Clindamycin-induced acute cholestatic hepatitis

We report a case of acute hepatotoxicity in a 42-yearold woman after administration of clindamycin for a dental infection. After 6 d of treatment, she had fatigue, nausea, vomiting, anorexia, pruritus and jaundice. Her laboratory analysis showed alanine aminotransferase （ALT）, 1795 IU/L （normal range 0-40）; aspartate aminotransferase （AST）, 1337 IU/L （normal range 5-34）; alkaline phosphatase （ALP）, 339 IU/L （normal range 40-150）; 7-glutamyl transpeptidase （GGT）, 148 IU/L （normal range 9-64 IU/L）; total bilirubin, 4.1 mg/dL; direct bilirubin, 2.9 mg/dL and prothrombin time （PT）, 13.5 s, with international normalized ratio （INR）, 1.04. She was hospitalized, with immediate drug discontinuation. Her liver biopsy specimen showed mixed-type （both hepatocellular and cholestatic） hepatic injury, compatible with a diagnosis of drug-induced hepatitis. An objective causality assessment using the Naranjo probability scale suggested that clindamycin was the probable cause of the acute hepatitis. In susceptible individuals, clindamycin use may lead to acute mixedtype liver toxicity. Complete recovery may be possible if the drug is discontinued before severe liver injury is established.     

Acute hepatitis A: combination of the relapsing and the cholestatic forms, two rare variants

Here we present an unusual case of a 23-year-old, otherwise healthy man who had a biphasic form of viral hepatitis A with a combination of two variants, the relapsing and cholestatic forms. One month after resolution of the first phase of acute hepatitis A, he was readmitted with jaundice and intense pruritus. During hospitalization, his serum bilirubin level increased to 50.2 mg/dL, with a slight increase in the other levels of liver enzymes. He was treated with ursodeoxycholic acid and later with corticosteroid therapy, resulting in resolution of symptoms and improvement of his liver function tests after 2 weeks. Medication therapy seems to be justified in markedly symptomatic patients with relapsing hepatitis.     

Suspected cross-hepatotoxicity of flutamide and cyproterone acetate.

Flutamide and cyproterone acetate (CPA) are both oral anti-androgens commonly used to treat advanced prostatic cancer. We report a case of drug-induced hepatotoxicity after consecutive treatment with flutamide and CPA. A 78-year-old male with advanced prostatic adenocarcinoma had been treated with flutamide 750 mg/day p.o. and leuproleride acetate 22.5 mg/3 months i.m. Three months later, the patient complained of choluria and jaundice. Laboratory examination revealed severe hepatocellular insufficiency. Flutamide-induced hepatotoxicity was suspected and therefore flutamide was withdrawn. His liver function abnormalities resolved after drug discontinuation. He was subsequently started on CPA 150 mg/day and again developed hepatotoxicity with severe hepatocellular impairment, which completely recovered after drug discontinuation. Other causes of acute liver failure were appropriately ruled out in both episodes and there was no evidence of active prostate cancer or liver metastases in both episodes. The occurrence of hepatotoxicity associated with flutamide and CPA on separated occasions suggests the possibility of a common mechanism of injury. It may become necessary to reassess the common practice of switching to another anti-androgen when hepatotoxicity appears. A closer monitoring of liver enzymes might be necessary in such cases, as an increased risk of a new severe hepatotoxicity event cannot be ruled out.     

Hepatic injury after nonmyeloablative conditioning followed by allogeneic hematopoietic cell transplantation: a study of 193 patients

Liver injury is a frequent, serious complication of allogeneic hematopoietic cell transplantation (HCT) following myeloablative preparative regimens. We sought to determine the frequency and severity of hepatic injury after nonmyeloablative conditioning and its relationship to outcomes. One hundred ninety-three consecutive patients who received 2 Gy total body irradiation with or without fludarabine were evaluated for end points related to liver injury. Patients with diseases treatable by HCT who were ineligible for conventional myeloablative allogeneic HCT because of advanced age and/or comorbid conditions were included. Fifty-one patients (26%) developed hyperbilirubinemia of 68.4 microM (4 mg/dL) or greater, most commonly resulting from cholestasis due to graft-versus-host disease (GVHD) or sepsis. Pretransplantation factors associated with liver dysfunction were a diagnosis of aggressive malignancy (hazard ratio [HR] 1.9; P =.04) and the inclusion of fludarabine in the conditioning regimen (HR 1.8; P =.07). Overall survival at 1 year was superior for patients who had maximal serum bilirubin levels in the normal (78%) or minimally elevated (22.23-66.69 microM [1.3-3.9 mg/dL]) ranges (69%) compared with those in the 68.4 to 117.99 microM (4-6.9 mg/dL; 20%), 119.7 to 169.29 microM (7.0-9.9 mg/dL; 17%), and 171.0 microM (10 mg/dL; 19%) or greater groups. In summary, significant jaundice occurred in 26% of patients and was predominantly due to cholestasis resulting from GVHD and/or sepsis. Aggressive malignancies (mainly advanced disease) and later development of jaundice after transplantation predicted inferior survival.     

Etiology of new-onset jaundice: how often is it caused by idiosyncratic drug-induced liver injury in the United States?

BACKGROUND AND AIM: The epidemiology of acute drug-induced liver injury (DILI) in the United States has not been well studied. We conducted a study of adults with new-onset jaundice at a nonreferral community hospital to better understand the epidemiology of acute DILI. METHODS: This is a retrospective study of adult outpatients and inpatients (> or =18 yr) with new-onset jaundice over a 5-yr period (1999-2003) at Wishard Memorial Hospital, Indiana. Patients with new-onset jaundice were identified using our electronic medical record system and individual medical records were reviewed to extract the required clinical data. New-onset jaundice was defined as the presence of total serum bilirubin >3 mg/dL in patients without a prior total bilirubin >3 mg/dL. RESULTS: A total of 732 eligible adults constituted our study cohort. Sepsis or altered hemodynamic state resulting in presumed ischemic liver injury is the single most common cause of jaundice (22%). Acute liver disease as a result of nonalcoholic etiologies caused new-onset jaundice in 97 patients (13%), with acute viral hepatitis in 66 patients (9%) and DILI in 29 patients (4%). Most cases of DILI were as a result of acetaminophen toxicity with idiosyncratic DILI occurring in only five patients (0.7%). No mortality was observed at 6 wk in patients who developed idiosyncratic DILI. CONCLUSION: Idiosyncratic DILI appears to be a rare cause of new-onset jaundice in a community hospital setting.     

Mastabol induced acute cholestasis: A case report

A 26-year-old male presented with three weeks of jaundice after the self-initiation of the injectable anabolic steroid, Mastabol [Dromastanolone Di-Propionate (17 beta-Hydroxy-2alpha-methyl-5alpha-androstan-3-one propionate)]. He reported dark urine, light stools, and pruritus. He denied abdominal pain, intravenous drug use, intranasal cocaine, blood transfusions, newly placed tattoos, or sexually transmitted diseases. He used alcohol sparingly. Physical exam revealed jaundice with deep scleral icterus. The liver was palpable 2 cm below the right costal margin with no ascites. The peak bilirubin was 23.6 mg/dL, alkaline phosphatase was 441 units/L, and aspartate aminotransferase/alanine aminotransferase were 70 units/L and 117 units/L respectively. A working diagnosis of acute intrahepatic cholestasis was made. Liver biopsy revealed a centrilobular insult with neutrophilic infiltrates and Ito cell hyperplasia consistent with acute drug induced cholestasis. The patient’s clinical symptoms resolved and his liver enzymes, bilirubin, and alkaline phosphatase normalized. Anabolic steroids with 17 alpha carbon substitutions have been associated with a bland variety of cholestatic injury with little hepatocellular injury. Cholestasis, under these circumstances, may be secondary to the binding of drugs to canalicular membrane transporters, accumulation of toxic bile acids from canalicular pump failure, or genetic defects in canalicular transport proteins. Mastabol is an injectable, 17 beta hydroxyl compound with no alpha alkyl groups at the 17 carbon position. As such, it has been reported to have little potential toxic effects on the liver. This is the first known reported case of Mastabol-induced cholestatic liver injury. It highlights the need for physicians to consider such widely available substances when faced with hepatic injury of unclear etiology.     

Successful liver transplantation for acute sickle cell intrahepatic cholestasis: A case report and review of the literature

BACKGROUND Sickle cell hepatopathy(SCH) is an inclusive term referring to any liver dysfunction among patients with sickle cell disease. Acute sickle cell intrahepatic cholestasis is one of the rarest and most fatal presentations of SCH. We present the 23 rd reported case of liver transplantation(LT) for SCH; a rare case of acute sickle cell intrahepatic cholestasis managed with LT from a hepatitis C virus(HCV) nucleic acid amplification test positive donor.CASE SUMMARY A 29-year-old male with a past medical history of sickle cell disease presented with vaso-occlusive pain crisis. On examination, he had jaundice and a soft, nontender abdomen. Initially he was alert and fully oriented; within 24 h he developed new-onset confusion. Laboratory evaluation was notable for hyperbilirubinemia, leukocytosis, anemia, thrombocytopenia, acute kidney injury and elevated international normalized ratio(INR). Imaging by ultrasound and computed tomography scan suggested a cirrhotic liver morphology with no evidence of biliary ductal dilatation. The patient was diagnosed with acute sickle cell intrahepatic cholestasis after excluding competing etiologies of acute liver injury. He underwent LT from an HCV nucleic acid amplification test positive donor 9 d after initial presentation. The liver explant was notable for widespread sinusoidal dilatation with innumerable clusters of sickled red blood cells and cholestasis. On postoperative day 3, HCV RNA was detectable in the patient's peripheral blood and anti-HCV therapy with glecaprevir/pibrentasvir was initiated on postoperative day 23. He subsequently achieved sustained virologic response after completing 3 mo of therapy and has been followed clinically for 12 mo post-transplant.CONCLUSION This case highlights the utility of LT as a viable treatment option for acute sickle cell intrahepatic cholestasis.     

Two cases of acute renal failure associated with nonfulminant acute hepatitis A]

We report two cases of acute renal failure in patients with nonfulminant acute hepatitis A. First case is a healthy 25 year-old man complained of myalgia and jaundice. Initial laboratory results showed BUN 40 mg/dL, creatinine 5.23 mg/dL, AST 2,220 IU/L, ALT 3,530 IU/L, total bilirubin 6.26 mg/dL, and positive anti-HAV IgM antibody. Supportive treatments including fluid therapy were started. Serum creatinine and total bilirubin levels were 7.98 mg/dL and 7.66 mg/dL respectively on the 5th hospital day, and decreased gradually. He was discharged on the 12th hospital day, and was being followed up in outpatient department. Second case is a 33 year-old woman who admitted for bilateral flank pain, high fever, nausea, and vomiting. She was diagnosed as acute pyelonephritis and acute hepatitis A. On admission, BUN 13 mg/dL, creatinine 0.74 mg/dL, AST 3,720 IU/L, ALT 2,280 IU/L, total bilirubin 0.9 mg/dL were noted, and acute renal failure developed next day. Fluid therapy with antibiotics administration were started, and maximal BUN and creatinine was 41.7 and 8.09 mg/dL respectively on the 8th day. She recovered without dialysis and was discharged on the 19th hospital day. Proper and prompt comprehensive supportive measures would decrease the need for dialysis in patient of acute renal failue associated with acute hepatitis A.     

Herbal hepatoxicity from Chinese skullcap: A case report

The use of herbal supplements has increased considerably over the last decade. We report a case of an elderly woman who began taking Move Free Advanced for arthritis, which in addition to glucosamine and chondroitin, contained two herbal ingredients, Chinese skullcap and Black Catechu. Our patient presented with significant cholestasis and hepatitis which significantly improved after discontinuation of the supplement. Since neither the patient nor the treating physician recognized this supplement as a potential hepatotoxin, she resumed taking the supplement and again suffered from considerable hepatotoxicity. Liver biopsy at that time was consistent with acute drug induced liver injury. She, once again, recovered after discontinuation of the supplement. Review of the literature confirms that Chinese skullcap has been implicated as a possible hepatotoxic agent which was demonstrated in this case.     

Cases from the Osler Medical Service at Johns Hopkins University. Antiglomerular basement membrane disease

A 47-year-old Taiwanese man with no notable medical history was admitted with low-grade fevers and night sweats that had persisted for 5 to 6 weeks. An extensive investigation at another hospital could not determine the cause of the fevers, but documented acute renal failure with a blood urea nitrogen level of 60 mg/dL and a serum creatinine level of 5.6 mg/dL. He was admitted to the Johns Hopkins Hospital for further evaluation.The patient, who had been living in the United States for the past 20 years, reported no recent travel and no behaviors that are associated with transmission of human immunodeficiency virus. He was not taking any medications, and he denied using herbal or nutritional supplements. He had no recent weight loss. There were no specific complaints on review of systems. On physical examination, he was a thin, middle-aged man in no distress. Vital signs included a temperature of 37.5 degrees C, a blood pressure of 166/86 mm Hg, a pulse of 70 beats per minute, a respiratory rate of 16 breaths per minute, and 99% oxygen saturation on room air. Sclera were anicteric, and he had no palpable adenopathy. His lungs were clear, and his heart rate was regular without extra sounds. His abdomen was thin, nontender, and without masses or organomegaly. There was no edema or signs of embolism in the extremities. Laboratory studies revealed a white blood cell count of 14,200/mL(3), a hematocrit of 23.1%, and a platelet count of 456,000/mL(3). Blood chemistries were notable for a blood urea nitrogen level of 61 mg/dL and a serum creatinine level of 7.6 mg/dL. Levels of aminotransferases, total bilirubin, and alkaline phosphatase were within normal limits. Urinalysis revealed large hemoglobin, 1+ protein, numerous red blood cells, and 3 to 5 white blood cells. Numerous red blood cell casts were seen on microscopic examination of the urine sediment. The patient's erythrocyte sedimentation rate was >130 mm/h, and his C-reactive protein level was elevated at 12.6 mg/dL. Serologies were negative for antinuclear antibodies and antineutrophil cytoplasmic antibodies; serum complement levels were normal. What is the diagnosis?     

Acute liver injury induced by weight-loss herbal supplements

We report three cases of patients with acute liver injury induced by weight-loss herbal supplements. One patient took Hydroxycut while the other two took Herbalife supplements. Liver biopsies for all patients demonstrated findings consistent with drug-induced acute liver injury. To our knowledge, we are the first institute to report acute liver injury from both of these two types of weight-loss herbal supplements together as a case series. The series emphasizes the importance of taking a cautious approach when consuming herbal supplements for the purpose of weight loss.     

A case of drug-induced hepatic injury associated with sitagliptin

A 58-year-old man with a 10-year history of type II diabetes mellitus presented with progressive jaundice that began three days before admission. Thorough history-taking revealed that the patient had started on a new medication, sitagliptin, one month previously for the treatment of diabetes mellitus. Laboratory investigations showed severe liver dysfunction. Ultrasonography detected no extrahepatic biliary duct dilatation or gallstones. Abdominal computed tomography excluded pancreatic and hepatic focal lesions. Liver function improved upon discontinuation of sitagliptin. Drugs are an important, often unrecognized, cause of acute liver injury. This report presents a rare case in which sitagliptin was responsible for acute hepatic damage. As demonstrated, a thorough drug history is helpful in any case of unexplained liver injury.     

Obstructive Jaundice Due to Duodenal Ulcer Induced by Lenvatinib Therapy for Hepatocellular Carcinoma

An 82-year-old man with hepatocellular carcinoma presented with upper abdominal pain, vomiting, and jaundice. He had been taking a standard lenvatinib dose for three months. Although acute cholangitis was suggested, imaging studies failed to detect the biliary obstruction site. An endoscopic examination following discontinuation of lenvatinib and aspirin revealed multiple duodenal ulcers, one of which was formed on the ampulla of Vater and causing cholestasis. Endoscopic biliary drainage and antibiotics improved concomitant Enterobacter cloacae bacteremia. Ulcer healing was confirmed after rabeprazole was replaced with vonoprazan and misoprostol. Our case shows that lenvatinib can induce duodenal ulcers resulting in obstructive jaundice.     

Serum alanine aminotransferase in skeletal muscle diseases

Although elevation of the levels of serum alanine aminotransferase (ALT) following liver injury is well known, confusion exists concerning skeletal muscle injury as the cause of this rise. We reviewed the records of 16 patients who had muscle necrosis without evidence of liver disease. The patients were divided into three groups: extreme exercise, polymyositis, and seizures. All patients exhibited markedly elevated creatine kinase and lactate dehydrogenase levels consistent with muscle injury. In acute cases, aspartate aminotransferase (AST) and ALT were both elevated, and the AST/ALT ratio was greater than 3, but this ratio approached 1 after a few days because of a faster decline in AST. In conclusion, this difference in half-life accounts for the comparable AST and ALT levels in our cases with chronic muscle injury.     

Hepatitis C virus cures after direct acting antiviral-related drug-induced liver injury: Case report

The United States Food and Drug Administration recently warned that the direct acting antiviral(DAA) combination hepatitis C virus(HCV) treatment of Paritaprevir, Ombitasvir, Dasabuvir, Ritonavir, and Ribavirin(PODr + R) can cause severe liver injury in patients with advanced liver disease. Drug induced liver injury was observed in a small number of patients with decompensated cirrhosis treated with other DAAs, but has not been reported in patients with compensated cirrhosis. We report a case of a 74-year-old woman with chronic HCV and Child-Pugh class A cirrhosis(compensated cirrhosis) treated with PODr + R. The patient presented on day 14 of PODr + R therapy with jaundice and new-onset ascites. Her total bilirubin level increased to 23 mg/dL and international normalized ratio rose to 1.65, while aminotransferase levels remained relatively stable. Hepatitis C treatment was discontinued on day 24 and she gradually recovered. Follow-up testing showed that she achieved a sustained virologic response. In conclusion, hepatic decompensation developed within two weeks of starting treatment withPODr + R in a patient with Child-Pugh class A cirrhosis and was characterized by jaundice and ascites with stable aminotransferase levels. Careful monitoring is warranted in patients with HCV-related cirrhosis treated with PODr + R.     

Profile of hepatitis A infection with atypical manifestations in children

We assessed the clinical course and biochemical profile of symptomatic children with viral hepatitis A who had atypical manifestations. Of 229 children with hepatitis A, atypical manifestations were found in 32 (14%) subjects. Prolonged cholestasis (n = 14), acute liver failure (9), relapse (9), ascites (8), and hematological problems (8) were the common presentations. Liver histology was suggestive of chronic liver disease in six children with protracted jaundice. Patients with atypical presentations were older (7.7 [1.6] years vs. 6.5 [2.6] years; p=0.012) and had higher total serum bilirubin (13.7 [8.1] mg/dL vs. 7.2 [4.0] mg/dL; p=<0.001) than those with typical presentation. Approximately 15% of children with acute hepatitis A infection have atypical presentation which is associated with increase in morbidity.     

Pazopanib-induced severe acute liver injury: A case report

Rationale:Drug-induced liver injury (DILI) is the most common cause of acute liver failure in the United States. Painkillers and fever antipyretics are the most common cause of DILI. Hepatic injury can be provoked by DILI as hepatocellular or cholestatic type.Patient concerns:A 48-year-old woman presented jaundice accompanied by nausea and vomiting. The patient was an inactive hepatitis B carrier with low viral titer and was diagnosed renal cell carcinoma (RCC) with hepatic metastasis requiring pazopanib treatment. Prior to administration of pazopanib, tenofovir administration was started to prevent exacerbation of hepatitis B. The patient was referred to clinic of gastroenterology department due to sudden elevation of bilirubin after 5 weeks of pazopanib treatment.Diagnoses:Abdominal ultrasound and computed tomography showed non-specific finding other than metastatic nodule in the liver and liver cirrhosis. After then, the patient was performed liver biopsy, and the biopsy result was acute cholestatic hepatitis with centrilobular area necrosis and portal inflammation. Therefore, considering the clinical history and biopsy results, the patient was diagnosed as DILI due to pazopanib.Interventions:After the biopsy, empirical steroid therapy was initiated and after 7 weeks of pazopanib discontinuation.Outcomes:The total bilirubin level returned to normal from peak level of 24.61 to 1.52 mg/dL.Lessons:In patients with renal cell carcinoma, pazopanib treatment requires clinical caution as it causes rare complications such as severe jaundice and acute cholestatic hepatitis.     

Acute hepatic failure in a patient with hyperthyroidism and virus B hepatitis: recovery after plasmapheresis and thyroidectomy--a case report

A 31-year-old man admitted with abdominal pain, nauseas, vomiting, jaundice and fever that had began 2 weeks before. He had a history of hyperthyroidism and an irregular treatment with propylthiouracil (PTU) for 2 years. He had stopped PTU when the current symptoms started. The patient presented diffuse goiter, about 120g, FT4 22.7 ng/dL (N: 0.8 - 1.9 ng/dL); THS < 0.002 microUI/mL (N 0.4-5 microUI/mL). Transaminases, serum total and direct bilirubins were increased. He was kept without PTU and propranolol was started and increased until the dose of 480 mg/day. Abdominal ultrasonography was normal and serologic markers for hepatitis A, B and C pointed to acute virus B hepatitis. The patient presented a worse of hepatic function and elevated thyroid hormones levels. To avoid the future need of antithyroid drugs, to get a fast normalization of thyroid hormones levels and because of the goiter size thyroidectomy was recommended. The patient underwent one therapeutic plasmapheresis session just before the surgery. A total thyroidectomy was performed without complications. At the 5th day after surgery the patient presented improvement of hepatic function and low FT4 serum levels. We concluded that preexisting hyperthyroidism may aggravate or perpetuate a hepatic failure caused for acute viral hepatitis and plasmapheresis is a rapid, reliable and effective way to lower thyroid hormones serum levels, allowing a successful thyroidectomy in patients with severe thyrotoxicosis.     

Lesser celandine(pilewort) induced acute toxic liver injury: The first case report worldwide

Lesser celandine, also known as Ranunculus ficaria, is a herbaceous perennial plant that commonly utilizes piles and is taken either internally or used externally.The causality assessment of several reports provided evidence for the existence of Greater Celandine hepatotoxicity. However, there hasn’t been any case report published thus far, about lesser celandine induced liver injury. Here, we present a case of 36-year-old woman admitted to the hospital with acute hepatitis and jaundice on her sclera with no history of drug abuse or alcohol consumption. However, the patient had a recent history of lesser celandine extract consumption for hemorrhoids, for about 10 d, prior to the admission. Viral hepatitis, autoimmune hepatitis, and drug induced toxic hepatitis were ruled out by further imaging studies and laboratory analysis. Using the Council for International Organizations of Medical Sciences scale, the type of liver injury was assumed as hepatocellular and was scored as 7 which shows probable causality. Immediate discontinuation of lesser celandine extract resulted in rapid decrease of the elevated enzymes. Herbs have been reported to cause liver injury and therefore should be suspected in the case of acute hepatitis with an unknown etiology. This case is important to be the first to explain hepatotoxicity caused by lesser celandine. Physicians should consider lesser celandine as a causative agent for hepatotoxicity.     

Drug-induced hepatitis with autoimmune features during minocycline therapy

A 25-year-old woman with no history of liver disease developed liver dysfunction associated with severe jaundice and general malaise following a prolonged therapy with minocycline for acne vulgaris. Serum anti-nuclear antibody was detected and immunoglobulin G level was elevated. Symptoms resolved and liver function normalized following minocycline discontinuation and corticosteroid administration. Our diagnosis was drug-induced hepatitis with autoimmune features, as liver histology revealed acute hepatitis. Drug-induced hepatitis should be considered when liver dysfunction or systemic symptoms develops during long-term minocycline therapy.