Analyzing the utility of renal replacement therapy to manage hepatorenal syndrome in alcoholic hepatitis without liver transplantation: a nationwide analysis.

BACKGROUND: Hepatorenal syndrome (HRS) frequently complicates alcoholic hepatitis (AH) and portends poor survival in this population. Published literature indicates mixed benefits from renal replacement therapy (RRT) for HRS refractory to medical management. Therefore, we sought to assess the utilization of RRT in AH and clinical outcomes at a national level. METHODS: Using the International Classification of Diseases, Tenth Revision (ICD-10) codes, we identified adult patients with AH with a coexisting diagnosis of HRS from the National Readmission Database 2016 through 2019. Mortality, morbidity, and resource utilization were compared. We compared proportions using the Fisher exact test and computed adjusted P-values based on multivariate regression analysis. Analyses were performed using Stata, version 14.2, considering a two-sided P < 0.05 as statistically significant. RESULTS: A total of 73 203 patients with AH were included in the analysis (mean age 46.2 years). A total of 3620 individuals had HRS diagnosis (5%), of which 14.7% (n: 532) underwent RRT. HRS patients receiving RRT had a higher mortality rate than those who did not (adjusted odds ratio [aOR] 1.8, 95% confidence interval [CI]: 1.3-2.6, P: 0.01), along with higher resource utilization. Only those patients with HRS who underwent liver transplantation (LT) experienced a mortality reduction (24.4% for those not receiving RRTs and 36.5% for those receiving RRT). CONCLUSIONS: RRT is associated with higher mortality and morbidity when offered to patients with AH and HRS, who do not undergo LT. Therefore, our results suggest careful selection of AH patients when deciding to initiate RRT for HRS.

Outcomes of kidney, liver, and simultaneous liver and kidney transplants from hepatitis c infected donors to hepatitis c naïve recipients: A large single center experience.

BACKGROUND: With the introduction of direct-acting antiviral therapies (DAAs), the non-use rate of hepatitis C virus (HCV)-positive donor organs (D+) has decreased significantly. We present the donor, recipient, and transplant allograft characteristics, along with recipient outcomes, in one of the largest cohorts of HCV-D+ transplants into HCV-naïve recipients (R-). METHODS: Charts of HCV D+/R- kidney (KT), liver (LT), and simultaneous liver-kidney (SLKT) transplant recipients between January 2019 and July 2022 were reviewed. Primary outcomes of interest included waitlist times and 1-year graft failure. Secondary outcomes included hospital and intensive care unit length of stay, post-transplant complications, effectiveness of DAA therapy, and characteristics of patients who relapsed from initial DAA therapy. RESULTS: Fifty-five HCV D+/R- transplants at our center [42 KT (26 nucleic acid testing positive [NAT+], 16 NAT-), 12 LT (eight NAT+, four NAT-), and one SLKT (NAT+)] had a median waitlist time of 69 days for KT, 87 days for LT, and 15 days for SLKT. There were no graft failures at 1 year. All viremic recipients were treated with a 12-week course of DAAs, of which 100% achieved end of treatment response (EOTR)-85.7% (n = 30) achieved sustained virologic response (SVR) and 14.3% relapsed (n = 5; four KT, one LT). All relapsed recipients were retreated and achieved SVR. The most common post-transplantation complications include BK virus infection (n = 9) for KT and non-allograft infections (n = 4) for LT. CONCLUSIONS: Our study has demonstrated no graft failures or recipient deaths at 1 year, and despite a 14.3% relapse rate, we achieved 100% SVR. Complications rates of D+/R- appeared comparable to national D-/R- complication rates. Further studies comparing D+/R- to D-/R- outcomes are needed.

Asymptomatic Hepatic Leiomyoma in an Immunocompetent Middle-Aged Woman.

Primary hepatic leiomyomas are rare tumors most commonly in immunosuppressed individuals who are coinfected with Epstein-Barr virus (EBV). From our literature review, there have been 50 published cases, of which 24 were immunocompetent individuals and only 5 were negative for EBV infection. We report a case of primary hepatic leiomyomas in an asymptomatic middle-aged woman without a history of immunosuppression or EBV infection.

Hepatitis C Treatment Differences in Elderly Patients: Single-Center Retrospective Study.

Background: Clinical studies evaluating direct-acting antivirals (DAAs) for hepatitis C virus (HCV) treatment show sustained virological response at 12 weeks (SVR12) rates >90%. However, there are few elderly patients included in these studies; thus, generalizability of high success rates to patients >70 years old cannot be assumed. Objective: To identify treatment differences between elderly and nonelderly patients. Methods: This is a retrospective cohort study of all patients who were treated with DAAs between June 2014 and September 2016 at our institution. Patients were divided into 2 groups: elderly, age ≥70 years at the time of initiation of DAAs, and nonelderly, <70 years. The primary outcome was achievement of SVR12. Results: Among the 551 patients, 60 with age range 70 to 86 years comprised the elderly group. SVR12 rates were significantly lower in the elderly population, especially in those with liver cirrhosis. SVR12 was achieved in 81% of the elderly group as compared with 95% in the nonelderly group. Among cirrhotic patients, 69.4% in the elderly group, and 94.1% in the nonelderly group achieved SVR12. Binary logistic regression modeling showed age >70 years to be the strongest predictor of treatment failure (odds ratio = 3.4), along with diagnosis of cirrhosis (odds ratio = 2.4), when corrected for gender, race, prior treatment experience, genotype, and presence of hepatocellular carcinoma. Conclusion and Relevance: Lower SVR12 was seen in elderly cirrhotic patients (69.4%), who are at higher risk of complications related to advanced liver disease and untreated HCV infection, highlighting the need to treat patients before cirrhosis develops.

The molecular basis for current targets of NASH therapies.

Introduction: Nonalcoholic steatohepatitis (NASH) is a leading cause of liver disease in children and adults, a major contributor to health-care expenditures, and now a leading reason for liver transplantation. Adopting lifestyle modifications with regular exercise and a focus on healthy eating habits is the primary recommendation. However, patients are often unable to achieve and sustain such changes for a variety of social, physical, psychological and genetic reasons. Thus, treatments that can prevent and reverse NASH and its associated fibrosis are a major focus of current drug development.Areas covered: This review covers the current understanding of lipotoxic liver injury in the pathogenesis of NASH and how lifestyle modification and the spectrum of drugs currently in clinical trials address the many pathways leading to the phenotype of NASH.Expert opinion: Contrary to the frequently expressed nihilistic view of our understanding of NASH and disappointment with clinical trial results, much is known about the pathogenesis of NASH and there is much reason to be optimistic that effective therapies will be identified in the next 5-10 years. Achieving this will require continued refinement of clinical trial endpoints, continued engagement of trial sponsors and regulatory authorities, and continued participation of dedicated patients in clinical trials.

Eight-Week Outcomes of Ledipasvir/Sofosbuvir in Noncirrhotic Treatment-Naive Patients with Hepatitis C: Analysis of Pharmacy-Based Data.

BACKGROUND: Clinical trials have demonstrated that 8 weeks of ledipasvir and sofosbuvir (LDV/SOF) achieved high rates of sustained virologic response at 12 weeks (SVR12) in patients with hepatitis C viral (HCV) genotype 1 infection. The effectiveness of this combination was noted to be robust in treatment-naive noncirrhotic patients and in patients with an HCV viral load of < 6 million IU/mL before treatment. Generalizability of these results to community clinical practice, however, was advised with caution due to the variability of staging methods, fluctuating nature of viral loads, lack of prospective trials, and real-life confirmation. OBJECTIVE: To evaluate the efficacy, defined as SVR12, of LDV/SOF in a real-world setting. METHODS: Patients met inclusion criteria if given 8 weeks of LDV/SOF by a specialty pharmacy from October 2014 to October 2015 and if SVR12 was assessed after therapy completion. Clinical outcomes data were obtained from the pharmacy database. RESULTS: Of the 6,391 prescriptions of LDV/SOF received by the pharmacy, 3,648 (57%) were covered by insurance, and among them, only 511 (14%) were for an 8-week regimen. SVR12 data were available for 380 (74%) patients who completed an 8-week regimen. 230 different prescribers wrote prescriptions, and 57 different insurance plans approved the 8-week regimen. The majority (74%) of patients were followed by gastroenterology clinics. The 380 patients included in the analysis were all treatment-naive HCV genotype 1 patients. Overall, SVR12 was achieved in 97% of patients, while 10 patients relapsed. The SVR12 rates were lower (93%) in patients with stage 3 fibrosis, particularly in African Americans (29 of 35: 83%). CONCLUSIONS: Outcomes were favorable for the 8-week use of LDV/SOF in a noncontrolled real-world setting in treatment-naive noncirrhotic patients with a baseline viral load < 6 million IU/mL. Use of this approach in African Americans with evidence of advanced fibrosis should be avoided. DISCLOSURES: No outside funding supported this study. Lott is an employee of Diplomat Pharmacy. Andres and Qureshi have nothing to disclose. Study concept and design were contributed by Lott and Qureshi, who also collected the data. All authors contributed equally to data interpretation and manuscript preparation. Andres revised the manuscript, along with Lott and Qureshi. This work was presented in part as a poster at the 2016 International Liver Conference; Barcelona, Spain; April 13-17, 2016.

Eight weeks of ledipasvir/sofosbuvir is effective for selected patients with genotype 1 hepatitis C virus infection.

Eight weeks duration of ledipasvir/sofosbuvir (LDV/SOF) can be considered in genotype 1 hepatitis C virus-infected patients who are treatment-naive, do not have cirrhosis, and have a pretreatment viral load <6,000,000 IU/mL. The effectiveness of this regimen, however, has not been fully confirmed by real-world experience. Using data from real-world cohorts, we aimed to determine the effectiveness of 8 weeks of LDV/SOF treatment, examine variables associated with relapse after treatment with this regimen, and compare the effectiveness of 8 weeks and 12 weeks of LDV/SOF treatment. To evaluate the effectiveness of 8 weeks of therapy and characteristics associated with relapse, we used individual patient data from the IFI (Institut für Interdisziplinäre Medizin), Burman's Pharmacy, and Kaiser Permanente Southern California. All patients had fibrosis staging assessed with biopsy, transient elastography, or serum biomarkers. We also performed a systematic review and meta-analysis of six additional real-world cohorts, to compare effectiveness of 8 weeks to 12 weeks duration. In our pooled data analysis, 634 patients were treated for 8 weeks with LDV/SOF, of whom all had outcomes of cure or relapse without loss to follow-up. Per protocol rates of sustained virologic response at 12 weeks were 98.1% (622/634) in the full cohort and 97.9% (571/583) among treatment-eligible patients. Exact logistic regression revealed no specific patient characteristics associated with relapse. Our meta-analysis of six additional real-world cohorts, comprised of 5,637 patients, demonstrated similar risk for relapse between 8 weeks and 12 weeks of LDV/SOF (relative risk = 0.99, 95% confidence interval 0.98-1.00). CONCLUSION: An 8-week duration of treatment with LDV/SOF is highly effective in properly selected patients; greater use of this regimen is recommended. (Hepatology 2017;65:1094-1103).

The Use of Thrombopoietin Receptor Agonists for Correction of Thrombocytopenia prior to Elective Procedures in Chronic Liver Diseases: Review of Current Evidence.

Patients with chronic liver diseases (CLD) undergo a range of invasive procedures during their clinical lifetime. Various hemostatic abnormalities are frequently identified during the periprocedural work-up; including thrombocytopenia. Thrombocytopenia of cirrhosis is multifactorial in origin, and decreased activity of thrombopoietin has been identified to be a major cause. Liver is an important site of thrombopoietin production and its levels are decreased in patients with cirrhosis. Severe thrombocytopenia (platelet counts < 60-75,000/µL) is associated with increased risk of bleeding with invasive procedures. In recent years, compounds with thrombopoietin receptor agonist activity have been studied as therapeutic options to raise platelet counts in CLD. We reviewed the use of Eltrombopag, Romiplostim, and Avatrombopag prior to various invasive procedures in patients with CLD. These agents seem promising in raising platelet counts before elective procedures resulting in reduction in platelet transfusions, and they also enabled more patients to undergo the procedures. However, these studies were not primarily aimed at comparing bleeding episodes among groups. Use of these agents had some adverse consequences, importantly being the occurrence of portal vein thrombosis. This review highlights the need of further studies to identify reliable methods of safely reducing the provoked bleeding risk linked to thrombocytopenia in CLD.

An Unexpected Interaction between Sofosbuvir/Ledipasvir and Atorvastatin and Colchicine Causing Rhabdomyolysis in a Patient with Impaired Renal Function.

Hepatitis C virus (HCV) infection affects roughly 170 million people worldwide. Sofosbuvir/Ledipasvir (Sof/Led) is a new once daily direct acting antiviral combination pill that was approved in October 2014 for use in patients with HCV genotype 1 infection. Coadministration of Sof/Led is studied only with rosuvastatin which shows significantly increased level of drug and is associated with increased risk of myopathy, including rhabdomyolysis. There is no mention of such HMG-CoA reductase inhibitor interaction as a class, as pravastatin did not have any clinically significant interaction with Sof/Led. Other myotoxic drugs, including colchicine are not studied. We present a case of a serious drug interaction between Sof/Led and atorvastatin, in the background of CKD and colchicine use.

Rapid Resolution of Cholangitic Abscess and Biliary Sepsis in a Liver Transplant Recipient after Hepatic Artery Revascularization.

Hepatic arterial flow is paramount in preserving biliary integrity. We present an interesting clinical scenario of a liver transplant recipient with biliary anastomotic stricture who developed biliary abscess and sepsis after Endoscopic Retrograde Cholangiopancreatography. The abscess did not respond to maximal medical management, percutaneous drainage, and adequate endoscopic biliary drainage. Clinically, patient continued to deteriorate and imaging identified hepatic artery stenosis which was treated with percutaneous intra-arterial stenting. Revascularization and perfusion of infected area led to rapid resolution of abscess and sepsis. This case emphasizes the anatomic basis of biliary ductal pathology. An important educational point is to understand that interrupted hepatic arterial supply can lead to biliary complications in liver transplant recipients and early correction of perfusion deficit should be pursued in such cases. In nonresolving hepatobiliary infections after liver transplantation, hepatic arterial compromise should be looked for and if present promptly treated. Reperfusion of biliary system in our patient led to improved antibiotics penetration, resolution of abscess and sepsis, and healing of biliary stricture.

Imaging Based Methods of Liver Fibrosis Assessment in Viral Hepatitis: A Practical Approach.

Liver fibrosis represents the repair mechanism in liver injury and is a feature of most chronic liver diseases. The degree of liver fibrosis in chronic viral hepatitis infections has major clinical implications and presence of advanced fibrosis or cirrhosis determines prognosis. Treatment initiation for viral hepatitis is indicated in most cases of advanced liver fibrosis and diagnosis of cirrhosis entails hepatology evaluation for specialized clinical care. Liver biopsy is an invasive technique and has been the standard of care of fibrosis assessment for years; however, it has several limitations and procedure related complications. Recently, several methods of noninvasive assessment of liver fibrosis have been developed which require either serologic testing or imaging of liver. Imaging based noninvasive techniques are reviewed here and their clinical use is described. Some of the imaging based tests are becoming widely available, and collectively they are shown to be superior to liver biopsy in important aspects. Clinical utilization of these methods requires understanding of performance and quality related parameters which can affect the results and provide wrong assessment of the extent of liver fibrosis. Familiarity with the strengths and weaknesses of each modality is needed to correctly interpret the results in appropriate clinical context.

Approach to the management of portal hypertensive gastropathy and gastric antral vascular ectasia.

Gastric antral vascular ectasia (GAVE) and portal hypertensive gastropathy (PHG) are important causes of chronic gastrointestinal bleeding. These gastric mucosal lesions are mostly diagnosed on upper endoscopy and can be distinguished based on their appearance or location in the stomach. In some situations, especially in patients with liver cirrhosis and portal hypertension, a diffuse pattern and involvement of gastric mucosa are seen with both GAVE and severe PHG. The diagnosis in such cases is hard to determine on visual inspection, and thus, biopsy and histologic evaluation can be used to help differentiate GAVE from PHG.

The treatment of cholangiocarcinoma: a hepatologist's perspective.

Cholangiocarcinoma (CCA) is a rare but lethal adenocarcinoma with cholangiocyte differentiation that arises within the biliary tree at variable locations. Curative options are available in the form of surgical resection and/or liver transplantation (LT) in early stage CCA; however, these are offered to a small fraction of patients as they are usually asymptomatic and remain undiagnosed. Primary sclerosing cholangitis (PSC) is a well-known risk factor of CCA, and cirrhosis, viral hepatitis, and metabolic syndrome are recently identified as risk factors of CCA. This emerging evidence places hepatologists in a vital position to diagnose, prognosticate, and manage CCA by planning treatment of each individual patient based on the stage and extent of malignancy. With appropriate selection of patients and the involvement of a multidisciplinary team, surgical resection of localized CCA, LT coupled with neoadjuvant chemoradiation for perihilar CCA, or locoregional or systemic chemotherapy and/or endoscopic interventions for advanced CCA can be offered.

Hemorrhagic ascites from spontaneous ectopic mesenteric varices rupture in NASH induced cirrhosis and successful outcome: a case report.

Bleeding from gastro-esophageal varices can often present as the first decompensating event in patients with cirrhosis. This can be a potentially life threatening event associated with a 15%-20% early mortality. We present a rare case of new onset ascites due to intra-abdominal hemorrhage from ruptured mesenteric varices; in a 37 years old male with newly diagnosed nonalcoholic steatohepatitis induced cirrhosis as the first decompensating event. The patient was successfully resuscitated with emergent evacuation of ascites for diagnosis, identification and control of bleeding mesenteric varices and eventually orthotopic liver transplantation with successful outcome. Various clinical presentations, available treatment options and outcomes of ectopic variceal bleeding are discussed in this report.

Severe Aplastic Anemia following Acute Hepatitis from Toxic Liver Injury: Literature Review and Case Report of a Successful Outcome.

Hepatitis associated aplastic anemia (HAAA) is a rare syndrome in which severe aplastic anemia (SAA) complicates the recovery of acute hepatitis (AH). HAAA is described to occur with AH caused by viral infections and also with idiopathic cases of AH and no clear etiology of liver injury. Clinically, AH can be mild to fulminant and transient to persistent and precedes the onset SAA. It is assumed that immunologic dysregulation following AH leads to the development of SAA. Several observations have been made to elucidate the immune mediated injury mechanisms, ensuing from liver injury and progressing to trigger bone marrow failure with the involvement of activated lymphocytes and severe T-cell imbalance. HAAA has a very poor outcome and often requires bone marrow transplant (BMT). The findings of immune related myeloid injury implied the use of immunosuppressive therapy (IST) and led to improved survival from HAAA. We report a case of young male who presented with AH resulting from the intake of muscle building protein supplements and anabolic steroids. The liver injury slowly resolved with supportive care and after 4 months of attack of AH, he developed SAA. He was treated with IST with successful outcome without the need for a BMT.

Acute cytomegalovirus infection in liver transplant recipients: An independent risk for venous thromboembolism.

Acute cytomegalovirus (CMV) infection is a commonly encountered complication in the post liver transplant setting. We present a case of a 71-year-old male with acute CMV infection, initially presenting with a gastrointestinal bleed due to acute CMV gastritis and later on complicated by acute venous thromboembolism occurring as an unprovoked event in the post liver transplant period. Traditional risk factors for venous thromboembolism have been well described in the medical literature. Sporadic cases of thromboembolism due to CMV infection in the immune compromised patients have been described, especially in the post kidney transplant patients. Liver transplant recipients are equally prone to CMV infection particularly in the first year after successful transplantation. Venous thromboembolism in this special population is particularly challenging due to the fact that these patients may have persistent thrombocytopenia and anticoagulation may be a challenge for the treating physician. Since liver transplantation is severely and universally limited by the availability of donor organs, we feel that this case report will provide valuable knowledge in the day to day management of these patients, whose clinical needs are complex and require a multidisciplinary approach in their care and management. Evidence and pathophysiology linking both the conditions is presented along with a brief discussion on the management, common scenarios encountered and potential impact in this special group of patients.

Comparative evaluation of whole body and hepatic insulin resistance using indices from oral glucose tolerance test in morbidly obese subjects with nonalcoholic Fatty liver disease.

Nonalcoholic Fatty Liver Disease (NAFLD) is the hepatic manifestation of metabolic syndrome and is a marker of Insulin Resistance (IR). Euglycemic-hyperinsulinemic clamp is the gold standard for measuring whole body IR (hepatic + peripheral IR). However, it is an invasive and expensive procedure. Homeostasis Model Assessment Index for Insulin Sensitivity (HOMA-IS), Quantitative Insulin Sensitivity Check Index (QUICKI) for hepatic IR and Insulin Sensitivity Index (ISI(0,120)), and Whole Body Insulin Sensitivity Index (WBISI) for whole body IR are the indices calculated after Oral Glucose Tolerance Test (OGTT). We used these indices as noninvasive methods of IR (inverse of insulin sensitivity) estimation and compared hepatic/peripheral components of whole body IR in NAFLD. Methods. 113 morbidly obese, nondiabetic subjects who underwent gastric bypass surgery and intraoperative liver biopsy were included in the study. OGTT was performed preoperatively and the indices were calculated. Subjects were divided into closely matched groups as normal, fatty liver (FL) and Non-Alcoholic Steatohepatitis (NASH) based on histology. Results. Whole body IR was significantly higher in both FL and NASH groups (NAFLD) as compared to Normal, while hepatic IR was higher only in NASH from Normal. Conclusions. FL is a manifestation of peripheral IR but not hepatic IR.

A review of risk factors for stroke in patients with chronic kidney disease.

BACKGROUND: Patients with chronic kidney disease (CKD) are at higher risk for stroke because of higher prevalence of traditional and non-traditional cardiovascular risk factors. METHODS: We performed an extensive literature review with pre-defined keywords. We summarized the results of the studies evaluating for risk factors predisposing to stroke in CKD patients. RESULTS: The incidence of stroke and stroke-related mortality is higher in CKD patients compared with the general population. Presence of anemia, hypoalbuminemia, malnutrition, uremia, and hyperhomocysteinemia in patients with CKD is associated with higher incidence of stroke. Hemodialysis and renal transplant patients are at higher risk of developing stroke compared with those who do not require renal replacement therapy. CONCLUSION: The early recognition of risk factors associated with stroke in CKD population is imperative. Early interventions may potentially decrease the incidence and associated mortality of stroke in CKD patients.