A case of acute liver failure due to carfilzomib in multiple myeloma.

WHAT IS KNOWN AND STUDY OBJECTIVE: Carfilzomib is a newer drug approved for the treatment of relapsing and refractory multiple myeloma. It has been rarely associated with acute liver failure (ALF). CASE SUMMARY: We present a case of 58-year-old man presenting with abnormal liver function tests and subsequently diagnosed with ALF due to carfilzomib. Liver enzymes improved significantly after discontinuation of the drug. WHAT IS NEW AND CONCLUSION: Even though ALF due to carfilzomib has been documented rarely in clinical studies, no detailed case report has been published so far. Patients on carfilzomib should be monitored for ALF, and prompt discontinuation of drug is necessary in such cases.

Manifestation and Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease in a Predominately African American Population at a Multi-Specialty Healthcare Organization.

African Americans (AA) have a high incidence of risk factors associated with MASLD (metabolic dysfunction-associated steatotic liver disease); the AA population has a lower incidence of MASLD and MASH (metabolic-associated steatotic hepatitis) than Caucasian and Hispanic Americans (non-AA). We investigated if underlying risk factor variation between AA and non-AA individuals could provide a rationale for the racial diversity seen in MASLD/MASH. Using ICD-10 codes, patients from 2017 to 2020 with MASLD/MASH were identified and confirmed to have either MASLD or MASH. Despite the large (>80%) AA population in our clinics, only 54% of the MASLD/MASH patients were African American. When the non-invasive NAFLD Fibrosis Scores (NFS) evaluated at early diagnosis were compared to the most recent values, the only increase in fibrosis score by NFS over time was in non-AA MASH patients. The increase in fibrosis only in non-AA MASLD patients is consistent with racial disparity in the disease progression in non-AA as compared to AA patients. Even with the large proportion of AA patients in our study, there was no significant racial disparity in the earliest assessment of either risk factors, laboratory values, or fibrosis scores that would account for racial disparity in the development and progression of MASLD.

Bleeding Mass in Remnant Stomach, Unveiling Lynch Syndrome 18 Years After Bariatric Roux-En-Y Gastric Bypass Surgery.

There is sparse literature on the development of malignancy in remnant gastric stomach after bariatric Roux-en-Y gastric bypass surgery. We report a case of overt upper gastrointestinal bleeding from malignant adenocarcinoma in the remnant stomach presenting several years after bariatric Roux-En-Y gastric bypass surgery. The mass in the remnant stomach was surgically resected, and the patient was subsequently diagnosed with Lynch syndrome on genetic analysis.

Impact of DAA Treatment for HCV on Hepatocellular Carcinoma in a Predominately African American Population.

PURPOSE: This study tested the hypothesis that our predominately AA medical center population would demonstrate a decline in HCV-driven HCC diagnosis following the initiation of DAA treatment in 2014. Also evaluated was whether achieving an SVR prior to diagnosis of HCC improved outcomes in patients who had an HCV diagnosis after completion of treatment. METHODS: All patients with HCC seen at the Detroit Medical Center from 2009 to 2021 were identified using ICD-10 codes, and medical records were evaluated. Outcomes were evaluated as either alive or death/hospice as of December of 2022. RESULTS: There were 461 patients with HCC of whom 433 (94%) had racial information in the database (AA = 351; non-AA = 82). HCC incidence regardless of race peaked in 2017, with a subsequent decline through 2021. HCV as a risk factor was higher in AA as compared to non-AA (85% vs. 53% p = 0.0001). Outcome (alive vs. death/hospice) was better for SVR patients compared to untreated patients (54% vs. 19%; p = 0.0009). HCC patients who achieved SVR also had better liver function at diagnosis as defined by Child-Pugh score (74% vs. 49% Class A p = 0.04) at the time of diagnosis. CONCLUSIONS: Racial disparity in HCC etiology was confirmed with AA more likely to have HCV than non-AA. The reduction in HCC patients with HCV confirms the impact of DAA treatment and prior successful treatment of HCV yields better outcomes. Increasing HCV treatment rates especially in AA patients will have a major impact on HCC development and treatment outcomes. WHAT IS KNOWN: • African Americans are more likely to have HCV infection as compared to non-AA. • Hepatocellular carcinoma is increasing in incidence in the US. • The role of HCV in the development of HCC remains to be further investigated. WHAT IS NEW: • HCC diagnosis in a single urban medical center study increased from 2009 as a result of HCV as a risk factor. • HCC declined post 2018 due primarily to a reduction in HCV infection as the risk factor. • African Americans were more likely to have HCV as the risk factor as compared to non-AA patients who were more likely to have no known risk factor on record (i.e., cryptogenic).

Racial Disparity in HCV Demographics and Treatment Between Interferon Era (2002-2003) and Direct Acting Anti-viral Era (2019).

Introduction  Direct-acting antiviral (DAA) treatment increased the sustained viral response (SVR) rate of patients with the hepatitis C virus (HCV) and eliminated response disparities between African American (AA) and non-AA patients seen with interferon (IFN). The aim of this study was to compare 2019 HCV patients (DAA era) to patients from January 1, 2002 and December 31, 2003 (IFN era) in our predominantly AA clinic population. Methods We extracted data on 585 HCV patients seen in 2019 (DAA era) and compared them to 402 patients seen in the IFN era. Results Most HCV patients were born between 1945 and 1965, but in the DAA era more younger patients were identified. Non-AA patients in both eras were less likely to be infected with genotype 1 compared to AA (95% vs 54%, P<0.001). Fibrosis was not increased in the DAA Era as compared to the IFN era as assessed either by serum-based assays (APRI, FIB-4) or transient elastography (FibroScan) (DAA era) vs biopsy (IFN era). More patients were treated in 2019 compared to 2002-2003 (159/585=27% vs 5/402=1%). For untreated patients, subsequent treatment within one year of the initial visit was low and similar in both eras (35%). Conclusion There continues to be a need to screen patients born between 1945 and 1965 for HCV as well as to identify increasing numbers of patients below this age cohort. Even though current therapies are oral, highly effective, and can be 8-12 weeks in duration, significant numbers of patients were not treated within a year of first visit.

Vanishing bile duct syndrome arising in a patient with HIV infection sequentially treated with trimethoprim/sulfamethoxazole and dapsone.

Trimethoprim/sulfamethoxazole is well known to cause intra-hepatic cholestasis which in rare instances can be prolonged and lead to vanishing bile duct syndrome. The risk regarding the potential for cross-reactivity between structurally related molecules such as dapsone and trimethoprim/sulfamethoxazole in causing hepatotoxicity is scarce. Herein, we report a case of vanishing bile duct syndrome following dapsone use in a patient with HIV infection and a recent history of trimethoprim/sulfamethoxazole-induced cholestasis. The patient had severe and protracted cholestasis during 2 years of follow-up and eventually died of liver failure.

Racial Diversity in Hepatocellular Carcinoma in a Predominately African-American Population at an Urban Medical Center.

PURPOSE: Surveillance, treatment, and outcomes for African-American (AA) populations with hepatocellular carcinoma (HCC) remain under evaluated. This study evaluated demographics, surveillance, therapy, and outcomes for a predominately AA population. METHODS: The electronic medical records of a large health-care provider were used to identify 274 patients with visits for HCC between 2010 and 2017. Tumor size at diagnosis was defined by imaging with ≤ 5 cm being defined as "small." Surveillance for HCC was defined based on ultrasound (US) assessments. RESULTS: Patients were primarily AA (78%) and male (76%) with an average age at diagnosis of 62 years. Hepatitis C virus (HCV) was more likely to be a risk factor for the development of HCC in AA as compared to non-AA (92% vs 67%; p < 0.005). Surveillance rates were low (16% for AA vs 7% for non-AA). An aspartate aminotransferase platelet ratio index (APRI) value > 0.7 within 2 years of tumor diagnosis was a strong predictor for the risk of the development of HCC (86% AA vs 79 % non-AA). In this study, race was not a factor in treatment or outcomes, and most patients received tumor ablative treatment. CONCLUSION: Given the low surveillance rates and the demonstrated increased survival for patients with small tumors, ways to increase surveillance must be initiated. The results of this study demonstrate the need for physician/patient education on the importance of surveillance US. Further, this study supports routine assessment of APRI in AA patients in an effort to identify patients in whom intensive surveillance will significantly improve earlier detection of tumors.

Hepatic Sinusoidal Obstruction Syndrome in a Patient With Multiple Myeloma Treated With CyBorD.

Hepatic sinusoidal obstruction syndrome (SOS) is a life-threatening state generally occurring as a complication of conditioning regimens used for hematopoietic stem cell transplant. Hepatic SOS after a standard dose of chemotherapy in malignancies is rare, and there are only a few cases in pediatric literature. We report a 56-year-old man with multiple myeloma who experienced SOS after being initiated on chemotherapy including cyclophosphamide, dexamethasone, and bortezomib and who experienced a delay in treatment with defibrotide, because it is currently approved by the Food and Drug Administration for only patients who develop SOS after hematopoietic stem cell transplant.

Potential role of lycopene in the treatment of hepatitis C and prevention of hepatocellular carcinoma.

Hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC) are growing health problems around the world. Oxidative stress plays a significant role in the initiation and progression of hepatocellular damage and possibly in the development of HCC in HCV infected patients. In vitro, animal and clinical studies suggest that lycopene, a nonprovitamin A carotenoid and a potent antioxidant, may attenuate the liver injury and possibly prevent the development of HCC. In this article, we discuss the relationship between HCV infection and oxidative stress and review the potential role of lycopene in the treatment of HCV and prevention of HCC.

Acute Retroviral Syndrome Presenting as Acute Hepatitis.

Acute retroviral syndrome (ARS) can present as a wide array of clinical manifestations. Establishing a diagnosis early in the disease course can provide an opportunity to minimize immunosuppression and limit further transmission of human immunodeficiency virus (HIV). We present a case of a previously healthy young male who presented with acute hepatitis, as a manifestation of ARS. Initial HIV antigen/antibody testing was negative; however, a high index of suspicion prompted HIV ribonucleic acid (RNA) virologic testing revealing >10 million RNA copies/mL. Anti-retroviral treatment was initiated, along with supportive measures, accomplishing resolution of the transaminitis and the restoration of CD4 counts within normal at one month. Early in the disease course, HIV screening immunoassay could still be negative; hence, confirmatory testing with HIV RNA virologic testing should be pursued when clinical suspicion is high. Prompt diagnosis and treatment can improve outcome and curtail viral transmission.

Percutaneous liver biopsy is safe in chronic hepatitis C patients with end-stage renal disease.

BACKGROUND & AIMS: Liver biopsy is useful for staging fibrosis in chronic hepatitis C (CHC) patients with end-stage renal disease (ESRD) to determine renal transplant eligibility and to make CHC treatment decisions. There is concern about an increased risk associated with percutaneous liver biopsy (PCNB) in ESRD patients. We compared the safety of PCNB in CHC patients with and without ESRD. METHODS: We reviewed PCNBs performed between 1996 and 2004 for technique, histology, and complications in 78 ESRD patients with CHC and in 241 control patients with CHC and no renal failure, randomly matched for age, sex, and race. Platelet counts, prothrombin, and partial thromboplastin times, but not bleeding times, were checked before biopsy. Deamino-8-D-arginine vasopressin was not given before the biopsy. RESULTS: The mean age of the patients was 50 years; 72% were male, 97% were African American, and 3% were Caucasian. The control group had a significantly higher proportion of patients with advanced fibrosis (P < .04). Only 1 patient with ESRD (1.3%) developed a moderate complication. Five controls (2.1%) developed complications, 3 of which were severe. CONCLUSIONS: Severe complications after PCNB are uncommon, and patients with ESRD and CHC are at no increased risk. Testing for bleeding time and the routine use of deamino-8-D-arginine vasopressin are not necessary before PCNB in patients with ESRD.

Decreasing racial disparity with the combination of ledipasvir-sofosbuvir for the treatment of chronic hepatitis C.

African Americans (AA) in the US are twice as likely to be infected with hepatitis C virus (HCV) compared to the non-Hispanic-white US population (Cau). They are also more likely to be infected with HCV genotype 1, more likely to develop hepatocellular carcinoma, and, in addition, have a lower response rate to interferon-based therapies. With the increase in response rates reported for combinations of direct-acting antivirals, the possibility that racial disparity would be eliminated by agents that directly inhibit virus replication has become a reality. The objective of this review is to evaluate the literature from clinical studies and retrospective analysis with respect to the response of AA to the most prescribed antiviral combination sofosbuvir plus ledipasvir. While few studies have focused on AA patients, sufficient information is availed from the literature and studies in our predominately AA clinic population to confirm that ledipasvir-sofosbuvir has a similar effectiveness in AA as compared to Cau.

Overestimate of Fibrosis by FIBROSpect® II in African Americans Complicates the Management of their Chronic Hepatitis C.

BACKGROUND: Evaluation of advanced fibrosis in patients with hepatitis C virus (HCV) infection is used to facilitate decisions on treatment strategy and to initiate additional screening measures. Unfortunately, most studies have predominately Caucasian (Cau) patients and may not be as relevant for African Americans (AA). AIMS: This study specifically addresses the issue of defining minimal vs. significant fibrosis in African Americans (AA) with chronic hepatitis C (CHC) using noninvasive assays. METHODS: All patients (n = 319) seen between 1 January 2008 and 30 June 2013 for whom a FibroSpect II® (FSII) assay was performed and had data for calculation of aspartate aminotransferase (AST) platelet ratio index (APRI) and Fibrosis-4 (FIB-4) were identified using the medical records. RESULTS: When liver biopsy score and FSII assay results for the AA patients with CHC were compared, 31% of AA had advanced FSII fibrosis scores (F2-F4) despite a biopsy score of F0-F1. In contrast, 10% of Cau over-scored. The AA false positive rate was 14% for APRI and 34% for FIB-4. Combining FSII with either APRI (7% false positive) or FIB-4 (10% false positive) improved the false positive rate in AA to 7% (FSII + APRI) and 10% (FSII + FIB-4) but reduced the sensitivity for significant fibrosis. CONCLUSIONS: The FSII assay overestimates fibrosis in AA and should be used with caution since these patients may not have significant fibrosis. If the APRI or FIB-4 assay is combined with the FSII assay, minimal fibrosis in AA can be defined without subjecting the patients to a subsequent biopsy.

Effect of Treatment for CHC on Liver Disease Progression and Hepatocellular Carcinoma Development in African Americans.

BACKGROUND AND AIMS: African Americans (AA) historically have a low response rate to hepatitis C therapies, and there is limited information available for this patient population regarding the development and treatment of chronic hepatitis C (CHC). The aim of this study was to evaluate liver disease progression and hepatocellular carcinoma (HCC) development in AA with CHC. METHODS: Between 1995 and 2008, 246 AA patients with CHC were identified from a database of patients and followed until 2012-2013 (average 8 years) or the development of HCC after 2008. RESULTS: Viral clearance (intent to treat; sustained virus response (SVR)) was achieved in 15% of patients with interferon based therapies with or without ribavirin. AA patients who achieved an SVR (n=22) did not develop HCC or new onset cirrhosis, whereas the HCC incidence in untreated AA patients was 23% (51/203). Patients who achieved an SVR also had improved fibrosis, as defined by the AST Platelet Ratio Index (APRI) and Fibrosis-4 (FIB-4) score, relative to nonresponders and untreated patients. CONCLUSIONS: The severity of liver disease at the first visit (except for cirrhosis) correlated with the development of HCC, but because of the overlap in values between patients, these measurements were not useful for predicting individual risk. Since cirrhosis at the first visit was not a predictive factor, treatment with newer antiviral therapies is the best option for reducing the incidence of advanced liver disease and its harmful outcomes in the AA population.

Latent hepatitis B is a risk factor for hepatocellular carcinoma in patients with chronic hepatitis C.

AIM: To study the potential association between hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CHC), cirrhosis and latent hepatitis B (LHB) infection, defined as the absence of detectable serum hepatitis B surface antigen (HBsAg) and the presence of hepatitis B core antibody (HBcAb). METHODS: This retrospective analysis is comprised of 185 cirrhotic patients with HCC who were hepatitis C virus antibody (HCV Ab) (+) and HBsAg(-) at Wayne State University between 1999 and 2008. From these, 108 patients had HCV polymerase chain reaction confirmation of viremia while the remaining (77) were considered to have CHC on the basis of a positive HCV Ab and the absence of any other cause of liver disease. Controls were drawn from our institutional database from the same time period and consisted of 356 HBsAg(-) age, race and gender matched patients with HCV RNA-confirmed CHC and without evidence of HCC. A subgroup of controls included 118 matched patients with liver cirrhosis. χ² test and t test were used for data analysis. RESULTS: Seventy-seven percent of patients in all 3 groups were African Americans. Patients with HCC had a significantly higher body mass index (P = 0.03), a higher rate of co-infection with human immunodeficiency virus (HIV) (P = 0.05) and a higher prevalence of alcohol abuse (P = 0.03) than the controls. More patients with HCC had LHB than controls (78% vs 39%, P = 0.01). Sixty three percent of patients with HCC were both hepatitis B surface antigen (HBsAb)(-) and HBcAb(+) compared to 23% of controls (P < 0.01). When compared to cirrhotic controls, the frequency of HBcAb(+) remained higher in patients with HCC (78% vs 45%, P = 0.02). Patients with HCC were more likely to be both HBsAb(-) and HBcAb(+) than the cirrhotic controls (63% vs 28%, P = 0.01). Although not statistically significant, 100% of CHC and HIV co-infected patients with HCC (n = 11) were HBcAb(+) when compared to controls (44%; n = 9). CONCLUSION: These data suggest that LHB occurs at a significantly increased frequency in patients with CHC and HCC than in patients with CHC without HCC.

Demographics of a large cohort of urban chronic hepatitis C patients.

PURPOSE: Recent studies suggest that African Americans (AA) with chronic hepatitis C (CHC) differ from non-Hispanic whites (NHW) with respect to the natural history and mortality resulting from the complications of chronic liver disease. The aim of this study was to examine the demographics of a large cohort of CHC patients and identify potential differences between AA and NHW. METHODS: This is a retrospective analysis, consisting of 2,739 hepatitis C antibody-positive patients seen at Wayne State University between 1995 and 2005. Patient demographics, risk factors, comorbidities, alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum hepatitis C (HCV) RNA levels, genotype, and liver biopsy results were recorded. RESULTS: AA constituted 75.4%, NHW 22.5%, and Asians or Hispanics 2.1% of the patients. Males predominated (58%), and the mean age of AA and NHW was 50.0 and 45.3 years, respectively (P