Acute Liver Injury as a Manifestation of Secondary Syphilis.

In the United States, the incidence of new cases of syphilis has been rising. The number of cases of primary and secondary syphilis has continued to increase almost every year over the past 2 decades. Secondary syphilis has a variety of clinical manifestations. A frequently overlooked presentation is that of syphilitic hepatitis, which should be part of the differential diagnosis for patients with elevated liver enzymes, a maculopapular rash, and/or risk factors for contracting syphilis. In this study, we report a rare and unusual case of a man with a remote history of syphilis infection who developed acute liver injury.

Bacterial Infections in Cirrhotic Patients in a Tertiary Care Hospital.

BACKGROUND AND AIMS: Patients with cirrhosis are immunocompromised and at higher risk of developing infections compared to the general population. The aim of this study was to assess the incidence of infections in cirrhotic patients in a large academic liver center and investigate potential associations between infections, bacteria isolated, therapeutic regimens used, and mortality. METHODS: This was a retrospective chart review study, including 192 patients. All patients had a diagnosis of cirrhosis and were admitted to University Hospital. Information collected included demographics, etiology of cirrhosis, identification of bacteria from cultures, multidrug-resistant (MDR) status, antibiotics administered, intensive care unit (ICU) admission, and patient mortality. RESULTS: Infections were present in 105 (54.6%) patients, and 60 (31.2%) patients had multiple infections during a hospitalization(s) for infections. A total of 201 infections were identified. Urinary tract infections (UTIs) were the most common infection (37.8%), followed by bacteremia (20.4%), pneumonia (12.9%), spontaneous bacterial peritonitis (SBP) (11.9%), abscess/cellulitis (6.0%), infectious diarrhea (6.0%), and other (5.0%). Escherichia coli was the most common bacteria isolated (13.4%), both among sensitive and MDR infections. MDR bacteria were the cause for 41.3% of all infections isolated. Fungi accounted for 9.5% of infections. 21.9% of patients had decompensation from their infection(s) that required ICU care, and 14.6% of patients died during hospitalization or soon after discharge. CONCLUSIONS: The incidence of infections in cirrhotic patients is much higher than in their non-cirrhotic counterparts (54.6%), even higher than prior studies suggest. As many of these infections are caused by MDR bacteria and fungal organisms, stronger empiric antibiotics and antifungals should be considered when initially treating this immunocompromised population. However, once organism sensitivities are discovered, narrowing of antibiotic regimens must occur to maintain good antibiotic stewardship.

Acute Liver Injury due to Severe Epstein-Barr Virus Infection.

Epstein-Barr virus (EBV) is a widely dispersed herpesvirus, transferred through close personal contact between susceptible individuals and asymptomatic shedders of the virus. The liver is often affected, and involvement is usually subclinical and self-limited. However, immunocompromised patients and, more rarely, immunocompetent individuals can develop a severe and potentially fatal acute liver injury. To differentiate EBV hepatitis from other conditions, such as autoimmune hepatitis, lymphoproliferative disorders, and drug-induced liver injury, correlation with clinical history, laboratory findings, and histopathologic features is crucial. We report a unique case of a man who developed acute liver injury from a severe EBV infection.

Liver Transplantation Beyond Milan Criteria.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, being the fifth most common cancer and the third most common cause of cancer-related mortality. The incidence of HCC has been rising in the USA over the last 20 years. Liver transplantation is an optimal treatment option, as it eliminates HCC as well as the underlying liver disease. The Milan criteria (1 lesion greater than or equal to 2 cm and less than or equal to 5 cm, or up to 3 lesions, each greater than or equal to 1 cm and less than or equal to 3 cm) have been adopted by many transplant societies worldwide as the criteria to determine whether patients with HCC can move forward with liver transplantation. However, many believe that the Milan criteria may be too strict in regard to its size requirements for lesions. This has led to a number of expanded criteria for liver transplantation, concerning both overall size and number of lesions, as well as incorporation of other markers of tumor biology. Tumor markers, such as alpha-fetoprotein, can also be used to follow treatment of HCC and possibly exclude patients from transplant. HCC presenting beyond Milan criteria can also be down-staged with locoregional therapy. Monitoring response to locoregional therapy and longer wait times after locoregional therapy prior to transplant can serve as surrogate markers of tumor biology as well.

Concurrent Langerhans Cell Histiocytosis and Autoimmune Hepatitis: A Case and Review of the Literature.

Autoimmune hepatitis (AIH) and Langerhans cell histiocytosis (LCH) are two independently rare disease processes that can have similar presentations. We present a unique, complex case that required a multidisciplinary approach to ultimately diagnose and treat the patient. A 20-year-old male with no significant history presented with worsening jaundice, diffuse, pruritic rash, and abdominal pain over one month. On admission, the patient's labs showed significantly elevated liver function tests (LFTs), eosinophilia, and anemia. The exam was notable for diffuse lymphadenopathy (LAD), hepatosplenomegaly, and a diffuse, non-blanching, morbilliform rash. Interdisciplinary workup was notable for positive anti-smooth muscle antibody (ASMA) and anti-neutrophilic antibody (ANA). A liver biopsy showed severe inflammation with interface activity, consistent with AIH. A lymph node (LN) biopsy showed findings consistent with LCH, including histiocyte clusters. He was started on high-dose steroids with LAD/LFT improvement; yet, his course was complicated by a gastrointestinal (GI) bleed requiring a hemicolectomy. The patient was transferred to a larger referral center where he continued to improve with steroids and was ultimately discharged. This case was notable for an LN biopsy showing histiocyte clusters with reniform nuclei, nuclear grooves, and eosinophils with immunohistochemical stains positive for S-100, CD1a, fascin, langerin, CD45, and CD68, consistent with LCH. The resected colon showed atypical histiocyte proliferation positive for fascin, CD4, and CD68. Other findings, including elevated LFTs, ASMA, and a liver biopsy showing inflammation with interface activity, eosinophils, plasma cells, and characteristic fibrosis, supported a diagnosis of AIH. In either case, steroids were indicated.

Acute Liver Injury in a Patient Treated With Rosuvastatin: A Rare Adverse Effect.

Drug-induced liver injury (DILI) is among the challenging liver conditions encountered by clinicians today. It has a low incidence in the general population with an approximated annual incidence of 10 - 15 cases per 10,000 - 100,000 persons who have taken prescription medications. Nevertheless, DILI remains the most frequent cause of acute liver injury in the United States. Rosuvastatin is a commonly prescribed medication that, similar to other statins, is associated with serum aminotransferase elevations that are mild, asymptomatic and usually self-limited. Here, we report a case of a man who developed acute liver injury after taking rosuvastatin for hypercholesterolemia treatment. Moreover, DILI with autoimmune features represents a key subgroup of hepatotoxicity attributable to medication exposure. Similar to idiopathic autoimmune hepatitis, circulating autoantibodies and a hypergammaglobulinemia are often present in the serum of such individuals. However, such findings are not invariable. In the case reported here, these laboratory features were absent, but a liver biopsy demonstrated interface hepatitis with a prominent plasma cell infiltrate, histologic components consistent with an immune-mediated drug reaction. After withdrawal of the offending medication did not result in complete resolution, corticosteroid therapy was administered with a subsequent clinical response, confirming the diagnosis.

CA-125 Significance in Cirrhosis and Correlation with Disease Severity and Portal Hypertension: A Retrospective Study.

Background and Aims: To evaluate the prevalence and significance of elevated cancer antigen-125 (CA-125) levels in patients with cirrhosis being treated in a tertiary care liver center and its correlation with objective markers of disease severity. Methods: We retrospectively reviewed medical records of 172 adult patients with cirrhosis (due to any etiology) after obtaining CA-125 serum analysis. Demographics, etiology of cirrhosis, model of end-stage liver disease (MELD) score, Child's Turcotte-Pugh classification, albumin bilirubin (ALBI) score, degree of ascites, presence of esophageal varices, serum CA-125 level and various other parameters were collected. Statistical analysis was performed using SPSS software and descriptive statistics. Results: Elevated CA-125 levels were noted in 147 patients (85%) of the study population. Higher MELD score was associated with higher CA-125 levels (p = 0.001). Statistically significant correlation was observed between elevated CA-125 levels and degree of ascites (p < 0.001), ALBI score (p < 0.001) and Child's Turcotte-Pugh class (p < 0.001). No correlation was observed with presence or absence of esophageal varices. Near-normal CA-125 levels were noted in patients with cirrhosis but undetectable ascites on ultrasound imaging. No differences were observed in mean values between male and female patients (p = 0.207). Regression analysis confirmed that CA-125 levels had a better correlation with degree of ascites than MELD score or ALBI score. Conclusions: Elevated CA-125 levels were noted in 85% of patients with cirrhosis at our center. Our study establishes that the more advanced the degree of decompensation based on MELD score, Child's Turcotte-Pugh classification and ALBI score, the higher the elevation in CA-125. Absence of ascites was associated with normal CA-125 level, with a direct correlation between high levels and worsening ascites, but there was no statistically significant correlation with esophageal varices, indicating that elevated CA-125 levels could be related to mechanical stretch of the peritoneum rather than portal hypertension itself. Further multi-centered studies are required to confirm and validate these findings.

Acute Liver Failure: Mechanisms of Disease and Multisystemic Involvement.

Acute liver failure is accompanied by a pathologic syndrome common to numerous different etiologies of liver injury. This acute liver failure syndrome leads to potentially widespread devastating end-organ consequences. Systemic dysregulation and dysfunction is likely propagated via inflammation as well as underlying hepatic failure itself. Decoding the mechanisms of the disease process and multisystemic involvement of acute liver failure offers potential for targeted treatment opportunities and improved clinical outcomes in this sick population.

The safety and efficacy of ledipasvir/sofosbuvir with or without ribavirin in the treatment of orthotopic liver transplant recipients with recurrent hepatitis C: real-world data.

BACKGROUND: Recurrent hepatitis C (RHC) in orthotopic liver transplantation (OLT) population is associated with accelerated rates of fibrosis, low efficacy and decreased tolerability with traditional therapies. AIM: The aim of this study was to evaluate the safety and efficacy of ledipasvir/sofosbuvir (LED/SOF) with or without ribavirin (RBV) in OLT patients with RHC. PATIENTS AND METHODS: Patients at least 3 months post-OLT and with documented RHC were treated with LED/SOF with or without RBV for either 12 or 24 weeks. End-of-treatment and sustained virological response 12 weeks after the completion of treatment were documented. Patients were closely monitored for treatment-related adverse effects and the potential need for adjustment in their immunosuppression. RESULTS: Seventy-one patients were included in the study. Median age was 62 years. Median time from OLT was 55 months. Twenty-six (36.6%) patients were treatment-naive and 45 (63.4%) had previously failed interferon-based therapies. The majority of patients (57.7%) had stage F0-F2 fibrosis. Sixty-seven (94.3%) patients completed 12 weeks of LED/SOF with RBV, three patients completed 12 or 24 weeks of LED/SOF without RBV, and one patient completed only 8 weeks of LED/SOF without RBV owing to severe allograft dysfunction. Sustained virological response was near universal in our cohort (98.5%) regardless of genotype, fibrosis stage, and regimen or treatment duration. Most commonly reported side effects were malaise and gastrointestinal upset. No patient required adjustment in immunosuppression and no episodes of rejection were documented during treatment. CONCLUSION: The combination of LED/SOF with RBV for 12 weeks or LED/SOF for 24 weeks is very effective and safe in treating OLT recipients with RHC.