The goal of HBV treatment is to improve survival by preventing disease progression to decompensated cirrhosis and HCC. This goal can be achieved if HBV replication is suppressed in a sustained manner. For these reasons the prolonged treatment with oral nucleos(t)ide analogues is recommended for selected patients with chronic HBV infection. These therapies have to be continued until the possible seroconversion (HBsAg/anti-HBsAg) which is actually an uncommon event. Therefore, NA-therapy can assume a lifelong duration. A variety of long-term adverse events have been reported in patients with HIV infection on antiretroviral therapy including one or more nucleoside reverse transcriptase inhibitors.

Here we describe 3 clinical cases of peripheral neuropathy related to long-term anti-HBV treatment possibly due to mitochondrial toxicity related to long-term NA treatment in HBV-infected patients.