, respectively. Only two children had mild fibrosis. Seven of nine had steatosis without steatohepatitis. There was no correlation between glycosylated hemoglobin (HbA1c), or other laboratory tests and liver fibrosis on biopsy. HbA1c was 11.2 (IQR 10.2-12.8) at GH diagnosis and 9.8 (IQR 9.5-10.8) with normalization of liver enzymes. GH appears to be related to poor glycemic control in teenagers with long-term diabetes. GH presents with high to very high aminotransferase especially AST > ALT and resolves with modestly improved glycemic control. Diffuse hepatocyte swelling, steatosis, minimal fibrosis without hepatocyte ballooning or lobular inflammation are most common histological features.

Aseptic Liver Abscess in a Patient With Diversion Colitis

ABSTRACT Aseptic abscess syndrome is a rare clinical entity mainly associated with systemic inflammatory conditions, particularly inflammatory bowel disease. The syndrome is characterized by an inflammatory infiltrate predominantly consisting of neutrophils, most commonly in the liver and spleen. We present a case of a patient with symptomatic diversion colitis diagnosed with a clinical and histological presentation consistent with aseptic abscess syndrome of the liver. Treatment and resolution of the inflamed colon was associated with complete disappearance of the liver lesions and normalization of liver enzymes. To the best of our knowledge, this is the first report suggesting the unique link between diversion colitis and aseptic liver abscess.

Clinical Outcomes in Patients with High-Dose Methotrexate Toxicity Treated with Vs. without Glucarpidase

Background. High-dose methotrexate (HDMTX) is a cornerstone of treatment for lymphoma and leukemia involving the central nervous system, but can cause significant toxicity, which manifests predominantly as acute kidney injury (AKI) as well as bone marrow suppression and hepatotoxicity. Glucarpidase is a recombinant bacterial enzyme that cleaves 99% of circulating MTX to inactive metabolites within 15 minutes of its administration. It is approved for use in the setting of supratherapeutic MTX levels to mitigate renal and extrarenal toxicity. Despite its potent biochemical effects, no study has rigorously examined whether glucarpidase improves clinical outcomes in patients with HDMTX toxicity compared to controls not treated with glucarpidase. This key evidence gap has led to wide variation in the use of glucarpidase across institutions. Methods. We examined the clinical outcomes of patients with HDMTX-associated AKI (HDMTX-AKI) treated with and without glucarpidase across a large multicenter cohort of 684 adults from 26 major cancer centers across the US from 2000 to 2022. HDMTX-AKI was defined as a ≥1.5-fold increase in serum creatinine (SCr) within 4 days following treatment with HDMTX. We collected data on demographics, comorbidities, medications, laboratory values, and outcomes. The primary outcome was renal recovery, defined as a return of SCr to <1.5-fold baseline and absence of renal replacement therapy-dependence at hospital discharge. Prespecified subgroup analyses included those treated with glucarpidase in the first 60 hours following MTX initiation, and those with AKI stage 3 (increase in SCr ≥3-fold baseline) in the first 4 days following treatment with HDMTX. Secondary outcomes included absence of neutropenia, transaminitis, and mucositis on day 7. We used multivariable logistic regression to adjust for potential confounders. Models were adjusted for age, sex, race, baseline eGFR, body mass index, hypertension, diabetes mellitus, coronary artery disease, congestive heart failure, chronic liver disease, baseline WBC count, serum albumin, and LDH, MTX dose and infusion duration, urine pH, volume of IV fluids administered, leucovorin dose, and maximum fold-change in SCr, oliguria, and receipt of concomitant nephrotoxins in the first 4 days following MTX initiation. Results. Among the 684 patients with HDMTX-AKI, 207 (30.3%) were treated with glucarpidase and 477 (69.7%) were not. All patients treated with glucarpidase received it within the first 96 hours following initiation of HDMTX. The median time from HDMTX initiation to glucarpidase receipt was 54 hours (IQR, 44-66), with 65% of the patients receiving it within 60 hours, and 85% within 72 hours. Patients treated vs. not treated with glucarpidase were similar with respect to age, sex, race, MTX dose and infusion duration, and most baseline labs, including SCr, but had high higher plasma MTX levels at 24 and 36 hours and more severe AKI ( Table). Glucarpidase receipt was associated with a 2.43-fold higher adjusted odds of renal recovery (95% CI, 1.38-4.27) compared to no glucarpidase receipt ( Figure). The magnitude of association was considerably higher when the analysis was restricted to those treated with glucarpidase in the first 60 hours (odds ratio 4.94 [95% CI, 2.42-10.06] and to those with AKI stage 3 (odds ratio 7.08 [95% CI, 2.27-22.10]) ( Figure). Glucarpidase receipt was also associated with a higher likelihood of recovery from neutropenia and normalization of alanine aminotransferase (ALT) by day 7 ( Figure). There was no significant association between glucarpidase receipt and mucositis on day 7 ( Figure). Conclusions. In the largest study to date of HDMTX-AKI and the only one, to our knowledge, to include control patients, we found that patients who received glucarpidase had considerably higher odds of renal recovery, as well as recovery from neutropenia and normalization of liver enzymes, compared to those who did not receive glucarpidase. The magnitude of association with renal recovery was particularly evident in those treated with glucarpidase in the first 60 hours and in those with AKI stage 3. Though this is an observational study with the potential for residual confounding, our data support use of glucarpidase in patients with HDMTX-AKI, particularly in the first 60 hours following initiation of MTX.

Real-life safety of Emtricitabine/Tenofovir Alafenamide/Bictegravir.

Integrase strand transfer inhibitors (INSTI) are one of the most prescribed drug classes for the treatment of HIV infection worldwide. Emtricitabine/Tenofovir Alafenamide/ Bictegravir (FTC/TAF/BIC) has been evaluated in randomized clinical trials; few studies have verified tolerability and safety in clinical practice. Our aim was to investigate the metabolic and hepatic safety in a real-life setting of FTC/TAF/BIC. Consecutive people living with HIV infection (PLWH) enrolled in the SCOLTA project, switching to or initiating their first antiretroviral treatment with FTC/TAF/BIC were included. PLWH with HBV co-infection were excluded. Metabolic and hepatic variables were collected at T0 and T1, were defined as baseline and 6-month follow-up respectively, and their modifications were analysed using the paired t-test and the analysis of variance. Five hundred and thirty-nine PLWH with at least one follow-up visit were included in the analysis. Mean age was 48 years (±12.1), 74% were male, 16.1% were naïve to antiretrovirals (ART). At T1, ART-experienced PLWH showed a significant reduction of total cholesterol (TC) and triglycerides, and a slight increase in blood glucose (BG) and ALT. On the contrary, in ART-naïve PLWH blood lipids significantly increased, although with an unaffected TC/high density lipoprotein (HDL)-c ratio, while alanine aminotransferase (ALT) decreased significantly, mainly in those with altered baseline level. The treatment interruptions were 45 (8.4%) over the whole observation period, 13 (2.4%) due to AEs. The most frequent AEs were related to the central nervous system (6 events of depression, insomnia, headache, agitation) and 3 PLWH discontinued the regimen because of grade 1-2 weight gain. In ART-experienced PLWH switching to FTC/TAF/BIC a significant improvement of lipid profile occurred but with significant BG and ALT variation without clinical relevance. In ART-naïve PLWH, blood lipids increased even though lipid profile did not worsen, and a trend towards normalization of liver enzymes was suggested. FTC/TAF/BIC is well tolerated in the real life setting.

Immunoglobulin G4-Seronegative Autoimmune Cholangiopathy With Pancreatic and Hepatic Involvement Mimicking as Primary Sclerosing Cholangitis

Immunoglobulin G4-seronegative autoimmune cholangiopathy is a rare cause of biliary strictures. We describe a 27-year-old man presenting with elevated liver enzymes, recurrent cholangitis/bacteremia, biliary strictures, and normal immunoglobulin G4 levels, who was initially diagnosed with primary sclerosing cholangitis, and later listed for transplantation for recurrent bacteremia. Subsequent surveillance imaging demonstrated morphologic changes consistent with biliary strictures and autoimmune pancreatitis. Initiating corticosteroids resulted in liver enzyme normalization and stricture improvement. Diagnosing seronegative autoimmune cholangiopathy remains challenging given similar presentation to primary sclerosing cholangitis. This case highlights importance of a wide differential for biliary strictures, with increased suspicion in those developing pancreatic changes in this setting.

A case of severe increase of liver enzymes in a ATTRv patient after one year of inotersen treatment.

Inotersen is an antisense oligonucleotide used to treat hereditary transthyretin amyloidosis (ATTRv). The most common drug-related adverse effects (AEs) include thrombocytopenia and glomerulonephritis. Hepatic damage is rare, but liver enzyme monitoring is mandatory. A 70-year-old man with ATTRv (Val30Met) treated with inotersen developed a severe increase of transaminases, with normal bilirubin and cholinesterase levels, that forced us to stop therapy. At the same time, other causes of acquired hepatitis were excluded, and the hypothesis of an inotersen-related hepatic toxicity was supported by the normalization of liver enzymes after 40days from the drug interruption. Our case showed that 1-year inotersen treatment can stabilize neurological impairment and even improve quality of life and suggests to carefully monitor liver enzymes in order to avoid an inotersen-related hepatic dysfunction.

Potential benefit and lack of serious risk from corticosteroids in drug-induced liver injury: An international, multicentre, propensity score-matched analysis.

The use of corticosteroids to treat patients with idiosyncratic drug-induced liver injury (DILI) relies on empirical clinical decisions. To investigate the relationship between corticosteroids and risk of acute liver failure (ALF) in patients with DILI and to assess if corticosteroid therapy was associated with improved outcomes in DILI patients. We analysed bona fideidiosyncratic DILI cases from the Spanish DILI Registry and Indiana University School of Medicine. Patients treated with corticosteroids were compared to those who did not receive any treatment. Nearest neighbour propensity score matching analyses were conducted. We enrolled 724 patients, 106 under corticosteroid therapy, in whom there was over-representation of more severe injury and autoimmune features, and 618 who did not receive any treatment. In an analysis of 80 pairs of propensity score-matched patients, corticosteroid administration was not associated with an increased risk of developing ALF (odds ratio=0.65; 95% confidence interval [CI]: 0.18-2.40; p=0.518). Furthermore, in an additional analysis, a Cox regression model that included 41 propensity score-matched pairs showed that patients receiving corticosteroids had a significantly higher normalisation rate of liver enzymes than untreated patients (hazard ratio [HR]=1.84; 95% CI: 1.02-3.32; p=0.043), particularly in patients with serious injury who did not resolve within 30 days (HR=2.79; 95% CI: 1.20-6.50; p=0.018). Corticosteroid therapy did not worsen outcome in DILI patients. Indeed, corticosteroid administration was associated with a greater rate of normalisation of liver enzymes in patients with serious DILI.

Nitrofurantoin-induced liver injury: long-term follow-up in two prospective DILI registries

Nitrofurantoin is a synthetic antibiotic that is recommended as first-choice treatment for uncomplicated urinary tract infections. The prescription of this drug has increased dramatically, especially in Latin American countries. We described the demographics, clinical characteristics, biochemical features, and outcome of nitrofurantoin-induced liver injury. We analyzed 23 cases from the Latin American DILI Network (LATINDILI) and the Spanish DILI Registry. Causality was assessed with the RUCAM and RECAM scale. Of the 23 DILI cases included in our series, 96% patients were women, and the mean age of the whole cohort was 61 years. The median time of drug exposure was 175 days (interquartile range [IQR] 96–760), with 11 patients who were prescribed nitrofurantoin for more than six months. Hepatocellular damage was the most frequent pattern of liver injury (83%), and nearly half of the patients had an asymptomatic presentation (52%). Neither death nor liver transplantation was documented in this series. Overall, 65% of the patients (n = 15) presented with positive autoantibody titres. The median time to resolution was 81 days (IQR 57–141), and 15 patients (83%) recovered within six months. Five patients (22%) developed nitrofurantoin-induced autoimmune-like hepatitis (NI-AILH), of whom two were characterized by a persistent increase in transaminases that required immunosuppressive treatment to achieve normalization of liver enzymes. Clinicians who prescribe nitrofurantoin should be aware that patients who had taken nitrofurantoin for a long term may be at risk of developing nitrofurantoin-induced autoimmune-like hepatitis.

S1910 A Rare Metastatic Lesion in the Pancreas Presenting With Biliary Obstruction

Introduction: Pancreatic malignancies can originate from either endocrine or non-endocrine cells of the pancreas. Ductal carcinoma is the most common type of non-endocrine tumor, of which adenocarcinomas constitute the most common pancreatic malignancy. Squamous cell carcinoma (SCC) is the other ductal tumor that is very rare as the pancreas is generally devoid of squamous cells. Primary SCC of the pancreas is thought to arise from the squamous metaplasia of the ductules secondary to chronic inflammatory conditions, however, metastasis remains the most common etiology. We present a patient with history of recurrent poorly differentiated SCC of the cervix complicated by pancreatic head metastasis and biliary obstruction. Case Description/Methods: A 46-year-old female diagnosed with poorly differentiated SCC of the cervix stage IIB, status post multiple rounds of chemotherapy over a period of 4 years, was started on a new medication – Tisotumab. Four months following the initiation of this medication, patient experienced abdominal pain and was noted to have a lipase level of 1160 U/L. She was diagnosed with acute pancreatitis and treated accordingly. Subsequent labs showed continued up trending of her liver chemistry, withalkaline phosphatase of 520 U/L and total bilirubin of 9.7 mg/dl. A CT abdomen performed revealed dilation of both common bile duct (CBD) and pancreatic duct (PD) with subtle hypodense area in the head of pancreas. Endoscopic ultrasound (EUS) was performed which revealed a 3 cm x 2 cm ill-defined hypoechoic and heterogenous mass in the pancreas head (Figure). Fine needle biopsy of the lesion revealed SCC, most likely metastatic from the cervix. ERCP was performed and a 10mm x 8cm fully covered metal CBD stent was placed with normalization of liver enzymes. Palliative immunotherapy with Keytruda is currently being pursued. Discussion: Metastasis to the pancreas is an uncommon clinical condition and accounts for 0.5-5% of all pancreatic malignancies. Because of the rarity, primary sources should always be excluded. Only a handful of reports of uterine and cervical cancer metastasis to pancreas have been reported, most of them being adenocarcinoma. We report a very rare case of SCC cervix metastasizing to the pancreas. Unfortunately, curative surgery is not an option with metastatic disease, and chemoradiation can be used palliatively. The median survival is generally poor with median rates of 4.8% and 1% at 1-yr and 5-yrs, respectively.Figure 1.: A - EUS image showing dilated CBD measuring up to x mm. B – EUS image demonstrating a 3 x 2 cm hypoechoic pancreatic head mass. C– H&E stain showing neoplastic clusters (black arrows) of metastatic SCC.

S3259 A Case of Propofol-Induced Acute Liver Failure

Introduction: Propofol is a parenteral anesthetic routinely used for procedures given its beneficial pharmacokinetic profile of rapid onset of action and reversal. Propofol drug toxicity is rare but has been associated with idiosyncratic acute liver injury in a small number of cases. To the best of our knowledge, we present the second case of propofol-induced acute liver failure (ALF) reported in literature. Case Description/Methods: An 88-year-old male with concern for gastrointestinal bleed underwent an upper endoscopy with propofol used as the anesthetic agent. The patient tolerated the endoscopy well with no hemodynamic compromise during or afterwards. No source of bleeding was identified so the plan was to proceed with a colonoscopy the next day. Shortly after the procedure, he was noted to have altered mental status. Evaluation with routine laboratory testing revealed elevated AST of 3248 IU/L and ALT of 2411 IU/L, both increased from 35 IU/L and 24 IU/L, respectively. He was also found to have high anion gap metabolic acidosis and bicarbonate level less than 9 mEq/L. His altered mentation continued to worsen, and he became hemodynamically unstable requiring transfer to the intensive care unit. He had no history of liver disease or excessive alcohol use, no risk factors for viral hepatitis, and took no medications known to cause liver injury. Work-up was unremarkable for acute and chronic liver disease. Propofol was ultimately surmised as the cause of ALF. Unfortunately, the patient’s mental status progressively worsened despite hemodynamic stabilization and normalization of liver enzymes. His family ultimately chose to transition to comfort measures and the patient passed soon after. Discussion: The incidence of drug-induced liver injury is increasing in developed countries and is a major etiology of ALF, accounting for greater than 50% of cases. Drug toxicity secondary to an idiosyncratic reaction is unpredictable and occurs infrequently in certain individuals. While propofol is generally considered a safe agent widely used for sedation, propofol-induced acute liver injury is a rare outcome. To the best of our knowledge, it is reported to have caused five cases of acute hepatitis and one other case of ALF. We report the second case of ALF due to propofol with a lethal outcome. We recommend close monitoring of patients treated with propofol for signs of hepatitis and that ALF due to a drug insult should be considered after common causes have been excluded.

S3158 Supplement Gone Wrong: Drug-Induced Liver Injury Caused by Artemisinin

Introduction: Drug-induced liver injury (DILI) is defined as hepatic dysfunction caused by prescription medications, supplements, or xenobiotics after alternative causes have been excluded. As one of the leading causes of acute liver failure, DILI should be considered when patients present with hepatic dysfunction. We present a case of symptomatic DILI secondary to artemisinin use. Case Description/Methods: A 78-year-old Chinese man with no medical history presented to the hepatology clinic with 10 weeks of jaundice, weakness, and pruritis. He started taking Artemisinin/ Bioperine 12 weeks ago to prevent COVID-19 but stopped 3 weeks ago. He denied abdominal pain, a family history of liver disease, substance/alcohol use, and taking other concomitant drugs. Physical examination revealed scleral icterus and no other signs of chronic liver disease. Laboratory studies showed total bilirubin 11 mg/dL, alkaline phosphatase 293 U/L, aspartate transaminase 170 U/L, and alanine transaminase 196 U/L with negative workup for hepatitis A, B, and C. CT abdomen and MRCP were unremarkable for liver or biliary pathology. Further serological workup was negative and follow-up labs revealed normalization of liver enzymes and bilirubin. Given the patient’s improvement, liver biopsy was not pursued. The patient was instructed to avoid supplements unless prescribed by a physician. Discussion: DILI is a global issue with an estimated annual incidence rate of 13.9 to 24.0 per 100,000 persons. Diagnosing DILI is important as it can cause acute liver injury and liver failure in certain cases. Since COVID-19 emerged, supplement use has increased given claims of boosting the immune system. Artemisinin is an herb used in traditional Chinese medicine with antimalarial activity investigated to be a possible COVID-19 treatment, but no current evidence exists to support it being effective against COVID-193. Our patient’s supplement also contained Bioperine, a black pepper extract, which is likely benign. Contrarily, artemisinin is a well-described cause of idiosyncratic acute liver injury and hepatotoxicity, causing self-limited mild to moderate transaminitis but also severe cases requiring emergent liver transplantation. Our patient’s unrevealing workup, his spontaneous improvement correlating with supplement discontinuation, and RUCAM score of 7 led to high suspicion of DILI secondary to artemisinin. Providers should always ask patients about supplement use and consider DILI when patients present with liver injury. Table 1. - The patient’s laboratory values, including total bilirubin, alkaline phosphatase (ALP), aspartate transaminase (AST), and alanine transaminase (ALT) improved after stopping Artemisinin/Bioperine Total bilirubin (mg/dL) ALP (U/L) AST (U/L) ALT (U/L) Initial labs with PCP 11 293 170 196 Repeat labs with PCP 5.6 143 75 98 3 weeks after stopping supplement 2.4 85 34 41

Outcomes of immunotherapy-related hepatotoxicity from a multi-disciplinary toxicity team.

Despite the efficacy of immune checkpoint inhibitors (ICIs), adverse events including hepatotoxicity limit their ongoing use. We investigated the outcomes and management of patients with immune-mediated hepatitis (IMH) and clinical predictors of toxicity resolution. Patients referred to our multidisciplinary immunotherapy-related toxicity group from August 2017 to December 2020 for IMH were evaluated. Toxicity was defined according to CTCAEv4.0. IMH resolution was defined as liver enzyme normalization after steroid initiation. Thirty-three patients were included in the study, 62% female, and 71% Caucasian. The most common ICI used was PD-1/PD-L1 (76%). Peak IMH occurred at a median of 89 [45,193] days, for which most patients received 1-2mg/kg/day prednisone equivalent with 35% requiring MMF. Median follow-up was 123 [33,472] days with IMH resolution seen in 48% of patients at a median of 111 [41,214] days. While high-dose steroid use was not associated with IMH resolution, liver enzyme improvement one week after steroids predicted resolution in univariate analysis (p = 0.041). All 11 patients without IMH resolution died from cancer progression or complications with three patients having acute liver failure. Available liver biopsies showed bile duct injury, with varying degrees of portal and lobular inflammation. IMH improvement one week after steroid initiation may predict ultimate IMH resolution.

Effectiveness and Safety of Direct-Acting Antiviral in Hemodialysis Patients with Chronic Hepatitis C: A Real Clinical Experience

Background and Aims: Several clinical studies using direct-acting antivirals (DAAs) in maintenance hemodialysis (MHD) patients with chronic hepatitis C virus (HCV) infection have reported excellent antiviral efficacy and tolerability. Our study aimed to assess both the effectiveness and safety of DAAs in MHD patients complicated with HCV in a “real-life” clinical setting. Materials and Methods: A multicenter retrospective analysis of five dialysis centers included 155 patients of age >18 years with chronic HCV on MHD treated with various DAAs regimens for 12-week duration. The primary endpoint was sustained viral response and the secondary was the frequency of adverse effects (AEs). Results: Among the studied cohort, 96 (61.9%) were males and the mean age was 48.2 ± 12.6 years. Sustained virological response (SVR) was achieved in 153/155 (98.7%) patients. Normalization of liver enzymes was observed in patients with SVR (P < 0.05). None of the patients demonstrated deterioration in renal function. The minor AEs were reported in 12 patients - 8.1%. There were no severe AEs, dropouts, or deaths. Conclusion: DAAs are well tolerated and effective in our MHD patients. Strategies to eradicate HCV from dialysis units should consider DAA as treatment along with the practice of standard precautions to prevent nosocomial HCV infection.

Marked Hypoleptinemia precedes Overt Fat Loss in Immune Checkpoint Inhibitor-induced Acquired Generalized Lipodystrophy

<h3>Lead Author's Financial Disclosures</h3> Nothing to disclose. <h3>Study Funding</h3> None. <h3>Background/Synopsis</h3> The development of immune checkpoint inhibitors (ICIs) targeting cancer cells that evade immune T-cell regulation has revolutionized the treatment of metastatic carcinomas. Unfortunately, secondary endocrinopathies associated with ICI use, including adrenal insufficiency, primary hypothyroidism, autoimmune diabetes, and rarely hypoparathyroidism, are increasing. Lipodystrophy, presumably due to autoimmune destruction of adipocytes, leading to metabolic complications is a less well recognized adverse effect of ICI therapy. <h3>Objective/Purpose</h3> To report the clinical features and evolution of Acquired Generalized Lipodystrophy (AGL) in a patient on ICI therapy. <h3>Methods</h3> Case Report: A 66-year-old woman with metastatic lung adenocarcinoma was started on combination chemo/immunotherapy with programmed cell death-1 (PD-1) inhibitor- pembrolizumab after surgical resection of cerebellar mass and radiation. She had good tumor response but developed primary hypothyroidism and secondary adrenal insufficiency approximately ten months after initiation of ICI. <h3>Results</h3> Approximately 15 months following the treatment, she developed new-onset insulin requiring diabetes mellitus but without autoantibodies associated with type 1 diabetes. At that time, she was also noted to have hypertriglyceridemia (436 mg/dL), and elevated liver enzymes (3-4 X ULN), and a subsequent liver biopsy revealed severe macrovesicular steatosis. Her BMI was 30 kg/m2 and she had mild loss of buccal fat. Skin fold thickness measurements over the trunk and limbs were in the normal range. However, she had an undetectable serum leptin level and whole body fluorodeoxyglucose (FDG)- positron emission tomography (PET) scan, obtained for cancer surveillance, showed mild diffuse FDG activity throughout the subcutaneous tissues. She was advised low fat diet and started on insulin therapy. Over the next three months, she lost about 20 kg weight with generalized loss of subcutaneous fat from face, trunk, and extremities. Pioglitazone was started but discontinued after 4 weeks due to pedal edema and no effect on fat loss. Despite generalized lipodystrophy, she has maintained good glucose control on moderate dose insulin therapy (0.6 â€" 0.8 units/kg) and with normalization of liver enzymes and serum triglycerides. <h3>Conclusions</h3> ICI therapy can be associated with AGL, and the diagnosis must be considered in patients who develop metabolic complications such as diabetes, dyslipidemia, or steatohepatitis. Interestingly, metabolic abnormalities may precede overt fat loss. Hypoleptinemia and diffuse FDG uptake of subcutaneous tissue suggest subclinical panniculitis and adipocyte dysfunction even before clinically evident lipodystrophy.

Impact of l-Carnitine Supplementation on Liver Enzyme Normalization in Patients with Chronic Liver Disease: A Meta-Analysis of Randomized Trials.

The effectiveness of l-carnitine in chronic liver disease remains controversial. We conducted this meta-analysis to assess the efficacy of various forms of l-carnitine in the treatment of chronic liver disease. Methods: We searched the Cochrane Library, EMBASE, KMBASE, and Medline databases for all relevant studies published until April 2022 that examined the ability of l-carnitine or its derivatives to normalize liver enzymes in patients with chronic liver disease. We performed meta-analyses of the proportion of patients with alanine aminotransferase (ALT) normalization and post-treatment serum aspartate aminotransferase (AST) and ALT levels. A random effects model was used for meta-analyses. Results: Fourteen randomized controlled trials (1217 patients) were included in this meta-analysis. The proportion of patients in whom ALT normalized was higher in the carnitine-orotate treatment group than in the control group (pooled odds ratio (OR), 95% confidence interval (CI) = 4.61 (1.48–14.39)). The proportion of patients in whom ALT normalized was also higher among those who received the carnitine-orotate complex, a combination of carnitine-orotate, biphenyl dimethyl dicarboxylate, and other minor supplementary compounds than in those who did not without significant heterogeneity (pooled OR (95% CI) = 18.88 (7.70–46.27); df = 1; p = 0.51; I2 = 0%). l-carnitine supplementation effectively lowered serum ALT levels compared to controls (pooled mean difference (95% CI) = −11.99 (−22.48 to −1.49)). Conclusions: l-carnitine supplementation significantly lowered ALT and AST levels and normalized ALT levels in patients with chronic liver disease.

Syphilis Presenting as Hepatitis in an HIV-Infected Patient

Abstract Syphilis presents with protean manifestations. We report the case of a 24-year-old Filipino, working in Zambia for the past 2 months, presenting with a 2-week history of fever and jaundice. Maculopapular rashes were noted on both palms of the hands and both soles of the feet. Workup revealed an abnormal cholestatic pattern of liver function tests, while negative for malaria, viral hepatitis, and bacteremia. He tested positive for both HIV and VDRL (Venereal Disease Research Laboratory). A magnetic resonance cholangiopancreatography showed only hepatomegaly and no signs of cholangiopathy or hepatobiliary tree anomalies. After administration of a single dose of penicillin G, resolution of fever and jaundice and normalization of liver enzymes were noted. Syphilitic hepatitis was the primary diagnosis because of the following: demonstration of liver injury, positive serology for syphilis, and exclusion of other causes of liver injury with resolution upon penicillin G administration.

Dili is rare amongst patients without liver metastases receiving cancer treatment in Iceland: a population-based cohort study

Background There is limited information on the frequency of idiosyncratic drug-liver injury (DILI) among cancer patients. The aim of the study was to evaluate the frequency of DILI due to cancer treatment in a population-based setting. Material and methods All patients diagnosed with genitourinary cancer, breast cancer or metastatic malignant melanoma in 2007–2018 were matched with a database containing laboratory results for all major hospitals in Iceland. Medical chart review was performed for cases with ALT/AST ≥5× upper limit of normal (ULN), ALP ≥2× ULN or bilirubin ≥2× ULN. Patients with liver-, and/or bone metastases and isolated elevations of ALP and patients with other etiologies of liver enzyme elevations were excluded. Cases with a RUCAM score of probable or highly probable were included. Results Among 4956 patients, 840 patients had liver enzyme elevations. Overall, nine (0.2%) cases of DILI were identified, seven women (78%), median age 59 years (IQR 52–66). Four patients had kidney cancer, four breast cancer and one metastatic prostate cancer. In eight cases, a single agent was implicated: Pazopanib (n = 3), axitinib, docetaxel, gemcitabine, letrozole and paclitaxel. In all cases, the treatment was interrupted or discontinued due to the liver injury. No patient developed jaundice or liver failure and no death was linked to DILI. Time to normalization of liver enzymes was 17 days (IQR 25–120). Conclusion DILI was found to be rare and no cases of severe liver injury occurred. However, approximately 90% of patients switched to another treatment which might have affected prognosis.

From the Editor’s Desk...

From the Editor’s Desk...

The incidence and risk factors of chronic rejection in acutely rejected pediatric liver transplantation

Background. Chronic graft rejection (CR) represents an increasing concern in pediatric liver transplantation (LT). Risk factors of CR in this population are uncertain. In present study, we aimed to ascertain if clinical parameters could predict the occurrence of CR in LT children.Methods. We retrospectively analyzed the results from 47 children who had experienced acute hepatic rejection in Namazee hospital, Shiraz, Iran during 2007–2017.Results. Out of 47 children, 22 (46.8%) and 25 (53.2%) were boys and girls respectively. Ascites, gastrointestinal bleeding, and spontaneous bacterial peritonitis were observed in 20 (44.4%), 14 (31.1%), and 4 (9.1%) respectively. Posttransplant vascular and biliary complications were observed in 3 (7%) and 4 (9.3%) cases respectively. The mean time from LT to normalization of liver enzymes was 14.2 ± 7.5 days. The mean of acute rejection episodes was 1.4 ± 0.6 (median = 1 (22, 46.8%), range of 1–3). Six (12.7%) patients experienced CR. The mean time from LT to CR was 75 ± 28.4 days. A significant association was found between CR and patients’ condition (being inpatient or outpatient) before surgery (P = 0.03). No significant relationship was found between CR and post-transplant parameters except for biliary complications (P = 0.01). Both biliary complication (RR = 33.7, 95% CI: 2.2–511, P = 0.01) and inpatient status (RR = 10.9, 95% CI: 1.1–102.5, P = 0.03) significantly increased the risk of CR.Conclusion. Being hospitalized at the time of LT, and development of biliary complications might predict risk factors for development of CR in LT children.