Jennifer C. Price

Liver Disease in the HIV-Infected Individual

Since the advent of effective antiretroviral therapy (ART) for human immunodeficiency virus-1 (HIV), there has been a substantial decrease in deaths related to acquired immunodeficiency syndrome (AIDS). However, in the ART era, liver disease is now the most common non-AIDS-related cause of death among HIV-infected patients, accounting for 14%-18% of all deaths in this population and almost half of deaths among hospitalized HIV-infected patients. Just as the burden of non-AIDS morbidity and mortality has changed in the ART era, the types of liver disease the clinician is likely to encounter among these patients have changed as well. This review will discuss the causes of liver disease in the HIV-infected population in the ART era, including chronic hepatitis C virus, chronic hepatitis B virus, medication-related hepatotoxicity, alcohol abuse, nonalcoholic fatty liver disease, and AIDS-related liver diseases.

Risk Factors for Fatty Liver in the Multicenter AIDS Cohort Study

OBJECTIVES:Human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) may increase the risk of fatty liver disease. We determined the prevalence of and risk factors for fatty liver by comparing HIV-infected men with HIV-uninfected men who have sex with men in the Multicenter AIDS Cohort Study (MACS).METHODS:In 719 MACS participants who consumed less than three alcoholic drinks daily, fatty liver was defined as a liver-to-spleen attenuation ratio <1 on noncontrast computed tomography (CT). We genotyped single nucleotide polymorphisms in the patatin-like phospholipase domain-containing 3 (PNPLA3) gene and in other genes previously associated with nonalcoholic fatty liver disease. Risk factors for fatty liver were determined using multivariable logistic regression.RESULTS:Among 254 HIV-uninfected men and 465 HIV-infected men, 56% were White with median age 53 years and median body mass index 25.8 kg/m2. The vast majority of HIV-infected men (92%) were on ART, and 87% of the HIV-infected men were treated with a nucleoside reverse transcriptase inhibitor for a median duration of 8.5 years. Overall, 15% of the cohort had fatty liver, which was more common in the HIV-uninfected compared with the HIV-infected men (19 vs. 13%, P=0.02). In multivariable analysis, HIV infection was associated with a lower prevalence of fatty liver (odds ratio (OR)=0.44, P=0.002), whereas a higher prevalence of fatty liver was seen in participants with PNPLA3 (rs738409) non-CC genotype (OR=2.06, P=0.005), more abdominal visceral adipose tissue (OR=1.08 per 10 cm2, P<0.001), and homeostatic model assessment of insulin resistance (HOMA-IR) ≥4.9 (OR=2.50, P=0.001). Among HIV-infected men, PNPLA3 (rs738409) non-CC genotype was associated with a higher prevalence of fatty liver (OR=3.30, P=0.001) and cumulative dideoxynucleoside exposure (OR=1.44 per 5 years, P=0.02).CONCLUSIONS:CT-defined fatty liver is common among men at risk for HIV infection and is associated with greater visceral adiposity, HOMA-IR, and PNPLA3 (rs738409). Although treated HIV infection was associated with a lower prevalence of fatty liver, prolonged exposure to dideoxynucleoside analogs is associated with higher prevalence.

HIV Monoinfection Is Associated With Increased Aspartate Aminotransferase-to-Platelet Ratio Index, a Surrogate Marker for Hepatic Fibrosis

BACKGROUND Although liver disease commonly causes morbidity and mortality among human immunodeficiency virus (HIV)-infected individuals, data are limited on its prevalence in HIV monoinfection. We used the aspartate aminotransferase-to-platelet ratio index (APRI) as a surrogate marker of hepatic fibrosis to characterize liver disease in the Multicenter AIDS Cohort Study. METHODS Men were categorized based on their HIV and viral hepatitis status: uninfected (n = 1170), HIV monoinfected (n = 509), viral hepatitis monoinfected (n = 74), and HIV-viral hepatitis coinfected (n = 66). RESULTS The median APRI in the HIV-monoinfected group was similar to that in the hepatitis-monoinfected group (0.42 vs 0.43; P > .05), higher than in the uninfected group (0.42 vs 0.27; P < .001) but lower than in the coinfected group (0.42 vs 1.0; P < .001). On multivariable analysis, HIV infection (1.39-fold increase [FI]; P < .001), viral hepatitis infection (1.52-FI; P < .001), and the interaction between HIV and viral hepatitis infections were independently associated with a higher APRI (1.57-FI; P < .001). Among the HIV-infected men, viral hepatitis coinfection (2.34-FI; P < .001), HIV RNA ≥100 000 copies/mL (1.26-FI; P = .007), and CD4 count ≤200 cells/mL (1.23-FI; P = .022) were independently associated with a higher APRI. CONCLUSIONS HIV and viral hepatitis are independently associated with an increased APRI. Further studies are needed to understand the biological basis for the association between HIV and liver disease.

Treatment of hepatitis C in liver transplant patients: Interferon out, direct antiviral combos in

Although chronic infection with hepatitis C virus (HCV) is the leading indication for liver transplantation in the United States, graft and patient survival rates are reduced because of HCV recurrence after transplant. Interferon‐based antiviral treatment administered either before or after transplant to prevent or treat HCV recurrence, respectively, is limited because of poor tolerability and low efficacy. However, the treatment of HCV in the transplant setting is changing considerably with the availability of newer direct‐acting antivirals and interferon‐free regimens. This article will review the experience to date with treating HCV in the setting of cirrhosis and liver transplantation and will discuss the unique challenges encountered when this population is being treated. Liver Transpl 21:423‐434, 2015.

Gastric sarcoidosis: case report and literature review.

Sarcoidosis involving the gastrointestinal tract is extremely rare. Clinically recognizable gastrointestinal system involvement occurs in 0.1% to 0.9% of patients with sarcoidosis. We encountered a 22-year-old African American female admitted to Johns Hopkins Hospital (Baltimore, Maryland) for a 2-week history of fever, chills, eye pain, and abdominal pain. Her abdominal CT scan showed multiple subcentimeter retroperitoneal lymph nodes. An upper endoscopy was performed and discovered an antral nodule that measured about 7 mm and antral gastritis in which biopsies showed active chronic necrotizing granulomatous gastritis. Biopsies of the antral polyp showed focal intestinal metaplasia and active chronic necrotizing granulomatous pattern. Stains for Helicobacter pylori, acid fast, and fungi were negative. A small-bowel series showed no abnormality. Ophthalmologic evaluation revealed panuveitis with bilateral optic disc edema. The patient was later prescribed 60 mg of prednisone by mouth once a day and subsequently her abdominal pain and fever resolved during follow-up 2 months later. This literature review demonstrates the importance in the diagnosis, pathophysiology, clinical manifestations, types of gastric sarcoidosis, major endoscopic findings, and management of gastric sarcoidosis.

Managing Acutely Ill Substance‐Abusing Patients in an Integrated Day Hospital Outpatient Program: Medical Therapies, Complications, and Overall Treatment Outcomes

BACKGROUND: Substance-abusing adults are admitted to hospitals for medical complications from their drug and alcohol use at substantially higher rates than the general public; yet, their care is often defined by against medical advice (AMA) discharges and low rates of referral to addiction treatment programs.METHODS: We present findings from a chart review of consecutive admissions to an integrated medical-substance abuse treatment program designed for acutely ill, hospitalized substance using adults. We specifically looked at factors associated with program completion and medical complications in this cohort of at-risk adults.RESULTS: Overall, 83 patient cases were studied. The mean age was 41.2 years; most were African American (73.5%), male (68.7%), and homeless (77.1%). Heroin (96.4%) and cocaine (88.0%), followed by alcohol (44.6%) were the most commonly used substances before admission. The most common admitting diagnoses were infectious endocarditis (43.4%), abscess or nonhealing ulcer (18.1%), and osteomyelitis (13.3%) with intravenous antibiotic (68.7%), physical therapy (48.2%), or wound care (41.0%), the most commonly prescribed care on the integrated care/day hospital unit. The mean length of stay in the day hospital was 12.4 days. Overall, 69.9% of patients successfully completed their medical therapy, and 63.9% were successfully referred to an outpatient substance abuse treatment program. Only 10.8% required an unscheduled hospital readmission and 15.7% required an after-hours emergency department visit during their stay.CONCLUSION: Outpatient/day hospital-based integrated treatment is a viable option for medically ill substance-abusing adults who would otherwise be hospitalized and is associated with higher than expected completion rates and low rate of complications. Co-locating the unit at a hospital and integrating extensive social supports appear to be key components to this model.

HTK preservative solution is associated with increased biliary complications among patients receiving DCD liver transplants: A single center experience

BACKGROUND This study compares biliary complication rates associated with use of two different preservative solutions, Histidine-Tryptophan-Ketoglutarate (HTK) and University of Wisconsin (UW), utilized in orthotopic liver transplantation (LT) with donations after cardiac death (DCDs). MATERIAL AND METHODS Between 1997-2010, we retrospectively studied 35 LTs performed utilizing DCD donors, preserved either with HTK (n=17) or UW(n=18). Biliary complications were defined by the presence of anastomotic strictures, non-anastomotic strictures, and/or biliary leak on endoscopic retrograde cholangiopancreatography. RESULTS HTK and UW cohorts were similar in terms of demographics as well as pre- and post-operative biochemical profile. Donor age was significantly higher among HTK compared to UW recipients (41.5 ± 11.9 vs. 26.2 ± 8.8 years, p<0.001). The incidence of post-LT biliary complications was higher in the HTK group (76% vs. 39% in UW group, p=0.041). Hepatic arterial thrombosis (HAT) was observed among 3 HTK patients (17.7%) and 1 UW patient (5.6%), p=0.33. No patients underwent retransplantation in UW group, five recipients in HTK group underwent retransplantation (29%), p=0.019; 4 due to biliary complications and 1 due to HAT. CONCLUSIONS This single-center study reveals that the use of HTK preservative among DCD donors is associated with an increased risk of biliary complications. Multicenter retrospective studies are suggested to further verify this observation.

Hepatitis C virus–HIV-coinfected patients and liver transplantation

Purpose of reviewTo review the experience to date and unique challenges associated with liver transplantation in hepatitis C virus (HCV)/HIV-coinfected patients. Recent findingsThe prevalence of cirrhosis and hepatocellular carcinoma is rising among HIV-infected individuals. With careful patient selection and in the absence of HCV infection, HIV-infected and HIV-uninfected liver transplant recipients have comparable posttransplant outcomes. However, in the presence of HCV infection, patient and graft survival are significantly poorer in HIV-infected recipients, who have a higher risk of aggressive HCV recurrence, acute rejection, sepsis, and multiorgan failure. Outcomes may be improved with careful recipient and donor selection and with the availability of new highly potent all-oral HCV direct acting antivirals (DAAs). Although all-oral DAAs have not been evaluated in HIV/HCV-coinfected transplant patients, HIV does not adversely impact treatment success in nontransplant populations. Therefore, there is great hope that HCV can be successful eradicated in HIV/HCV-coinfected transplant patients and will result in improved outcomes. Careful attention to drug–drug interactions with HIV antiretroviral agents, DAAs, and posttransplant immunosuppressants is required. SummaryLiver transplant outcomes are poorer in HIV/HCV-coinfected recipients compared with those with HCV-monoinfection. The new HCV DAAs offer tremendous potential to improve outcomes in this challenging population.

Myosin VI mediates the movement of NHE3 down the microvillus in intestinal epithelial cells.

ABSTRACT The intestinal brush border Na+/H+ exchanger NHE3 is tightly regulated through changes in its endocytosis and exocytosis. Myosin VI, a minus-end-directed actin motor, has been implicated in endocytosis at the inter-microvillar cleft and during vesicle remodeling in the terminal web. Here, we asked whether myosin VI also regulates NHE3 movement down the microvillus. The basal NHE3 activity and its surface amount, determined by fluorometry of the ratiometric pH indicator BCECF and biotinylation assays, respectively, were increased in myosin-VI-knockdown (KD) Caco-2/Bbe cells. Carbachol (CCH) and forskolin (FSK) stimulated NHE3 endocytosis in control but not in myosin VI KD cells. Importantly, immunoelectron microscopy results showed that NHE3 was preferentially localized in the basal half of control microvilli but in the distal half in myosin VI KD cells. Treatment with dynasore duplicated some aspects of myosin VI KD: it increased basal surface NHE3 activity and prevented FSK-induced NHE3 endocytosis. However, NHE3 had an intermediate distribution along the microvillus (between that in myosin VI KD and untreated cells) in dynasore-treated cells. We conclude that myosin VI is required for basal and stimulated endocytosis of NHE3 in intestinal cells, and suggest that myosin VI also moves NHE3 down the microvillus.

Sofosbuvir and ribavirin use in wait‐listed patients with hepatitis C should be selective

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