Nikroo Hashemi

Treatment of hepatitis C virus–associated mixed cryoglobulinemia with direct-acting antiviral agents

Hepatitis C virus (HCV) is the most common cause of mixed cryoglobulinemia syndrome (MCS). The efficacy and safety of all‐oral direct‐acting antiviral (DAA) therapy in HCV‐associated MCS (HCV‐MCS) is largely unknown. The authors studied case series of patients with HCV‐MCS who were treated with sofosbuvir‐based regimens and historical controls treated with pegylated interferon and ribavirin in a single health care network. HCV‐MCS was defined by circulating cryoglobulin associated with systemic vasculitis symptoms. Renal involvement (n = 7) was established by kidney biopsy (n = 5) or by two or more of the following clinical findings: reduced kidney function, proteinuria, or hematuria with other causes excluded (n = 2). Twelve patients received DAA therapy between December 2013 and September 2014. Median age was 61 years, 58% were male, and 50% had cirrhosis. Median baseline serum creatinine was 0.97 mg/dL (range 0.7‐2.47). Four patients received rituximab concurrent with DAA therapy. Sustained virological response rate at 12 weeks (SVR12) was 83% overall. Patients with glomerulonephritis who achieved SVR12 experienced an improvement in serum creatinine and a reduction in proteinuria. Cryoglobulin levels decreased in 89% of patients, with median percent decreasing from 1.5% to 0.5% and completely disappearing in four of nine cases who had cryoglobulins measured after treatment. Serious adverse events were infrequent (17%). In contrast, the historical cohort treated with pegylated interferon and ribavirin experienced only 10% SVR12, with 100% experiencing at least one adverse event and 50% experiencing premature discontinuation due to adverse events. Conclusion: SVR12 rates for sofosbuvir‐based DAA regimens in HCV‐MCS were 83%, significantly higher than historical controls treated with pegylated interferon and ribavirin; patients with glomerulonephritis experienced improvement in renal function, including those not concomitantly treated with immunosuppression. (Hepatology 2016;63:408–417)

MELD score less than 15 predicts prolonged survival after transjugular intrahepatic portosystemic shunt for refractory ascites after liver transplantation.

Background. Transjugular intrahepatic portosystemic shunt (TIPS) is used in the management of refractory ascites (RA) and variceal bleeds. Little data exist on TIPS safety, efficacy, and survival after liver transplantation (LT). Methods. We conducted a retrospective analysis of patients who underwent TIPS placement after LT for RA. Clinical success was defined as a reduction of portosystemic gradient (PSG) and resolution of RA. Results. Twenty-six patients underwent TIPS. The most common indication for LT was hepatitis C virus (88%). Median time from LT to TIPS was 17 months (1–89 months). Median pre-TIPS model for end-stage liver disease (MELD) score was 15 (7–33). The median pre-TIPS PSG was 18 mm Hg (7–38 mm Hg). Median change in the PSG after TIPS was 11 mm Hg (1–27 mm Hg). Fifty-eight percent (15/26) of TIPS were considered clinically successful. Median post-TIPS patient survival was 15 months (1–109 months). Cumulative 1-year post-TIPS patient survival was 50%. On multivariate analysis, pre-TIPS MELD was a significant and independent predictor of patient survival (P<0.01). The 3- and 6-month patient mortality and graft loss for patients with a pre-TIPS MELD of more than or equal to 15 were significantly higher than those with a pre-TIPS MELD score of less than 15 (P<0.01). The overall median survival for patients with a pre-TIPS MELD score of more than or equal to 15 was 3 months (1–59 months) compared with 45 months (2–109 months) for patients with pre-TIPS MELD score of less than 15. Conclusions. TIPS after LT can be clinically effective in patients with RA with a MELD score less than 15. This suggests that TIPS could be used as a means to extend posttransplant survival but should be carefully individualized in patients with a MELD score more than or equal to 15.

Manometric evaluation of achalasia in the elderly

Background : The effect of ageing on oesophageal motility in patients with achalasia is not well described. Oesophageal contraction amplitude is decreased in otherwise healthy elderly subjects.

Liver histology during Mipomersen therapy for severe hypercholesterolemia

BACKGROUND Mipomersen is an antisense oligonucleotide that inhibits apolipoprotein B synthesis and lowers plasma low-density lipoprotein cholesterol even in the absence of low-density lipoprotein receptor function, presumably from inhibition of hepatic production of triglyceride-rich very low-density lipoprotein particles. By virtue of this mechanism, mipomersen therapy commonly results in the development of hepatic steatosis. Because this is frequently accompanied by alanine aminotransferase elevations, concern has arisen that mipomersen could promote the development of steatohepatitis, which could in turn lead to fibrosis and cirrhosis over time. OBJECTIVE The objective of this study was to assess the liver biopsy findings in patients treated with mipomersen. METHODS We describe 7 patients who underwent liver biopsy during the mipomersen clinical development programs. Liver biopsies were reviewed by a single, blinded pathologist. RESULTS The histopathological features were characterized by simple steatosis, without significant inflammation or fibrosis. CONCLUSION These findings suggest that hepatic steatosis resulting from mipomersen is distinct from nonalcoholic steatohepatitis.

Safety of peginterferon in the treatment of chronic hepatitis C.

Background: Combination of ‘pegylated’ interferons (IFNs) plus ribavirin, the standard treatment of chronic hepatitis C (CHC), is frequently associated with side effects. Anticipation, recognition and proper management of these side effects are important to ensure compliance with therapy and achievement of sustained virologic response. Objective: To illustrate the side effect profile of pegIFN-α in the treatment of CHC. Methods: Studies and abstracts were identified through a computerized, English language literature search. Key search terms included peginterferon and CHC. Information available only in abstract form was retrieved from national and international hepatology associations. Results: Most adverse events occurring with combination therapy can be anticipated and managed appropriately; therefore, premature discontinuation of therapy owing to side effects is not required in most patients.

Lupus-like Immune Complex-mediated Glomerulonephritis in Patients with Hepatitis C Virus Infection Treated with Oral, Interferon-free, Direct-acting Antiviral Therapy.

Novel, all-oral interferon-free direct-acting antiviral agents have revolutionized the management of hepatitis C virus (HCV) infection by producing exceptional cure rates with minimal adverse events. While provocation or exacerbation of autoimmunity has been reported in HCV-infected patients receiving interferon, this phenomenon has not been reported in patients receiving interferon-free HCV therapy. We report the occurrence of three cases of lupus-like immune complex-mediated glomerulonephritis occurring shortly after exposure to sofosbuvir-based direct-acting antiviral therapies. In all three cases, renal function quickly improved with immunosuppression. However, two of the three patients developed infectious complications of immunosuppression and died. This is the first report of a lupus-like immune complex mediated glomerulonephritis occurring in the context of HCV eradication with all-oral direct-acting antiviral therapies.

Acute liver failure as a rare initial manifestation of peripheral T-cell lymphoma.

Acute liver failure (ALF) is an uncommon disease in the United States, affecting more than 2 000 people each year. Of all the various causes, malignant infiltration is one of the least well known and carries with it a high mortality. We describe a case of ALF as the presenting manifestation of peripheral T-cell lymphoma in an elderly woman. By reporting this case, we hope to increase early recognition of this disease process in order to potentially improve treatment outcomes.

An extended treatment protocol with pegylated interferon and ribavirin for hepatitis C recurrence after liver transplantation

AIM To evaluate the efficacy and tolerability of an extended treatment protocol and to determine the predictors of sustained virological response (SVR) after liver transplantation (LT). METHODS Between August 2005 and November 2008, patients with recurrent hepatitis C virus (HCV) after LT were selected for treatment if liver biopsy showed at least grade 2 inflammation and/or stage 2 fibrosis. All patients were to receive pegylated interferon (PEG)/regimens combining ribavirin (RBV) for an additional 48 wk after HCV undetectability. RESULTS Extended protocol treatment was initiated in thirty patients. Overall, 73% had end of treatment response and 60% had SVR. Nineteen patients completed treatment per protocol, of them, sixteen (84%) had end of treatment response, and fourteen (74%) achieved SVR. Both early virological response and 24-week virological response were individually associated with SVR but this association was not significant on multivariate analysis. Eleven patients (37%) discontinued therapy due to adverse effects. Cytopenias were the most common and most severe adverse effect, and required frquent growth factor use, dose adjustments and treatment cessations. The risk of rejection was not increased. CONCLUSION Recurrent HCV after LT can be safely treated with extended virological response-guided therpy using PEG/RBV, but requires close monitoring for treatment-related adverse effects, particularly cytopenias.

Practice Pattern of Hepatitis B Testing in Rheumatoid Arthritis Patients: A Cross-National Comparison Between the US and Taiwan

The hepatitis B virus (HBV) testing rates and patterns in rheumatoid arthritis (RA) patients starting disease‐modifying antirheumatic drugs (DMARDs) have not been well studied. We describe and compare the practice patterns of HBV testing among RA patients in the US and Taiwan.

Acute liver failure complicating jejunojejunal intussusception presentation in a gastric bypass patient

Over 200 000 weight loss procedures are performed annually in the United States. Physicians must therefore be cognizant of the unique array of complications associated with these procedures. We describe a case of jejunojejunal intussusception in a gastric bypass patient who presented with acute liver failure (ALF) due to acetaminophen (APAP) toxicity. Our patient is a 29 year-old female who had undergone Roux-en-Y gastric bypass surgery seven years prior. She was evaluated in the emergency department for confusion. Her family reported a 3-wk history of progressive abdominal pain and vomiting, for which she had ingested 40 acetaminophen/oxycodone tablets over the past 2 d. Physical examination showed icteric sclerae, a distended abdomen, and grade I encephalopathy. She fulfilled the criteria for ALF and was listed for liver transplantation. Abdominal computed tomography scan revealed a jejunojejunal intussusception. She underwent emergent exploratory laparotomy and resection of the infarcted intussusceptum and the previous jejunojejunostomy. She had rapid clinical improvement, with decreasing liver enzymes and improved hepatic synthetic function. She had complete resolution of coagulopathy and encephalopathy, and was removed from the liver transplant list. She was discharged home 20 d after hospitalization with normal liver tests. This case demonstrates that acute abdominal catastrophes can potentiate liver injury in the setting of acetaminophen toxicity. Encephalopathy may obscure history and physical exam findings. This case also exemplifies the pitfalls in the management of the bariatric surgery patient and the importance of multispecialty collaboration in patients presenting with organ failure.