Current therapeutic strategies for recurrent hepatitis B virus infection after liver transplantation

Hepatitis B virus (HBV)-related liver disease is the leading indication for liver transplantation (LT) in Asia,especially in China.With the introduction of hepatitis B immunoglobulin (HBIG) and oral antiviral drugs,the recurrent HBV infection rate after LT has been evidently reduced.However,complete eradication of recurrent HBV infection after LT is almost impossible.Recurrent graft infection may lead to rapid disease progression and is a frequent cause of death within the fi rst year after LT.At present,the availability of new oral medications,especially nucleoside or nucleotide analogues such as adefovir dipivoxil,entecavir and tenofovir disoproxil fumarate,further strengthens our ability to treat recurrent HBV infection after LT.Moreover,since combined treatment with HBIG and antiviral agents after liver re-transplantation may play an important role in improving the prognosis of recurrent HBV infection,irreversible graft dysfunction secondary to recurrent HBV infection in spite of oral medications should no longer be considered an absolute contraindication for liver re-transplantation.Published reviews focusing on the therapeutic strategies for recurrent HBV infection after LT are very limited.In this article,the current therapeutic strategies for recurrent HBV infection after LT and evolving new trends are reviewed to guide clinical doctors to choose an optimal treatment plan in different clinical settings.

Risks faced by donors of right lobe for living donor liver transplantation

BACKGROUND: Because of the shortage of deceased donors with livers fit for transplantation, living donor liver transplantation (LDLT) is becoming an attractive alternative. Attention should be paid to the donors, especially to those of the right lobe. In this study, we evaluated the risks faced by donors of the right lobe for adult-to-adult LDLT. METHODS: The perioperative data from 105 consecutive living donors of the right lobe performed in West China Hospital from January 2002 to December 2007 were retrospectively studied. Preoperative evaluation included CT, MRCP, and intraoperative cholangiography, showing liver volume, hepatic vasculature and the biliary system. The standard liver volume (SLV) and the ratio of left lobe volume to SLV were calculated. The right lobe grafts were obtained by transecting the liver on the right side of the middle hepatic vein without inflow vascular occlusion, using an ultrasonic dissector. After operation the donors were monitored in the Intensive Care Unit for about three days. Each donor was followed up for at least 6 months. RESULTS: There was no donor mortality. Major complications occurred in 14 donors (13.3%), of whom 3 received conservative treatment, 8 required invasive paracentesis, and 3 required further surgery. All donors were recovered well and resumed their previous occupations. CONCLUSIONS: Donors of the right lobe face low risks. The preoperative evaluation, especially evaluation of the volume of the remnant liver, should be exact. During the operation, the patency of the remnant hepatic vasculature and bile duct must be preserved, and the extent of injury to the remnant liver should be limited as much as possible. The detection and treatment of postoperative complications should be diligently performed.

Clinicopathological characteristics of 15 patients with combined hepatocellular carcinoma and cholangiocarcinoma

BACKGROUND: Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is a rare subtype of primary liver cancer, and clinicopathological features of cHCC-CC have seldom been reported in detail. This study was undertaken to explore the diagnosis and clinicopathological characteristics of cHCC-CC in comparison with hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC), respectively. METHODS: The clinical data from 15 patients with cHCC-CC, 132 patients with HCC and 44 patients with CC who had undergone hepatic resection were analyzed retrospectively. Clinicopathological characteristics of cHCC-CC, HCC and CC such as hepatitis B viral infection, serum hepatitis C virus (HCV) antibody, serum alpha-fetoprotein (AFP) level, cirrhosis, vascular invasion, lymph node metastasis, surgical procedure and adjuvant treatment were also analyzed. Follow up was carried out in the patients, and their 1-, 3-, and 5-year survival rates were calculated. RESULTS: Two patients with cHCC-CC were correctly diagnosed by enhanced CT before operation, the other 13 patients were diagnosed by histology and immunohistochemistry after operation. Radical (8/15) and conservative hepatectomy (7/15) for cHCC-CC was similar to that for HCC and CC (P > 0.05). Pathologically cHCC-CC showed more significantly vascular invasion and lymph node metastasis than HCC (P < 0.05), and a similarity to CC (P > 0.05). Hepatitis B viral infection, serum HCV antibody, cirrhosis, and serum AFP level of cHCC-CC patients were similar to those of HCC patients (P > 0.05) but different from CC patients (P < 0.05). The cumulative 1-, 3-, and 5-year survival rates in patients with cHCC-CC were poorer than in patients with HCC or CC (P < 0.05). CONCLUSIONS: Patients with cHCC-CC are seldom diagnosed before operation. The progression of cHCC-CC is more rapid than that of HCC or CC. Survival rate of patients with cHCC-CC after hepatic resection is poorer than that of patients with HCC or CC.

Autologous transfusion with modified total hepatic vascular exclusion for extracapsular resection of giant hepatic cavernous hemangioma

BACKGROUND: This paper was to review the effects of intraoperative autologous transfusion during modified, normal-temperature, total hepatic vascular exclusion (THVE) for extracapsular resection of giant hepatic cavernous hemangioma. METHODS: The clinical data from 28 patients, who underwent hepatic resection requiring intraoperative autologous transfusion with the cell-saver apparatus, were analyzed retrospectively. The tumors in the 28 patients involved the proximal hepatic veins and inferior vena cava. The diameters of these hemangiomas ranged from 12x15 cm to 18-40 cm. All patients had varying degrees of THVE. ' RESULTS: The 28 patients with hemangioma received integrated resection and recovered. One patient had rupture of tumors resulting in massive hemorrhage of 6000 ml during liver resection; 4 patients had blood transfusions of 400-800 ml; the other 23 patients had no blood transfusion. Only 6 patients underwent the Pringle maneuver with resection. The other 22 patients underwent THVE during the liver resection. The interval of THVE was 5-30 minutes (mean 16 minutes). CONCLUSIONS: Intraoperative autologous transfusion during modified, normal-temperature THVE for extracapsular resection of huge hepatic cavernous hemangioma is feasible.

Efficacy of middle hepatic vein reconstruction in adult right-lobe living donor liver transplantation

BACKGROUND: Congestion of the right anterior segment may lead to graft dysfunction in right-lobe living donor liver transplantation (LDLT) without a middle hepatic vein (MHV) trunk. Selective reconstruction of MHV tributaries with the interposition of vascular grafts has been introduced to overcome this problem. However, there is still no consensus on the definite criteria of MHV reconstruction. METHODS: LDLT patients were reviewed to evaluate the effects of MHV reconstruction. From March 2005 to September 2008 in our transplantation center, 120 consecutive LDLTs were performed using a right-lobe graft without a MHV. Excluding 11 patients, among the remainder, 73 (67%) had reconstructed MHV tributaries, and the others 36 (33%) did not. The values of liver functional index and liver graft regeneration ratio were compared between the two groups. RESULTS: There was a prolonged period of liver functional recovery in patients with small-for-size grafts and a graft-recipient weight ratio (GRWR) <1.0%, and without MHV reconstruction. The ratio of liver regeneration 1 month postoperatively in reconstruction cases was 81%, versus 78% in patients without reconstruction (P=0.352), but among small-for-size grafts, there was a significant difference between the two groups (95% vs. 80%). CONCLUSION: Our study shows that reconstruction of MHV tributaries is not necessary in all patients, but is beneficial for patients with GRWR <1.0%. (Hepatobiliary Pancrent Dis Int 2010; 9: 135-138)

Microsurgical reconstruction of hepatic artery in A-A LDLT:124 consecutive cases without HAT

AIM:To retrospectively investigate microsurgical hepatic artery(HA) reconstruction and management of hepatic thrombosis in adult-to-adult living donor liver transplantation(A-A LDLT).METHODS:From January 2001 to September 2009,182 recipients with end-stage liver disease underwent A-A LDLT.Ten of these patients received dual grafts.The 157 men and 25 women had an age range of 18 to 68 years(mean age,42 years).Microsurgical techniques and running sutures with back-wall first techniques were performed in all arterial reconstructions under surgical loupes(3.5 ×) by a group of vascular surgeons.Intimal dissections were resolved by interposition of the great saphenous vein(GSV) between the donor right hepatic artery(RHA) and recipient common HA(3 cases) or abdominal aorta(AA)(2 cases),by interposition of cryopreserved iliac vessels between the donor RHA and recipient AA(2 cases).RESULTS:In the 58 incipient patients in this series,hepatic arterial thrombosis(HAT) was encountered in 4 patients,and was not observed in 124 consecutive cases(total 192 grafts,major incidence,2.08%).All cases of HAT were suspected by routine color Doppler ultrasonographic examination and confirmed by contrast-enhanced ultrasound and hepatic angiography.Of these cases of HAT,two occurred on the 1st and 7th d,respectively,following A-A LDLT,and were immediately revascularized with GSV between the graft and recipient AA.HAT in one patient occurred on the 46th postoperative day with no symptoms,and the remaining case of HAT occurred on the 3rd d following A-A LDLT,and was cured by thrombolytic therapy combined with an anticoagulant but died of multiorgan failure on the 36th d after A-A LDLT.No deaths were related to HAT.CONCLUSION:Applying microsurgical techniques and selecting an appropriate anastomotic artery for HA reconstruction are crucial in reducing the high risk of HAT during A-A LDLT.

Outcome of hepatocellular carcinoma treated by liver transplantation:comparison of living donor and deceased donor transplantation

BACKGROUND: Liver transplantation (LT) has been widely accepted as the treatment of choice for end-stage liver diseases. Due to the scarcity of cadaveric donors, adult-to-adult living donor liver transplantation (LDLT) is advocated as a practical alternative to deceased donor liver transplantation (DDLT). However, some reports suggest that the long-term and recurrence-free survival rates of LDLT are poorer than those of DDLT for hepatocellular carcinoma (HCC). This study aimed to compare the long-term and recurrence-free survival rates of HCC between LDLT and DDLT. METHODS: We retrospectively analyzed the clinical data of 150 patients with HCC from January 2005 to March 2009. Eleven patients who died of complications during the perioperative period were excluded. The remaining 139 eligible patients (101 DDLT and 38 LDLT) were regularly followed up to October 2009. The Chi-square test or Fisher's exact test were used to compare the characteristics of LDLT and DDLT. The long-term and recurrence-free survival curves of both groups were determined using the Kaplan-Meier method with comparisons performed using the log-rank test. One-way analysis of variance was performed to compare the waiting time of the two groups. RESULTS: Survival rates at 1, 2, 3, and 4 years for LDLT were 81%, 62%, 53%, and 45% and for DDLT were 86%, 60%, 50%, and 38%, respectively. The overall 1-, 2-, 3-, and 4-year recurrence-free rates for LDLT were 71%, 49%, 42%, and 38%, and for DDLT were 76%, 52%, 41%, and 37%, respectively. No significant differences were found by the log-rank test on both long-term and recurrence-free survival rates. CONCLUSIONS: The role of LDLT is reinforced by our study. It may expand the donor pool and achieve the same long-term and recurrence-free survival rates of DDLT.

Improved early diagnosis of cystadenocarcinoma of the pancreas

BACKGROUND: Cystadenocarcinoma of the pancreas is insensitive to radiotherapy and chemotherapy, and surgery is at present the definitive treatment. Early and accurate diagnosis of cystadenocarcinoma is crucial for increasing the five-year survival rate and the resectable rate. There is no definitive and effective method of early diagnosis of cystadenocarcinoma of the pancreas in China and other countries. METHODS: We compared endoscopic ultrasonography-guided (EUS-guided) fine needle aspiration biopsy combined with cyst fluid carcinoembryonic antigen (CEA), CA19-9 examination with computed tomography (CT), B-ultrasonography (B-US) and serum CEA and CA19-9, to explore methods of early diagnosis of cystadenocarcinoma of the pancreas. Retrospective analysis was made on the clinical data of 126 cases of benign pancreatic lesion (90 cases) and cystadenocarcinoma (36). RESULTS: The sensitivity of B-US and CT for cystadenocarcinoma was 52.8% and 77.8%, while the specificity was 78.9% and 86.7%, respectively. When measurement of CEA and CA19-9 of cyst fluid was combined with EUS-guided fine needle aspiration biopsy, the sensitivity was 94.4%, higher than that of B-US and CT (P<0.05). The sensitivity of cyst fluid CEA, CA19-9 examinations was considerably higher than that of serum CEA, CA19-9 (P<0.05). Upper gastrointestinal barium meal and endoscopic retrograde cholangiopancreatography (ERCP) had low sensitivity and specificity. CONCLUSIONS: EUS-guided fine needle aspiration biopsy combined with examination of cyst fluid CEA, CA19-9 is a credible means for early diagnosis of cystadenocarcinoma of the pancreas. B-US, CT and serum CEA, CA19-9 measurements are in common use, their findings are also very important.

Postoperative complications after liver transplantation with cavoportal hemitransposition

BACKGROUND: Extensive portal vein thrombosis (PVT) in the recipient of liver transplantation increases postoperative morbidity and mortality. Cavoportal hemitransposition (CPHT) has been described as a salvage technique in the presence of extensive portal and superior mesenteric venous thrombosis. METHODS: We report three patients who underwent this procedure, review the literature, and discuss the postoperative complications of CPHT. RESULTS: Fifty-six patients with extensive PVT who underwent CPHT have been reported. Seventeen patients have died to date. The common complications of CPHT were ascites (55.4%), renal insufficiency (48.2%), variceal bleeding (30.4%), or thrombosis of cavoportal anastomosis or portal branch (14.3%). CONCLUSION: CPHT is a salvage measure to maintain the patency of portal inflow to the liver graft in the presence of extensive PVT.

Treatment of hepatic venous outflow stenosis after living donor liver transplantation by insertion of an expandable metallic stent

BACKGROUND: Hepatic venous outflow stenosis is an uncommon but serious complication after right lobe living donor liver transplantation (LDLT). Failure to recognize and treat this complication early can result in graft failure and even death. The early diagnosis and management of hepatic venous outflow stenosis has become an important issue. METHOD: We report a case with this complication treated by endovascular stent placement in the early period after right lobe LDLT and review related reports to explore the possible mechanism. RESULTS: A 44-year-old man with end-stage hepatitis B liver cirrhosis underwent right lobe LDLT. On postoperative day 13, his liver function deteriorated and he developed refractory ascites for maximal diuretic therapy. Hepatic venography showed a stenosis with an element of torsion of the venous drainage proximal to the anastomosis of the right hepatic venous orifice and inferior vena cava. The stenosis was successfully treated by insertion of an expandable metallic stent. CONCLUSIONS: The result demonstrates that stent placement for stenosis is safe and effective. We suspect that rapid hypertrophy of an asymmetric right lobe graft may result in hepatic venous outflow stenosis caused by twisting or external compression of the hepatic veins.

Potential etiopathogenesis of seventh day syndrome following living donor liver transplantation:ischemia of the graft?

BACKGROUND: Seventh-day syndrome (7DS) is an early serious complication following liver transplantation with a high mortality because of its unknown etiopathogenesis. This study aimed to analyze the potential etiopathogenesis of 7DS. METHODS: A retrospective analysis of 98 consecutive living donor liver transplants performed from 2001 to 2007 at our center revealed that 5 patients had suffered from 7DS; their age, MELD score, portal vein inflow and other parameters were compared with those of the other recipients. RESULTS: The 5 patients showed common features: (a) initial uneventful recovery, and a dramatic rise of serum liver enzyme levels I to 2 weeks later; (b) decreased inflow in the portal vein accompanied by augmentation of serum creatinine and urea nitrogen level; and (c) serial liver biopsy findings of apoptosis and ischemic necrosis of hepatocytes. Four of the 5 patients died. Age, waiting time to transplantation, MELD score, operation time, cold ischemic time, portal interceptive time and diameter of the portal vein were not significantly different between the 2 groups, but a difference was found in the flow rate of the portal vein (t=3.234, P<0.001). CONCLUSIONS: The 5 patients suffered from a decreased portal vein inflow, ischemic liver necrosis, and renal failure. Hence, hypoperfusion of the liver graft was considered to be the etiopathogenesis of 7DS, for which, however sufficient evidence is lacking. More studies of 7DS are needed.

Adult-to-adult living donor liver transplantation for malignant metastatic melanoma to the liver

BACKGROUND. Metastases from malignant melanoma to the liver are rare in China, and surgical resection may be of potential benefit. Liver transplantation for this disease has never been reported. METHODS. We report a case of adult-to-adult living donor liver transplantation (A-A LDLT) for metastatic melanoma. With a surgical history of ocular melanoma, the recipient presented with emaciation from a large right hepatic mass which also probably had portal vein invasion. A-A mur was successfully performed and no postoperative complications were observed in either the donor or the recipient. Postoperative pathology confirmed the diagnosis of metastatic malignant melanoma; however no adjuvant chemotherapy was employed after transplantation. We also reviewed the literature on the surgical treatment of metastatic malignant melanoma to the liver and discussed the LDLT indications. RESULT: Recurrence occurred 6 months after surgery and the patient died from recurrence of the disease 8 months post-transplant. CONCLUSIONS. Review of the literature suggested that only a small subset of selected patients may benefit from liver resection. Large metastatic disease in the liver potentially involving a major vessel, as in this case, should be contraindicated for liver transplantation. (Hepatobiliary Pancreat Dis Int 2010; 9: 329-332)

Measures for increasing the safety of donors in living donor liver transplantation using right lobe grafts

BACKGROUND: The safety of donors in living donor liver transplantation (LDLT) should be the primary consideration. The aim of this study was to report our experience in increasing the safety of donors in LDLTs using right lobe grafts. METHODS: We retrospectively studied 37 living donors of right lobe grafts from January 2002 to March 2006. The measures for increasing the safety of donors in LDLT included carefully selected donors, preoperative evaluation by ultrasonography, angiography and computed tomography; and necessary intraoperative cholangiography and ultrasonography. Right lobe grafts were obtained using an ultrasonic dissector without inflow vascular occlusion on the right side of the middle hepatic vein. The standard liver volume and the ratio of left lobe volume to standard liver volume were calculated. RESULTS: There was no donor mortality in our group. Postoperative complications only included bile leakage (I donor), biliary stricture (1) and portal vein thrombosis (1). All donors recovered well and resumed their previous occupations. In recipients, complications included acute rejection (2 patients), hepatic artery thrombosis (1), bile leakage (1), intestinal bleeding (1), left subphrenic abscess (1) and pulmonary infection (1). The mortality rate of recipients was 5.4% (2/37); one recipient with pulmonary infection died from multiple organ failure and another from occurrence of primary disease. CONCLUSIONS: The first consideration in adult-to-adult LDLT is the safety of donors. The donation of a right lobe graft is safe for adults if the remnant hepatic vasculature and bile duct are ensured, and the volume-of the remnant liver exceeds 35% of the total liver volume.

A successful pregnancy following liver transplantation

BACKGROUND: The safety and possibility of pregnancy following liver transplantation has been the hot topic in transplant. A case is reported with a review the of literature. METHOD: The data of a 22-year-old pregnant patient with end-stage liver disease who had undergone orthotopic liver transplantation in September 28, 2000 were analyzed retrospectively. RESULTS: After surgery, the patient was uneventfully recovered and was pregnant at the time of the 33rd month postoperation. The patient experienced a rejection on the 8th week of pregnancy and was successfully treated at this hospital. The patient was closely monitored throughout her pregnancy, and received routine antenatal care with respect to sonographic screening. Caesarean section was performed in March 18, 2004, and a health live-born infant weighing 2000 g was delivered at full-term. After the delivery, the patient was satisfactory with, her health and the baby was healthy. CONCLUSION: Under close monitoring, successful pregnancy following liver transplantation is possible and safe in women with end-stage liver diseases.