Antiviral Therapy Improves Hepatocellular Cancer Survival.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is a common risk factor for hepatocellular cancer (HCC). Patients with HCV infection are at a higher risk of developing HCC because the virus induces fibrosis in the liver, which may lead to cirrhosis. Early treatment of HCV and achieving a sustained virologic response (SVR) may lead to decreased incidence and mortality associated with HCC. METHODS: We performed a retrospective review of patients at the Memphis Veterans Affairs Medical Center (VAMC) in Tennessee from November 2008 to March 2019 to determine whether treatment of HCV infection makes a difference in overall survival (OS) among patients who develop HCC. Patients were treated with an interferon-based regimen or direct-acting antiviral agents (DAAs). Among the patients with HCV infection who were treated, we identified those who did achieve or did not achieve SVR. RESULTS: We identified 111 patients with HCV and HCC; 68 were treated for HCV infection. Forty-eight patients received DAA and 20 patients received an interferon-based regimen and 51 achieved SVR. In a multivariate analysis accounting for severity of liver disease, treated patients had an improved 5-year OS rate, median 1338 days (95% CI, 966-3202) when compared with untreated patients whose median OS was 452 days (95% CI, 242-853) (P = .0005). The treatment group had a longer median progression-free survival (PFS) than did the nontreatment group (460 days [95% CI, 294-726] vs 286 days [95% CI, 205-405], P = .04). Patients with SVR had an increased 5-year OS compared with patients without SVR (median 1973 days [95% CI, 1222-NA] vs 470 days [95% CI, 242-853], P < .001). HCV treatment type (interferon vs DAA) was not found to be associated with either OS or PFS, regardless of time period. Advanced liver disease stage as characterized by a high model for end-stage liver disease (MELD) score (> 10) or high Child-Pugh score (B or C) was associated with worse survival outcome. CONCLUSIONS: A retrospective analysis of patients with HCV infection and HCC confirms that treatment of HCV infection leads to OS benefit among patients with HCC. We further demonstrate that patients with HCV infection who achieve SVR have an OS benefit over patients unable to achieve SVR. The type of treatment, DAA vs an interferon-based regimen, did not show a significant survival benefit.

Elevated liver function tests in COVID-19: Causes, clinical evidence, and potential treatments.

COVID-19 causes severe respiratory and multiorgan failure, including liver damage and elevated transaminase levels. This article addresses the potential causes of liver function abnormalities in patients diagnosed with COVID-19 and management approaches for NPs focusing on preventing and alleviating liver injury.

Accuracy of Endoscopic Ultrasound in Staging of Early Rectal Cancer.

Endoscopic ultrasound can be highly accurate for the staging of neoplasms in early rectal cancer.

Liver Imaging Reporting and Data System in Patients at High Risk for Hepatocellular Carcinoma in the Memphis Veterans Affairs Population.

Although hepatocellular carcinoma can be difficult to detect, use of the LI-RADS algorithm could lead to earlier identification in at-risk patients.

Blistering Disease During the Treatment of Chronic Hepatitis C With Ledipasvir/Sofosbuvir.

Hepatitis C virus-associated porphyria cutanea tarda can result from viral-induced inhibition of uroporphyrinogen decarboxylase and the subsequent accumulation of uroporphyrins and associated metabolites in urine.

Rifaximin for the prevention of spontaneous bacterial peritonitis and hepatorenal syndrome in cirrhosis: a systematic review and meta-analysis.

Prophylactic antibiotics have been recommended in patients with a previous history of spontaneous bacterial peritonitis (SBP). Recently, there has been interest in the use of rifaximin for the prevention of SBP and hepatorenal syndrome (HRS). We conducted a meta-analysis to evaluate this association of rifaximin. We searched several databases from inception through 24 January 2017, to identify comparative studies evaluating the effect of rifaximin on the occurrence of SBP and HRS. We performed predetermined subgroup analyses based on the type of control group, design of the study, and type of prophylaxis. Pooled odds ratios (ORs) were calculated using a random effects model. We included 13 studies with 1703 patients in the meta-analysis of SBP prevention. Pooled OR [95% confidence interval (CI)] was 0.40 (95% CI: 0.22-0.73) (I=58%). On sensitivity analysis, adjusted OR was 0.29 (95% CI: 0.20-0.44) (I=0%). The results of the subgroup analysis based on type of control was as follows: in the quinolone group, pooled OR was 0.42 (95% CI: 0.14-1.25) (I=55%), and in the no antibiotic group, pooled OR was 0.40 (95% CI: 0.18-0.86) (I=64%). However, with sensitivity analysis, benefit of rifaximin was demonstrable; pooled ORs were 0.32 (95% CI: 0.17-0.63) (I=0%) and 0.28 (95% CI: 0.17-0.45) (I=0%) for the comparison with quinolones and no antibiotics, respectively. Pooled OR based on randomized controlled trials was 0.41 (95% CI: 0.22-0.75) (I=13%). For the prevention of HRS, the pooled OR was 0.25 (95% CI: 0.13-0.50) (I=0%). Rifaximin has a protective effect against the development of SBP in cirrhosis. However, the quality of the evidence as per the GRADE framework was very low. Rifaximin appeared effective for the prevention of HRS.

Telaprevir in treatment of recurrent hepatitis C infection in liver transplant recipients.

OBJECTIVES: Recurrent hepatitis C infection leads to accelerated graft loss in liver transplant recipients. Telaprevir offers a higher chance of cure in these patients. We sought to assess the effectiveness of telaprevir in treatment of hepatitis C in liver transplant recipients. MATERIALS AND METHODS: We report a series of 17 patients who received telaprevir for recurrent hepatitis C virus infection. These patients were previous treatment failures including 10 null responders. All patients received pegylated interferon alpha 2a (180 µg/wk) and ribavirin (800 mg/d) for 1 year and telaprevir 750 mg every 8 hours for 12 weeks. The immunosuppressive regimen was not changed during therapy, but the dosages were modified based on serum levels of the drugs. RESULTS: In an intention-to-treat analysis, the overall sustained virologic response 12 was 58%, with a relapse rate of 24%. Nine patients (52%) achieved extended rapid virologic response. Seven patients (77%) with extended rapid virologic response achieved sustained virologic response 12. Four patients (40%), who were previous null responders to interferon and ribavirin also achieved sustained virologic response 12. Anemia and ribavirin dosage reduction were common. Severe thrombocytopenia was seen in 2 patients resulting in discontinuation of therapy. A tacrolimus-based immunosuppressive regimen could be continued with close monitoring. During the initial 4 weeks of therapy, there were wide fluctuations in tacrolimus levels. However, after 4 weeks, tacrolimus could be dosed weekly maintaining a trough level of 3 to 10 ng/mL. CONCLUSIONS: Telaprevir can be used effectively in liver transplant recipients receiving tacrolimus-based immunosuppression. Sustained virologic response 12 can be achieved in a significant number of these "difficult-to-treat" patients.

Hepatitis C and neutropenia.

PURPOSE OF REVIEW: This review describes the pathogenesis and therapeutic implications of neutropenia in patients with hepatitis C. RECENT FINDINGS: Mild-to-moderate neutropenia is increasingly recognized as the hepatitis C population has caused increased cirrhosis. Multiple mechanisms for the neutropenia have been postulated, with recent evidence pointing toward a combination of hypersplenism, autoimmunity, and direct viral infection of bone marrow cells. Advances in antiviral therapy are associated with worsened neutropenia and dose modification. Severe neutropenia is underreported and is generally not associated with increased rates of infection. SUMMARY: Although neutropenia is common in hepatitis C patients it generally has a benign course and may not prohibit antiviral therapy.

Severe neutropenia in patients with chronic hepatitis C: a benign condition.

BACKGROUND/AIMS: Patients with chronic hepatitis C virus (HCV) infection may develop neutropenia, which can delay or prevent treatment. Severe neutropenia, absolute neutrophil counts (ANC) ≤0.500 × 10(9)/l, is a rare finding, with only two isolated reports published in the literature. The aim of this study was to evaluate the incidence and natural history of severe neutropenia in hepatitis C patients. METHODS: The records of 685 patients with active HCV were reviewed to identify those with severe neutropenia. The laboratory parameters and clinical history data of patients with severe neutropenia were then compared to a cohort of patients with HCV patients who had the more common minor neutropenia (ANC = 1.000-1.500 10(9)/l). RESULTS: There was no significant difference in race, MELD (Model for End Stage Liver Disease) scores, portal hypertension, splenomegaly, viral load, viral type, or hemoglobin or platelet levels. Neither group suffered serious systemic infections. CONCLUSIONS: Severe neutropenia in HCV patients is underreported and not associated with serious HCV complications such as elevated MELD score or cirrhosis. Serious infection is rare and patients respond well to granulocyte colony-stimulating factor. Severely neutropenic patients with HCV appear to have a benign course and may be candidates for antiviral therapy.

Combination therapy efavirenz/emtricitabine/tenofovir disoproxil fumarate associated with hepatic failure.

A single pill daily fixed dose combination of Efavirenz, Emtricitabine, and Tenofovir Disoproxil Fumarate (EFV/FTC/TDF) provides a potent and convenient treatment option for HIV/AIDS. The components have been shown to be well tolerated and are effective in randomized controlled trials. A literature search revealed no case of hepatic failure reported with this drug combination. We here in describe the 1st case of acute hepatic failure developing after 3 months of treatment with EFV/FTC/TDF in a 41 year old African American male without pre-existing liver disease or risk factors.

Nonalcoholic Fatty liver disease and metabolic syndrome in hypopituitary patients.

BACKGROUND: Increased incidence of cardiovascular mortality and nonalcoholic fatty liver disease (NAFLD) has been reported in hypopituitarism, but previous studies did not correct for obesity in these patients. Therefore, it remained unclear if endocrine deficiency in hypopituitarism is associated with metabolic consequences independent of obesity. This study was designed to determine the burden of cardiovascular disease and NAFLD in hypopituitarism. METHODS: We performed a retrospective case-control analysis of hypopituitary patients at Veterans Affair Medical center, Memphis, from January 1997 to June 2007. After matching for age, gender, obesity, and race, relevant data were abstracted from the subjects' records to determine the presence of hypopituitarism, cardiovascular risk factors, and fatty liver disease. Cases and controls were characterized by descriptive statistics and compared using chi(2) and Student t tests. RESULTS: Hypopituitary patients exhibited higher prevalence of hypertension- 88% versus 78% (P < 0.03), hypertriglyceridemia-80% versus 70% (P = 0.05), low high-density lipoprotein cholesterol-84% versus 70% (P < 0.001), and metabolic syndrome-90% versus 71% (P < 0.001). Patients also had higher mean plasma glucose levels-228 +/- 152 versus 181 +/- 83 mg/dL (P < 0.01). Despite higher preponderance of cardiovascular risk factors in hypopituitary patients, prevalence of cardiovascular morbidity was similar in both groups (P > 0.3). Hypopituitary patients had higher elevations in serum aminotransferase levels and hyperbilirubinemia-24% versus 11% (P < 0.01), as well as higher international normalized ratio (INR) and hypoalbuminemia 40% versus 23% (P < 0.01). CONCLUSIONS: There is an increased prevalence of metabolic syndrome and liver dysfunction consistent with NAFLD in hypopituitarism. Although hypopituitary patients had higher prevalence of cardiovascular risk factors than controls, they were not disproportionately affected by cardiovascular disease.

Electrophysiologic, morphologic, and serologic features of chronic unexplained nausea and vomiting: lessons learned from 121 consecutive patients.

BACKGROUND: Despite substantive morbidity, unexplained nausea and vomiting has not been evaluated in a systematic manner via surgically obtained biopsies and direct electrophysiology of the gut, and this information has not been correlated with serologic information. We investigated consecutive patients with unexplained and refractory chronic nausea and vomiting to define the presence of morphologic, physiologic, and/or serologic abnormalities. METHODS: In all, 101 of 121 consecutive patients who experienced chronic nausea and vomiting of unknown etiology evaluated in 1 tertiary referral center over a 10-year period were profiled qualitatively by full-thickness small bowel biopsies with hematoxylin and eosin (H&E) and Smith's Silver stains, quantitatively by intraoperative gastric electrophysiology, and semiquantitatively, when it became available, by serum autoimmune Western blot analysis. RESULTS: Overall, 79 of 101 patients had abnormal full-thickness biopsy (70 neuropathies and 9 myopathies) and frequent serum autoimmune abnormalities (mean score = 13.2, normal < 3.0). In addition, 96 of 101 patients had abnormal frequency and/or uncoupling on gastric electrophysiology. Patients with small-intestinal myopathy showed a diversity of diagnoses; some patients with neuropathy had abdominal pain that correlated with autoimmune scores on Western blot. CONCLUSION: Patients with refractory and unexplained nausea and vomiting have a high incidence of both small bowel morphologic abnormalities (primarily neuropathies) and gastric electrophysiologic abnormalities, which are associated commonly with serologic autoimmune activation. Similar histomorphologic, physiologic, and serologic measures should be considered in the diagnostic evaluation of any patient with refractory or unexplained nausea and vomiting.

Transplantation of a liver with the C282Y mutation into a recipient heterozygous for H63D results in iron overload.

Hemochromatosis is a common hereditary disease associated with progressive iron overload eventually leading to parenchymal damage of the liver, heart, pancreas, and other organs. Liver transplantation has been the single most important therapy to extend long-term survival in patients with a variety of acute and chronic liver diseases. We report a case of inadvertent transplantation of a hemochromatotic liver into a nonhemochromatotic recipient, resulting in rapid iron overload. Neither the recipient nor the donor had iron overload at the time of transplantation, but the donor liver was subsequently found to be homozygous for C282Y mutation. The report includes 8 years follow-up, serial biopsies, and molecular studies. Iron overload in our patient transplanted with a C282Y homozygous liver provides an "in vivo" model for the pathophysiology of hemochromatosis and further supports liver playing a primary role in the maintenance of iron hemostasis rather intestine being the sole regulatory site.

Biliary strictures after liver transplantation. Predictive factors for response to endoscopic management and long-term outcome.

BACKGROUND: Biliary strictures after liver transplantation are frequent. The long-term prognosis and predictive factors of response to endoscopic treatment are not well known. METHODS: The aim of this study was to demonstrate the role of endoscopic treatment, predictive factors of response, and outcome in patients with biliary stricture after liver transplantation. We performed a retrospective review of medical records of all consecutive post-liver transplantation patients who underwent endoscopic retrograde cholangiography in our center during the period from October 2001 to October 2006. RESULTS: Twenty-five of 43 patients referred for endoscopic retrograde cholangiography had biliary stricture. Eighteen had stricture at the area of the anastomosis alone, 2 patients had a stricture at the area of the anastomosis and also another area, and 5 had nonanastomotic biliary strictures. Twenty-one patients had a single stricture and 4 had more than 1 stricture. Initially 19 of 24 patients (79%) responded to endoscopic management with normalization of liver enzymes. Four patients (16%) did not respond clinically despite a successful endoscopic approach. All patients who did not respond to endoscopic dilation had more than 1 area of stricture. There was a significantly better response to endoscopic treatment in patients with an anastomotic stricture versus patients with nonanastomotic strictures 17/19 versus 2/5 (P = 0.042). CONCLUSIONS: In our experience, endoscopic treatment of anastomotic biliary strictures is highly effective with a good long-term outcome. The presence of nonanastomotic and multiple strictures should be considered a factor associated with poor response to endoscopic management.

Sarcoidosis mimicking primary sclerosing cholangitis requiring liver transplantation.

Sarcoidosis is a systemic granulomatous disease of unknown etiology. The association of the cholestatic pattern usually seen in sarcoidosis, with biliary duct changes resembling primary sclerosing cholangitis (PSC) is rare. Liver transplantation permits the histological evaluation of the complete explanted liver, making the diagnosis more reliable. In conclusion we present our experience with two patients with sarcoidosis requiring liver transplantation, who presented with clinical and radiological findings characteristics of primary sclerosing cholangitis.

Bronchobiliary fistula in a cirrhotic patient: a case report and review of the literature.

Bronchobiliary fistula is defined as the passage of bile in the bronchi. The presence of bronchobiliary fistula in patient with cirrhosis is extremely rare. Management of these fistulas is often very difficult and can be associated with high morbidity and mortality. We are presenting a patient with ethanol related cirrhosis and biliptysis in whom a diagnosis of bronchobiliary fistula was made. A review of the literature including diagnosis and management is performed.

Intraperitoneal rupture of ectopic varices: two case reports and a review of literature.

Intraperitoneal rupture of ectopic varices is a rare complication of portal hypertension. Few case reports have been published in the literature. We report 2 cases of ectopic varices with intraperitoneal hemorrhage. This review details their presentation, hospital course and treatment. The first patient was managed conservatively, and second had a successful TIPS (transjugular intrahepatic portosystemic shunt). Few guidelines for treatment are available. The management is individualized according to the condition of the patient and the resources available. Objectives of management include early diagnosis, aggressive fluid resuscitation, correction of coagulopathy, reduction of portal hypertension and if possible direct control of the bleeding vessel.

Neuropsychiatric complications after liver transplantation: role of immunosuppression and hepatitis C.

Neuropsychiatric complications are an important source of morbidity following orthotopic liver transplantation. Etiology of liver disease and type of immunosuppression are possible related factors. The aim of this study was to describe the prevalence of neuropsychiatric complications after liver transplantation, the role of immunosuppression, and the association between these and specific liver diseases such as hepatitis C. One hundred twenty-eight patients with liver transplants were studied. Tacrolimus was the primary immunosuppressant in 101 patients and cyclosporine in 27 patients. Seventy-five complications in 49 patients (38.2%) were reported. In 43 patients, the etiology was associated with immunosuppression: 36 on tacrolimus and 7 on cyclosporine (P = 0.34). Seventeen and four-tenths percent of patients with hepatitis C and 4.6% of patients without hepatitis C developed depression (P = 0.02). There is no difference between types of primary immunosuppression and neuropsychiatric complications. There is a significantly greater incidence of depression in patients transplanted for hepatitis C.

Polyarteritis nodosa and cryoglobulinemic glomerulonephritis related to chronic hepatitis C.

CASE REPORT: A 53-year-old man with hepatitis C virus (HCV) infection underwent cholecystectomy for presumed cholecystitis. Gallstones were not present, and histological examination demonstrated medium-sized arteritis, consistent with polyarteritis nodosa (PAN). The patient later developed rapidly progressive glomerulonephritis. Kidney biopsy demonstrated cryoglobulinemic glomerulonephritis. Because of the severity of the patient's vasculitic manifestations, treatment included pulse methylprednisolone followed by oral prednisone and monthly intravenous cyclophosphamide for 6 months. During treatment, microhematuria resolved, proteinuria decreased, and serum creatinine concentration stabilized. The patient subsequently underwent treatment for HCV with interferon resulting in a marked decrease in HCV RNA. The patient has had no relapse of his vasculitis, his renal function is stable, and viral load remains low after completing 36 weeks of interferon. CONCLUSION: Life-threatening vasculitis related to HCV was successfully treated with immunosuppressive therapy. After obtaining clinical remission, antiviral therapy was instituted, resulting in a dramatic decrease in HCV RNA.

Prospective multicenter study of eligibility for antiviral therapy among 4,084 U.S. veterans with chronic hepatitis C virus infection.

BACKGROUND: Many veterans may not be candidates for hepatitis C virus (HCV) treatment due to contraindications to therapy. The aims of this study were to determine the proportion of HCV-infected veterans who were eligible for interferon alfa and ribavirin therapy and to evaluate barriers to HCV treatment. METHODS: We prospectively enrolled 4,084 veterans who were referred for HCV treatment over a 1-yr period at 24 Veterans Affairs (VA) Medical Centers. Treatment candidacy was assessed using standardized criteria and the opinion of the treating clinician. RESULTS: Overall, 32.2% (95% CI, 30.8-33.7%) were candidates for HCV treatment according to standardized criteria, whereas 40.7% (95% CI, 39.2-42.3%) were candidates in the opinion of the treating clinician. Multivariable analysis identified ongoing substance abuse (OR = 17.68; 95% CI, 12.24-25.53), comorbid medical disease (OR = 9.62; 95% CI, 6.85-13.50), psychiatric disease (OR = 9.45; 95% CI, 6.70-13.32), and advanced liver disease (OR = 8.43; 95% CI, 4.42-16.06) as the strongest predictors of not being a treatment candidate. Among patients who were considered treatment candidates, 76.2% (95% CI, 74.0-78.3%) agreed to be treated and multivariable analysis showed that persons >/=50 yr of age (OR = 1.37; 95% CI, 1.07-1.76) and those with >50 lifetime sexual partners (OR = 1.44; 95% CI, 1.08-1.93) were more likely to decline treatment. CONCLUSIONS: The majority of veteran patients are not suitable candidates for HCV treatment because of substance abuse, psychiatric disease, and comorbid medical disease, and many who are candidates decline therapy. Multidisciplinary collaboration is needed to overcome barriers to HCV therapy in this population.