The impact of hepatitis C burden: an evidence-based approach.

BACKGROUND: Infection with the hepatitis C virus (HCV) has been considered a major cause of mortality, morbidity and resource utilisation in the US. In addition, HCV is the main cause of hepatocellular cancer (HCC) in the US. Recent developments in the diagnosis and treatment of HCV, including new recommendations pertaining to screening for HCV by the Centers for Disease Control and Prevention and newer treatment regimens with high efficacy, short duration and the potential for interferon-free therapies, have energised the health care practitioners regarding HCV management. AIM: To assess the full impact of HCV burden on clinical, economic and patient-reported outcomes. METHODS: An expert panel was convened to assess the full impact of HCV burden on a number of important outcomes using an evidence-based approach predicated on Grading of Recommendations Assessment, Development and Evaluation methodology. The literature was summarised, graded using an evidence-based approach and presented during the workshop. Workshop presentations were intended to review recent, relevant evidence-based literature and provide graded summary statements pertaining to HCV burden on topics including the relationships between HCV and the development of important outcomes. RESULTS: The associations of HCV with cirrhosis, HCC, liver-related mortality, type 2 diabetes mellitus, rheumatological diseases and quality of life impairments are supported by strong evidence. Also, there is strong evidence that sustained viral eradication of HCV can improve important outcomes such as mortality and quality of life. CONCLUSIONS: The current evidence suggests that HCV has been associated with tremendous clinical, economic and quality of life burden.

Treatment of Budd-Chiari syndrome in a liver transplant unit, the role of transjugular intrahepatic porto-systemic shunt and liver transplantation.

BACKGROUND: Budd-Chiari syndrome is an uncommon cause of liver failure usually associated with an underlying hypercoagulable state. AIM: To evaluate current trends in management of Budd-Chiari syndrome at our institution. METHODS: Twenty-two patients with Budd-Chiari syndrome underwent transjugular intrahepatic porto-systemic shunt, liver transplantation, or both in between 1992 and 2001. We analysed underlying diagnosis, medical therapy, complications, follow-up and overall outcomes. RESULTS: Five patients (17%) presented with fulminant liver failure and 17 patients (83%) with new-onset ascites or chronic liver disease. Seventeen patients (74%) underwent transjugular intrahepatic porto-systemic shunt: improvement or stabilization occurred initially in 14 (82%), whereas the other three patients died within a month. At a mean 3 years follow-up eight patients (47%) continued to do well clinically and four have died (23.5%); seven have required transjugular intrahepatic porto-systemic shunt revisions (mean 2.3 interventions), five have experienced transjugular intrahepatic porto-systemic shunt occlusion managed with new transjugular intrahepatic porto-systemic shunt placement and five patients underwent subsequent transplantation. Of the 10 patients who underwent liver transplantation, patient and graft survival are 80% at a mean 5.7 years of follow-up. No patient developed post-transplant Budd-Chiari syndrome. CONCLUSIONS: Transjugular intrahepatic porto-systemic shunt is usually feasible in patients with Budd-Chiari syndrome, and is best suited as a bridge to more timely liver transplantation. Long-term success of transjugular intrahepatic porto-systemic shunt is limited and usually requires revision, placement of a new shunt or liver transplantation. Liver transplantation with chronic anticoagulation offers excellent short- and medium-term patient and graft survival. In our series, there was no recurrence of Budd-Chiari syndrome after liver transplantation.

Immunosuppression in liver transplantation.

This article highlights the currently available immunosuppressive medications that are used to prevent or treat hepatic allograft rejection. Currently-available immunosuppressive medications are highly effective in prevention of allograft rejection, graft loss, and patient death. However, side effects of medications are common, usually dose-related, and specific to the administered drug. Maintenance immunosuppression which has been primarily based upon calcineurin inhibitors (Cyclosporine, CsA, or tacrolimus, Tac) is commonly modified to reduce metabolic complications of therapy. Toxic consequences of steroids may be ameliorated by steroid withdrawal without risk of acute rejection or immunologic graft loss. Calcineurin-sparing regimens may include use of mycophenolate mofetil (MMF) or sirolimus, and allow reduction in doses and plasma levels of CsA and Tac. Recurrence of hepatitis C is universal after liver transplantation and progresses rapidly, compared to its natural history in non-immunocompromised patients. Unfortunately, no single immunosuppressive agent or strategy has yet been shown to convincingly modify the course of post-transplant recurrence. Most centers manage recurrenc hepatitis C by either steroid avoidance, reduction in immunosuppression, or institution of antiviral therapy. Ongoing advances in immunosuppressive and antiviral medications will allow tailoring of the immunosuppressive prescription, which undoubtedly will benefit current and future liver recipients.

Adult-to-adult living donor liver transplantation using right-lobe grafts: results and lessons learned from a single-center experience.

Living donor liver transplantation (LDLT) for adults is now a practical alternative to cadaveric liver transplantation. Use of right-lobe grafts has become the preferred donor procedure. Because of the complexity of this operation, a learning curve is to be expected. We report the outcome of our first 41 LDLTs at the University of Colorado Health Sciences Center (Denver, CO). We also discuss the lessons learned and the resultant modifications in the procedure that evolved during our series. Patient records were retrospectively reviewed between August 1997 and February 2001 for the following end points: recipient survival, graft survival, and donor and recipient complications. Thirty-eight of 41 living donor liver transplant recipients (93%) are alive and well postoperatively with a mean follow-up of 9.6 months. Four patients required retransplantation secondary to technical problems (9.8%); all 4 patients were in our initial 11 cases. Modification of the donor liver plane of transection resulted in venous outflow improvement. Also, biliary management was modified during the series. Donor complications are listed; all 41 donors have returned to normal pretransplantation activity. Our results indicate that LDLT can be performed safely with excellent donor and recipient outcomes. Dissemination of our experience can help shorten the learning curve for other institutions.

Right hepatic lobe donation for living donor liver transplantation: impact on donor quality of life.

Adult right hepatic lobe living donor liver transplantation (LDLT) has rapidly gained widespread acceptance as an effective procedure for selected patients with end-stage liver disease. However, there are currently no published data on the effect of this procedure on the quality of life of donors. We report the results of a survey of our living liver transplant donors to determine the effect of right hepatic lobe donation on quality of life. We have performed 30 LDLTs since 1997; 24 of these have a follow-up of 4 months or longer. In August 2000, these patients were sent a questionnaire (including a Medical Outcomes Study 36-Item Short-Form Survey) regarding psychosocial outcomes and symptoms after surgery. Major complications occurred in 4 of 24 patients (16%), and minor complications, in 4 of 24 patients (16%). Complete recovery occurred in 75% of patients at a mean time of 3.4 months. Ninety-six percent of patients returned to the same predonation job after a mean time of 2.4 months, and 66% of patients required a period of light-duty work for a mean of 2.8 months before returning to full-duty work. A change in body image was reported in 42% of patients, and 71% reported mild ongoing symptoms (primarily abdominal discomfort) that they related to the donor surgery for which 29% sought evaluation by a physician. The donor's relationship with the recipient was the same or better in 96% of donors, and the relationship with the donor's significant other was the same or better in 88% of donors. Mean out-of-pocket expenses incurred by donors were $3,660. Sixty-three percent of donors reported experiencing more pain than anticipated. All patients would donate again if necessary, and 96% benefited from the donor experience. In conclusion, (1) all our donors are alive and well after donation; (2) almost all donors were able to return to predonation employment status within a few months; (3) most donors have mild persistent abdominal symptoms, and some donors had a change in body image that they attribute to the donor surgery; and (4) this information should be provided to potential donors so they may better understand the impact of donor surgery.

Endoscopic localization and management of colonic bleeding in patients with portal hypertension.

In patients with portal hypertension, vascular lesions in the colon may develop that have been collectively termed portal hypertensive colopathy. Endoscopic diagnosis of these lesions is now established, but the management of hemorrhage from them is not. We report five cases of endoscopic management of bleeding colonic vascular lesions in patients with portal hypertension. Endoscopy data from January 1, 1996 to June 30, 1999 identified 158 patients with portal hypertension who underwent colonoscopy. Forty-five of these 158 patients had portal hypertensive colopathy (angiodysplasias or varices). Those who had colonoscopic hemostasis attempted were identified and reviewed. Five patients underwent colonoscopic intervention for bleeding. Initial hemostasis was achieved in four of five cases. Repeat endoscopic intervention was necessary in three of the four cases. One patient required surgery. In patients with portal hypertension, colonic vascular lesions may develop. Hemorrhage from these lesions is rare. Colonoscopy is effective for localization and diagnosis of bleeding vascular lesions and permits simultaneous hemostatic intervention.

Dyslipidemia during sirolimus therapy in liver transplant recipients occurs with concomitant cyclosporine but not tacrolimus.

Since its approval as an immunosuppressive agent in renal transplantation, sirolimus (RAPA) recently has been used in the primary immunosuppression regimen at several liver transplant centers. One of the major side effects of RAPA is hypercholesterolemia, which is reported in up to 44% of patients. We describe our experience in 57 primary liver transplant recipients treated with RAPA and either cyclosporine A (CSA) or tacrolimus (TAC). We report the incidence and severity of hypercholesterolemia using a prednisone-free immunosuppressive regimen. Between January 2000 and September 2000, a total of 57 patients underwent transplantation at the University of Colorado Health Sciences Center (Denver, CO) with RAPA and either CSA or TAC. The initial 10 patients who underwent transplantation under this protocol were not administered corticosteroids, and the subsequent 47 patients were administered only 3 doses of methylprednisolone days 0, 1, and 2 postoperatively (1, 0.5, and 0.5 g, respectively). Total fasting cholesterol, high-density cholesterol, low-density cholesterol, and triglyceride levels were measured at monthly intervals. Mean serum cholesterol level was significantly greater in CSA patients (200 mg/dL) compared with TAC patients (158 mg/dL; P =.0003). Serum triglyceride levels were more than 2-fold greater with CSA (292 mg/dL) compared with TAC (134 mg/dL; P =.002). Hypercholesterolemia (cholesterol > 240 mg/dL) was present in 10 of 57 patients (18%) and was significantly more common in CSA-treated patients (8 of 27 patients; 30%) compared with TAC-treated patients (2 of 30 patients; 6%; P <.05). Hypertriglyceridemia (serum triglyceride > 300 mg/dL) was present in 10 of 57 patients (18%) and was significantly more common in CSA-treated patients (9 of 27 patients; 33%) compared with TAC-treated patients (1 of 30 patients; 3%; P <.05). We conclude that (1) concomitant use of TAC with RAPA reduces the prevalence and severity of posttransplantation dyslipidemia, and (2) these findings have important implications in the prevention of complications of hypercholesterolemia in liver transplant recipients.

Cirrhosis in Turner's syndrome: case report and literature review.

A case of cryptogenic cirrhosis in a patient with Turner's syndrome is presented. The individual was admitted for upper gastrointestinal bleeding due to oesophageal varices. After failure of medical treatment, a transjugular intra-hepatic portal systemic shunt was used to control the bleeding. A liver biopsy revealed cirrhosis with minimal necro-inflammatory activity and no steatosis. Immunohistochemical staining for HCV, HBsAg and HBcAg was negative. No other risk factor for liver disease was recognized and none of the known causes of chronic liver disease was identified after a thorough evaluation for such. Turner's syndrome is a genetic disorder due to X chromosome monosomy in which a wide range of congenital anomalies can occur. Cardiac, renal and skeletal anomalies are all well recognized. The possible association of Turner's syndrome with cirrhosis is herein discussed along with a review of the published literature.

Preliminary observation: oral zinc sulfate replacement is effective in treating muscle cramps in cirrhotic patients.

BACKGROUND: While not life threatening, muscle cramps severely affect the quality of life of patients with cirrhosis. AIM: To determine whether oral zinc sulfate therapy decreases the frequency and severity of muscle cramps in cirrhotic patients. METHODS: 12 patients with cirrhosis (5 Child's A, 3 Child's B, and 4 Child's C), hypozincemia and muscle cramps at least thrice weekly received oral zinc sulfate 220 mg BID for 12 weeks. Patients answered a questionnaire regarding their muscle cramps symptoms at the beginning and end of the study. RESULTS: Muscle cramps occurred in all patients at rest, mainly while sleeping (8/12), and in two patients also during exercise. Cramps were located in calves (10/12), feet (4/12) and hands (4/12) more commonly. Zinc supplementation improved cramps in 10/12 patients, and in seven of these patients the cramps completely resolved. One patient experienced mild watery diarrhea that resolved upon discontinuation of the zinc sulfate. No other complication of zinc supplementation was noted. CONCLUSION: A potential relationship between zinc deficiency and muscle cramps in the setting of cirrhosis has not been suggested before. Zinc supplementation may lead to improvement in symptoms associated with muscle cramps in cirrhosis.

Cytokines in alcoholic liver disease.

Cytokines are low-molecular-weight mediators of cellular communication produced by multiple cell types in the liver, with the Kupffer cell critically important. Inflammatory cytokines such as tumor necrosis factor, interleukin-1, and interleukin-8, and hepatic acute-phase cytokines such as interleukin-6 play a role in modulating certain metabolic complications in alcoholic liver disease and probably play a role in the liver injury of alcoholic liver disease. Two potential inducers of cytokine production in alcoholic liver disease are endotoxin and reactive oxygen species generated after ethanol metabolism. Cytotoxic cytokines likely induce liver cell death by both necrosis and apoptosis in alcoholic liver disease. Anticytokine therapy has been highly successful in attenuating cell injury/death in a variety of toxin-induced models of liver injury, including alcohol-related liver injury. Anticytokine therapy has been used successfully in humans in disease processes such as Crohn's disease and rheumatoid arthritis. There is an emerging rationale for use of anticytokine therapy in alcoholic liver disease, with the goal of maintaining beneficial effects of cytokines and inhibition of the deleterious effects of these potentially toxic agents.

Budd-Chiari syndrome. Treatment options and the value of liver transplantation.

The Budd-Chiari syndrome encompasses a group of conditions that cause partial or complete obstruction of the hepatic venous outflow tract. This leads to hepatocyte necrosis which can manifest as a devastating fulminant illness, or a more indolent condition that eventually presents with features of portal hypertension. Doppler ultrasonography of the hepatic veins and inferior vena cava has become the initial diagnostic test of choice, but most patients require venography and liver biopsy prior to definitive therapy. Multiple therapeutic modalities have been used for the Budd-Chiari syndrome, including medical, radiological, and surgical approaches. The role, indications, and outcome of liver transplantation for individuals with the Budd-Chiari syndrome are discussed.

Immunosuppressive drug-induced leukoencephalopathy in patients with liver transplant.

Organ transplantation has become a practical and effective option for patients with acute and/or chronic irreversible organ disease. However, solid organ transplantation is associated with many different complications which depend upon the specific surgical procedure and/or confounding medical problems (e.g. rejection, infection, adverse effect of immunosuppressive agents) experienced by a given patient. Tacrolimus and cyclosporin A are immunosuppressive drugs used to prevent rejection following allogeneic solid organ transplantation. Adverse events are common with both drugs and include long-term organ dysfunction, opportunistic infections, haematopoietic alterations, nephrotoxicity and neurotoxicity. Neurological complications, both central and peripheral, occur in 10-42% of transplant recipients using either of these two immunosuppressive agents. Two cases of reversible posterior leukoencephalopathy manifested by headache, nausea and seizures associated with the use of immunosuppressive drugs following liver transplantation are reported.

Alcoholic liver disease. Treatment strategies for the potentially reversible stages.

Even modest alcohol ingestion can increase the risk of steatosis, and long-term, excessive consumption can lead to alcoholic hepatitis and eventually cirrhosis. Most patients with clinically significant alcoholic liver disease have histologic findings typical of all three conditions. The only clearly beneficial treatment is abstinence from alcohol. Abstinence in combination with proper nutrition and general supportive care is state of the art. Steatosis is reversible upon withdrawal of alcohol, but alcoholic hepatitis can persist even with abstinence and may progress to cirrhosis. Corticosteroid therapy may reduce short-term mortality rates in patients with moderate or severe alcoholic hepatitis who have hepatic encephalopathy but no evidence of infection or gastrointestinal bleeding. Treatment with colchicine may decrease the risk of cirrhosis; however, once cirrhosis has developed, the liver damage is irreversible. The prognosis is improved with abstinence, but complications (e.g., ascites, gastrointestinal bleeding) often occur. Liver transplantation may be considered in patients with severe complications.

Nontraumatic abdominal pain.

Nontraumatic abdominal pain is a common complaint of adult patients in acute care settings. The causes of abdominal pain are numerous and can be benign or life threatening. The advanced practice nurse must be able to differentiate abdominal pain from acute and nonacute sources so that rapid and effective treatment can be implemented.

Chronic alcohol consumption intensifies caerulein-induced acute pancreatitis in the rat.

Rats were chronically fed either an ethanol-containing diet (36% of total calories derived from alcohol) or a pair-fed, control diet (no alcohol) for 8 wk, and acute pancreatitis (AP) was subsequently induced by a 3-h i.v. infusion of caerulein (CR) at a dose of 5 micrograms/kg/hr. CR-induced AP in control rats (no alcohol) was characterized by a significant elevation in serum lipase content, pancreatic interstitial edema, infrequent occurrences of karyorrhexis, and the appearance of vacuoles in acinar cells. Chronic feeding of the ethanol diet followed by treatment with CR resulted in increases in serum lipase content, interstitial edema, karyorrhexis, and acinar vacuolization that were significantly greater than that seen in rats fed the control diet and treated with CR. It is concluded that chronic ethanol intake in the rat intensifies AP that is subsequently induced by CR.